title: Vaccination against COVID-19 and society return to normality in England: a modelling study of impacts of different types of naturally acquired and vaccine induced immunity

abstract:
ObjectivesTo project impacts of mass vaccination against COVID-19, and investigate possible impacts of different types of naturally acquired and vaccine-induced immunity on future dynamics of SARS-CoV-2 transmission from 2021 to 2029 in England.

DesignDeterministic, discrete-time population dynamic modelling.

ParticipantsPopulation in England.

Interventionsmass vaccination programmes.

Outcome measuresdaily and cumulative number of deaths from COVID-19.

ResultsIf vaccine efficacy is [≥] 70%, the vaccine-induced sterilising immunity lasts [≥] 182 days, and the reinfectivity is greatly reduced (by [≥] 40%), mass vaccination programmes can prevent further COVID-19 outbreaks in England. Under such optimistic scenarios, the cumulative number of COVID-19 deaths is estimated to be from 113,000 to 115,000 by the end of 2029 in England. However, under plausible scenarios with lower vaccine efficacy, shorter durability of immunity, and smaller reduction in reinfectivity, repeated vaccination programmes could not prevent further COVID-19 outbreaks.

ConclusionsUnder optimistic scenarios, mass immunisation using efficacious vaccines may enable society safely to return to normality. However, under plausible scenarios with low vaccine efficacy and short durability of immunity, COVID-19 could continue to cause recurrent waves of severe morbidity and mortality despite frequent vaccinations. It is crucial to monitor the vaccination effects in the real world, and to better understand characteristics of naturally acquired and vaccine induced immunity against SARS-CoV-2.

ARTICLE SUMMARYO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIWe used a population dynamic model to assess impacts of vaccination programmes on future dynamics of SARS-CoV-2 transmission dynamics, and to explicitly investigate the impacts of different types of immune responses to SARS-CoV-2 infection and vaccines on the COVID-19 epidemic in England.
C_LIO_LIThe model has been verified based on historically observed outcome data in England, and a large number of projection scenarios are explored.
C_LIO_LIFindings from our study improves the understanding of key immunological parameters relevant to future SARS-CoV-2 transmission dynamics and vaccination strategies.
C_LIO_LIThis is a deterministic simulation model, and uncertainty in estimated parameters may have not been fully accommodated. There remain many uncertainties regarding durability and types of naturally acquired and vaccine-induced immunity.
C_LI


title: Local prevalence of transmissible SARS-CoV-2 infection : an integrative causal model for debiasing fine-scale targeted testing data

abstract: Targeted surveillance testing schemes for SARS-CoV-2 focus on certain subsets of the population, such as individuals experiencing one or more of a prescribed list of symptoms. These schemes have routinely been used to monitor the spread of SARS-CoV-2 in countries across the world. The number of positive tests in a given region can provide local insights into important epidemiological parameters, such as prevalence and effective reproduction number. Moreover, targeted testing data has been used inform the deployment of localised non-pharmaceutical interventions. However, surveillance schemes typically suffer from ascertainment bias; the individuals who are tested are not necessarily representative of the wider population of interest. Here, we show that data from randomised testing schemes, such as the REACT study in the UK, can be used to debias fine-scale targeted testing data in order to provide accurate localised estimates of the number of infectious individuals. We develop a novel, integrative causal framework that explicitly models the process underlying the selection of individuals for targeted testing. The output from our model can readily be incorporated into longitudinal analyses to provide local estimates of the reproduction number. We apply our model to characterise the size of the infectious population in England between June 2020 and January 2021. Our local estimates of the effective reproduction number are predictive of future changes in positive case numbers. We also capture local increases in both prevalence and effective reproductive number in the South East from November 2020 to December 2020, reflecting the spread of the Kent variant. Our results illustrate the complementary roles of randomised and targeted testing schemes. Preparations for future epidemics should ensure the rapid deployment of both types of schemes to accurately monitor the spread of emerging and ongoing infectious diseases.

category: infectious diseases


title: Comparison of dried blood spots and venous blood for the detection of SARS-CoV-2 antibodies in a population of nursing home residents

abstract:
IntroductionIn the current SARS-CoV-2 pandemic, testing for SARS-CoV-2 specific antibodies is paramount to monitor immune responses in post-authorization vaccination and sero-epidemiology studies. However, large scale and iterative serological testing by venipuncture in older persons can be challenging. Capillary blood sampled using a finger prick and collected on protein saver cards, i.e., dried blood spots (DBS), has already proven to be a promising alternative. However, elderly persons have a reduced cutaneous microvasculature, which may affect DBS-based antibody testing. Therefore, we aimed to evaluate the performance of DBS for the detection of SARS-CoV-2 antibodies in nursing homes residents.

Materials and methodsWe collected venous blood and paired Whatman and EUROIMMUN DBS from nursing home residents, and from staff as a reference population. Venous blood samples were analyzed for the presence of SARS-CoV-2 IgG antibodies using the Abbot chemiluminescent microparticle immunoassay (CMIA). DBS were analyzed by the EUROIMMUN enzyme-linked immuno sorbent assay (ELISA) for SARS-CoV-2 IgG antibodies. We performed a statistical assessment to optimize the ELISA cut-off value for the DBS using the Youdens J index.

ResultsA total of 273 paired DBS-serum samples were analyzed, of which 129 were positive as assessed by the reference test. The sensitivities and specificities of DBS ranged from 95.0% to 97.1% and from 97.1% to 98.8%, respectively, depending on population (residents or staff) or DBS card type.

ConclusionDBS sampling is a valid alternative to venipuncture for the detection of SARS-CoV-2 antibodies in the elderly.


title: Multicenter cohort study of multisystem inflammatory syndrome in children (MIS-C)

abstract:
BACKGROUNDSARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We investigated risk factors for severe disease and explored changes in severity over time.

METHODSChildren up to 17 years of age admitted March 1, 2020 through March 7th, 2021 to 15 hospitals in Canada, Iran and Costa Rica with confirmed or probable MIS-C were included. Descriptive analysis and comparison by diagnostic criteria, country, and admission date was performed. Adjusted absolute average risks (AR) and risk differences (RD) were estimated for characteristics associated with ICU admission or cardiac involvement.

RESULTSOf 232 cases (106 confirmed) with median age 5.8 years, 56% were male, and 22% had comorbidities. ICU admission occurred in 73 (31%) but none died. Median length of stay was 6 days (inter-quartile range 4-9). Children 6 to 12 years old had the highest AR for ICU admission (44%; 95% confidence interval [CI] 34-53). Initial ferritin greater than 500 mcg/L was associated with ICU admission. When comparing cases admitted up to October 31, 2020 to those admitted later, the AR for ICU admission increased from 25% (CI 17-33) to 37% (CI 29-46) and for cardiac involvement from 44% (CI 35-53) to 75% (CI 66-84). Risk estimates for ICU admission in the Canadian cohort demonstrated a higher risk in December 2020-March 2021 compared to March-May 2020 (RD 25%; 95%CI 7-44).

INTERPRETATIONMIS-C occurred primarily in previously well children. Illness severity appeared to increase over time. Despite a high ICU admission incidence, most children were discharged within one week.

category: pediatrics


title: Neural bases of Frustration-Aggression Theory: A multi-domain meta-analysis of functional neuroimaging studies.

abstract: Early evidence suggests that unexpected non-reward may increase the risk for aggressive behaviors. Despite the growing interest in understanding brain functions that may be implicated in aggressive behaviors, the neural processes underlying such frustrative events remain largely unknown. Furthermore, meta-analytic results have produced discrepant results, potentially due to substantial differences in the definition of anger/aggression constructs. Therefore, coordinate-based meta-analyses on unexpected non-reward and retaliatory behaviors in healthy subjects were conducted. Conjunction analyses were further examined to discover overlapping brain activations across these meta-analytical maps. Frustrative non-reward deactivated the orbitofrontal cortex, ventral striatum and posterior cingulate cortex, whereas increased activations were observed in midcingulo-insular regions, as well as dorsomedial prefrontal cortex, amygdala, thalamus and periaqueductal gray, when using liberal threshold. Retaliation activated of midcingulo-insular regions, the dorsal caudate and the primary somatosensory cortex. Conjunction analyses revealed that both strongly activated midcingulo-insular regions. Our results underscore the role of anterior midcingulate/pre-supplementary motor area and fronto-insular cortex in both frustration and retaliatory behaviors. A neurobiological framework for understanding frustration-based impulsive aggression is provided.

category: psychiatry and clinical psychology


title: Contact tracing indicators for COVID-19: rapid scoping review and conceptual framework

abstract:
BackgroundContact tracing is one of the key interventions in response to the COVID-19 pandemic but its implementation varies widely across countries. There is little guidance on how to monitor contact tracing performance, and no systematic overview of indicators to assess contact tracing systems or conceptual framework for such indicators exists to date.

MethodsWe conducted a rapid scoping review using a systematic literature search strategy in the peer-reviewed and grey literature as well as open source online documents. We developed a conceptual framework to map indicators by type (input, process, output, outcome, impact) and thematic area (human resources, financial resources, case investigation, contact identification, contact testing, contact follow up, case isolation, contact quarantine, transmission chain interruption, incidence reduction).

ResultsWe identified a total of 153 contact tracing indicators from 1,555 peer-reviewed studies, 894 studies from grey literature sources, and 15 sources from internet searches. Two-thirds of indicators were process indicators (102; 67%), while 48 (31%) indicators were output indicators. Only three (2%) indicators were input indicators. Indicators covered seven out of ten conceptualized thematic areas, with more than half being related to either case investigation (37; 24%) or contact identification (44; 29%). There were no indicators for the input area "financial resources", the outcome area "transmission chain interruption", and the impact area "incidence reduction".

ConclusionsAlmost all identified indicators were either process or output indicators focusing on case investigation, contact identification, case isolation or contact quarantine. We identified important gaps in input, outcome and impact indicators, which constrains evidence-based assessment of contact tracing systems. A universally agreed set of indicators is needed to allow for cross-system comparisons and to improve the performance of contact tracing systems.

category: public and global health


title: Assessment of the infectious threshold of SARS-CoV-2 in primary airway epithelial cells

abstract: Comparison of virus isolation success from clinical samples across a range of viral loads inoculated in parallel on Vero E6 and human airway epithelia (HAE) showed lower success of virus isolation in HAE, suggesting an overestimation of actual infectiousness in humans using Vero E6 cell lines, commonly considered as reference.


title: Potential contributors to increased pulmonary embolism hospitalizations during the Covid-19 pandemic

abstract:
BackgroundAfter the first Covid-19 infection wave, a constant increase of pulmonary embolism (PE) hospitalizations not linked with active PCR-confirmed Covid-19 has been observed but potential contributors to this observation are unclear. Therefore, we analyzed associations between changes in PE hospitalizations and (1) the incidence of non-Covid-19 pneumonia, (2) the use of computed tomography pulmonary angiography (CTPA), (3) volume depletion and (4) preceding Covid-19 infection numbers in Germany.

MethodsClaims data of Helios hospitals in Germany were used and consecutive cases with a hospital admission between May 6 and December 15, 2020 (PE surplus period) were analyzed and compared to corresponding periods covering the same weeks in 2016-2019 (control period). We analyzed the number of PE cases in the target period with multivariable Poisson general linear mixed models (GLMM) including (a) cohorts of 2020 versus 2016- 2019, (b) the number of cases with pneumonia, (c) CTPA, and (d) volume depletion and adjusted for age and sex. In order to associate the daily number of PE cases in 2020 with the number of preceding SARS-CoV-2 infections in Germany, we calculated the average number of daily infections (divided by 10,000) occurring 14 up to 90 days with increasing window sizes before PE cases and modelled the data with Poisson regression.

ResultsThere were 2,404 PE hospitalizations between May 6 and December 15, 2020 as opposed to 2,112 - 2,236 (total 8,717) in the corresponding 2016 - 2019 control periods. (crude rate ratio [CRR] 1.10, 95% CI 1.05 - 1.15, P<0.01). Using multivariable Poisson GLMM adjusted for age, sex and volume depletion, PE cases were significantly associated with the number of cases with pneumonia (CRR 1.09, 95 % CI 1.07-1.10, P<0.01), and with CTPA (CRR 1.10, 95 % CI 1.09-1.10, P<0.01). The increase of PE cases in 2020 compared with the control period remained significant (CRR 1.07, 95 % CI 1.02-1.12, P<0.01) when controlling for those factors. In the 2020 cohort, number of preceding average daily Covid-19 infections were associated with increased PE case incidence in all investigated windows, i.e. including preceding infections from 14 to 90 days. The best model (log likelihood -576) was with a window size of 4 days, i.e. average Covid-19 infections 14 - 17 days before PE hospitalization had a risk of 1.20 (95 % CI 1.12- 1.29, P<0.01).

ConclusionsThere is an increase in PE cases since early May 2020 compared to corresponding periods in 2016 - 2019. This surplus was significant even when controlling for changes in potential modulators such as demographics, volume depletion, non-Covid-19 pneumonia, CTPA use and preceding Covid-19 infections. Future studies are needed (1) to investigate a potential causal link for increased risk of delayed PE with preceding SARS-CoV-2 infection, and (2) to define optimal screening for SARS-CoV-2 in patients presenting with pneumonia and PE.

category: cardiovascular medicine


title: A comprehensive assessment of statin discontinuation among patients who concurrently initiate statins and CYP3A4-inhibitor drugs; a multistate transition model

abstract:
AimsTo describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs.

MethodsA retrospective new-user cohort study design was used to identify (N=160828) patients who concurrently initiated CYP3A4-inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104774) vs. other statins (unexposed, n = 56054) from the MarketScan Commercial claims database (2012 - 2017). These groups were matched (2:1) through propensity score-matching techniques. We applied a multistate transition model to compare the 1-year transition probabilities involving four distinct states (start, adverse drug events [ADEs], discontinuation of CYP3A4-inhibitor drugs, and discontinuation of statin therapy) between those exposed to statin DDIs, vs. unexposed. Statistically significant differences were assessed by comparing the 95% confidence intervals (CIs) of probabilities.

ResultsPatients exposed to statin DDIs, vs. unexposed, were significantly less likely to discontinue statin therapy (71.4 [95% CI: 71.1, 71.6] vs. 73.3 [95% CI: 72.9, 73.6]) but more likely to experience an ADE (3.4 [95% CI: 3.3, 3.5] vs. 3.2 [95% CI: 3.1, 3.3]) and discontinue with CYP3A4-inhibitor therapy (21.0 [95% CI: 20.8, 21.3] vs. 19.5 [95% CI: 19.2, 19.8]) directly after concurrently starting stains and CYP3A. Subsequent to experiencing an ADE, those exposed to statin DDIs were still less likely to discontinue statin therapy but were significantly more likely to discontinue CYP3A4-inhibitor therapy.

ConclusionWhile statin DDI exposure was associated with higher likelihood of ADEs, this did not increase the risk of premature statin discontinuation among patients exposed to statin DDIs, versus unexposed.

category: pharmacology and therapeutics


title: Early mineralocorticoid receptor antagonism in diabetic nephropathy limits albuminuria by preserving the glomerular endothelial glycocalyx

abstract:
The glomerular endothelial glycocalyx (GEnGlx) forms the first part of the glomerular filtration barrier (GFB). We have previously shown that excess mineralocorticoid receptor (MR) activation causes GEnGlx damage and albuminuria. Damage to the GEnGlx occurs early in the pathogenesis of diabetic nephropathy (DN). Here we sought to determine whether MR antagonism with spironolactone could prevent the development of albuminuria in diabetes, by preserving the GEnGlx to maintain the GFB. Streptozotocin-induced diabetic Wistar rats developed increased glomerular albumin permeability (Psalb) and albuminuria, with associated GEnGlx loss and increases in plasma and urine active matrix metalloproteinase 2 (MMP2). MR antagonism reduced urine active MMP2, preserved the GEnGlx, restored Psalb to control values and prevented diabetes-induced albuminuria progression. Enzymatic degradation of the GEnGlx, with hyaluronidase, reversed the effect of MR antagonism in diabetic rats, confirming the importance of GEnGlx preservation in this model. Using this model we validated a novel fluorescent profile peak-to-peak confocal imaging technique and applied it to assess GEnGlx damage on renal biopsies from patients with DN and compared them to healthy controls. We confirmed that GEnGlx loss occurs in human DN and may contribute to the disease phenotype. Taken together our work suggests GEnGlx preservation as an important novel mechanism for reno-protection by MR inhibitors in diabetes.

Translational StatementMineralocorticoid receptor (MR) antagonists reduce albuminuria in diabetic nephropathy (DN), but side effects limit their clinical utility, and the mechanism is unknown. This paper demonstrates that MR antagonism prevented the development of glomerular endothelial glycocalyx (GEnGlx) dysfunction and albuminuria. Highly specific, enzyme mediated, removal of the GEnGlx abolished this effect, confirming the importance of EnGlx preservation in this model. Our data also confirm that GEnGlx damage occurs in human DN and may contribute to the clinical phenotype. This work suggests directly targeting glycocalyx preservation in DN could reproduce the protective effects seen with MR inhibition, whilst avoiding side effects.

category: nephrology


title: Identifying Patterns of ALS Progression from Sparse Longitudinal Data

abstract:
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that is complex in its onset, pattern of spread, and disease progression. The heterogeneity of ALS makes it extremely challenging to determine if a disease modifying therapy is effectively slowing progression. While accurately modeling ALS progression is critical to developing therapeutics, current computational methods fail to capture the complexity of disease progression. We aimed to robustly characterize disease progression patterns in ALS.

We obtained data from four clinical cohorts that cover more than 3,500 patients and include both observational and clinical trial studies. To determine whether there were common patterns of disease progression, we developed an approach based on a Mixture of Gaussian Processes (MoGP) to model longitudinal clinical data. Our approach automatically identifies clusters of patients who show similar disease progression patterns, modeling their average trajectory and the spread of the distribution in each cluster. Importantly, the method does not require any prior knowledge of the expected number of clusters.

The MoGP approach revealed that ALS progression, as measured using the ALS functional rating scale (ALSFRS-R) or forced vital capacity, is often non-linear with periods of stable disease preceded or followed by rapid decline. Patterns of progression in ALSFRS-R were robust to sparse data. When at least one year of longitudinal data were available, MoGP predictions were significantly more accurate than linear models, which are commonly used in clinical trials. Progression patterns were consistent across different cohorts despite differences in the frequency of data collection and the lengths of follow-up periods. We further showed that clusters identified from one large, publicly available study population could be used to stratify unseen participants in other studies. We also showed that these progression trajectories correspond with survival outcomes.

This work highlights the importance of modeling nonlinear disease progression for developing more advanced clinical trial endpoint analysis models. In ALS, sporadic, rapid decline ("functional cliffs") and sigmoidal patterns in disease progression in untreated patients may obscure detection of therapeutic efficacy if linear models are used. We provide a pre-trained computational model of observed clinical patterns that can be used by others to analyze new ALS patient cohorts. We expect that the MoGP approach can also be applied to additional ALS outcome measures and to other progressive diseases. Our results provide a critical advance in characterizing the complex disease progression patterns of ALS.

category: neurology


title: A new perspective on the BO06 trial in osteosarcoma: short- and long-term prognostic value of histologic response and intensified chemotherapy

abstract:
PurposeCure rate models accounting for cured and uncured patients, provide additional insights into long and short term survival. We aim to better understand the prognostic value of histologic response and chemotherapy intensification on cure fraction and progression-free survival (PFS) for the uncured patients.

MethodsA logistic model is assumed for the effect of histologic response and intensified chemotherapy on the cure status, while a Cox regression model is estimated only for the uncured patients on PFS. The mixture cure model is used to simultaneously study these two effects.

ResultsHistologic response is a strong prognostic factor for the cure status (OR: 3.00 [1.75-5.17]), but it has no clear effect on PFS for the uncured patients (HR: 0.78 [0.53-1.16]). The cure fractions are 55% [46%-63%] and 29% [22%-35%] among patients with good histologic response (GR) and poor responders (PR) respectively. The intensified regimen was associated with higher cure fraction among PR (OR: 1.90 [0.93 - 3.89]), with no evidence of effect for GR (OR: 0.78 [0.38 - 1.59]).

ConclusionsAccounting for cured patients is valuable in distinguishing the covariate effects on cure and PFS. Estimating cure chances based on these prognostic factors is relevant for counseling patients and can affect treatment decisions.

category: oncology


title: Performance of polygenic risk scores for cancer prediction in a racially diverse academic biobank

abstract:
PurposeGenome-wide association studies (GWAS) have identified hundreds of single nucleotide polymorphisms (SNPs) significantly associated with several cancers, but the predictive ability of polygenic risk scores (PRS) is unclear, especially among non-Whites.

MethodsGenome-wide genotype data was available for 20,079 individuals enrolled in an academic biobank. PRS were derived from significant DNA variants for 15 cancers. We determined the discriminatory accuracy of each cancer-specific PRS in patients of genetically-determined African and European ancestry separately.

ResultsAmong individuals of European genetic ancestry, PRS for breast, colon, melanoma, and prostate were significantly associated with their respective cancers (OR 1.25-1.47). Among individuals of African genetic ancestry, PRS for breast, colon, and prostate were significantly associated with their respective cancers. The AUC of a model comprised of age, sex, and principal components was 0.617-0.709 and increased by 1-4% with the PRS in individuals of European genetic ancestry. In individuals of African genetic ancestry, AUC was overall higher in the model without PRS (0.740-0.811) but increased < 1% with the PRS in the majority of cancers.

ConclusionPRS constructed from SNPs moderately increased discriminatory ability for cancer status in individuals of European but not African ancestry. Further large-scale studies are needed to identify ancestry-specific genetic factors in non-White populations to incorporate PRS into cancer risk assessment.

category: genetic and genomic medicine


title: Hypervirulent extensively-drug resistant (XDR) Klebsiella pneumoniae associated with complicated urinary tract infection in Northern India

abstract: Klebsiella pneumoniae associated with hospital acquired infections in South Asia are frequently extensively-drug resistant (XDR), making treatment and control problematic. It is important to understand the epidemiology and genetic structure of XDR K. pneumoniae and to determine their potential to be hypervirulent (hv) through the presence of siderophores. Here, we characterized the genomes of 20 colistin-resistant XDR K. pneumoniae isolated from 16 patients with complicated UTI over a six-month period in a healthcare facility in northern India. The 16 organisms comprised five STs: ST14 (10/20), ST147 (5/20), ST231 (3/20), ST2096 (1/20), and ST25 (1/20). Notably, several patients admitted to a single ward were infected with the same ST, potentially indicating a common infection source. Additionally, some patients had recurrent infections with multiple STs that were circulating concurrently in a particular ward, providing further evidence for hospital transmission. Beta lactamase genes (blaCTX-M-1, blaSHV, blaLEN, and blaAMP-H) were present in all isolates and the blaNDM, blaOXA1-90, and blaOXA48 carbapenemases were present in 17, 18, and 3 isolates, respectively. Disruption of mgrB with various IS elements was identified in six organisms and was the most common mechanism of colistin resistance. The most frequent K type was K2 (11/20), followed by K10, K51, and K64. Notably, we identified one XDR convergent hypervirulent K. pneumoniae (hvKp) associated with prolonged hospitalisation (iuc+ybt+ESBL+OXA-1, OXA-48), belonging to ST2096. Our data suggest that convergent XDR-hvKp is circulating in our healthcare facility. We speculate that such organisms may have outbreak potential, warranting more effective antimicrobial stewardship and better infection control strategies.


title: Delta-9-tetrahydrocannabinol and cannabidiol in psychosis: A balancing act of the principal phyto-cannabinoids on human brain and behavior?

abstract:
Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the principal phyto-cannabinoids in the cannabis plant. The differential and possibly antagonistic effects of these compounds on specific brain and behavioral responses, and the mechanisms underlying their effects have generated extensive interest in pre-clinical and clinical neuroscience investigations. In this double-blind randomized placebo-controlled counterbalanced human laboratory experiment, we examined the effects of three different dose ratios of CBD: THC (1:1, 2:1 and 3:1) on  neural noise, an electrophysiological biomarker of psychosis known to be sensitive to cannabinoids as well as subjective and psychotomimetic effects. Interestingly, the lowest CBD:THC ratio (1:1) resulted in maximal attenuation of both THC induced psychotomimetic effects (PANSS positive - ATS = 7.83, df = 1, pcorr = 0.015) and neural noise (ATS = 8.83, df = 1, pcorr = 0.009) with an inverse-linear dose response relationship. Further, in line with previous studies, addition of CBD did not reduce the subjective experience of THC induced "high" (p > 0.05 for all CBD doses).

These novel results demonstrate that CBD attenuates THC induced subjective and objective effects relevant to psychosis- but in a dose/ratio dependent manner. Given the increasing global trend of cannabis liberalization and application for medical indications, these results assume considerable significance given the potential dose related interactions of these key phyto-cannabinoids.

category: addiction medicine


title: Association of C-reactive protein and Interleukin-6 single nucleotide polymorphisms with preterm labour: results of a pilot study

abstract: Preterm labour (PTL) can be described as an inflammatory event. C-reactive protein (CRP) and Interleukin-6 (IL-6) are key members of the innate immune response that play major roles in inflammation. The main objective of this case-control study was to determine the association of specific CRP and IL-6 polymorphisms with PTL. The study was carried out in a total of 31 Japanese women with PTL and 28 control women with normal pregnancy. Four SNPs in the CRP gene (rs1800947, rs3091244, rs2794521, and rs3093059) and two SNPs in the IL-6 gene (rs2097677 and rs1800795) were genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Biochemical parameters were assayed and cervical length measurements were performed with ultrasound sonography. There were no significant differences in inflammatory markers, including white blood cell count, CRP, neutrophil elastase in cervical mucous, and foetal fibronectin in vaginal discharge, between the PTL and control groups. The frequency of rs1800947 minor allele (G) was significantly higher in the PTL group than in the control group. This finding has not been previously reported. We suggest that mutations in rs1800947 may lead to PTL. Thus, the rs1800947 SNP may be useful as a genetic marker for PTL risk assessment in pregnant women.

category: obstetrics and gynecology


title: Dementia Prediction in Older People through Topic-cued Spontaneous Conversation

abstract: AO_SCPLOWBSTRACTC_SCPLOWAn increase in dementia cases is producing significant medical and economic pressure in many communities. This growing problem calls for the application of AI-based technologies to support early diagnostics, and for subsequent non-pharmacological cognitive interventions and mental well-being monitoring. We present a practical application of a machine learning (ML) model in the domain known as  AI for social good. In particular, we focus on early dementia onset prediction from speech patterns in natural conversation situations. This paper explains our model and study results of conversational speech pattern-based prognostication of mild dementia onset indicated by predictive Mini-Mental State Exam (MMSE) scores. Experiments with elderly subjects are conducted in natural conversation situations, with four members in each study group. We analyze the resulting four-party conversation speech transcripts within a natural language processing (NLP) deep learning framework to obtain conversation embedding. With a fully connected deep learning model, we use the conversation topic changing distances for subsequent MMSE score prediction. This pilot study is conducted with Japanese elderly subjects within a healthy group. The best median MMSE prediction errors are at the level of 0.167, with a median coefficient of determination equal to 0.330 and a mean absolute error of 0.909. The results presented are easily reproducible for other languages by swapping the language model in the proposed deep-learning conversation embedding approach.

category: health informatics


title: Predicting bloodstream infection outcome using machine learning

abstract: Bloodstream infections (BSI) are a main cause of infectious disease morbidity and mortality world-wide. Early prediction of patients at high risk of poor outcomes of BSI is important for earlier decision making and effective patient stratification. We developed electronic medical record-based machine learning models that predict patient outcomes of BSI. The area under the receiver-operating characteristics curve was 0.82 for a full featured inclusive model, and 0.81 for a compact model using only 25 features. Our models were trained, using electronic medical records that include demographics, blood tests, and the medical and diagnosis history of 7,889 hospitalized patients diagnosed with BSI. Among the implications of this work is implementation of the models as a basis for selective rapid microbiological identification, toward earlier administration of appropriate antibiotic therapy. Additionally, our models may help reduce the development of BSI and its associated adverse health outcomes and complications.


title: Economic Impact Payment, Human Mobility and the COVID-19 Mitigation in the United States

abstract:
This paper studies the relationship between the individuals income and COVID-19 mitigation effort contribution. The paper suggests that in addition to the government mandatory policies, the income compensation policy is an alternative government instrument that helps increase the individual and social aggregate COVID-19 mitigation effort. I empirically test the effect of the income compensation policy by utilizing the United States economic impact payment (EIP) in April 2020 as a quasi-natural experiment, and use the cellphone GPS measured human mobility data as the outcome indicator of the COVID-19 mitigation effort. I find that by receiving EIP, individuals on average significantly increase median home dwell time by 3% - 5% (about 26-45 minutes). This paper highlights an unintended effect of EIP: in addition to providing economic assistance, EIP also helps mitigate the COVID-19 virus transmission.

JEL codesD11 D12 H41 I12 I14 I18

category: health policy


title: Development and validation of a framework to improve neglected tropical diseases surveillance and response at the sub-national level in Kenya

abstract:
BackgroundAssessment of surveillance and response system functions focusing on notifiable diseases has widely been documented in literature. However, there is limited focus on diseases targeted for elimination or eradication, particularly preventive chemotherapy neglected tropical diseases (PC-NTDs). There are limited strategies to guide strengthening of surveillance and response system functions concerning PC-NTDs. The aim of this study was to develop and validate a framework to improve surveillance and response to PC-NTDs at the sub-national level in Kenya.

MethodsFramework development adopted a multi-phased approach. The first phase involved a systematic literature review of surveillance assessment studies conducted in Africa to derive generalised recommendations. The second phase utilised primary data surveys to identify disease- specific recommendations to improve PC-NTDs surveillance in Kenya. The third phase utilised a Delphi survey to assess stakeholders consensus on feasible recommendations. The fourth phase drew critical lessons from existing conceptual frameworks. The final validated framework was based on resolutions and inputs from concerned stakeholders.

ResultsFramework components constituted inputs with the first domain combining surveillance tools, equipment and infrastructure while the second domain combined financial, technical and logistical support. Processes were categorised into four sub-domains with activities for strengthening existing surveillance tools, surveillance core, support and attribute functions. The intended results phase comprised of ten distinct outputs with the anticipated outcomes categorised into three sub domains. Lastly, the overall impact alluded to reduced disease burden, halted disease transmission and reduced costs for implementing treatment interventions to achieve PC-NTDs control and elimination.

ConclusionIn view of the mixed methodological approach used to develop the framework coupled with further inputs and consensus among concerned stakeholders, the validated framework appears to be relevant in guiding decisions by policy makers to strengthen the existing surveillance and response system functions towards achieving PC-NTDs elimination.

Author summaryNeglected tropical diseases (NTDs) affect marginalised and underserved populations with sub- national levels providing first contact healthcare services to the afflicted communities. NTDs amenable to chemoprophylaxis are primarily controlled through mass treatment interventions. However, identification of disease transmission hotspots requires strengthened health information systems (HIS) to inform targeted public health action and response. Using a multi-phased approach, we developed and validated a framework, which provided a logical approach for guiding actions to strengthen surveillance system functions in view of NTDs. Framework development involved undertaking a systematic literature review to retrieve generalised recommendations for improving surveillance system functions within the African context, conducting primary data surveys to identify disease-specific recommendations on improving surveillance system core, support and attribute functions regarding NTDs and determining feasibility for implementing recommended actions at the sub-national levels. A review of relevant conceptual frameworks provided information underpinning overall framework development. The study identified framework component interlinkages to achieve the desired results of reduced costs for implementing treatment interventions, halted disease transmission and reduced disease burden. Overall, the framework provides a logical approach for strengthening HIS at sub-national levels in NTD endemic regions, considering stakeholders perspectives and the available resources to achieve the ultimate goal of disease elimination.

category: health systems and quality improvement


title: Frequent suboptimal thermocycler ramp rate usage negatively impacts MTBDRsl performance for second-line drug resistant tuberculosis diagnosis

abstract:
Strengthening the detection of second-line drug-resistance is a key tuberculosis (TB) control priority. The performance of MTBDRplus, a multidrug-resistant (MDR)-TB assay is reduced when suboptimal ramp rates are used. We investigated ramp rates effect on MTBDRsl; the most widely-used molecular second-line drug-resistant TB assay.

We tested 52 smear-negative Xpert MTB/RIF Ultra-positive sputa and a Mycobacterium tuberculosis (Mtb) dilution series at manufacturer-recommended (2.2{degrees}C/s) or most common suboptimal ramp rate (4.0{degrees}C/s; identified via an earlier survey). Mtb-complex DNA (TUB-band)-positivity, indeterminate rates, fluoroquinolone- and second-line injectable-resistance accuracy, banding differences and, separately, inter-reader variability were assessed.

39% of re-surveyed laboratories (5/13) did not use the manufacturer-recommended MTBDRsl ramp rate. On sputum, this ramp rate improved indeterminates vs. 4.0{degrees}C/s (0/52 vs. 7/51; p=0.006), false drug-resistance calls (0/104 vs. 6/102; p=0.013), and incorrect banding calls (0/1300 vs. 55/1275; p<0.001). Valid results (neither TUB-negative, indeterminate, nor any false drug-resistance calls) (52/52 vs. 41/51; p=0.001) on sputa hence improved by +21% (95% CI: 8-34%) with optimal ramp rate usage. Suboptimal ramp rate increased banding call inter-reader variability [52/1300 (4%) vs. 34/1300 (3%); p=0.030] on sputa but not dilution series; highlighting the importance of using clinical specimens for assay performance evaluations.

Suboptimal ramp rate contributes to poor MTBDRsl performance. Ramp rate correction will improve second-line drug-resistant TB diagnoses. Laboratories must ensure the optimal manufacturer-recommended ramp rate is used.


title: Socioeconomic Status and COVID-19 Related Outcomes in India: Hospital Based Study

abstract:
Background & ObjectiveCOVID-19 infection has disproportionately affected ethnic minorities and deprived populations in Europe and North America. Influence of socioeconomic status on COVID-19 related outcomes has not been studied in India. To determine association of educational status, as marker of socioeconomic status, with COVID-19 related outcomes we performed a study.

MethodsClinically and virologically confirmed successive patients of COVID-19 presenting at a government hospital in India were recruited. Demographic and clinical details were recorded. The cohort was classified according to educational status into Group 1-illiterate or < primary, Group 2-higher secondary, and Group 3-some college. To compare outcomes among groups we performed univariate and multivariate logistic regression and odds ratios (OR) and 95% confidence intervals (CI) were calculated.

ResultsFrom March-September 2020 we recruited 4645 patients (men 3386, women 1259) with laboratory confirmed COVID-19. Mean age was 46+18y, most lived in moderate or large households and 30.5% had low educational status. Smoking or tobacco use was in 29.5%, co-morbidities in 28.6% and low oxygen concentration (SpO2 <95%) at admission in 30%. Average length of hospital stay was 6.8+3.7 days, supplemental oxygen was provided in 18.4%, high flow oxygen or non-invasive ventilation 7.1%, and mechanical ventilation in 3.6%. 340 patients (7.3%) died. Group 1 patients were younger, more women, larger households, higher tobacco use and were more hypoxic at admission with lower lymphocyte counts, elevated liver enzymes and greater kidney dysfunction. In Group 1 vs Groups 2 and 3 requirement of oxygen (21.6 vs 16.7 and 17.0%), non-invasive ventilation (8.0 vs 5.9 and 7.1%), invasive ventilation (4.6 vs 3.5 and 3.1%) and deaths (10.0 vs 6.8 and 5.5%) were significantly greater (p<0.05). Compared to Group 3, OR for deaths were significantly higher in Group 1 (1.91, 1.46-2.51) and Group 2 (1.24, 0.93-1.66). Adjustment for age, sex, household size, risk factors and comorbidities led to attenuation in OR in Groups 1 (1.44, 1.07-1.93) and 2 (1.38, 1.02-1.85) that remained with adjustments for clinical and laboratory parameters and oxygen support in Groups 1 (1.38, 0.99-1.93) and 2 (1.52, 1.01-2.11).

ConclusionIlliterate and less educational (socioeconomic) status patients with COVID-19 in India have significantly greater adverse in-hospital outcomes and mortality. This is related to more severe disease at presentation.


title: Epidemiology and genetic diversity of SARS-CoV-2 lineages circulating in Africa

abstract:
COVID-19 disease dynamics have been widely studied in different settings around the globe, but little is known about these patterns in the African continent.

To investigate the epidemiology and genetic diversity of SARS-CoV-2 lineages circulating in Africa, more than 2400 complete genomes from 33 African countries were retrieved from the GISAID database and analyzed. We investigated their diversity using various clade and lineage nomenclature systems, reconstructed their evolutionary divergence and history using maximum likelihood inference methods, and studied the case and death trends in the continent. We also examined potential repeat patterns and motifs across the sequences.

In this study, we show that after almost one year of the COVID-19 pandemic, only 143 out of the 782 Pango lineages found worldwide circulated in Africa, with five different lineages dominating in distinct periods of the pandemic. Analysis of the number of reported deaths in Africa also revealed large heterogeneity across the continent. Phylogenetic analysis revealed that African viruses cluster closely with those from all continents but more notably with viruses from Europe. However, the extent of viral diversity observed among African genomes is closest to that of the Oceania outbreak, most likely due to genomic under-surveillance in Africa. We also identified two motifs that could function as integrin-binding sites and N-glycosylation domains.

These results shed light on the evolutionary dynamics of the circulating viral strains in Africa, elucidate the functions of protein motifs present in the genome sequences, and emphasize the need to expand genomic surveillance efforts in the continent to better understand the molecular, evolutionary, epidemiological, and spatiotemporal dynamics of the COVID-19 pandemic in Africa.


title: Preserved metacognition despite impaired perception of intentionality cues in schizophrenia

abstract:
Social cognition and metacognition are frequently impaired in schizophrenia, and these impairments complicate recovery. Recent work suggests that different aspects of metacognition may not be impaired to the same degree. Furthermore, metacognition and the cognitive capacity being monitored need not be similarly impaired. Here, we assessed performance in detecting cues of intentional behaviour as well as metacognition about detecting those cues in schizophrenia. Thirty patients and controls categorized animations of moving dots into those displaying a dyadic interaction demonstrating a chase or no chase and indicated their confidence in these judgments. Perception and metacognition were assessed using signal detection theoretic measures, which were analysed using frequentist and Bayesian statistics. Patients showed a deficit compared to controls in detecting intentionality cues, but showed preserved metacognitive performance into this task. Our study reveals a selective deficit in the perception of intentionality cues, but preserved metacognitive insight into the validity of this perception. It thus appears that impairment of metacognition in schizophrenia varies across cognitive domains - metacognition should not be considered a monolithic stone that is either impaired or unimpaired.

Highlights- Impaired detection of chasing between two moving objects in schizophrenia
- No impairment in metacognition during this task in schizophrenia
- Preserved metacognition into social perception despite impaired social perception


title: Decline in COPD Admissions During the COVID-19 Pandemic Associated with Lower Burden of Community Respiratory Viral Infections

abstract:
BackgroundThe COVID-19 pandemic has led to widespread implementation of public health measures, such as stay-at-home orders, social distancing, and masking mandates. In addition to decreasing spread of SARS-CoV2, these measures also impact the transmission of seasonal viral pathogens, which are common triggers of COPD exacerbations. Whether reduced viral prevalence mediates reduction in COPD exacerbation rates is unknown.

MethodsWe performed retrospective analysis of data from a large, multicenter healthcare system to assess admission trends associated with community viral prevalence and with initiation of COVID-19 pandemic control measures. We applied difference-in-differences (DiD) analysis to compare season-matched weekly frequency of hospital admissions for COPD before and after implementation of public health measures for COVID-19. Community viral prevalence was estimated using regional Center for Disease Control and Prevention test positivity data and correlated to COPD admissions.

ResultsData involving 4,422 COPD admissions demonstrated a season-matched 53% decline in COPD admissions during COVID-19 pandemic, which correlated to community viral burden (r=0.73; 95% CI: 0.67 to 0.78) and represented a 36% greater decline over admission frequencies observed in other medical conditions less affected by respiratory viral infections (IRR, 0.64; 95% CI, 0.57 to 0.71, p<0.001). The post-COVID-19 decline in COPD admissions was most pronounced in patients with fewer comorbidities and without recurrent admissions.

ConclusionThe implementation of public health measures during the COVID-19 pandemic was associated with decreased COPD admissions. These changes are plausibly explained by reduced prevalence of seasonal respiratory viruses.

category: respiratory medicine


title: Prognostic accuracy of shock index for severe postpartum hemorrhage in high-income country: Protocol for a systematic review and meta-analysis

abstract:
BackgroundThis review aims to conduct a systematic review and meta-analysis to assess the prognostic value of shock index for prediction of severe Postpartum hemorrhage (PPH) in high-income countries.

MethodWe will perform a systematic review and meta-analysis for diagnostic test accuracy (DTA). We will search CENTRAL, MEDLINE (Ovid), Web of Science, and other sources and include all relevant reports on the prognostic accuracy of shock index for severe PPH. The target condition is defined as severe PPH required higher-level care. Two review authors will independently screen the study eligibility and extract data from included studies. Two authors will also assess study quality using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. We will use the hierarchical models comprising both the bivariate model and the hierarchical summary receiver operating characteristic (HSROC) model for data synthesis if appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs).

Trial registrationThis review is submitted with University hospital medical information network clinical trial registry (UMIN-CTR) [UMIN 000044230].

Conflicts of interestAll authors declare to have no conflicts of interest

FundingNone


title: Cancer and the risk of COVID-19 diagnosis, hospitalisation, and death: a population-based multi-state cohort study including 4,618,377 adults in Catalonia, Spain

abstract:
ObjectivesTo investigate the associations between cancer and risk of outpatient COVID-19 diagnosis, hospitalisation, and COVID-19-related death, overall and by years since cancer diagnosis (<1-year, 1-5-years, >5-years), sex, age, and cancer type.

DesignPopulation-based cohort study

SettingPrimary care electronic health records including [~]80% of the population in Catalonia, Spain, linked to hospital and mortality records between 1 March and 6 May 2020.

ParticipantsIndividuals aged [≥]18 years with at least one year of prior medical history available from the general population. Cancer was defined as any prior diagnosis of a primary invasive malignancy excluding non-melanoma skin cancer.

Main outcome measuresCause-specific hazard ratios (aHR) with 95% confidence intervals for each outcome. Estimates were adjusted by age, sex, deprivation, smoking status, and comorbidities.

ResultsWe included 4,618,377 adults, of which 260,667 (5.6%) had a history of cancer. Patients with cancer were older and had more comorbidities than cancer-free patients. A total of 98,951 individuals (5.5% with cancer) were diagnosed and 6,355 (16.4% with cancer) were directly hospitalised (no prior diagnosis) with COVID-19. Of those diagnosed, 6,851 were subsequently hospitalised (10.7% with cancer) and 3,227 died without being hospitalised (18.5% with cancer). Among those hospitalised, 1,963 (22.5% with cancer) died. Cancer was associated with an increased risk of COVID-19 diagnosis (aHR: 1.08; 95% confidence interval [1.05-1.11]); direct COVID-19 hospitalisation (1.33 [1.24-1.43]); and death following a COVID-19 hospitalisation (1.12 [1.01-1.25]). These associations were stronger for patients recently diagnosed with cancer, aged <70 years, and with haematological cancers.

ConclusionsPatients recently diagnosed with cancer, aged <70 years, or with haematological cancers are a high-risk population for COVID-19 diagnosis and severity. These patients should be prioritised in COVID-19 vaccination campaigns and continued non-pharmaceutical interventions.

What is already known on this subjectO_LIPrior studies addressing the relationship between cancer and COVID-19 infection and adverse outcomes have found conflicting results
C_LIO_LIThe majority of these studies had small sample sizes, were not population-based (i.e. restricted to hospitalised patients), thus increasing the risks of selection and collider bias.
C_LIO_LIIn addition, they used different definitions for cancer (i.e. some included only patients with active cancer, while others focused on specific cancer types, etc.), which limits the comparability of their findings, and only a few analysed the effect of cancer across different patient subgroups.
C_LI

What this study addsO_LIWe conducted a population-based cohort study to analyse the associations between having a prior diagnosis of cancer and the risks of COVID-19 diagnosis, hospitalisation and COVID-19-related deaths from 1 March to 6 May 2020.
C_LIO_LIIn a population of 4,618,377 adults, we found that cancer was associated with an increased risk of COVID-19 diagnosis (aHR: 1.08; 95% confidence interval [1.05-1.11]); direct COVID-19 hospitalisation (1.33 [1.24-1.43]); and death following a COVID-19 hospitalisation (1.12 [1.01-1.25]).
C_LIO_LIThese risks were higher for patients recently diagnosed with cancer (within the last year), younger than 70 years, or with haematological cancers. We also found a particularly high risk of COVID-19 hospitalisation and death among patients with lung and bladder cancer.
C_LI

category: epidemiology


title: A multi-site, multi-participant magnetoencephalography resting-state dataset to study dementia: The BioFIND dataset

abstract: Early detection of Alzheimers Disease (AD) is vital to reduce the burden of dementia and for developing effective treatments. Neuroimaging can detect early brain changes, such as hippocampal atrophy in Mild Cognitive Impairment (MCI), a prodromal state of AD. However, selecting the most informative imaging features by machine-learning requires many cases. While large publically-available datasets of people with dementia or prodromal disease exist for Magnetic Resonance Imaging (MRI), comparable datasets are missing for Magnetoencephalography (MEG). MEG offers advantages in its millisecond resolution, revealing physiological changes in brain oscillations or connectivity, before structural changes are evident with MRI. We introduce a MEG dataset with 324 individuals: patients with MCI and healthy controls. Their brain activity was recorded while resting with eyes closed, using a 306-channel MEG scanner at one of two sites (Madrid or Cambridge), enabling tests of generalization across sites. A T1-weighted MRI is provided to assist source localisation. The MEG and MRI data can be formatted according to international BIDS standards, and analysed freely on the DPUK platform (https://portal.dementiasplatform.uk/Apply).


title: The impact of leadership on the nursing workforce during the COVID-19 pandemic

abstract:
AimsTo determine how the learning about protective factors from previous pandemics were implemented and the impact of this on nurses experience.

BackgroundThe COVID-19 pandemic led to systemic change within healthcare settings and demands placed on frontline nurses has been overwhelming. Lessons learned from previous pandemics indicate that clear communication and strong visible leadership can mitigate the impact stressful events may have on nurses. Conversely, a lack of clear leadership and regulatory protocols in times of crisis can lead to an increase in psychological distress for nurses.

DesignSecondary analysis of semi-structured interview transcripts.

MethodsSecondary data analysis was conducted on data collected during a hospital-wide evaluation of barriers and facilitators to changes implemented to support the surge of COVID-19 related admissions in wave one of the pandemic. Participants represented three-levels of leadership: whole trust (n=17), division (n=7), ward/department-level (n=8), and individual nurses (n=16). Data were collected through semi-structured video interviews between May and July 2020. Interviews were analysed using Framework analysis.

ResultsKey changes that were implemented in wave one reported at whole trust level included: a new acute staffing level, redeploying nurses, increasing the visibility of nursing leadership, new staff wellbeing initiatives, new roles created to support families and various training initiatives. Two main themes emerged from the interviews at division, ward/department and individual nurse level: impact of leadership, and impact on the delivery of nursing care.

ConclusionsLeadership through a crisis is essential for the protective effect of nurses emotional wellbeing. While nursing leadership was made more visible during wave one of the pandemic and processes were in place to increase communication, system-level challenges resulting in negative experiences existed. By identifying these challenges, it has been possible to overcome them during wave two by employing different leadership styles, to support nurse wellbeing

category: nursing


title: Evaluation of the Family Liaison Officer (FLO) role during the COVID-19 Pandemic

abstract:
ObjectivesDuring the first wave of COVID-19 heavy restrictions were placed on hospital visitations in the United Kingdom. To support communication between families and patients a central London hospital introduced the role of the Family Liaison Officer. Communication within healthcare settings is often the subject of contention, particularly for patients families. During periods of crisis communication can become strained for patients and their families. We aimed to evaluate the rapid implementation of this role to provide guidance if it was required in the future and to explore the potential for this to become a standard role.

DesignService evaluation

SettingSingle National Health Service hospital in London.

MethodsSemi-structured video interviews with a convenience sample of 12 participants. Data were analysed using Framework Analysis.

ParticipantsFamily Liaison Officers (n=5) and colleagues who experienced working alongside them (n=7).

ResultsKey themes were identified from the interviews pertaining to the role, the team, the impact and the future. Two versions of the role emerged though the process based on the Family Liaison Officers previous background: Clinical Family Liaison Officers (primarily nurses) and Pastoral Family Liaison Officers (primarily play specialists). Both the Family Liaison Officers and their colleagues agreed that the role had a very positive impact on the wards during this time. Negative aspects of the role, such as a lack of induction, boundaries or clear structure were also discussed.

ConclusionThe Family Liaison Officer was a key role during the pandemic in facilitating communication between patient, clinical team and family. The challenges associated with the role reflect the speed in which it was implemented but it was evident to those in the role and clinicians who the role was supporting that it has potential to help improve hospital communication, and the work of healthcare staff outside of a pandemic.

Strengths and limitations of this studyO_LIThis was an in-depth evaluation of the Family Liaison Officer role from the perspective of those in the role and the clinical team who they were providing support.
C_LIO_LIThe sample included representation of the different disciplines who worked in the FLO role.
C_LIO_LIThe evaluation only represents the professional perspective and not the experience of the family.
C_LI


title: Getting the Nod: Characterizing pediatric head motion in movie- and resting-state fMRI.

abstract:
Head motion continues to be a major problem in fMRI research, particularly in developmental studies where an inverse relationship exists between head motion and age. Despite multifaceted and costly efforts to mitigate motion and motion-related signal artifact, few studies have characterized in-scanner head motion itself.

This study leverages a large public dataset (N=1388, age 5-21y, The Healthy Brain Network Biobank) to characterize pediatric head motion in space, frequency, and time. We focus on practical aspects of head motion that could impact future study design, including comparing motion across groups (low, medium, and high movers), across conditions (movie-watching and rest), and between males and females.

Analyses showed that in all conditions, high movers exhibited a different pattern of motion than low and medium movers that was dominated by x-rotation, and z- and y-translation. High motion spikes (>0.3mm) from all participants also showed this pitch-z-y pattern. Problematic head motion is thus composed of a single type of biomechanical motion, which we infer to be a nodding movement, providing a focused target for motion reduction strategies. A second type of motion was evident via spectral analysis of raw displacement data. This was observed in low and medium movers and was consistent with respiration rates. We consider this to be a baseline of motion best targeted in data preprocessing. Further, we found that males moved more than, but not differently from, females.

Significant cross-condition differences in head motion were found. Movies had lower mean motion, and especially in high movers, movie-watching reduced within-run linear increases in head motion (i.e., temporal drift). Finally, we used intersubject correlations of framewise displacement (FD-ISCs) to assess for stimulus-correlated motion trends. Subject motion was more correlated in movie than rest and stimulus-correlated stillness occurred more often than stimulus-correlated motion. Possible reasons and future implications of these findings are discussed.

category: radiology and imaging


title: Covariance of Interdependent Samples with Application to GWAS

abstract:
Proximal genetic variants are frequently correlated, implying that also the corresponding effect sizes detected by genome-wide association studies (GWAS) are not independent. There are already methods taking this into account when aggregating effects from a single GWAS across genes or pathways. Here we present a rigorous, yet fast method for detecting genes with coherent association signals for two traits, facilitating cross-GWAS analyses. To this end we devised a new significance test for covariance of datapoints not drawn independently, but with known inter-sample covariance structure. We show that the distribution of its test statistic is a linear combination of{chi} 2 distributions, with positive and negative coefficients. The corresponding cumulative distribution function can be efficiently calculated with Davies algorithm at high precision. We apply this general framework to test for dependence between SNP-wise effect sizes of two GWAS at the level of genes. We extend this test to detect also gene-wise causal links. We demonstrate the utility of our method by uncovering potential shared genetic links between severity of COVID-19 and (1) being prescribed class M05B medication (drugs affecting bone structure and mineralization), (2) rheumatoid arthritis, (3) vitamin D (25OHD), and (4) serum calcium concentrations. Our method detects a potential role played by chemokine receptor genes linked to TH1 versus TH2 immune reaction, a gene related to integrin beta-1 cell surface expression, and other genes potentially impacting severity of COVID-19. Our approach will be useful for similar analyses involving data-points with known auto-correlation structures.

Author summaryGenome wide association studies (GWAS) deliver effect size estimates of a given trait for millions of Single Nucleotide Polymorphisms (SNPs). There are already powerful tools to use these summary statistics to elucidate the global joint genetic contribution to a pair of traits, such as cross-trait LD-score regression, but these methods cannot reveal the joint contributions at the level of genes and pathways. Here we present a novel methodology to co-analyse the association data from a pair of GWAS in order to identify genes and pathways that may be of relevance to both of the respective traits. The novelty in our test is that a gene is considered to be co-relevant if the SNP-wise effects from both GWAS tend to have the same sign and magnitude in the gene window. This is different from the commonly used approach asking only for the aggregate signals from two GWAS to be jointly significant. Our method is made feasible due to a novel insight into the product-normal distribution. We apply our new method to test for co-significant genes for severe COVID-19 and conditions leading to prescription of common medications. Out of the 23 medication classes we tested for coherent cosignificant genes, only one, M05B (drugs affecting bone structure and mineralization), yielded Bonferroni significant hits. We then searched for available GWAS data for related conditions, and found that also rheumatoid arthritis, calcium concentration and vitamin D are traits pointing to a number of co-relevant genes in our new coherence analysis. Furthermore, testing for anti-coherence showed that the medication classes H03A (thyroid preparations), R03A and R03BA (drugs for obstructive airway diseases) feature Bonferroni co-significant genes. Our joint analysis provides new insights into potential COVID-19 disease mechanisms.


title: Strategies that make vaccination easy and promote autonomy could increase COVID-19 vaccination in those who remain hesitant.

abstract:
The COVID-19 vaccination campaign in the US has been immensely successful in vaccinating those who are receptive, further increases in vaccination rates however will require more innovative approaches to reach those who remain hesitant, deliberative or indifferent. Phenomena such empty mass vaccination sites and wasted vaccine doses in some regions suggest that in addition to dispelling misinformation and building trust, developing more person-centered vaccination strategies, that are modelled on what people want could further increase uptake. To inform vaccine distribution strategies that are aligned with public preferences for COVID-19 vaccination campaign features we conducted a survey and discrete choice experiment among a representative sample of 2,895 people in the US, between March 15 and March 22, 2021. We found that on average the public prioritized ease, preferring single to two dose vaccinations, vaccinating once rather than annually and reduced waiting times at vaccination sites - for some these were the primary preference drivers. Vaccine enforcement reduced overall vaccine acceptance, with a trend of increasing  control aversion with increasing vaccine hesitancy, particularly among those who were young, Black/African American or Republican. These data suggest that making vaccination easy and promoting autonomy by offering the public choices of vaccination brands and locations may increase uptake, and that vaccine mandates could compromise autonomy and increase control aversion in those who are hesitant - reducing vaccination in such groups and potentially undermining the goals of COVID-19 vaccination campaigns.

SignificanceDCEs are a novel tool in public health that allow examination of preferences for a product, service or policy, identifying how the public prioritizes personal risks and cost in relation to health behaviors. Using this method to establish preferences for COVID-19 vaccination campaign strategies, our results suggest that: firstly, vaccination should be made as easy as possible for the public, second, that individuals should be offered choices of vaccine brand and vaccination location, and third, that vaccine enforcement could activate  control aversion in the public and particularly in those who are most hesitant - potentially causing these groups to double down on vaccine resistance, a scenario which would impede the success of vaccination programs in the US.

category: infectious diseases


title: Adapting the UK Biobank brain imaging protocol and analysis pipeline for the C-MORE multi-organ study of COVID-19 survivors

abstract:
SARS-CoV-2 infection has been shown to damage multiple organs, including the brain. Multiorgan MRI can provide further insight on the repercussions of COVID-19 on organ health but requires a balance between richness and quality of data acquisition and total scan duration. We adapted the UK Biobank brain MRI protocol to produce high-quality images while being suitable as part of a post-COVID-19 multiorgan MRI exam. The analysis pipeline, also adapted from UK Biobank, includes new imaging-derived phenotypes (IDPs) designed to assess the effects of COVID-19. A first application of the protocol and pipeline was performed in 51 COVID-19 patients post-hospital discharge and 25 controls participating in the Oxford C-MORE study.

The protocol acquires high resolution T1, T2-FLAIR, diffusion weighted images, susceptibility weighted images, and arterial spin labelling data in 17 minutes. The automated imaging pipeline derives 1575 IDPs, assessing brain anatomy (including olfactory bulb volume and intensity) and tissue perfusion, hyperintensities, diffusivity, and susceptibility. In the C-MORE data, these quantitative measures were consistent with clinical radiology reports. Our exploratory analysis tentatively revealed that recovered COVID-19 patients had a decrease in frontal grey matter volumes, an increased burden of white matter hyperintensities, and reduced mean diffusivity in the total and normal appearing white matter in the posterior thalamic radiation and sagittal stratum, relative to controls. These differences were generally more prominent in patients who received organ support. Increased T2* in the thalamus was also observed in recovered COVID-19 patients, with a more prominent increase for non-critical patients.

This initial evidence of brain changes in COVID-19 survivors prompts the need for further investigations. Follow-up imaging in the C-MORE study is currently ongoing, and this protocol is now being used in large-scale studies. The pipeline is widely applicable and will contribute to new analyses to hopefully clarify the medium to long-term effects of COVID-19.

HighlightsO_LIUK Biobank brain MRI protocol and pipeline was adapted for multiorgan MRI of COVID-19
C_LIO_LIHigh-quality brain MRI data from 5 modalities are acquired in 17 minutes
C_LIO_LIAnalysis pipeline derives 1575 IDPs of brain anatomy, perfusion, and microstructure
C_LIO_LIEvidence of brain changes in COVID-19 survivors was found in the C-MORE study
C_LIO_LIThis MRI protocol is now being used in multiple large-scale studies on COVID-19
C_LI


title: Rapid Screening of COVID-19 Disease Directly from Clinical Nasopharyngeal Swabs using the MasSpec Pen Technology

abstract: The outbreak of COVID-19 has created an unprecedent global crisis. While PCR is the gold standard method for detecting active SARS-CoV-2 infection, alternative high-throughput diagnostic tests are of significant value to meet universal testing demands. Here, we describe a new design of the MasSpec Pen technology integrated to electrospray ionization (ESI) for direct analysis of clinical swabs and investigate its use for COVID-19 screening. The redesigned MasSpec Pen system incorporates a disposable sampling device refined for uniform and efficient analysis of swab tips via liquid extraction directly coupled to a ESI source. Using this system, we analyzed nasopharyngeal swabs from 244 individuals including symptomatic COVID-19 positive, symptomatic negative, and asymptomatic negative individuals, enabling rapid detection of rich lipid profiles. Two statistical classifiers were generated based on the lipid information aquired. Classifier 1 was built to distinguish symptomatic PCR-positive from asymptomatic PCR-negative individuals, yielding cross-validation accuracy of 83.5%, sensitivity of 76.6%, and specificity of 86.6%, and validation set accuracy of 89.6%, sensitivity of 100%, and specificity of 85.3%. Classifier 2 was built to distinguish symptomatic PCR-positive patients from negative individuals including symptomatic PCR-negative patients with moderate to severe symptoms and asymptomatic individuals, yielding a cross-validation accuracy of 78.4% accuracy, specificity of 77.21%, and sensitivity of 81.8%. Collectively, this study suggests that the lipid profiles detected directly from nasopharyngeal swabs using MasSpec Pen-ESI MS allows fast (under a minute) screening of COVID-19 disease using minimal operating steps and no specialized reagents, thus representing a promising alternative high-throughput method for screening of COVID-19.


title: A baseline transcriptional signature associates with clinical malaria risk in RTS,S/AS01-vaccinated African children

abstract: In a phase 3 trial in African infants/children, the RTS,S/AS01 (GSK) vaccine showed moderate efficacy against clinical malaria. We aimed to identify RTS,S/AS01-induced signatures associated with clinical malaria by analyzing antigen-stimulated peripheral blood mononuclear cells sampled from a subset of trial participants at baseline and month 3 (one month post-third dose). RTS,S/AS01 vaccination was associated with downregulation of B-cell and monocyte-related blood transcriptional modules (BTMs) and upregulation of T-cell related BTMs, as well as higher month 3 (vs baseline) circumsporozoite protein (CSP)-specific CD4+ T-cell responses. There were few RTS,S/AS01-associated BTMs whose month 3 levels correlated with malaria risk. In contrast, baseline levels of BTMs associated with dendritic cells and with monocytes (among others) correlated with malaria risk. A cross-study analysis supported generalizability of the baseline dendritic cell- and monocyte-related BTM correlations with malaria risk to healthy, malaria-naive adults, suggesting inflammatory monocytes may inhibit protective RTS,S/AS01-induced responses.


title: Associations of socioeconomic position and adverse childhood experiences with health-related behaviour changes and changes to employment during the first COVID-19 lockdown in the UK

abstract:
BackgroundNon-pharmaceutical interventions to reduce the spread of COVID-19 may have disproportionately affected already disadvantaged populations.

MethodsWe analysed data from 2710 young adult participants of the Avon Longitudinal Study of Parents and Children. We assessed the associations of socioeconomic position (SEP) and Adverse Childhood Experiences (ACEs, e.g. abuse, neglect, measures of family dysfunction) with changes to health-related behaviours (meals, snacks, exercise, sleep, alcohol and smoking/vaping), and to financial and employment status during the first UK lockdown between March-June 2020.

ResultsExperiencing 4 or more ACEs was associated with reporting decreased sleep quantity during lockdown (OR 1.53, 95% CI: 1.07-2.18) and increased smoking and/or vaping (OR 1.85, 95% CI: 0.99-3.43); no other associations were seen between ACEs or SEP and health-related behaviour changes. Adverse financial and employment changes were more likely for people with low SEP and for people who had experienced multiple ACEs; e.g. people who had been in the  never worked or long-term unemployed or  routine and manual occupation categories pre-lockdown were almost 3 times more likely to have stopped working during lockdown compared with people who were in a higher managerial, administrative or professional occupation pre-lockdown (OR 2.83, 95% CI: 1.45-5.50 and OR 2.68, 95% CI: 1.63-4.42 respectively).

ConclusionAdverse financial and employment consequences of lockdown were more likely to be experienced by people who have already experienced socioeconomic deprivation or childhood adversity, thereby widening social inequalities. Despite this, in this sample of young adults, there was little evidence that lockdown worsened inequalities in health-related behaviours.

BOXO_ST_ABSWhat is already known on this subject?C_ST_ABSO_LINon-pharmaceutical interventions implemented to mitigate the spread of COVID-19 (e.g. nationwide lockdown) have affected the lifestyles and livelihoods of many, with potential consequences for physical health and financial wellbeing.
C_LIO_LIExisting evidence suggests sociodemographic inequalities in the effects of lockdown, but details of the factors influencing these inequalities remain unclear.
C_LI

What this study adds?O_LIA history of adverse childhood experiences may be associated with decreased sleep and increased smoking/vaping during lockdown. SEP and ACEs were not associated with changes in other health-related behaviours in this cohort of young adults.
C_LIO_LIAdverse financial and employment consequences of lockdown were more likely to be experienced by people who have already experienced socioeconomic deprivation or childhood adversity, thereby widening social inequalities. Our findings highlight a need for continued support of people who experience ACEs into adulthood, and demonstrate that this need may have increased during the COVID-19 pandemic.
C_LI


title: Analysis of the Second COVID-19 Wave in India Using a Birth-Death Model

abstract: India is witnessing the second wave of the COVID-19 disease from the first half of February 2021. The method in [5] is applied here to analyze the second wave in India. We start with fitting a birth-death model to the active and total cases data for the period from 13th to 28th February 2021. This initial dataset is expanded step by step by adding the two future weeks data to it until 14th May 2021. This resulted in six models in total. The efficacy of each model is tested in terms of predictions made for the next two weeks. The infectivity rates are found to be ever-increasing in the case of the five initial models. The infectivity rate for the sixth model, which is based on the data from 13th February to 14th May 2021, shows a decreasing nature with an increase in time. This indicates a decline in the second wave, which may start from 4th June 2021 according to the fitted parameters.


title: Remote, unsupervised functional motor task evaluation in older adults across the United States using the MindCrowd electronic cohort

abstract: The COVID-19 pandemic has impacted the ability to evaluate motor function in older adults, as motor assessments typically require face-to-face interaction. This study tested whether motor function can be assessed at home. One hundred seventy-seven older adults nationwide (recruited through the MindCrowd electronic cohort) completed a brief functional upper-extremity assessment at home and unsupervised. Performance data were compared to data from an independent sample of community-dwelling older adults (N=250) assessed by an experimenter in-lab. The effect of age on performance was similar between the in-lab and at-home groups for both the dominant and non-dominant hand. Practice effects were also similar between the groups. Assessing upper-extremity motor function remotely is feasible and reliable in community-dwelling older adults. This test offers a practical solution in response to the COVID-19 pandemic and telehealth practice and other research involving remote or geographically isolated individuals.

category: rehabilitation medicine and physical therapy


title: Virtually in Synch: A Pilot Study on Affective Dimensions of Dancing with Parkinson's during COVID- 19

abstract: Loss of social supports and community programs due to lockdowns and other measures associated with COVID-19 has been linked with concerns over mental health and feelings of isolation. These challenges can be particularly acute for the elderly and people living with chronic or pervasive health conditions. Dance for PD, a program specifically developed for people living with Parkinsons Disease, formerly offered in hundreds of locations around the globe, either halted or shifted to a virtual format. Our study investigates the transition of these dance-based programs to an online environment, with the aim of determining the extent to which a virtual format provides affective support or other benefits. Given the increased incidence of mental health problems and social isolation associated with COVID-19, this investigation aims to contribute to the development of better supports for vulnerable populations while helping us understand the specific contributions of dance-based programs in a virtual environment.


title: Integrating health behavior theories to predict COVID-19 vaccine acceptance: differences between medical students and nursing students in Israel

abstract:
BackgroundThis study aimed to explore behavioral-related factors predicting the intention of getting a COVID-19 vaccine among medical and nursing students using an integrative model combining the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB).

MethodsA cross-sectional online survey was conducted among medical and nursing students aged > 18 years in their clinical years in Israel between 27 August and 28 September 2020. Hierarchical logistic regression was used to predict acceptance of a COVID-19 vaccine.

ResultsA total number of 628 participants completed the survey. Medical students expressed higher intentions of getting vaccinated against COVID-19 than nursing students (88.1% vs. 76.2%, p < 0.01). The integrated model based on HBM and TPB was able to explain 66% of the variance (adjusted R2 = 0.66). Participants were more likely to be willing to get vaccinated if they reported higher levels of perceived susceptibility, benefits, barriers, cues to action, attitude, self-efficacy and anticipated regret. Two interaction effects revealed that male nurses had a higher intention of getting vaccinated than did female nurses and that susceptibility is a predictor of the intention of getting vaccinated only among nurses.

ConclusionsThis study demonstrates that both models considered (i.e., HBM and TPB) are important for predicting the intention of getting a COVID-19 vaccine among medical and nursing students, and can help better guide intervention programs, based on components from both models. Our findings also highlight the importance of paying attention to a targeted group of female nurses, who expressed low vaccine acceptance.

category: occupational and environmental health


title: Integrating Health Behavior Theories to Predict COVID-19 Vaccine Acceptance: Differences between Medical Students and Nursing Students


title: One year of SARS-CoV-2: Genomic characterization of COVID-19 outbreak in Qatar

abstract: The state of Qatar has emerged as a major transit hub connecting all parts of the globe, making it as a hotspot for infectious disease introduction and providing an ideal setting to monitor the emergence and spread of variants. In this study, we report on 2634 SARS-CoV-2 whole-genome sequences from infected patients in Qatar between March-2020 and March-2021, representing 1.5% of all positive cases in this period. Despite the restrictions on international travel, the viruses sampled from the populace of Qatar mirrored nearly the entire global populations genomic diversity with nine predominant viral lineages that were sustained by local transmission chains and the emergence of mutations that are likely to have originated in Qatar. We reported an increased number in the mutations and deletions in B.1.1.7 and B.1.351 lineages in a short period. This raises the imperative need to continue the ongoing genomic surveillance that has been an integral part of the national response to monitor SARS-CoV-2 profile and re-emergence in Qatar.


title: Vaccination and three non-pharmaceutical interventions determine the end of COVID-19 at 381 metropolitan statistical areas in the US

abstract: The rapid rollout of the COVID-19 vaccine global raises the question of whether and when the ongoing pandemic could be eliminated with vaccination and non-pharmaceutical interventions (NPIs). Despite advances in the impact of NPIs and the conceptual belief that NPIs and vaccination control COVID-19 infections, we lack evidence to employ control theory in real-world social human dynamics in the context of disease spreading. We bridge the gap by developing a new analytical framework that treats COVID-19 as a feedback control system with the NPIs and vaccination as the controllers and a computational and mathematical model that maps human social behaviors to input signals. This approach enables us to effectively predict the epidemic spreading in 381 Metropolitan statistical areas (MSAs) in the US by learning our model parameters utilizing the time series NPIs (i.e., the stay-at-home order, face-mask wearing, and testing) data. This model allows us to optimally identify three NPIs to predict infections actually in 381 MSAs and avoid overfitting. Our numerical results universally demonstrate our approachs excellent predictive power with R2 > 0.9 of all the MSAs regardless of their sizes, locations, and demographic status. Our methodology allows us to estimate the needed vaccine coverage and NPIs for achieving Re to the manageable level and the required days for disease elimination at each location. Our analytical results provide insights into the debates on the aims for eliminating COVID-19. NPIs, if tailored to the MSAs, can drive the pandemic to an easily containable level and suppress future recurrences of epidemic cycles.


title: The late positive potentials evoked by negative emotional pictures predict autonomic responses to an acute psychosocial stressor in healthy adults

abstract: Individuals vary substantially in their response to an acute stressor. Identifying the factors contributing to these individual differences in stress reactivity is of particular interest but still remains largely unknown in the stress and resilience domain. The present study aimed to investigate whether and how brain reactivity to negative stimuli during a non-stressful state could predict autonomic and neuroendocrine stress responses to an acute psychosocial stressor in healthy adults. To address this issue, fifty-two healthy young adults were recruited to view negative or neutral pictures while their electroencephalogram was recorded during a non-stressful state on the first experimental day. On the second experimental day, their autonomic and neuroendocrine responses to the Trier Social Stress Test (TSST) were measured. Results showed that increased late positive potential (LPP) to negative relative to neutral pictures was significantly associated with higher heart rate response but not with the cortisol response to acute social stress. These results implicate greater neural reactivity to negative stimuli as a physiological marker of heightened acute autonomic responses. These findings may help identify individuals who are at increased risk of developing negative outcomes under stress.

category: psychiatry and clinical psychology


title: Spectrum of neurological manifestations and systematic evaluation of cerebrospinal fluid for SARS-CoV2 in patients admitted to hospital during the COVID-19 epidemic in South Africa

abstract: Neurological manifestations of COVID-19 are increasingly described in the literature. There is uncertainty whether these occur due to direct neuroinvasion of the virus, para-infectious immunopathology, as result of systemic complications of disease such as hypercoagulability or due to a combination of these mechanisms. Here we describe clinical and radiological manifestations in a sequential cohort of patients presenting to a district hospital in South Africa with neurological symptoms with and without confirmed COVID-19 during the first peak of the epidemic. In these patients, where symptoms suggestive of meningitis and encephalitis were most common, thorough assessment of presence in CSF via PCR for SARS-CoV2 did not explain neurological presentations, notwithstanding very high rates of COVID-19 admissions. Although an understanding of potential neurotropic mechanisms remains an important area of research, these results provide rationale for greater focus towards the understanding of para-immune pathogenic processes and the contribution of systemic coagulopathy and their interaction with pre-existing risk factors in order to better manage neurological disease in the context of COVID-19. These results also inform the clinician that consideration of an alternative diagnosis and treatment for neurological presentations in this context is crucial, even in the patient with a confirmed diagnosis COVID-19.


title: Modeling waning and boosting of COVID-19 in Canada with vaccination

abstract: SARS-CoV-2, the causative agent of COVID-19, has caused devastating health and economic impacts around the globe since its appearance in late 2019. The advent of effective vaccines leads to open questions on how best to vaccinate the population. To address such questions, we developed a model of COVID-19 infection by age that includes the waning and boosting of immunity against SARS-CoV-2 in the context of infection and vaccination. The model also accounts for changes to infectivity of the virus, such as public health mitigation protocols over time, increases in the transmissibility of variants of concern, changes in compliance to mask wearing and social distancing, and changes in testing rates. The model is employed to study public health mitigation and vaccination of the COVID-19 epidemic in Canada, including different vaccination programs (rollout by age), and delays between doses in a two-dose vaccine. We find that the decision to delay the second dose of vaccine is appropriate in the Canadian context. We also find that the benefits of a COVID-19 vaccination program in terms of reductions in infections is increased if vaccination of 15-19 year olds are included in the vaccine rollout.


title: Novel application of capture-recapture methods to estimate the completeness of contact tracing during a large outbreak of Ebola Virus Disease, Democratic Republic of Congo, 2018-2020

abstract: Despite its critical role in containing outbreaks, the efficacy of contact tracing (CT), measured as the sensitivity of case detection, remains an elusive metric. We estimated the sensitivity of CT by applying unilist capture-recapture methods on data from the 2018-2020 outbreak of Ebola virus disease in the Democratic Republic of Congo. We applied different distributional assumptions to the zero-truncated count data to estimate the number of unobserved cases with a) any contacts and b) infected contacts, to compute CT sensitivity. Geometric distributions were the best fitting models. Our results indicate that CT efforts identified almost all (n=792, 99%) of the cases with any contacts, but only half (n=207, 48%) of the cases with infected contacts, suggesting that CT efforts performed well at identifying contacts during the listing stage, but performed poorly during the contact follow-up stage. We discuss extensions to our work and potential applications for the current COVID-19 pandemic.


title: FOCUS: Forecasting COVID-19 in the United States

abstract: Infectious disease forecasting has been a useful tool for public health planning and messaging during the COVID-19 pandemic. In partnership with the CDC, the organizers of the COVID-19 Forecast Hub have created a mechanism for forecasters from academia, industry, and government organizations to submit weekly near-term predictions of COVID-19 targets in the United States. Here we describe our efforts to participate in the COVID-19 Forecast Hub through the Forecasting COVID-19 in the United States (FOCUS) project. The effort led to more than three months of weekly submissions and development of an automated pipeline to generate forecasts. The models used in FOCUS yielded forecasts that ranked relatively well in terms of precision and accuracy.


title: Seroconversion following SARS-CoV-2 Infection or Vaccination in Pediatric IBD Patients

abstract:
ObjectiveInflammatory bowel disease (IBD) patients are commonly treated with immunomodulatory medications, and the effect of these medications on seroconversion to SARS-CoV-2 infection and vaccination are scant, particularly in pediatrics. We sought to determine serologic responses to SARS-CoV-2 infection and vaccination in pediatric IBD patients.

DesignWe conducted a single-center, retrospective study of all pediatric ([≤]21 years old) IBD patients in whom a SARS-CoV-2 IgG Antibody Assay was performed between April 2020 and May 2021 at our tertiary care center. This assay measures IgG antibody to the full-length SARS-CoV-2 spike protein and was routinely collected at infusion and outpatient clinic visits. The primary outcome was SARS-CoV-2 seroconversion, and the secondary outcome was titer level, with high titer defined as [≥]960 titer or >40 AU/mL. Clinical characteristics, including demographics, IBD location, behavior, activity, and therapy, SARS-CoV-2 exposures, COVID-19 testing and symptoms, SARS-CoV-2 infection status (WHO COVID-19: Case Definitions, 2020) and COVID-19 vaccination status and type, were gathered, and univariate analyses examined associations between clinical characteristics and outcome measures.

ResultsThere were 340 pediatric patients with SARS-CoV-2 Antibody Testing; 15% for confirmed or probable COVID-19, 2% for suspected COVID-19, 16% for asymptomatic exposure to a close contact with SARS-CoV-2 infection, 61% without any prior symptoms or exposures, and 6% for history of COVID-19 vaccination. Patients with confirmed or probable COVID-19 infection had a 90% rate of seroconversion, with 76% of these patients on biologic therapy. Patients post-infection without seroconversion had a significantly longer interval between infection and antibody assay (P=0.03). Within those with asymptomatic SARS-CoV-2 exposure, 43% had seroconversion, and there were no identified clinical characteristics associated with positive titer.

All pediatric patients who received vaccination seroconverted, and all who received mRNA vaccinations, including one after a single dose, achieved high titer levels; 100% of those who received vaccination were on biologic or small molecule therapy, including one on combination therapy with ustekinumab and tofacitinib.

ConclusionPediatric IBD patients have strong serologic antibody responses to SARS-CoV-2 infection and COVID-19 vaccination despite high rates of immunomodulatory therapy.

category: gastroenterology


title: Can alcohol consumption in Germany be reduced by alcohol screening, brief intervention and referral to treatment in primary health care? Results of a simulation study

abstract:
BackgroundScreening, brief intervention and referral to treatment (SBIRT) is a programme to reduce alcohol consumption for drinkers with high alcohol consumption levels. Only 2.9% of patients in primary health care (PHC) are screened for their alcohol use in Germany, despite high levels of alcohol consumption and attributable harm. We developed an open-access simulation model to estimate the impact of higher SBIRT delivery rates in German PHC settings on population-level alcohol consumption.

Methods and findingsA hypothetical population of drinkers and non-drinkers was simulated by sex, age, and educational status for the year 2009 based on survey and sales data. Risky drinking persons receiving BI or RT were sampled from this population based on screening coverage and other parameters. Running the simulation model for a ten-year period, drinking levels and heavy episodic drinking (HED) status were changed based on effect sizes from meta-analyses.

In the baseline scenario of 2.9% screening coverage, 2.4% of the adult German population received a subsequent intervention between 2009 and 2018. If every second PHC patient would have been screened for alcohol use, 21% of adult residents in Germany would have received BI or RT by the end of the ten-year simulation period. In this scenario, population-level alcohol consumption would be 12% lower than it was in 2018, without any impact on HED prevalence. Screening coverage rates below 10% were not found to have a measurable effect on drinking levels.

ConclusionsLarge-scale implementation of SBIRT in PHC settings can yield substantial reductions of alcohol consumption in Germany. As high screening coverage rates may only be achievable in the long run, other effective alcohol policies are required to achieve short-term reduction of alcohol use and attributable harm in Germany. There is large potential to apply this open-access simulation model to other settings and for other alcohol interventions.

category: primary care research


title: A model framework for projecting the prevalence and impact of Long-COVID in the UK

abstract:
BackgroundThe objective of this paper is to model lost Quality Adjusted Life Years (QALYs) from symptoms arising from COVID-19 in the UK population, including symptoms of  long-COVID. The scope includes QALYs lost to symptoms, but not deaths, due to acute COVID-19 and long COVID.

MethodsThe prevalence of symptomatic COVID-19, encompassing acute symptoms and long-COVID symptoms, was modelled using a decay function. Permanent injury as a result of COVID-19 infection, was modelled as a fixed prevalence. Both parts are combined to calculate QALY loss due to COVID-19 symptoms.

ResultsAssuming a 60% final attack rate for SARS-CoV-2 infection in the population, we modelled 299,719 QALYs lost within 1 year of infection (90% due to symptomatic COVID-19 and 10% permanent injury) and 557,754 QALYs lost within 10 years of infection (49% due to symptomatic COVID-19 and 51% due to permanent injury). The UK Government willingness-to-pay to avoid these QALY losses would be {pound}17.9 billion and {pound}32.2 billion, respectively. Additionally, 90,143 people were subject to permanent injury from COVID-19 (0.14% of the population).

ConclusionGiven the ongoing development in information in this area, we present a model framework for calculating the health economic impacts of symptoms following SARS-CoV-2 infection. This model framework can aid in quantifying the adverse health impact of COVID-19, long COVID and permanent injury following COVID-19 in society and assist the proactive management of risk posed to health. Further research is needed using standardised measures of patient reported outcomes relevant to long COVID and applied at a population level.

category: public and global health