title: Reducing COVID-19 Airborne Transmission Risks on Public Transportation Buses: An Empirical Study on Aerosol Dispersion and Control

abstract: This study is one of the first COVID-19 related bus studies to fully characterize cough aerosol dispersion and control in the highly turbulent real-world environment of driving regular bus routes on both a school bus and a transit bus. While several other bus studies have been conducted, they were limited to clinical contact tracing, simulation, or partial characterization of aerosol transmission in the passenger areas with constraint conditions. When considering the risk of transmission of SARS-CoV-2 (COVID-19) and other highly infectious airborne diseases, ground based public transportation systems are high-risk environments for airborne transmission particularly since social distancing of six feet is not practical on most buses. This study demonstrates that wearing of masks reduced the overall particle count released into the bus by an average of 50% or more depending on mask quality and reduced the dispersion distance by several feet. The study also demonstrates an 84.36% reduction in aerosol particles and an 80.28% reduction in the mean aerosol residence time for some test cases. We conducted 84 experimental runs using nebulized 10% sodium chloride and a mechanical exhalation simulator that resulted in 78.3 million data points and 124 miles of on-the-road testing. Our study not only captures the dispersion patterns using 28 networked particle counters, as well as quantifies the effectiveness of using on-board fans, opening of various windows, use of face coverings or masks, and the use of the transit bus HVAC system. This work also provides empirical observations of aerosol dispersion in a real-world turbulent air environment, which are remarkably different than many existing fluid dynamics simulations, and also offers substantial discussion on the implications for inclement weather conditions, driver safety, retrofit applications to improve bus air quality, and operational considerations for public transportation organizations.


title: COVID-19 Vaccine hesitancy in Addis Ababa, Ethiopia: A mixed-methods study

abstract:
BackgroundCOVID-19 infection is a global pandemic threatening the public health. Due to the development and initiation of vaccination, currently significant difference upon vaccine acceptance is seen between developed and developing countries. However, there are no data on the level of COVID-19 vaccine hesitancy and its associated factors in Addis Ababa, Ethiopia.

MethodsAn embedded mixed method study [QUAN(quali)] was conducted among residents of Akaki Kality sub-city in Addis Ababa, Ethiopia. For the quantitative part, a multi-stage sampling technique was used to recruit the study participants (n = 422). Twenty four adults were included purposively for the qualitative in-depth interview. Data was collected by face-to-face interview by using a semi-structured questionnaire. Factors associated with COVID-19 vaccine hesitancy were identified by multivariable binary logistic regression model.

ResultThe mean age of the participants was 34.1 years ({+/-}12.9). Nearly half (46.7%) of the participants exhibited poor level of knowledge and 51.8% had negative attitude towards COVID-19 and its preventive measures. One out five (19.1%) participants were not willing to get vaccinated when it becomes available. In the multivariable analysis, vaccine hesitancy was significantly associated with being female (aOR=1.97; 95% CI: 1.10 - 3.89, p=0.03), negative attitude towards COVID-19 and its preventive measures (aOR=1.75; 95% CI: 1.08 - 3.02, p=0.04), and information source being social media (internet) (aOR=3.59; 95% CI: 1.75 - 7.37, P <0.0001).

ConclusionA considerable proportion of the people in Addis Ababa have concerns on COVID-19 vaccine and unwilling to accept once it is available. Several conspiracy theories were put forth to justify their stance and this was mainly due to the misconceptions distributed from the use of social media as source of information. Overall, providing the community with health education and consistent government efforts in uphold the prevention measures are of paramount importance to tackle this pandemic.

category: public and global health


title: Mental Health of International Migrant Workers Amidst Large-Scale Dormitory Outbreaks of COVID-19: A Population Survey

abstract:
BackgroundIn the COVID-19 pandemic, international migrant workers have faced increased vulnerability on account of their status. This study examined the mental health burden of COVID-19 amongst low-waged migrant workers involved in large-scale dormitory outbreaks within Singapore.

MethodsBetween 22 June to 11 October 2020, questionnaires were distributed in-person and online to 1011 migrant workers undergoing movement restrictions. Mental health symptoms were measured using the 21-item Depression, Anxiety and Stress Scale (DASS-21). As covariates, we assessed participants socio-demographics, quarantine status, COVID-19 health concerns, financial stability, and exposure to news and misinformation. Linear regression models were fitted to identify factors associated with each DASS-21 subscale.

FindingsComplete movement restrictions were associated with increased depression and stress symptoms, while being diagnosed with COVID-19 was associated with increased anxiety. Participants who harboured fears about their health or job, perceived their health to be poorer, or had greater exposure to COVID-19 rumours reported higher depression, anxiety, and stress levels. Across the cohort, rates of severe or extremely severe depression (3.1%, 95% CI: 2.1-4.3%), anxiety (4.1%, 95% CI: 2.9-5.5%), and stress (1.3%, 95% CI: 0.7-2.2%) were similar to those observed in the general population for the host country (Singapore).

InterpretationThe risk factors identified underscore how the ongoing pandemic may impact the mental health of migrant workers. At the same time, we observed resilience within the cohort, with no evidence of increased symptomology (relative to the general population).

FundingJY Pillay Global Asia Grant

Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and Google Scholar for articles published in English between Jan 1, 2020 and Feb 20, 2021 using the following keywords: ("COVID*" OR "coronavirus") AND ("mental*" OR "psychiatr*") AND ("labo*r migra*" OR "migrant work" OR "foreign-work" OR "immigrant work" OR "economic migra*" OR "economic immigra*"). Focusing on international migrant workers employed in low-wage manual labour positions, we identified commentaries and interview-based studies describing the stressors faced by workers during the COVID-19 pandemic. However, we found no study documenting mental health symptoms within this group.

Added value of this studyTo our knowledge, this is the first mental health survey of low-wage migrant workers during the COVID-19 pandemic. We observed that the mental health burden was highest amongst participants who encountered pandemic-related adversities (complete movement restrictions, testing positive for COVID-19), perceived the situation negatively (being fearful of their health or job, or judging their health to be poorer), or had higher exposure to COVID-19 rumours.

Implications of the available evidenceOur findings provide a basis to identify and support at-risk migrant workers during the pandemic. Although we did not observe elevated rates of depression, anxiety, and stress symptoms within the migrant worker cohort, individual workers who experience poor mental health may find it harder to access health-care services (relative to the general population). Correspondingly, targeted support for at-risk migrant workers may serve to reduce mental health inequalities.


title: Proteome profiling of Cryoglobulinemia

abstract:
ObjectiveTo better understand and identify candidate protein biomarkers of cryoglobulinemia (CGE) from healthy patients or benign brain disease control patients.

MethodsThe tandem mass tag (TMT)-labeled quantitative proteomics approach was used to identify differential proteins in the serum proteome of 10 CGE patients and 10 disease control patients with negative cryoglobulin (CG), respectively. GO, KEGG and protein domain enrichment analysis was used for functional annotation of differential proteins. The biomarker candidates were validated by the parallel reaction monitoring (PRM) method in 20 samples (10 CGE patients, 5 healthy control patients, and 5 disease control patients).

ResultsA total of 1004 proteins were quantitatively identified. Among these, 62 proteins were upregulated, and 56 proteins were downregulated. 25 candidate biomarkers were validated by PRM. 5 upregulated proteins of A2M, MMP2, VCAM1, MCAM, and PCSK9, and 4 downregulated proteins of C3, IGHG2, PROZ, PPBP were consistent with TMT results. Upregulated proteins mostly related with cholesterol metabolism, while downregulated proteins were associated with immune regulation.

ConclusionThis study is the first proteomic study of cryoglobulinemia in China These findings might contribute to the application of proteomics for detecting and monitoring CGE. And our findings indicated cholesterol metabolism accelerates the development of CGE.

category: rheumatology


title: Muscle Strength Explains the Protective Effect of Physical Activity against COVID-19 Hospitalization among Adults aged 50 Years and Older

abstract:
ObjectivesPhysical activity has been proposed as a protective factor for COVID-19 hospitalization. However, the mechanisms underlying this association are unclear. Here, we examined the association between physical activity and COVID-19 hospitalization and whether this relationship was explained by other risk factors for severe COVID-19.

MethodWe used data from adults aged 50 years and older from the Survey of Health, Ageing and Retirement in Europe. The outcome was self-reported hospitalization due to COVID-19 measured before August 2020. The main exposure was usual physical activity, self-reported between 2004 and 2017. Data were analyzed using logistic regression models.

ResultsAmong the 3139 participants included in the study (69.3 {+/-} 8.5 years, 1763 women), 266 were tested positive for COVID-19 and 66 were hospitalized. Results showed that individuals who engaged in physical activity more than once a week had lower odds of COVID-19 hospitalization than individuals who hardly ever or never engaged in physical activity (odds ratios = 0.41, 95% confidence interval = 0.22-0.74, p = .004). This association between physical activity and COVID-19 hospitalization was explained by muscle strength, but not by other risk factors.

ConclusionThese findings suggest that, after 50 years of age, engaging in physical activity more than once a week is associated with lower odds of COVID-19 hospitalization. The protective effect of physical activity on COVID-19 hospitalization is explained by muscle strength.

category: sports medicine


title: Clinical outcome evaluations and CBT response prediction in Myotonic Dystrophy

abstract:
BackgroundThe European OPTIMISTIC clinical trial has demonstrated a significant, yet heterogenous effect of Cognitive Behavioural Therapy (CBT) for Myotonic Dystrophy type 1 (DM1) patients. One of its remaining aims was the assessment of efficacy and adequacy of clinical outcome measures, including the relatively novel primary trial outcome, the DM1-Activ-c questionnaire.

ObjectivesAssessment of the relationship between the Rasch-built DM1-Activ-c questionnaire and 26 commonly used clinical outcome measurements. Identification of variables associated with CBT response in DM1 patients.

MethodsRetrospective analysis of the to date largest clinical trial in DM1 (OPTIMISTIC), comprising of 255 genetically confirmed DM1 patients randomized to either standard care or CBT with optionally graded exercise therapy. Correlations of 27 different outcome measures were calculated at baseline (cross-sectional) and of their respective intervention induced changes (longitudinal). Bootstrap enhanced Elastic-Net (BeEN) regression was validated and implemented to select variables associated with CBT response.

ResultsIn cross-sectional data, DM1-Activ-c correlated significantly with the majority of other outcome measures, including Six Minute Walk Test and Myotonic Dystrophy Health Index. Fewer and weaker significant longitudinal correlations were observed. Nine variables potentially associated with CBT response were identified, including measures of disease severity, executive cognitive functioning and perceived social support.

ConclusionsThe DM1-Activ-c questionnaire appears to be a well suited cross-sectional instrument to assess a variety of clinically relevant dimensions in DM1. Yet, apathy and experienced social support measures were less well captured. CBT response was heterogenous, requiring careful selection of outcome measures for different disease aspects.

category: neurology


title: Multi-transcriptomic analysis points to early organelle dysfunction in human astrocytes in Alzheimer's disease

abstract:
Recent single-nucleus RNA sequencing of astrocytes in postmortem Alzheimers disease (AD) samples is limited by the low number of sequenced astrocytes and small cohort sizes. We developed a systems biology approach to identify astrocytic genes in public large bulk AD transcriptomes. Brain cell specific gene clusters were generated from RNA sequencing data from isolated healthy human brain cells using cell-type enrichment scoring and clustering. Cell-specific gene clusters were localized in whole-brain transcriptomes from 766 subjects diagnosed with AD or mild cognitive impairment (MCI) from the Mount Sinai Hospital, the Mayo Clinic, and the Religious Order Study/Memory and Aging Project (ROSMAP). Gene clusters were organized into manually curated functional categories including astrocytic categories absent from existing platforms, such as perisynaptic astrocytic processes (PAP). Changes among subjects were determined by gene set variation analysis (GSVA) and principal component analysis (PCA). Hierarchical clustering revealed molecular heterogeneity in individuals with the same clinical diagnosis. Particularly in the Mayo Clinic and ROSMAP cohorts, over 50% of Controls presented the massive down-regulation of genes encoding synaptic proteins typical of AD, whereas 30% of AD patients presented Control-like transcriptomic profiles. According to GSVA and PCA, down-regulation of neuronal genes related to synaptic proteins correlated with down-regulation of astrocytic genes encoding mitochondrial and endolysosomal proteins, and up-regulation of genes related to PAP. Transcriptomic data thus unravel a deep phenotypic transformation of human astrocytes in AD, affecting organelles and astrocyte-neuron interactions. We posit that therapies preventing organelle dysfunction in astrocytes may protect neural circuits in preclinical and clinical AD.

Main pointsO_LITranscriptomes of control subjects and AD patients segregate in two main molecular profiles regardless of clinical diagnosis.
C_LIO_LIDysregulation of the endolysosomal/mitochondrial axis in astrocytes correlates with impaired synaptic plasticity in neurons.
C_LI


title: The Charitable Feeding System helps Food Insecure Participants maintain Fruit and Vegetable intake during COVID-19.

abstract: Charitable food services, including food banks and pantries, support individual and households food access, potentially maintaining food security and diet quality during emergencies. During the COVID-19 pandemic, the use of food banks and pantries has increased in the US. Here we examine perceptions of the charitable food system and its relationship to food security and dietary quality, specifically fruit and vegetable (FV) intake during the first six months of the COVID-19 pandemic, using a statewide representative survey (n=600) of residents of Vermont. We find that demand for charitable food services increased by 68%. The utilization of food pantries was more common among food insecure households and households with children. Among food insecure respondents, those who used the charitable food system were less likely to reduce their FV intake during the pandemic than those who did not use the charitable food system. Further, we find significant interactions between food pantry use and food insecure households, suggesting that, for food, insecure households, utilizing a food pantry since the onset of the COVID-19 pandemic was associated with higher fruit consumption. These results indicate that these services may support food access and diet quality for at-risk populations during emergencies.

category: nutrition


title: Computed-tomography estimates of interaural mismatch in insertion depth and scalar location in bilateral cochlear-implant users

abstract:
HypothesisWe hypothesized that the bilateral cochlear-implant (BI-CI) users would have a range of interaural insertion-depth mismatch because of different physical placements or characteristics of the arrays, but less than half of electrodes would have less than 75{degrees} or 3 mm of interaural insertion-depth mismatch. We also hypothesized that interaural insertion- depth mismatch would be more prevalent nearer the apex, when electrodes were located outside of scala tympani (i.e., possible interaural scalar mismatch), and when the arrays were a mix of pre-curved and straight types.

BackgroundBrainstem neurons in the superior olivary complex are exquisitely sensitive to interaural differences, the cues to sound localization. These binaurally sensitive neurons rely on interaurally place-of-stimulation-matched inputs at the periphery. BI-CI users may have interaural differences in insertion depth and scalar location, causing interaural place- of-stimulation mismatch that impairs binaural abilities.

MethodsInsertion depths and scalar locations were calculated from temporal-bone computed-tomography (CT) scans of 107 BI-CI users (27 Advanced Bionics, 62 Cochlear, and 18 Med-El). Each subject had either both pre-curved, both straight, or one of each type of array (mixed).

ResultsThe median interaural insertion-depth mismatch was 23.4{degrees} or 1.3 mm. Relatively large interaural insertion-depth mismatch sufficient to disrupt binaural processing occurred for about 15% of electrode pairs [defined as >75{degrees} (13.0% of electrode pairs) or >3 mm (19.0% of electrode pairs)]. There was a significant three-way interaction of insertion depth, scalar location, and array type. Interaural insertion-depth mismatch was most prevalent when electrode pairs were more apically located, electrode pairs had interaural scalar mismatch (i.e., one in Scala Tympani, one in Scala Vestibuli), and when the arrays were both pre-curved.

ConclusionLarge interaural insertion-depth mismatch can occur in BI-CI users. For new BI-CI users, improved surgical techniques to avoid interaural insertion-depth and scalar mismatch is recommended. For existing BI-CI users with interaural insertion-depth mismatch, interaural alignment of clinical frequency allocation tables by an audiologist might remediate any negative consequences to spatial-hearing abilities.

category: otolaryngology


title: A Statistical Framework to Identify Cell Types Whose Genetically Regulated Proportions are Associated with Complex Diseases

abstract: Finding disease-relevant tissues and cell types can facilitate the identification and investigation of functional genes and variants. In particular, cell type proportions can serve as potential disease predictive biomarkers. Here, we introduce a novel statistical framework, cell-type Wide Association Study (cWAS), that integrates genetic data with transcriptomics data to identify cell types whose genetically regulated proportions (GRPs) are disease/trait-associated. On simulated and real GWAS data, cWAS showed substantial statistical power with newly identified significant GRP associations in disease-associated tissues. More specifically, GRPs of endothelial and myofibroblasts in lung tissue were associated with Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease, respectively. For breast cancer, the GRP of blood CD8+ T cells was negatively associated with breast cancer (BC) risk as well as survival. Overall, cWAS is a powerful tool to reveal cell types associated with complex diseases mediated by GRPs.

category: genetic and genomic medicine


title: Clinical presentation and in-hospital outcomes of older patients hospitalized with COVID-19 in Montreal, Canada: a retrospective review

abstract:
BackgroundOlder adults are more vulnerable to severe infection and mortality due to COVID-19. They often have atypical presentations of the disease without respiratory symptoms, which makes early diagnosis clinically challenging. We aimed to compare the baseline characteristics, presentation, and disease course of older and younger patients hospitalized with COVID-19.

MethodsThe charts of 429 consecutive patients hospitalized in Montreal, Canada, with PCR-confirmed COVID-19 were retrospectively reviewed. Baseline health, presentation, in-hospital complications, and outcomes were recorded. Desegregation by age was performed to compare older ([≥]70) versus younger (<70) individuals.

ResultsOlder patients presented with more comorbidities compared to younger patients as captured by the Charlson Comorbidity Index (mean 6 vs 2), including higher rates of cardiovascular, cerebrovascular, chronic obstructive pulmonary, and chronic kidney disease. Older patients were less likely than younger patients to present with cough (27% vs 47%) or dyspnea (33% vs 48%). Fifty-two (52%) had no respiratory symptoms on presentation compared to 32% in the younger group (p<0.001); however, they were more likely to present with geriatric syndromes such as delirium (29% vs 7%), functional decline (14% vs 0.6%), or falls (15% vs 5%). Twelve (12%) of older patients presented with a geriatric syndrome as their sole symptom compared to 3% in the younger group (p=0.002). Older adults were more likely to develop acute kidney injury (35% vs 22%), malnutrition (9% vs 4%), delirium (29% vs 17%) and hypernatremia (32% vs 17%). They had higher in-hospital mortality (33% vs 13%, p<0.001).

DiscussionOlder adults presenting to hospital with COVID-19 commonly have no respiratory symptoms and can present with only a geriatric syndrome. A new geriatric syndrome in an older person should trigger isolation and evaluation for COVID-19. Furthermore, older adults are particularly vulnerable to complications related to dehydration, warranting early initiation of multidisciplinary care.

category: geriatric medicine


title: COVID-19 Vaccination Priority Evaluation

abstract: Computing the COVID-19 vaccination priority is an urgent and ubiquitous decision problem. In this paper we propose a solution of this problem using the LSP evaluation method. Our goal is to develop a justifiable and explainable quantitative criterion for computing a vaccination priority degree for each individual in a population. Performing vaccination in the order of the decreasing vaccination priority produces maximum positive medical, social, and ethical effects for the whole population. The presented method can be expanded and refined using additional medical and social conditions. In addition, the same methodology is suitable for solving other similar medical priority decision problems, such as priorities for organ transplants.

category: health informatics


title: Performance of RT-PCR on saliva specimens compared to nasopharyngeal swabs for the detection of SARS-CoV-2 in children: A prospective comparative clinical trial

abstract:
BackgroundSaliva RT-PCR is an attractive alternative for the detection of SARS-CoV-2 in adults with much less known in children.

MethodsChildren and adolescents with symptoms suggestive of COVID-19 were prospectively enrolled in a comparative clinical trial of saliva and nasopharyngeal (NP) RT-PCR between November and December 2020. Detection rates and sensitivities of saliva and NP RT-PCR were compared. Participants with discordant NP and saliva RT-PCR results including viral load (VL) were also analyzed.

ResultOut of 405 patients enrolled, 397 patients had two tests performed. Mean age was 12.7 years (range 1.2-17.9). Detection rates were 22.9% (95%CI 18.8-27.1%) by saliva RT-PCR, 25.4% (21.2-29.7%) by NP RT-PCR, and 26.7% (22.4-31.1%) by any test. The sensitivity of saliva was 85.2% (78.2-92.1%) when using NP as the gold standard; in contrast, when saliva was considered the gold standard, the sensitivity of NP was 94.5% (89.8-99.2%).For a NP RT-PCR VL threshold of [≥]103 and [≥]104 copies/ml, sensitivity of saliva increases to 88.7% and 95.2% respectively. Sensitivity of saliva and NP swabs was respectively 89.5% and 95.3% in patient with symptoms less than 4 days (p=0.249) and 70.0% and 95.0% in those with symptoms [≥] 4 to 7 days (p=0.096). The 15 patients who had an isolated positive NP RT-PCR were significantly younger (p=0.034), had a lower NP VL (median 5.6x103 vs 3.9x107, p<0.001), and were not able to drool saliva at the end of the sampling (p=0.002). VLs were significantly lower with saliva PCR than with NP RT-PCR (median 8.7 cp/ml x104; IQR 1.2x104-5.2x105; vs median 4.0x107cp/ml; IQR 8.6x105-1.x108; p<0.001).

ConclusionSaliva PCR shows diagnostic performances close to NP RT-PCR for SARS-CoV2 detection in most symptomatic outpatient children and adolescents.

category: infectious diseases


title: Healthcare utilisation survey as part of the Hybrid model of the Surveillance of Enteric Fever in India (SEFI) study: processes, results, and challenges

abstract:
BackgroundEnteric fever is a significant health challenge in low and middle-income countries. "Surveillance of Enteric Fever in India" (SEFI) network was set up to obtain reliable incidence data. Six sites utilised a hybrid surveillance model, a combination of facility-based surveillance and community-based healthcare utilisation survey (HCUS). HCUS was performed to determine the percentage of the catchment population utilising the study facilities for febrile episodes, and is described here.

MethodsA two-stage sampling process was utilised for the HCUS to select 5000 households per site. Demographic data and healthcare-seeking behaviour were assessed.

ResultsFebrile hospitalisation rate ranged from 2.5/1000 in Kullu to 9.6/1000 in Anantapur. The percentage of febrile admissions that sought care in the study hospital from the catchment area is 17% in Anantapur, 38% in Karimganj, 38% in Chandigarh, 10% in Nandurbar, 36% in Kullu and 24% in East Champaran respectively.

ConclusionsThe variability in healthcare utilisation for fever admissions in the study hospitals underscores the importance of periodic healthcare utilisation surveys in hybrid surveillance. It is essential to adjust for those cases which have slipped out of the facility surveillance radar for obtaining an accurate estimate of the disease burden.


title: SARS-CoV-2 Total and Subgenomic RNA Viral Load in Hospitalized Patients

abstract: Understanding viral load in patients infected with SARS-CoV-2 is critical to epidemiology and infection control. Previous studies have demonstrated that SARS-CoV-2 RNA can be detected for many weeks after symptom onset. The clinical significance of this finding is unclear and, in most patients, likely does not represent active infection. There are, however, patients who shed infectious virus for weeks. Detection of subgenomic RNA transcripts expressed by SARS-CoV-2 has been proposed to represent productive infection and may be a tractable marker for monitoring infectivity. Here, we use RT-PCR to quantify total and subgenomic nucleocapsid (N) and envelope (E) transcripts in 190 SARS-CoV-2 positive samples collected on hospital admission. We relate these findings to duration of symptoms. We find that all transcripts decline at the same rate; however, subgenomic E becomes undetectable before other transcripts. In Kaplan-Meier analysis the median duration of symptoms to a negative test is 14 days for sgE and 25 days for sgN. There is a linear decline in subgenomic RNA compared to total RNA suggesting subgenomic transcript copy number is highly dependent on copy number of total transcripts. The mean difference between total N and subgenomic N is 16-fold (4.0 cycles) and the mean difference between total E and sub-genomic E is 137-fold (7.1 cycles). This relationship is constant over duration of symptoms allowing prediction of subgenomic copy number from total copy number. Although Subgenomic E is undetectable at a time that may more closely reflect the duration of infectivity, its utility in determining active infection may be no more useful than a copy number threshold determined for total transcripts.


title: Ongoing long-lasting insecticide-treated net distribution efforts are insufficient to maintain high rates of use among children in rural Uganda

abstract:
BackgroundLong-lasting insecticide-treated nets (LLINs) remain a cornerstone of malaria control, but optimal distribution strategies to sustain universal coverage are not well-defined

MethodsWe conducted a cross-sectional survey of 2,190 households in the highlands of western Uganda to examine LLIN source and use among children age with elevation and distance to clinic being the primary variables of interest.

ResultsWe found that only 64.7% (95% CI 64.0 - 65.5%) of children were reported to have slept under a LLIN the previous night. Compared to those living <1 km from a health center, households at [≥] 2 km were less likely to report the child sleeping under a LLIN (RR 0.86, 95% CI: 0.83 - 0.89, p<.001). Households located farther from a health center received a higher proportion of nets from government distributions compared to households living closer to health centers.

ConclusionsContinuous, clinic-based distribution efforts were insufficient to sustain high rates of LLIN use among children between mass distribution campaigns. More frequent campaigns and complementary approaches are required to achieve and maintain universal LLIN coverage in rural areas.


title: Is Rapid Molecular Testing Enough In Screening Drug-Resistant Tuberculosis In Community?

abstract:
BackgroundThe study aimed to compare the sensitivity and specificity of cartridge based nucleic acid amplification test (CBNAAT) for diagnosis of Drug-Resistant tuberculosis (DRTB) with culture sensitivity assays.

MethodsPatients with cough symptoms for more than two weeks with any one symptom such as night sweats, fever, and unintentional weight loss were enrolled. Cases where Mycobacterium Tuberculosis was detected on sputum CBNAAT, were included in the study. Demographic variables, clinical features, and chest radiographs were collected. Each sputum sample was divided into three aliquots: smear microscopy, culture, and genotypic drug sensitivity testing (DST). Results of all three diagnostic modalities were compared with CBNAAT.

ResultsOut of 236 patients with sputum positive CBNAAT, 49.4 % (117/236) were rifampicin-resistant while 50. 6 % (119/236) were Rifampicin sensitive. The genotypic DST assays carried out on all enrolled patients showed that 76. 3 % (181/236) patients were resistant to one or more first-line or second-line antitubercular (ATT) drugs, while 23.7 % (55/236) patients were sensitive to all ATT drugs. On concordant analysis of CB NAAT with DST assays, we found that among 119 CB NAAT rifampicin sensitive patients, 66 patients were resistant to first-line or second-line antitubercular drugs.

ConclusionThis study found that the screening of DRTB with CBNAAT at the community level is suboptimal compared to the gold standard. Although CBNAATs sensitivity in detecting DRTB is significantly higher, the specificity is lower in that population who have received ATT earlier.


title: Evaluation of a SARS-CoV-2 Vaccine NVX-CoV2373 in Younger and Older Adults

abstract:
BackgroundNVX-CoV2373 is a recombinant severe acute respiratory coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant.

MethodsThe phase 2 component of our randomized, placebo-controlled, phase 1-2 trial was designed to identify which dosing regimen of NVX-CoV2373 should move forward into late phase studies in younger (18-59 years) and older (60-84 years) participants and was based on immunogenicity and safety data through day 35 (14 days after the second dose). Participants were randomly assigned to receive either one or two intramuscular doses of 5-{micro}g or 25-{micro}g NVX-CoV2373 or placebo, 21 days apart. Primary endpoints were immunoglobulin G (IgG) anti-spike protein response, 7-day solicited reactogenicity, and unsolicited adverse events. A key secondary endpoint was wild-type virus neutralizing antibody response.

ResultsAfter randomization, approximately 250 participants each were assigned to one of four vaccine groups or placebo. Of these, approximately 45% were older participants. Reactogenicity was predominantly mild to moderate in severity and of short duration (median <3 days) after first and second vaccination with NVX-CoV2373, with higher frequencies and intensity after second vaccination and with the higher dose, and occurred less frequently and was of lower intensity in older participants. The two-dose regimen of 5-{micro}g NVX-CoV2373 induced robust geometric mean titer (GMT) IgG anti-spike protein (65,019 and 28,137 EU/mL) and wild-type virus neutralizing antibody (2201 and 981 titers) responses in younger and older participants, respectively, with seroconversion rates of 100% in both age groups. Neutralizing antibody responses exceeded those seen in convalescent sera for both age groups.

ConclusionsThe study confirmed that the two-dose regimen of 5-{micro}g NVX-CoV2373 is highly immunogenic and well tolerated in both younger and older participants.

(Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number: NCT04368988).


title: Screening for SARS-CoV-2 infections in daycare facilities for children in a large city in Germany

abstract:
BackgroundThe role of pre-school children as a source and distributor of SARS-CoV-2 infections is still unclear. Daycare facilities that care particularly for young children with limited hygiene measures may contribute to the infection dynamics during the pandemic. The aim of this study was to implement and evaluate a voluntary SARS-CoV-2 screening program in daycare facilities.

MethodsThe study was conducted over a period of 4 weeks, from June 10th to July 7th 2020. The aim was to screen a representative group of 5000 individuals (children and staff at a ratio 3:1) attending daycare facilities in Dusseldorf, North Rhine-Westphalia. Tests were performed twice per week with oral rinsing water as sample material for the detection of SARS-CoV-2-RNA by molecular pool testing.

ResultsA total number of 5210 participants (75.9% children and 24.1% staff) from 115 day care centers participated in the study. Of a total of 34,068 returned samples (81.7%) during the study period, only one SARS-CoV-2 infection of a child was detected in the study cohort with one likely secondary infection within the daycare facility. Of note, during the study phase, no increase of SARS- CoV-2 infections was observed in daycare center compared to the overall incidence in Dusseldorf.

ConclusionsA voluntary screening program for SARS-CoV-2 infections could successfully be implemented in daycare facilities. Although the low overall incidence during the study period precludes firm conclusions, there was no evidence for increased transmission in children attending daycare facilities compared to the general population of Dusseldorf.

SummarySARS-CoV-2 screening programs in daycare facilities may help to detect asymptomatic infections at an early stage and thereby support containment. Here, a large screening study was evaluated suggesting similar infection rates in daycare facilities compared to the general population.


title: A Multilayer Model for Early Detection of COVID-19

abstract: Current efforts for COVID-19 screening mainly rely on reported symptoms and potential exposure to infected individuals. Here, we developed a machine-learning model for COVID-19 detection that utilizes four layers of information: 1) sociodemographic characteristics of the tested individual, 2) spatiotemporal patterns of the disease observed near the testing episode, 3) medical condition and general health consumption of the tested individual over the past five years, and 4) information reported by the tested individual during the testing episode. We evaluated our model on 140,682 members of Maccabi Health Services, tested for COVID-19 at least once between February and October 2020. These individuals had 264,516 COVID-19 PCR-tests, out of which 16,512 were found positive. Our multilayer model obtained an area under the curve (AUC) of 81.6% when tested over all individuals, and of 72.8% when tested over individuals who did not report any symptom. Furthermore, considering only information collected before the testing episode - that is, before the individual may had the chance to report on any symptom - our model could reach a considerably high AUC of 79.5%. Namely, most of the value contributed by the testing episode can be gained by earlier information. Our ability to predict early the outcomes of COVID-19 tests is pivotal for breaking transmission chains, and can be utilized for a more efficient testing policy.


title: Early genomic detection of SARS-CoV-2 P.1 variant in Northeast Brazil

abstract:
Tracking the spread of SARS-CoV-2 variants of concern is crucial to inform public health efforts and control the ongoing pandemic. Here, we report genetic evidence for circulation of the P.1 variant in Northeast Brazil. We advocate for increased active surveillance to ensure adequate control of this variant throughout the country.

Article Summary LineActive genomic surveillance of SARS- CoV-2 suspected cases from recent travelers reveals the circulation of the P1 variant of concern in Bahia state, Northeast Brazil.


title: Epidemiology and costs of post-sepsis morbidity, nursing care dependency, and mortality in Germany

abstract:
PurposeTo quantify the frequency and co-occurrence of new diagnoses consistent with post-sepsis morbidity, mortality, new nursing care dependency, and total healthcare costs after sepsis.

MethodsPopulation-based cohort study using healthcare claims data from 23 million beneficiaries of a German health insurance provider. We included adult patients with incident hospital-treated sepsis identified by ICD-10 codes in 2013-2014. New medical, psychological and cognitive diagnoses associated with post-sepsis morbidity; mortality; dependency on nursing care; and total health care costs in survivors were assessed to 3 years after hospital discharge.

ResultsAmong 116,507 sepsis patients who survived hospitalization for sepsis, 74.3% had a new medical, psychological or cognitive diagnosis in the first year after discharge. 20.6% and 3.8% had new diagnoses in two and three domains, respectively. 31.5% were newly dependent on nursing care, and 30.7% died within the first year. In the second and third year, 65.8% and 59.4% of survivors had new diagnoses, respectively. Healthcare costs totaled an average 36,585 Euro/patient in three years, including index hospitalization costs. Occurrence of new diagnoses in predefined subgroups was: 73.7% (survivors of non-severe sepsis), 75.6% (severe sepsis), 78.3% (ICU-treated sepsis), 72.8% (non-ICU treated sepsis) and 68.5% (survivors without prior diagnoses).

ConclusionsNew medical, psychological and cognitive diagnoses consistent with post-sepsis morbidity are common after sepsis, including among patients with less severe sepsis, no prior diagnoses, and younger age. This calls for more efforts to elucidate the underlying mechanisms, define optimal screening for common new diagnoses, and test interventions to prevent and treat post-sepsis morbidity.

Trial RegistrationDRKS00016340

Take home messageThis large population-based cohort of over 100,000 survivors of hospital-treated sepsis found high rates and a broad spectrum of new diagnoses consistent with post-sepsis morbidity, frequent new nursing care dependency, and high long-term mortality 1-3 years post sepsis. Post-sepsis morbidity was not limited to the oldest survivors or those with the most severe illness, but also affected younger survivors and those without pre-existing diagnoses.

category: intensive care and critical care medicine


title: Characterization and mitigation of aerosols and splatters from ultrasonic scalers

abstract:
BackgroundDental procedures often produce aerosols and splatter which have the potential to transmit pathogens such as SARS-CoV-2. The existing literature is limited.

MethodsAerosols and splatter were generated from an ultrasonic scaling procedure on a dental mannequin and characterized by two optical imaging methods - digital inline holography (DIH) and laser sheet imaging (LSI). Capture efficiencies of various aerosol mitigation devices were evaluated and compared.

ResultsThe ultrasonic scaling procedure generates a wide size range of aerosols up to a few hundred micrometers and occasional large splatter which emit at low velocity (mostly below 3 m/s). Use of a saliva ejector (SE) and high-volume evacuator (HVE) resulted in 63% and 88% of overall reduction respectively while an extraoral local extractor (ELE) resulted in a reduction of 96% at the nominal design flow setting.

ConclusionsThe study results showed that the use of ELE or HVE significantly reduced aerosol and splatter emission. The use of HVE generally requires an additional person to assist a hygienist, while an ELE can be operated "hands-free" when a dental hygienist is performing ultrasonic scaling and other operations.

Practical ImplicationsAn extraoral local extractor aids in the reduction of aerosols and splatters during ultrasonic scaling procedures, potentially reducing transmission of oral or respiratory pathogens, like SARS-CoV-2. Position and airflow of the device are important to effective aerosol mitigation.

category: dentistry and oral medicine


title: Impact of surface decontamination and systemic antimicrobials for surgical treatment of peri-implantitis: A systematic review and meta-analysis of randomized clinical trials

abstract:
BackgroundEfficient control of infection is essential to achieve desired outcomes in the surgical treatment of peri-implantitis lesions, although methods employed are largely heterogeneous.

PurposeTo compare the impact of different decontamination protocols and adjunctive systemic antimicrobials on the outcomes of surgical treatment of peri-implantitis.

Materials and methodsRandomized clinical trials (RCTs) on surgical treatment of peri-implantitis were selected through an electronic search on Medline, Embase, Scopus, and Central databases. Only studies comparing two or more anti-infective strategies were included. Following data extraction, two different sets of meta-analyses were performed. Firstly, overall impact of different implant surface decontamination methods was assessed by comparing baseline values with outcomes at 6-12 months. Secondly, pairwise comparisons evaluated the potential benefit of adjunctive systemic antimicrobials over placebo. Results were expressed as weighted mean effect (WME), weighed mean difference (WMD) or risk ratio (RR).

ResultsSixteen RCTs were included. No pairwise comparisons were available for different surface decontamination methods. Use of curettes resulted in improved probing depth (PD) (WME = 2.13 mm), but the results in terms of marginal bone levels (MBL) and percentage of disease resolution were unsatisfactory. Moreover, the adjunctive benefit of systemic antimicrobials over placebo was evaluated in two studies, representing a total of 178 implants. Despite not being statistically significant, the meta-analyses identified a higher probability of disease resolution (RR = 1.50) for test procedures. In terms of overall outcome, systemic antimicrobials with open flap debridement resulted in improved MBL (WME = 0.44 mm), reduced PD (WME = 2.46 mm) and 51.4% of disease resolution.

ConclusionsThere is not enough evidence to support adjunctive usage of systemic antimicrobials together with the surgical treatment of peri-implantitis. Moreover, higher consistency is required to prove the superiority of a surface decontamination protocol over another (PROSPERO CRD42020182303).

SUMMARY BOXO_ST_ABSWhat is knownC_ST_ABSO_LIPeri-implantitis is a common biological complication occurring at dental implants, and surgery is usually required to obtain thorough peri-implant infection control.
C_LIO_LINo systematic reviews with meta-analysis have assessed surface decontamination protocols for surgical treatment of peri-implantitis, as well as the adjunctive benefit of peri-operative systemic antimicrobials.
C_LI

What this study addsO_LIThis study offered the first evidence-based synthesis of randomized clinical trials regarding this relevant topic.
C_LIO_LIAlthough protocol heterogeneity was high, a combination of mechanical and chemical implant surface decontamination is recommendable.
C_LIO_LITitanium brushes and local delivery of minocycline showed encouraging results; while the additional benefit of systemic antimicrobials needs to be further determined.
C_LI


title: The CREBRF diabetes-protective rs373863828-A allele is associated with enhanced early insulin release in men of Maori and Pacific ancestry

abstract:
AimThe minor A allele of rs373863828 (CREBRF p.Arg457Gln) is associated with increased body mass index (BMI), but reduced risk of type 2 and gestational diabetes in Polynesian (Pacific peoples and Aotearoa New Zealand M[a]ori) populations. This study investigates the effect of the A allele on insulin release and sensitivity in overweight/obese men without diabetes.

MethodsA mixed meal tolerance test was completed by 172 men (56 with the A allele) of M[a]ori or Pacific ancestry, and 44 (24 with the A allele) had a frequently sampled intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp. Mixed linear models with covariates age, ancestry and BMI were used to analyse the association between the A allele of rs373863828 and markers of insulin release and blood glucose regulation.

ResultsThe A allele of rs373863828 is associated with a greater increase in plasma insulin 30 min following a meal challenge without affecting the elevation in plasma glucose or incretins GLP-1 or GIP. Consistent with this point, following an intravenous infusion of a glucose bolus, participants with an A allele had higher early (p<0.05 at 2 and 4 min) plasma insulin and C-peptide concentrations for a similar elevation in blood glucose as those homozygous for the major (G) allele. Despite increased plasma insulin, rs373863828 genotype was not associated with a significant difference (p>0.05) in insulin sensitivity index or glucose disposal during hyperinsulinemic-euglycemic clamp.

Conclusion/interpretationrs373863828-A allele associates with increased glucose-stimulated insulin release without affecting insulin sensitivity, suggesting that CREBRF p.Arg457Gln may increase maximal ability for {beta}-cells to release insulin to reduce the risk of type 2 diabetes.

category: endocrinology


title: Vaccination and herd immunity thresholds in heterogeneous populations

abstract: It has been suggested, without rigorous mathematical analysis, that the classical vaccine-induced herd immunity threshold (HIT) assuming a homogeneous population can be substantially higher than the minimum HIT obtained when considering population heterogeneities. We investigated this claim by developing, and rigorously analyzing, a vaccination model that incorporates various forms of heterogeneity and compared it with a model of a homogeneous population. By employing a two-group vaccination model in heterogeneous populations, we theoretically established conditions under which heterogeneity leads to different HIT values, depending on the relative values of the contact rates for each group, the type of mixing between groups, relative vaccine efficacy, and the relative population size of each group. For example, under biased random mixing and when vaccinating a given group results in disproportionate prevention of higher transmission per capita, it is optimal to vaccinate that group before vaccinating other groups. We also found situations, under biased assortative mixing assumption, where it is optimal to vaccinate more than one group. We show that regardless of the form of mixing between groups, the HIT values assuming a heterogeneous population are always lower than the HIT values obtained from a corresponding model with a homogeneous population. Using realistic numerical examples and parametrization (e.g., assuming assortative mixing together with vaccine efficacy of 95% and basic reproduction number of 2.5), we demonstrate that the HIT value considering heterogeneity (e.g., biased assortative mixing) is significantly lower (40%) compared with a HIT value of (63%) assuming a homogeneous population.

category: epidemiology


title: Impact of Vaccine Failure on the Transmission Dynamics of Measles in Nigeria

abstract: Measles is a vaccine preventable disease. However, it is still a major public health challenge in Nigeria.We therefore formulate a mathematical model for the transmission of measles with a two dose vaccination strategy and weaning of vaccine derived immunity. Using weekly measles cases for Nigeria in 2020 from the Nigeria Center for Disease Control (NCDC), the model was validated. This modelling study via numerical simulations showed that there is a possibility of disease control with a ten fold increase in the vaccination rates. Also, it was shown that primary vaccine failure has more impact on disease dynamics than secondary vaccine failure. Thus control strategies should not just focus on increase the vaccination rates but also look at measures that will help in reducing primary vaccine failure.


title: Predicting the effects of COVID-19 related interventions in urban settings by combining activity-based modelling, agent-based simulation, and mobile phone data

abstract:
Epidemiological simulations as a method are used to better understand and predict the spreading of infectious diseases, for example of COVID-19.

This paper presents an approach that combines a well-established approach from transportation modelling that uses person-centric data-driven human mobility modelling with a mechanistic infection model and a person-centric disease progression model. The model includes the consequences of different room sizes, air exchange rates, disease import, changed activity participation rates over time (coming from mobility data), masks, indoors vs. outdoors leisure activities, and of contact tracing. The model is validated against the infection dynamics in Berlin (Germany).

The model can be used to understand the contributions of different activity types to the infection dynamics over time. The model predicts the effects of contact reductions, school closures/vacations, masks, or the effect of moving leisure activities from outdoors to indoors in fall, and is thus able to quantitatively predict the consequences of interventions. It is shown that these effects are best given as additive changes of the reinfection rate R. The model also explains why contact reductions have decreasing marginal returns, i.e. the first 50% of contact reductions have considerably more effect than the second 50%.

Our work shows that is is possible to build detailed epidemiological simulations from microscopic mobility models relatively quickly. They can be used to investigate mechanical aspects of the dynamics, such as the transmission from political decisions via human behavior to infections, consequences of different lockdown measures, or consequences of wearing masks in certain situations. The results can be used to inform political decisions.

Author summaryEvidently, there is an interest in models that are able to predict the effect of interventions in the face of pandemic diseases. The so-called compartmental models have difficulties to include effects that stem from spatial, demographic or temporal inhomongeneities. Person-centric models, often using social contact matrices, are difficult and time-consuming to build up. In the present paper, we describe how we built a largely data-driven person-centric infection model within less than a month when COVID-19 took hold in Germany. The model is based on our extensive experience with mobility modelling, and a synthetic data pipeline that starts with mobile phone data, while taking the infection dynamics and the disease progression from the literature. The approach makes the model portable to all places that have similar so-called activity-based models of travel in place, which are many places world-wide, and the number is continuously increasing. The model has been used since its inception to regularly advise the German government on expected consequences of interventions.


title: Household COVID-19 risk and in-person schooling

abstract:
In-person schooling has proved contentious and difficult to study throughout the SARS-CoV-2 pandemic. Data from a massive online survey in the United States indicates an increased risk of COVID-19-related outcomes among respondents living with a child attending school in-person. School-based mitigation measures are associated with significant reductions in risk, particularly daily symptoms screens, teacher masking, and closure of extra-curricular activities. With seven or more mitigation measures, the association between in-person schooling and COVID-19-related outcomes all but disappears. Teachers working outside the home were more likely to report COVID-19-related outcomes, but this association is similar to other occupations (e.g., healthcare, office work). In-person schooling is associated with household COVID-19 risk, but this risk can likely be controlled with properly implemented school-based mitigation measures.

One sentence summaryLiving with children attending in-person school is linked to a higher risk of COVID-19 outcomes, which school-based interventions can mitigate.


title: Trends in homelessness and injection practices among young urban and suburban people who inject drugs: 1997-2017

abstract:
BackgroundAmong young people who inject drugs (PWID) homelessness is associated with numerous adverse psychosocial and health consequences, including risk of relapse and overdose, psychological distress and suicidality, limited treatment access, and injection practices that increase the risk of HIV and hepatitis C (HCV) transmission. Homeless PWID may also be less likely to access sterile syringes through pharmacies or syringe service programs.

MethodsThis study applied random-effects meta-regression to examine trends over time in injection risk behaviors and homelessness among young PWID in Chicago and surrounding suburban and rural areas using data from 11 studies collected between 1997 and 2017. In addition, subject-level data were pooled to evaluate the effect of homelessness on risk behaviors across all studies using mixed effects logistic and negative binomial regression with random study effects.

ResultsThere was a significant increase in homelessness among young PWID over time, consistent with the general population trend of increasing youth homelessness. In mixed-effects regression, homelessness was associated with injection risk behaviors (receptive syringe sharing, syringe mediated sharing, equipment sharing) and exchange sex, though we detected no overall changes in risk behavior over time.

ConclusionsIncreases over time in homelessness among young PWID highlight a need for research to understand factors contributing to youth homelessness to inform HIV/STI, HCV, and overdose prevention and intervention services for this population.


title: Mathematical modeling to inform vaccination strategies and testing approaches for COVID-19 in nursing homes

abstract:
BackgroundNursing home residents and staff were included in the first phase of COVID-19 vaccination in the United States. Because the primary trial endpoint was vaccine efficacy (VE) against symptomatic disease, there are limited data on the extent to which vaccines protect against SARS-CoV-2 infection and the ability to infect others (infectiousness). Assumptions about VE against infection and infectiousness have implications for possible changes to infection prevention guidance for vaccinated populations, including testing strategies.

MethodsWe use a stochastic agent-based SEIR model of a nursing home to simulate SARS-CoV-2 transmission. We model three scenarios, varying VE against infection, infectiousness, and symptoms, to understand the expected impact of vaccination in nursing homes, increasing staff vaccination coverage, and different screening testing strategies under each scenario.

ResultsIncreasing vaccination coverage in staff decreases total symptomatic cases in each scenario. When there is low VE against infection and infectiousness, increasing staff coverage reduces symptomatic cases among residents. If vaccination only protects against symptoms, but asymptomatic cases remain infectious, increased staff coverage increases symptomatic cases among residents through exposure to asymptomatic but infected staff. High frequency testing is needed to reduce total symptomatic cases if the vaccine has low efficacy against infection and infectiousness, or only protects against symptoms.

ConclusionsEncouraging staff vaccination is not only important for protecting staff, but might also reduce symptomatic cases in residents if a vaccine confers at least some protection against infection or infectiousness.

SummaryThe extent of efficacy of SARS-CoV-2 vaccines against infection, infectiousness, or disease, impacts strategies for vaccination and testing in nursing homes. If vaccines confer some protection against infection or infectiousness, encouraging vaccination in staff may reduce symptomatic cases in residents.


title: The localized rise of a B.1.526 variant containing an E484K mutation in New York State

abstract: The E484K mutation in the spike protein of SARS CoV-2 contributes to immune escape from monoclonal antibodies as well as neutralizing antibodies in COVID-19 convalescent plasma. It appears in two variants of concern - B.1.351 and P.1 - but has evolved multiple times in different SARS-CoV-2 lineages, suggesting an adaptive advantage. Here we report on the emergence of a 484K variant in the B.1.526 lineage that has recently become prevalent in New York State, particularly in the New York City metropolitan area. In addition to the E484K mutation, these variants also harbor a D235G substitution in spike that might help to reduce the efficacy of neutralizing antibodies.


title: The impact of varying class sizes on epidemic spread in a university population

abstract: A common non-pharmaceutical intervention (NPI) during the Covid-19 pandemic has been group size limits. Further, educational settings of schools and universities have either fully closed or reduced their class sizes. As countries begin to reopen classrooms, a key question will be how large classes can be while still preventing local outbreaks of disease. Here we develop and analyse a simple, stochastic epidemiological model where individuals (considered as students) live in fixed households and are assigned to a fixed class for daily lessons. We compare key measures of the epidemic - the peak infected, the total infected by day 180 and the calculated R0 - as the size of class is varied. We find that class sizes of 10 could largely restrict outbreaks and often had overlapping inter-quartile ranges with our most cautious case of classes of 5. However, class sizes of 30 or more often result in large epidemics. Reducing the class size from 40 to 10 can reduce R0 by over 30%, as well as signficantly reducing the numbers infected. Intermediate class sizes show considerable variation, with the total infected varying by as much as from 10% to 80% for the same class size. We show that additional in-class NPIs can limit the epidemic still further, but that reducing class sizes appears to have a larger effect on the epidemic. We do not specifically tailor our model for Covid-19, but our results stress the importance of small class sizes for preventing large outbreaks of infectious disease.


title: Excess deaths reveal the true spatial, temporal, and demographic impact of COVID-19 on mortality in Ecuador

abstract:
BackgroundIn early 2020, Ecuador reported one of the highest surges of per capita deaths across the globe.

MethodsWe collected a comprehensive dataset containing individual death records between 2015 and 2020 from the Ecuadorian National Institute of Statistics and Census and the Ecuadorian Ministry of Government. We computed the number of excess deaths across time, geographical locations and demographic groups using Poisson regression methods.

ResultsBetween January 1st and September 23rd, 2020, the number of excess deaths in Ecuador is 36,402 (95% CI: 35,762-36,827) or 208 per 105 population, which is 171% of the expected deaths in that period in a typical year. Only 20% of the excess deaths are attributable to confirmed COVID-19 deaths. Strikingly, in provinces that were most affected by COVID-19, such as Guayas and Santa Elena, the all-cause deaths are more than double the expected number of deaths that would have occurred in a normal year. The extent of excess deaths in men is higher than in women, and the number of excess deaths increases with age. Indigenous populations had the highest level of excess deaths among all ethnic groups.

ConclusionsOverall, the exceptionally high level of excess deaths in Ecuador highlights the enormous burden and heterogeneous impact of COVID-19 on mortality especially in older age groups and indigenous populations in Ecuador that was not fully revealed by COVID-19 death counts. Together with the limited testing in Ecuador, our results suggest that the majority of the excess deaths were likely to be undocumented COVID-19 deaths.


title: Olanzapine inhibits hepatic apolipoprotein A5 secretion inducing hypertriglyceridemia in schizophrenia patients and mice

abstract: Olanzapine, an antipsychotic drug, was reported to induce hypertriglyceridemia, whereas the underlying mechanism remains incompletely understood. This study was to determine the role of apolipoprotein A5 (apoA5) in olanzapine-induced hypertriglyceridemia. In this study, 36 drug-naive and first-episode schizophrenic adult patients (aged 18-60 years) in a multi-center clinical trial (ClinicalTrials.gov NCT03451734) were enrolled. Before and after olanzapine treatment, plasma lipid and apoA5 levels were detected. Moreover, 21 female C57BL/6 J mice (8 weeks old) were divided into 3 groups (n = 7/each group): low-dose olanzapine (3 mg/kg/day), high-dose olanzapine (6 mg/kg/day) and control group. After 6 weeks, plasma glucose, lipids and apoA5 as well as hepatic apoA5 protein and mRNA expression in these animals were detected. In our study in vitro, primary mouse hepatocytes and HepG2 cells were treated with olanzapine of 25, 50, 100 mol/L, respectively. After 24 hours, apoA5 protein and mRNA levels in hepatocytes were detected. Our study showed that olanzapine treatment significantly increased plasma triglyceride levels and decreased plasma apoA5 levels in these schizophrenic patients. A significant negative correlation was indicated between plasma triglyceride and apoA5 levels in these patients. Consistently, olanzapine dose-dependently increased plasma triglyceride levels and decreased plasma apoA5 levels in mice. Surprisingly, an elevation of hepatic apoA5 protein levels was detected in mice after olanzapine treatment, with no changes of APOA5 mRNA expression. Likewise, olanzapine increased apoA5 protein levels in hepatocytes in vitro, without changes of hepatocyte APOA5 mRNA. Therefore, our study provides the first evidence about the role of apoA5 in olanzapine-induced hypertriglyceridemia. Furthermore, plasma apoA5 reduction, resulting in hypertriglyceridemia, could be attributed to olanzapine-induced inhibition of hepatic apoA5 secretion.

category: psychiatry and clinical psychology


title: Self-Reported Stress and Questionnaires in People With Autism Spectrum Disorder: a Systematic Review

abstract:
BackgroundTo gain more insight into the experience of stress in individuals with ASD, it is important to use appropriate self-report questionnaires. The goal of this systematic review was to provide an overview of these.

MethodThe PRISMA guidelines were followed and four online databases were systematically searched.

ResultsSeven questionnaires have been used previously in individuals with ASD. None of the 22 included studies intended to assess the psychometric properties, leading towards scarce evidence concerning their reliability and validity in this population.

ConclusionsIt is important to consider which concept of stress one aims to measure as not all questionnaires cover the same aspects of stress. Further research concerning psychometric properties of the questionnaires in this population is required.


title: Aberrant levels of cortical myelin distinguish individuals with unipolar depression from healthy controls

abstract: The association of unipolar depression (UD), relative to healthy controls (HC), with cortical myelin is underexplored, despite growing evidence of associations with white matter tract integrity. We characterized cortical myelin in the 360 Glasser atlas regions using the T1w/T2w ratio in 39 UD and 47 HC participants (ages=19-44, 75% female). A logistic elastic net regularized regression with nested cross-validation and a subsequent linear discriminant analysis conducted on held-out samples were used to select brain regions and classify UD vs. HC. True-label model performance was compared against permuted-label model performance. Cortical myelin distinguished UD from HC with 68% accuracy (p<0.001; sensitivity=63.8%, specificity=71.5%). Brain regions contributing to this classification performance were located in the orbitofrontal cortex, anterior cingulate, extended visual, and auditory cortices, and showed statistically significant decreases and increases in myelin levels in UD vs. HC. The patterns of cortical myelin in these regions may be a biomarker of UD.


title: When thinking you are better leads to feeling worse: Self-other asymmetries in prosocial behavior and increased anxiety during the Covid-19 pandemic

abstract: Thinking one is better than peers is generally associated with positive psychological outcomes like increased self-esteem and resilience. However, this tendency may be problematic in the context of collective action problems, wherein individuals are reliant on others prosocial behaviors to achieve larger goals. We examined this question in the context of the Covid-19 pandemic, and recruited participants (n = 1022) from a university community in Spring 2020. We found evidence for a self-peer asymmetry, such that participants reported that they were doing more to stop the spread of the disease and were more prosocially motivated than peers. Actual peer reports indicated that these were overestimations. This self-enhancement tendency comes with a cost: the perceived self-peer asymmetry mediated the relationship between Covid-specific worry and general anxiety during the early lockdown period. This indicates that while believing one is doing more than others may be maladaptive in collective action problems.


title: COVID-19 International Border Surveillance Cohort Study at Toronto's Pearson Airport

abstract:
ObjectivesThe primary objective was to estimate the positivity rate of air travelers coming to Toronto, Canada in September and October, 2020, at arrival, day 7 and day 14. Secondary objectives were to estimate degree of risk based on country of origin; to assess knowledge and attitudes towards COVID-19 control measures; and subjective well-being during the quarantine period.

DesignProspective cohort of arriving international travelers.

SettingToronto Pearson Airport Terminal 1, Toronto, Canada.

ParticipantsPassengers arriving on international flights. Inclusion criteria were those aged 18 or older who had a final destination within 100 km of the airport; spoke English or French; and provided consent. Excluded were those taking a connecting flight; who had no internet access; who exhibited symptoms of COVID-19 on arrival; or who were exempted from quarantine.

Main outcome measuresPositive for SARS-CoV-2 virus on RT-PCR with self-administered nasal-oral swab, and general well-being using the WHO-5 index.

ResultsOf 16,361 passengers enrolled, 248 (1{middle dot}5%, 95% CI 1.3%,1.5%) tested positive. Of these, 167 (67%) were identified on arrival, 67 (27%) on day 7, and 14 (6%) on day 14. The positivity rate increased from 1% in September to 2% in October. Average well-being score declined from 19.8 (out of a maximum of 25) to 15.5 between arrival and day 7 (p<0.001).

ConclusionsA single arrival test will pick up two-thirds of individuals who will become positive, with most of the rest detected on the second test at day 7. These results support strategies identified through mathematical models that a reduced quarantine combined with testing can be as effective as a 14 day quarantine.

Article SummaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIDecisions regarding border restrictions have been based on trial and error and mathematical models with limited empirical data to support such decision-making.
C_LIO_LIThis study assessed the prevalence of SARS-CoV-2 in a cohort of international travellers at arrival, day 7 and 14 of quarantine.
C_LIO_LIIt is limited to one airport and there is the potential from bias due to non-participation and loss to follow-up.
C_LIO_LISelf-collected nasal-oral swabs were used which facilitated participation but may have reduced sensitivity.
C_LI


title: The negative consequences of failing to communicate uncertainties during a pandemic:The case of COVID-19 vaccines

abstract: Uncertainties pervade our health choices, particularly in the context of a novel pandemic. Despite this, rather little is known about when and how to effectively communicate these uncertainties. The focus in the medical literature so far has been on how patients respond to mentions of uncertainty relating to diagnosis or treatment, showing that these can have detrimental effects on trust and satisfaction. On the other hand, how patients are affected by these communications over time, particularly in the face of conflicting information, has received little attention. This is particularly important in the context a novel pandemic where uncertainty is rife and information changes over time. To fill this gap, we conducted an online study with UK participants on hypothetical communications relating to COVID-19 vaccines. Participants first read a vaccine announcement, which either communicated with certainty or uncertainty, and then received information which conflicted with the announcement. Those who were exposed to the certain announcement reported a greater loss of trust and vaccination intention than those who were exposed to the uncertain announcement. This shows that communicating with unwarranted certainty can backfire in the long-term, whereas communicating uncertainties can protect people from the negative impact of exposure to conflicting information.


title: Covid-19 lockdown: Ethnic differences in childrens self-reported physical activity and the importance of leaving the home environment. A longitudinal and cross-sectional

abstract:
BackgroundIn England, the onset of COVID-19 and a rapidly increasing infection rate resulted in a lockdown (March-June 2020) which placed strict restrictions on movement of the public, including children. Using data collected from children living in a multi-ethnic city with high levels of deprivation, this study aimed to: (1) report childrens self-reported physical activity (PA) during the first COVID-19 UK lockdown and identify associated factors; (2) examine changes of childrens self-reported PA prior to and during the first UK lockdown.

MethodsThis study is part of the Born in Bradford (BiB) COVID-19 Research Study. PA (amended Youth Activity Profile), sleep, sedentary behaviours, daily frequency/time/destination/activity when leaving the home, were self-reported by 949 children (9-13 years). A sub-sample (n=634) also self-reported PA (Physical Activity Questionnaire for Children) pre-pandemic (2017-February 2020). Univariate analysis assessed differences in PA between sex and ethnicity groups; multivariable logistic regression identified factors associated with childrens PA. Differences in childrens levels of being sufficiently active were examined using the McNemar test examined change in PA prior to and during the lockdown, and multivariable logistic regression to identify factors explaining change.

ResultsDuring the pandemic, White British (WB) children were more sufficiently active (34.1%) compared to Pakistani Heritage children (PH) (22.8%) or  Other ethnicity children (O) (22.8%). WB children reported leaving the home more frequently and for longer periods than PH and O children. Modifiable variables related to being sufficiently active were frequency, duration, type of activity, and destination away from the home environment. There was a large reduction in children being sufficiently active during the first COVID-19 lockdown (28.9%) compared to pre-pandemic (69.4%).

ConclusionsPromoting safe extended periods of PA everyday outdoors is important for all children, in particular for children from ethnic minority groups. Childrens PA during the first COVID-19 UK lockdown has drastically reduced from before. Policy and decision makers, and practitioners should consider the findings in order to begin to understand the impact and consequences that COVID-19 has had upon childrens PA which is a key and vital behaviour for health and development.


title: Covid-19 lockdown: Ethnic differences in childrens self-reported physical activity and the importance of leaving the home environment. A longitudinal and cross-sectional study from the Born in Bradford birth cohort study.


title: Opening schools and trends in SARS-CoV-2 transmission in European countries

abstract:
BackgroundIt is important to understand the role of schools in the community transmission of SARS-CoV-2, bearing in mind that children and adolescents can spread the infection within families, even when their own symptoms are mild. The aim of this study was to examine the trends of contagion before and after schools reopened across 27 countries in the European Union.

MethodsAll data on the number of people testing positive for COVID-19 in each European country were collected from 20 days before schools reopened to 45 days afterwards. The Joinpoint regression method was used to detect single change points on the trend of contagion. The Bayesian Information Criterion (BIC) was used for model selection purposes.

ResultsWe calculated 27 linear regression models for the daily case numbers of SARS-CoV-2 infection in the 27 countries from 20 days before schools reopened to 45 days afterwards. A significant increase in the number of daily infections was seen for 21 countries after a change point in the linear regression lines. The change points in different countries varied, ranging from 10 to 42 days after schools reopened, with the majority occurring beyond the 21st day.

ConclusionThis study analysed the trend of SARS-CoV-2 transmission before and after schools reopened in Europe. We observed a significant increase in the number of new daily cases in most countries. This issue poses a public health problem that needs to be taken into account in deciding strategies to contain the spread of COVID-19.


title: Topographic volume-standardization atlas of the human brain

abstract:
ObjectiveSpecific anatomical patterns are seen in various diseases affecting the brain. Clinical studies on the topography of pathologies are often limited by the absence of a normalization of the prevalence of pathologies to the relative volume of the affected anatomical structures. A comprehensive reference on the relative volumes of clinically relevant anatomical structures serving for such a normalization, is currently lacking.

MethodsThe analyses are based on anatomical high-resolution three-dimensional T1-weighted magnetic resonance imaging data of 30 healthy Caucasian volunteers, including 14 females (mean age 37.79 years, SD 13.04) and 16 males (mean age 38.31 years, SD 16.91). Semi-automated anatomical segmentation was used, guided by a neuroanatomical parcellation algorithm differentiating 96 structures. Relative volumes were derived by normalizing parenchymal structures to the total individual encephalic volume and ventricular segments to the total individual ventricular volume.

ResultsThe present investigation provides the absolute and relative volumes of 96 anatomical parcellation units of the human encephalon. A larger absolute volume in males than in females is found for almost all parcellation units. While parenchymal structures display a trend towards decreasing volumes with increasing age, a significant inverse effect is seen with the ventricular system. The variances in volumes as well as the effects of gender and age are given for each structure before and after normalization.

ConclusionThe provided atlas constitutes an anatomically detailed and comprehensive analysis of the absolute and relative volumes of the human encephalic structures using a clinically oriented parcellation algorithm. It is intended to serve as a reference for volume-standardization in clinical studies on the topographic prevalence of pathologies.

category: radiology and imaging


title: Large-scale evaluation of an AI system as an independent reader for double reading in breast cancer screening

abstract:
Screening mammography with two human readers increases cancer detection and lowers recall rates, but high resource requirements and a shortage of qualified readers make double reading unsustainable in many countries. The use of AI as an independent reader may yield more objective, accurate and outcome-based screening. Clinical validation of AI requires large-scale, multi-site, multi-vendor studies on unenriched cohorts.

This retrospective study evaluated the performance of the Mia version 2.0.1 AI system from Kheiron Medical Technologies on an unenriched sample (275,900 cases from 177,882 participants) collected across seven screening sites in two countries and four hardware vendors, and is representative of a real-world screening population over 10 years. Performance was determined for standalone AI and simulated double reading to assess non-inferiority and superiority on relevant screening metrics.

Standalone AI showed superiority on sensitivity and non-inferiority on specificity while detecting 29.7% of cancers found within three years after screening, and 29.8% of missed interval cancers. Double reading with AI was at least non-inferior compared to human double reading at every metric, with superiority for recall rate, specificity and positive predictive value (PPV). AI as an independent reader reduced the workload, but increased arbitration rate from 3.3% to 12.3%. Applying the AI system under investigation would have reduced the overall number of human reads required by 44.8%. The recall rate was reduced by a relative 4.1%, suggesting there could be fewer follow-up procedures, reduced stress for patients, and less administrative and clinical work.

Using the AI system as an independent reader maintains the standard of care of double reading, detects cancers missed by human readers, while automating a substantial part of the workflow, and could therefore bring significant clinical and operational benefits.


title: Basivertebral nerve block during vertebral augmentation: An alternative approach to intraprocedural pain management.

abstract: Vertebral compression fractures secondary to osteoporosis can be treated with vertebral augmentation. Since intraprocedural pain is common during vertebral body endplate manipulation, these procedures are often carried out using conscious sedation or general anesthesia. Research has shown that the vertebral endplates are innervated by the basivertebral nerve, which has been successfully targeted via radiofrequency ablation to treat chronic vertebrogenic lower back pain. With this physiology in mind, we treated ten patients with vertebral compression using intraosseous basivertebral nerve block as the primary intraprocedural analgesia. In this case series, we describe our successful experience with this novel approach.


title: Early medical abortion by telemedicine in the United Kingdom: A cost-effectiveness analysis

abstract:
ObjectiveTo determine the potential cost savings resulting from the introduction of routine early medical abortion at home by telemedicine in the United Kingdom.

DesignA cost-effectiveness analysis Setting: United Kingdom

PopulationWomen in 2020 undergoing early medical abortion provided by three independent abortion providers and two NHS abortion clinics.

MethodsComputation of the costs of each abortion procedure and of managing failed or incomplete abortion and haemorrhage requiring blood transfusion.

Outcome measuresCost savings

ResultsOverall estimated cost savings are {pound}15.80 per abortion undertaken by independent abortion providers representing a saving to the NHS of over {pound}3 million per year. Limited data from NHS services resulted in an estimated average saving of {pound}188.84 per abortion.

ConclusionsWere telemedicine EMA to become routine, an increase in the number of women eligible for medical rather than surgical abortion, and a reduction in adverse events resulting from earlier abortion could result in significant cost-savings.

Tweetable AbstractEarly medical abortion at home using telemedicine could save the NHS {pound}3 million per year

category: sexual and reproductive health


title: Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study

abstract:
ObjectivesTo report the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic.

Design and settingAnalysis of electronic health record data from the National Health Service (NHS) in England and Wales.

MethodsWe used hospital episode statistics for all adult patients undergoing surgery between 1st January 2020 and 31st December 2020. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from the years 2016-2019 with the actual number of procedures in 2020. We estimated the cumulative number of cancelled procedures by 31st December 2021 according patterns of activity in 2020.

ResultsThe total number of surgical procedures carried out in England and Wales in 2020 was 3,102,674 compared to the predicted number of 4,671,338. This represents a 33.6% reduction in the national volume of surgical activity. There were 763,730 emergency surgical procedures (13.4% reduction), compared to 2,338,944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1,568,664. We estimate that this will increase to 2,358,420 by 31st December 2021.

ConclusionsThe volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in over 1,568,664 cancelled operations. This deficit will continue to grow in 2021.

Summary boxesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIThe COVID-19 pandemic necessitated a rapid change in the provision of care, including the suspension of a large proportion of surgical activity
C_LIO_LISurgical activity has yet to return to normal and has been further impacted by subsequent waves of the pandemic
C_LIO_LIThis will lead to a large backlog of cases
C_LI

What this study addsO_LI3,102,674 surgical procedures were performed in England and Wales during 2020, a 33.6% reduction on the expected yearly surgical activity
C_LIO_LIOver 1.5 million procedures were not performed, with this deficit likely to continue to grow to 2.3 million by the end of 2021
C_LIO_LIThis deficit is the equivalent of more than 6 months of pre-pandemic surgical activity, requiring a monumental financial and logistic challenge to manage
C_LI

category: surgery


title: Co-occurrence of apathy and impulsivity in progressive supranuclear palsy

abstract:
BackgroundApathy and impulsivity are common problems in progressive supranuclear palsy (PSP) and can worsen its prognosis. They can co-exist in the same patients although their concomitant prevalence remains unclear. Their relationship to emotional lability is also unknown.

ObjectivesTo estimate the co-occurrence of apathy and impulsivity and their relationship to emotional lability in PSP. To characterize the demographic, clinical, and cognitive features of PSP patients with apathy and impulsivity.

MethodsIn a retrospective study of a long-term clinical cohort, we assessed the prevalence of apathy, impulsivity, and emotional lability from clinical interviews, medical records, and contemporary carer questionnaires. N=154 patients with a diagnosis of probable or possible PSP (according to the 2017 Movement Disorder Society criteria) were identified. N=64 of these patients had neuropathological confirmation of PSP. PSP patients with both apathy and impulsivity were compared in terms of demographic, clinical, and cognitive characteristics to PSP patients with either one or neither of these neuropsychiatric features.

ResultsApathy and impulsivity co-existed in two-thirds of people with PSP. A fifth displayed emotional lability in addition to apathy and impulsivity. Apathy and impulsivity were more commonly co-expressed than by chance. There was no single demographic, clinical or cognitive feature that distinguished between PSP patients with versus patients without apathy and impulsivity.

ConclusionsThe co-existence of apathy and impulsivity in PSP suggests that these neuropsychiatric features may share similar risk factors and etio-pathogenetic mechanisms. Apathy and impulsivity should be jointly assessed when planning symptomatic treatments for behavioural problems in PSP.


title: Bidirectional Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of intermediate potential

abstract: Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in Trans-Omics for Precision Medicine (TOPMed) program (N=63,302) and UK Biobank (N=48,658). Bidirectional Mendelian randomization studies were consistent with LTL lengthening increasing propensity to develop CHIP, but CHIP then in turn hastening LTL shortening. We also demonstrated evidence of modest mediation between CHIP and CAD by LTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.


title: Successful incorporation of a genetic risk prediction research platform into routine newborn screening

abstract:
An increasing number of diseases can be offered treatments that are transformative if administered in a timely manner. However, many of these diseases are currently not included in the newborn screening programs because they lack sensitive and specific metabolic biomarkers, and detection of children at increased risk relies on genetic methods. Type 1 diabetes (T1D) constitutes a potential example of such disease.

Between April 2018 and November 2020, over 15500 babies were enrolled into  INGR1D (Investigating Genetic Risk for T1D), a research study to identify newborns with an increased genetic risk of T1D. This project, performed as part of a T1D primary prevention study (the Primary Oral Insulin Trial, POInT), has helped to pioneer the integration of genetic screening into the NHS Newborn Blood Spot Screening Programme (NBSSP) for consenting mothers, without affecting the screening pathway. The use of prospective consent to perform personalised genetic testing on samples obtained through the routine NBSSP represents a novel mechanism for clinical genetic research in the UK and provides a model for further population based genetic studies in the newborn.

This project builds on the UKs role as a world leader in genomic medicine, e.g. through its inception and completion of the 100 000 Genomes Project, and its subsequent ambition to map 5 million further genomes over the next 5 years.

Our aim is therefore to describe the methodology used by INGR1D as a way to demonstrate how a successful research and clinical trial tool can be integrated into a national screening programme, with the potential for the tool to be developed to incorporate multiple diseases with genetic markers without altering the screening pathway.


title: Drug repurposing: Hydroxyurea therapy improves the transfusion-free interval in HbE/beta thalassemia major patients with Xmn1 polymorphism

abstract:
AimsHbE/{beta}-thalassemia is the prevalent form of severe {beta}-thalassemia in Asian countries. Hydroxyurea (HU) is the most common drug used for the management of sickle-cell anemia but not thalassemia. Here, we aimed to assess clinical HU response among patients with HbE/{beta}-thalassemia with respect to Xmn1 {gamma}Gglobin polymorphism and elucidate the association between this polymorphism and HU response efficacy.

MethodsWe enrolled 49 transfusion-dependent patients with HbE/{beta}-thalassemia. Fetal hemoglobin level was measured using High-performance liquid chromatography (HPLC) and complete blood count was determined pre- and post-HU therapy. Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) was performed for genotyping Xmn1 {gamma}Gglobin polymorphism.

ResultsA total of 30 (61.22%) patients were found to be responders, whereas the remaining 19 (38.78%) were non-responders. We found 33 patients with heterozygous (C/T) and three with homozygous mutant (T/T) genotype status. We obtained a statistically significant correlation (p < 0.001) between Xmn1 polymorphism and transfusion-free interval. Patients with Xmn1 polymorphism were found to be good responders for HU therapy and showed increased hemoglobin levels.

ConclusionsOur findings indicate that HU is a potential drug candidate for thalassemia management, particularly HbE/{beta}-thalassemia. The results hold implications in repurposing HU as an effective and efficient therapy for HbE/{beta}-thalassemia.


title: Impact of the COVID-19 pandemic on cognitive function in Japanese community-dwelling older adults in a class for preventing cognitive decline

abstract: We examined the effects of lifestyle and thoughts on cognitive function and change in cognitive function due to restrictions in daily life during the coronavirus disease 2019 (COVID-19) pandemic in community-dwelling older adults with mild cognitive decline. This was a retrospective case-control study. The participants were 88 older adults with mild cognitive decline who participated in a class designed to help prevent cognitive decline. The class was suspended from early-March to end of May 2020 to prevent the spread of COVID-19, and resumed in June 2020. We collected demographic and cognitive function test data (Touch Panel-type Dementia Assessment Scale [TDAS]) before and after class suspension and questionnaire data on their lifestyle and thoughts during the suspension. Change in TDAS scores from before and after the suspension was used to divide the participants into decline (2 or more points worsening) and non-decline (all other participants) groups, with 16 (18.2%) and 72 (81.8%) participants in each group, respectively. A logistic regression model showed that the odds ratio (OR) for cognitive decline was lower in participants whose responses were "engaged in hobbies" (OR = 0.07, p = 0.015), "worked on a worksheet about cognitive training provided by the town hall" (OR = 0.19, p = 0.026), and "had conversations over the phone" (OR = 0.28, p = 0.0495). There was a significant improvement in TDAS scores after class was resumed (p < 0.01). A proactive approach to intellectual activities and social ties may be important for the prevention of cognitive decline during periods of restrictions due to COVID-19. We found that cognitive function test scores before class suspension significantly improved after resuming classes. We speculate that continued participation in the class led to positive behavioral changes in daily life during periods of restriction due to COVID-19.


title: Clinical Decision Support in Cardiovascular Medicine: Effectiveness, Implementation Barriers, and Regulation

abstract: Despite considerable progress in addressing cardiovascular disease (CVD) over the past 50 years, there remain many gaps in CVD care quality. Multiple missed opportunities have been identified at every step in the prevention and treatment of CVD, such as failure to make risk factor modifications, failure to diagnose CVD, and failure to use proper evidence-based treatments. With the digital transformation of medicine and advances in health information technology, clinical decision support (CDS) tools offer promise to enhance the efficiency and effectiveness of cardiovascular care delivery. Yet, to date, the promise of CDS delivering scalable and sustained value for patient care in clinical practice has not been realized. Here, we review evidence on key emerging questions around the development, implementation, and regulation of CDS with a focus on CVD. We first review evidence on the effectiveness of CDS on patient health and health delivery outcomes related to CVD and features predictive of effectiveness. We then review the barriers encountered during CDS implementation in cardiovascular care with a focus on unintended consequences and strategies to promote successful implementation. Finally, we review the current legal and regulatory environment of CDS with specific examples for CVD.


title: Factors Associated with Serious Psychological Distress during the COVID-19 Pandemic in Japan

abstract:
ImportanceThe coronavirus disease 2019 (COVID-19) pandemic may have a negative impact on mental health of the population, leading to higher suicide rates, in many countries. However, little is known about risk factors associated with worsened mental health during the COVID-19 pandemic.

ObjectiveTo investigate the factors associated with serious psychological distress (SPD) during the COVID-19 pandemic in Japan.

Design, Setting, and ParticipantsA cross-sectional study using a large-scale internet survey conducted between August 25 and September 30, 2020, in Japan.

ExposuresDemographics (age, gender, marital status, family composition, and caregiving burden), socio-economic status (income level, employment type, educational attainment), the experience of domestic violence (DV), the state of emergency, fear of COVID-19, and stigma related to COVID-19.

Main Outcomes and MeasuresPrevalence of SPD, defined as Kessler 6 scale score [≥]13.

ResultsAmong 25,482 individuals included in this study, 2,556 (10%) met the criteria of SPD. Overall, women (adjusted odds ratio [aOR] 1.59; 95%CI, 1.17-2.16; P=0.003), ages 15-29 (aOR compared with ages 45-59, 2.35; 95%CI, 1.64-3.38; P<0.001), low income (aOR compared with intermediate income, 1.70; 95%CI, 1.16-2.49; P=0.007), providing caregiving to family members (aOR, 5.48; 95%CI, 3.51-8.56; P<0.001), experiencing DV (aOR, 5.72; 95%CI, 3.81-8.59; P<0.001), and fear of COVID-19 (aOR, 1.96; 95%CI, 1.55-2.48; P<0.001) were associated with a higher rate of SPD. Among women aged 15-29 years, who experienced the highest rate of SPD, caregiving, DV, fear of COVID-19, and COVID-19-related stigma were associated with a higher rate of SPD; whereas economic situation (income level and employment type) and social isolation (marital status) were not associated with the prevalence of SPD.

Conclusions and RelevanceEconomic situation, caregiving burden, DV, and fear of COVID-19 were independently associated with SPD during the COVID-19 pandemic. Among young women--who have a higher risk of suicide during the COVID-19 pandemic in Japan--similar factors, except economic situation, were associated with a higher rate of SPD. Targeted interventions based on age and gender may be more effective in mitigating the negative impact of the COVID-19 pandemic on the populations mental health.

category: health policy