title: Pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal anti-SARS-CoV-2 antibody, for COVID-19-related moderate pneumonia: a randomized, double-blind, placebo-controlled, phase IIa study

abstract:
BackgroundWe assessed the pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2, in COVID-19-related moderate pneumonia. In vitro, 100% neutralization activity is seen with XAV-19 concentrations above 5 g/mL.

MethodsIn this phase 2a trial, adults with COVID-19-related moderate pneumonia of [≤]10 days duration were randomized to infusion of XAV-19 0.5 mg/kg at day 1 and day 5 (group 1), 2 mg/kg at day 1 and day 5 (group 2), 2 mg/kg at day 1 (group 3) or placebo.

ResultsEighteen patients (n=7 for group 1, n=1 for group 2, n=5 for group 3, and n=5 for placebo) were enrolled. Baseline characteristics were similar across groups, XAV-19 serum concentrations (g/mL, median, range) at Cmax and at day 8 were 9.1 (5.2-18.1) and 6.4 (2.8-11.9), 71.5 and 47.2, and 50.4 (29.1-55.0) and 20.3 (12.0-22.7) for groups 1, 2 and 3, respectively (p=0.012). Terminal half-life (median, range) was estimated at 11.4 (5.5-13.9) days for 2 mg/kg of XAV-19 at day 1. Serum XAV-19 concentrations were above the target concentration of 10 g/mL (tow fold the in vitro 100% inhibitory concentration [IC100]) from the end of perfusion to more than 8 days for XAV-19 2 mg/kg at day 1. No hypersensitivity or infusion-related reactions were reported during treatment, there was no discontinuation for adverse events and no serious adverse events related to study drug.

ConclusionsSingle intravenous dose of 2 mg/kg of XAV-19 demonstrated high serum concentrations, predictive of potent durable neutralizing activity with good tolerability.

Trial registrationClinicalTrials.gov Identifier: NCT04453384

Main pointIn this first-in-human trial including patients with COVID-19-related pneumonia, a single 2mg/kg dose of a swine glyco-humanized polyclonal anti-SARS-CoV-2 antibody, achieved serum concentrations above the target of neutralization threshold for 8 days in all patients, with good tolerability and safety.


title: COVID-19 transmission in a theme-park

abstract:
BackgroundAs COVID-19 vaccination coverage increases, public health and industries are contemplating re-opening measures of public spaces, including theme-parks. To re-open, theme-parks must provide public health mitigation plans. Questions on implementation of public health mitigation strategies such as park cleaning, COVID-19 testing, and enforcement of social distancing and the wearing of personal protective equipment (PPE) in the park remain.

MethodsWe have developed a mathematical model of COVID-19 transmission in a theme-park that considers direct human-human and indirect environment-human transmission of the virus. The model thus tracks the changing infection/disease landscape of all visitors, workers, and environmental reservoirs in a theme park setting.

FindingsModels results show that theme-park public health mitigation must include mechanisms that reduce virus contamination of the environment to ensure that workers and visitors are protected from COVID-19 transmission in the park. Thus, cleaning rates and mitigation of human-environment contact increases in importance.

ConclusionOur findings have important practical implications in terms of public health as policy- and decision-makers are equipped with a mathematical tool that can guide theme-parks in developing public health mitigation strategies for a safe re-opening.

category: infectious diseases


title: Post-COVID-19 syndrome in outpatients: a cohort study

abstract:
BackgroundAfter mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed.

ObjectivesTo characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors.

ParticipantsOutpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative).

DesignMonocentric cohort study with prospective phone interview between more than three months to ten months after initial visit to the emergency department and outpatient clinics.

Main MeasuresData of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey.

Key resultsThe study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p=0.020) and health care workers (67% versus 82%; p=0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p=0.006). Overall, 21% COVID-positive and 15% COVID-negative patients (p=0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio [or] 2.14, 95%CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16) and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (1.67, 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persistent symptoms.

ConclusionsMore than half of COVID-positive outpatients report persistent symptoms up to ten months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society.


title: Diagnostic accuracy of SARS-CoV-2 rapid antigen detection testing in symptomatic and asymptomatic children in the clinical setting

abstract:
ImportanceAntigen-based rapid diagnostic tests (RDTs) have shown good sensitivity for SARS-CoV-2 detection in adults and are used in children despite the lack data from children.

ObjectiveWe evaluated the diagnostic performance of the Panbio-COVID-19 Ag Rapid Test Device (P-RDT) in symptomatic and asymptomatic children against reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swabs (NPS).

DesignProspective diagnostic study from 11.2020 to 03.2021.

SettingSingle-center.

ParticipantsConsecutive symptomatic and asymptomatic participants 0-16yo.

InterventionTwo NPS for both RT-PCR and P-RDT.

Main outcomeP-RDT sensitivity and specificity.

ResultsEight-hundred and twenty-two participants completed the study, of which 533 (64.9%) were symptomatic. Among the 119 (14.5%) RT-PCR positive patients, the overall P-RDT sensitivity was 0.66 (95%CI 0.57-0.74). Mean viral load (VL) was higher among P-RDT positive than negative ones (p<0.001). Sensitivity was 0.87 in specimens with VL>1.0E6 copies/mL (95%CI 0.87-1.00), which is the accepted cut-off for the presence of infectious virus, and decreased to 0.67 (95%CI 0.59-0.76) for specimens >1.0E3 copies/mL.

Among symptomatic participants, the P-RDT displayed a sensitivity of 0.73 (95%CI 0.64-0.82), which peaked at 1.00 at 2 days post onset of symptoms (DPOS; 95%CI 1.00-1.00), then decreased to 0.56 (95%CI 0.23-0.88) at 5 DPOS. There was a trend towards lower P-RDT sensitivity in symptomatic children <12 years (0.62 [95%CI 0.45-0.78]) versus [≥]12 years (0.80 [95%CI 0.69-0.91]; p=0.09). VL which was significantly lower in asymptomatic participants than in symptomatic ones (p<0.001). The P-RDT displayed a sensitivity of 0.43 (95%CI 0.26-0.61).

Specificity was 1.00 in symptomatic and asymptomatic children (95%CI 0.99-1.00).

Conclusion and relevanceThe overall respective 73% and 43% sensitivities of P-RDT in symptomatic and asymptomatic children was below the 80% cut-off recommended by the World Health Organization. These findings are likely explained by lower VLs in children at the time of diagnosis. As expected, we observed a direct correlation between VL and P-RDT sensitivity as well as variation of sensitivity according to DPOS, a major determinant of VL. These data highlight the limitations of RDTs both in symptomatic and asymptomatic children, with the potential exception in early symptomatic children [≥]12yrs where sensitivity reached 80%.


title: Are epidemic growth rates more informative than reproduction numbers?

abstract: Summary statistics, often derived from simplified models of epidemic spread, inform public health policy in real time. The instantaneous reproduction number, Rt, is predominant among these statistics, measuring the average ability of an infection to multiply. However, Rt encodes no temporal information and is sensitive to modelling assumptions. Consequently, some have proposed the epidemic growth rate, rt, i.e., the rate of change of the log-transformed case incidence, as a more temporally meaningful and model-agnostic policy guide. We examine this assertion, identifying if and when estimates of rt are more informative than those of Rt. We assess their relative strengths both for learning about pathogen transmission mechanisms and for guiding epidemic interventions in real time.


title: Seroprevalence of hepatitis A and hepatitis E viruses among pregnant women in Northern Iran

abstract:
BackgroundHepatitis A (HAV) and Hepatitis E viruses (HEV) are endemic in Iran and are known major causes of acute viral hepatitis. Also, during pregnancy, they are associated with severe outcomes. Therefore, it is vital to evaluate the antibody levels against HAV and HEV in pregnant women to avoid severe outcomes incidence.

Study design and methodsA total of 247 pregnant women were enrolled in this prospective cross-sectional study. In addition to completing the questionnaire and interviewing all participants, the serum samples were tested for anti-HAV and anti-HEV IgG using the enzyme-linked immunosorbent assay (ELISA). The association between anti-HAV and anti-HEV antibodies status and risk factors was evaluated.

ResultsThe mean age of patients was 28.06 {+/-} 5.29 years. Anti-HAV antibody was found in 111 patients (44.9%), while anti-HEV antibody was detected in only two pregnant women (0.8%). The seroprevalence of HAV was inversely related to the level of education. There was no significant correlation between HAV antibody levels and age, marital status, residence location, and pregnancy trimesters.

ConclusionConsidering many complications of these diseases in pregnancy, the detection of enteroviral hepatitis, especially HAV in pregnant women, is necessary, and therefore, proactive measures, such as promoting education, improving people awareness, and vaccination, are recommended


title: Ascorbic acid attenuates activation and cytokine production in sepsis-like monocytes

abstract:
ObjectiveTo investigate the effects of high dose ascorbic acid (AA) on monocyte polarization and cytokine production in vitro

DesignExperimental in vitro study of cells from healthy subjects and patients with sepsis

SettingUniversity research laboratory and academic hospital

SubjectsSix healthy controls and three patients with sepsis

InterventionsMonocytes were isolated from whole blood of healthy donors (n=6) and polarized in vitro for 48hrs using LPS or LTA. Polarization was confirmed by surface marker expression using flow cytometry. As a comparison, monocytes were also isolated from septic patients (n=3) and analyzed for polarization markers. The effect of AA on monocyte polarization was evaluated. As a functional assay, AA-treated monocytes were analyzed for cytokine production of TNF and IL-8 by intracellular staining and flow cytometry following activation with LPS or LTA.

Measurements and Main ResultsBoth LPS and LTA induced polarization in healthy monocytes in vitro, with increased expression of both pro-(CD40 and PDL1, p<0.05) and anti-inflammatory (CD16 and CD163, p<0.05) polarization markers, with non-significant effects on CD86 and CD206. This pattern resembled, at least partly, that of monocytes from septic patients. Treatment with AA significantly inhibited the upregulation of surface expression of CD16 and CD163 (p<0.05) in a dose dependent manner, but not CD40 or PDL-1. Finally, AA attenuated LPS or LTA-induced cytokine production of IL-8 and TNF in a dose-dependent manner (both p<0.05).

ConclusionsAA inhibits upregulation of anti-, but not pro-inflammatory related markers in LPS or LTA polarized monocytes. Additionally, AA attenuates cytokine production from in vitro polarized monocytes, displaying functional involvement. This study provides important insight into the immunological effects of high dose AA on monocytes, and potential implications in sepsis.


title: On whether therapeutic plasma exchange is an effective cure for severe/critical COVID-19 pneumonia

abstract:
BackgroundThere is a risk of novel mutations of SARS-CoV-2 that may render COVID-19 resistant to most of the therapies, including antiviral drugs. The evidence around the application of therapeutic plasma exchange (TPE) for the management of critically ill COVID-19 patients is still provisional and further investigations are needed to confirm its eventual beneficial effects.

MethodsWe therefore carried out a single-centered retrospective observational non-placebo-controlled trial enrolling 73 inpatients from Baqiyatallah Hospital in Tehran (Iran) with diagnosis of COVID-19 pneumonia confirmed by real-time polymerase chain reaction (RT-PCR) on nasopharyngeal swabs and high-resolution computerized tomography chest scan. These patients were broken down into two groups: Group 1 (30 patients) receiving standard of care (corticosteroids, ceftriaxone, azithromycin, pantoprazole, hydroxychloroquine, lopinavir/ritonavir); and Group 2 (43 patients) receiving the above regimen plus TPE (replacing 2 liter of patients plasma by a solution, 50% of normal plasma and 50% of albumin at 5%) administered according to various time schedules. The follow-up time was 30 days and all-cause mortality was the endpoint.

ResultsDeaths were 6 (14%) in Group 2 and 14 (47%) in Group 1. However, different harmful risk factors prevailed among patients not receiving TPE rather than being equally split between the intervention and control group. We used an algorithm of Structural Equation Modeling (of STATA) to summarize a large pool of potential confounders into a single score (called with the descriptive name "severity"). Disease severity was significantly (Wilkinson rank sum test p-value=0.0000) lower among COVID-19 patients undergoing TPE (median: -2.82; range: -5.18; 7.96) as compared to those non receiving TPE (median: -1.35; range: -3.89; 8.84), confirming that treatment assignment involved a selection bias of patients according to the severity of COVID-19 at hospital admission. The adjustment for confounding was carried out using severity as covariate in Cox regression models. The univariate Hazard Ratio (HR) of 0.68 (95%CI: 0.26; 1.80; p=0.441) for TPE turned to 1.19 (95%CI: 0.43; 3.29; p=0.741) after adjusting for severity.

ConclusionsThe lower mortality observed among patients receiving TPE was due to a lower severity of COVID-19 rather than TPE effects.

TRIAL REGISTRATIONIRCT registration number: IRCT20080901001165N58 (Iranian Registry of Clinical Trials)

Registration date: 2020-05-27, 1399/03/07 (retrospectively registered)

category: intensive care and critical care medicine


title: Development and validation of a deep learning algorithm using fundus photographs to predict 10-year risk of ischemic cardiovascular diseases among Chinese population

abstract:
BackgroundIschemic cardiovascular diseases (ICVD) risk predict models are valuable but limited by its requirement for multidimensional medical information including that from blood drawing. A convenient and affordable alternative is in demand.

ObjectivesTo develop and validate a deep learning algorithm to predict 10-year ICVD risk using retinal fundus photographs in Chinese population.

MethodsWe firstly labeled fundus photographs with natural logarithms of ICVD risk estimated by a previously validated 10-year Chinese ICVD risk prediction model for 390,947 adults randomly selected (95%) from a health checkup dataset. An algorithm using convolutional neural network was then developed to predict the estimated 10-year ICVD risk by fundus images. The algorithm was validated using both internal dataset (the other 5%) and external dataset from an independent source (sample size = 1,309). Adjusted R2 and area under the receiver operating characteristic curve (AUC) were used to evaluate the goodness of fit.

ResultsThe adjusted R2 between natural logarithms of the predicted and calculated ICVD risks was 0.876 and 0.638 in the internal and external validations, respectively. For detecting ICVD risk [≥] 5% and [≥] 7.5%, the algorithm achieved an AUC of 0.971 (95% CI: 0.967-0.975) and 0.976 (95% CI: 0.973-0.980) in internal validation, and 0.859 (95% CI: 0.822-0.895) and 0.876 (95% CI: 0.816-0.837) in external validation.

ConclusionsThe deep learning algorithm developed in the study using fundus photographs to predict 10-year ICVD risk in Chinese population had fairly good capability in predicting the risk and may have values to be widely promoted considering its advances in easy use and lower cost. Further studies with long term follow up are warranted.

category: cardiovascular medicine


title: Emergence of the SARS-CoV-2 B.1.1.7 lineage and its characteristics at an outpatient testing site in Berlin, Germany, January-March 2021

abstract: Within five weeks in early 2021, B.1.1.7 became the dominant SARS-CoV-2 lineage at an outpatient testing site in Berlin. Characteristics including Ct-values of 193 and 125 recently ill outpatients with B.1.1.7 and wildtype virus, respectively, were similar, except for more commonly reported sore throat and travel, and less frequently stated loss of smell and taste in the former.

category: epidemiology


title: The relationship between human mobility measures and SAR-Cov-2 transmission varies by epidemic phase and urbanicity: results from the United States

abstract: Global efforts to prevent the spread of the SARS-COV-2 pandemic in early 2020 focused on non-pharmaceutical interventions like social distancing; policies that aim to reduce transmission by changing mixing patterns between people. As countries have implemented these interventions, aggregated location data from mobile phones have become an important source of real-time information about human mobility and behavioral changes on a population level. Human activity measured using mobile phones reflects the aggregate behavior of a subset of people, and although metrics of mobility are related to contact patterns between people that spread the coronavirus, they do not provide a direct measure. In this study, we use results from a nowcasting approach from 1,396 counties across the US between January 22nd, 2020 and July 9th, 2020 to determine the effective reproductive number (R(t)) along an urban/rural gradient. For each county, we compare the time series of R(t) values with mobility proxies from mobile phone data from Camber Systems, an aggregator of mobility data from various providers in the United States. We show that the reproduction number is most strongly associated with mobility proxies for change in the travel into counties compared to baseline, but that the relationship weakens considerably after the initial 15 weeks of the epidemic, consistent with the emergence of a more complex ecosystem of local policies and behaviors including masking. Importantly, we highlight potential issues in the data generation process, representativeness and equity of access which must be addressed to allow for general use of these data in public health.


title: Access to palivizumab among children at high risk of respiratory syncytial virus complications in English hospitals

abstract:
ObjectivesPalivizumab is a monoclonal antibody which can prevent infection with respiratory syncytial virus (RSV). Due to its high cost, it is recommended for high-risk infants only. We aimed to determine the proportion of infants eligible for palivizumab treatment in England who receive at least one dose.

MethodsWe used the Hospital Treatment Insights database containing hospital admission records linked to hospital pharmacy dispensing data for 43/153 hospitals in England. Infants born between 2010 and 2016 were considered eligible for palivizumab if their medical records indicated chronic lung disease (CLD), congenital heart disease (CHD), or severe immunodeficiency (SCID), and they met additional criteria based on gestational age at birth and age at start of the RSV season (beginning of October). We calculated the proportion of infants who received at least one dose of palivizumab in their first RSV season, and modelled the odds of treatment according to multiple child characteristics using logistic regression models.

ResultsWe identified 3,712 eligible children, of whom 2,479 (67%) had complete information on all risk factors. Palivizumab was prescribed to 832 of eligible children (34%). Being born at <30 weeks gestation, aged <6 months at the start of RSV season, and having two or more of CLD, CHD or SCID were associated with higher odds of treatment.

ConclusionIn England, palivizumab is not prescribed to the majority of children who are eligible to receive it. Doctors managing these infants might be unfamiliar with the eligibility criteria or are constrained by other considerations, such as cost.


title: The risk of symptomatic reinfection during the second COVID-19 wave in individuals previously exposed to SARS-CoV-2

abstract: To what extent infection with SARS-CoV-2 protects against subsequent reinfection or symptomatic reinfection is still unclear. In this cohort study, we analyzed surveillance records of COVID-19 cases identified between June 2020 and January 2021 in five Italian municipalities, where 77.7% of the entire population was screened for IgG antibodies in May 2020. We compared the risk of observing symptomatic infections in two mutually exclusive groups defined by the initial serological response. We estimated that the cumulative incidence of identified symptomatic infections in the IgG negative and positive cohorts was 2.67% (95%CI: 2.12% - 3.37%) and 0.14% (95%CI: 0.04% - 0.58%), respectively. The adjusted odd ratio of developing symptomatic infection in individuals previously exposed to SARS-CoV-2 was estimated at 0.054 (95%CI: 0.009 - 0.169). Quantifying protective immunity against COVID-19 disease elicited by natural infection with SARS-CoV-2 is essential to inform strategies for controlling the pandemic in the forthcoming months.


title: Quantifying aerosol and droplet generation during upper and lower gastrointestinal endoscopy: whole procedure and event-based analysis

abstract:
ObjectiveAerosol generating procedures have become an important healthcare issue due to the COVID-19 pandemic, as the SARS-CoV-2 virus can be transmitted via aerosols. We aimed to characterise aerosol and droplet generation in gastrointestinal endoscopy, where there is little evidence.

DesignThis prospective observational study included patients undergoing routine per-oral gastroscopy (POG, n=36), trans-nasal endoscopy (TNE, n=11) and lower gastrointestinal (LGI) endoscopy (n=48). Particle counters took measurements near the appropriate orifice (two models used, diameter ranges 0.3{micro}m-25{micro}m and 20{micro}m-3000{micro}m). Quantitative analysis was performed by recording specific events and subtracting the background particles.

ResultsPOG produced 2.06x the level of background particles (p<0.001), and 2.13x the number of particles compared to TNE. LGI procedures produce significant particle counts (p<0.001), with a rate of 8.8x106/min/m3 compared to 13.0x106/min/m3 for POG. Events significant relative to the noise floor of background particles were: POG-throat spray (112.3x, p<0.01), oesophageal extubation (36.7x, p<0.001), coughing/gagging (30.7x, p<0.01); TNE-nasal spray (32.8x, p<0.01), nasal extubation (25.6x, p<0.01), coughing/gagging (23.3x, p<0.01); LGI-rectal intubation (3.5x, p<0.05), rectal extubation (11.8x, p<0.01), application of abdominal pressure (4.9x, p<0.05). These all produced particle counts larger than or comparable to volitional cough.

ConclusionsGastrointestinal endoscopy performed via the mouth, nose or rectum all generates significant quantities of aerosols and droplets. As the infectivity of procedures is not established, we therefore suggest adequate PPE is used for all GI endoscopy where there is a high population prevalence of COVID-19. Avoiding throat and nasal spray would significantly reduce particles generated from UGI procedures.

SIGNIFICANCE OF THIS STUDYO_ST_ABSWhat is already known on this subject?C_ST_ABSThe way we deliver healthcare has dramatically changed since the start of the COVID-19 pandemic. This includes gastrointestinal endoscopy, with precautions in place such as enhanced personal protective equipment, ventilation standards and prioritisation of procedures. Little research has been performed on establishing endoscopy as an aerosol generating procedure (AGP). Two recent studies indicate per-oral gastroscopy is an AGP. However, there is no data on the causative events within procedures, limited particle size analysis, and no data on trans-nasal endoscopy (TNE) or lower gastrointestinal (LGI) endoscopy.

What are the new findings?This study greatly expands our knowledge of aerosol and droplet generation during gastrointestinal endoscopy. We show that per-oral gastroscopy (POG), TNE and LGI endoscopy all produce aerosols and droplets. We have quantified this to show that POG produces double the amount of background particles, whilst TNE produces half the particles and LGI a third lower particles than POG per unit time. We use a novel subtraction technique to analyse individual events within endoscopic procedures. This shows that anaesthetic spray is the major contributor for upper gastrointestinal (UGI) endoscopy, followed by coughing/gagging as well as extubation. For LGI endoscopy, the main contributors are rectal extubation, abdominal pressure application and rectal intubation, which produce more particles in the droplet range. All these events are at least comparable to volitional cough, whilst anaesthetic throat spray produces particle counts ten times higher. Furthermore, the presence of a hiatus hernia appears to increase particle generation for UGI endoscopy, whilst high patient discomfort does this for LGI endoscopy. Lastly, we show that particles sizes of some events, such as oral and rectal extubation, are significantly greater than the average particle size of a volitional cough. We also use a spray characteriser to show that particles of up to 300{micro}m are produced in UGI extubation and fundal retroflexion.

How might it impact on clinical practice in the foreseeable future?The results in this study give important information for how we deliver endoscopy when there is a threat to the safety of healthcare workers and patients from transmissible infections. It is therefore relevant not only for the current COVID-19 pandemic, but also for other potential respiratory and gastrointestinal pathogens. As the infectivity of procedures is not established, we therefore suggest adequate PPE is used for all GI endoscopy where there is a high population prevalence of COVID-19. We show that for UGI endoscopy, alternatives to local anaesthesia spray would significantly reduce aerosol and droplet generation. The use of TNE would be desirable as it produces less aerosols than POG, but still additional mitigating strategies would be required. For LGI endoscopy, good technique that limits patient discomfort may mitigate aerosol and droplet generation. Further research needs to be done on infectivity of endoscopic procedures and barrier mitigating devices.

category: gastroenterology


title: A Retrospective Analysis of Feeding Practices and Complications in Patients with Critical Bronchiolitis on Non-invasive Respiratory Support

abstract: Limited data exist regarding feeding pediatric patients managed on non-invasive respiratory support (NRS) modes that augment oxygentation and ventilation in the setting of respiratory failure. We conducted a retrospective cohort study to explore the safety of feeding patients managed on NRS with acute respiratory failure secondary to bronchiolitis. Children up to 2 years old with critical bronchiolitis managed on RAM, CPAP, or BiPAP were included. Of the 178 eligible patients, 64 were reportedly NPO while 114 were fed (EN). Overall equivalent in severity of illness, younger patients populated the EN group, while the NPO group experienced a higher incidence of intubation. Duration of PICU stay and NRS were shorter in the NPO group, though intubation eliminated the former difference. Within the EN group, ninety percent had feeds initiated within 48 hours and 94% reached full feeds within 7 days of NRS initiation, with an 8% complication and <1% aspiration rate. Reported complications did not result in escalation of respiratory support. Notably, a significant improvement in heart rate and respiratory rate was noted after feeds initiation. Taken together, our study supports the practice of early enteral nutrition in patients with critical bronchiolitis requiring non-invasive respiratory support.

category: pediatrics


title: Contracting COVID-19: A Longitudinal Investigation of the Impact of Beliefs and Knowledge

abstract: Recent work has found that an individuals beliefs and personal characteristics can impact perceptions of and responses to the COVID-19 pandemic. Certain individuals--such as those who are politically conservative, endorse conspiracy theories, or who believe the threat of COVID-19 to be exaggerated--are less likely to engage in such preventative behaviors as social distancing. The current research aims to address whether these individual difference variables not only affect peoples subjective and behavioral reactions to the pandemic, but also whether they actually impact individuals likelihood of contracting COVID-19. In the early months of the pandemic, U.S. participants responded to a variety of individual difference measures as well as questions specific to COVID-19 and the pandemic itself. Four months later, 2,120 of these participants responded with whether they had contracted COVID-19. Nearly all of our included individual difference measures significantly predicted whether a person reported believing they had contracted COVID-19 as well as whether they had actually tested positive for the virus in this four-month period. Additional analyses revealed that all of these relationships were primarily mediated by whether participants held accurate knowledge about COVID-19. These findings offer useful insights for developing more effective interventions aimed at slowing the spread of both COVID-19 and future diseases. Moreover, some findings offer critical tests of the validity of such theoretical frameworks as those concerning conspiratorial ideation and disgust sensitivity within a real-world context.

category: public and global health


title: Assess the Benefit of Interventional Radiologist Performing an Image Guided Biopsy

abstract:
PurposeTo determine whether there is any benefit in diagnostic accuracy, reduction in periprocedural complications, when image-guided biopsies are performed by interventional radiologist as compared to a general radiologist or other physician without prior special interventional training.

Patients and MethodsThis study is a retrospective chart review of all consecutive patients that underwent imaging-guided core biopsies during one year in our hospital. Information collected included: patient age, gender, coagulation status, organ biopsied, imaging modality and equipment used, number of samples obtained, post-biopsy complications, histopathological results, and previous interventional training of a physician performing the biopsy. The quantitative data from patient charts was analyzed using a statistical program, Statistical Package for Social Sciences (SPSS).

Results449 patients were included in this study: 132 were performed using Computed Tomography guidance and 317 were performed under ultrasound guidance. The success rate of core biopsies was compared between different specialists, and was measured based on periprocedural complications, necessity of medical intervention and/or hospitalization after biopsy procedure, true positive histopathology results, and need to perform repeat biopsy of the same lesion owing to inconclusive results. Overall, IR had a success rate of 88.13%, non-IR had a success rate of 61.07%, and nephrologists had a success rate of 77.65%. The post biopsy complication rates were 5.48%, 27.52%, and 17.65% for procedures performed by IR, non-IR, and nephrologists respectively.

ConclusionOur study shows an overall higher success rate and improved patient outcome when image guided biopsies were performed by IR, as compared to other non-IR physicians.

category: radiology and imaging


title: Impaired antigen-specific memory B cell and plasma cell responses including lack of specific IgG upon SARS-CoV-2 BNT162b2 vaccination among Kidney Transplant and Dialysis patients

abstract:
Patients with kidney failure are at increased risk during the COVID-19 pandemic and effective vaccinations are needed. It is not known how efficient mRNA vaccines mount B and plasma cell responses in dialysis patients (DP) or kidney transplant recipients (KTR) compared to healthy controls (HC). We studied humoral and B cell responses of 25 HC, 44 DP and 40 KTR. Markedly impaired anti-BNT162b2 responses were identified among KTR and DP compared to 100% seroconversion in HC. In DP, the response was delayed (3-4 weeks after boost) and reduced with anti-S1 IgG positivity in 31 (70.5%) and anti-S1 IgA in 30 (68.2%) of 44, respectively. In contrast, KTR did not develop IgG response except one patient who had prior unrecognized infection and developed anti-S1 IgG. The majority of antigen-specific B cells (RBD+) were identified in the plasmablast or post-switch memory B cell compartments in HC, whereas these RBD+ B cells were enriched among pre-switch and naive B cells from DP and KTR. Single cell transcriptome and CITE-seq analyses found reduced frequencies of plasmablasts, TCF7+CD27+GZMK+ T cells and proliferating MKI67-expressing lymphocytes among KTR non-responders. Importantly, the frequency and absolute number of antigen-specific circulating plasmablasts in the whole cohort correlated with the Ig response, a characteristic not reported for other vaccinations. In conclusion, this data indicate that lack of T cell help related to immunosuppression results in impaired germinal center differentiation of B and plasma cell memory. There is an urgent need to improve vaccination protocols in patients after kidney transplantation or on chronic dialysis.

One Sentence SummaryKidney transplant recipients and dialysis patients show a markedly diminished humoral response and impaired molecular B cell memory formation upon vaccination with BNT162b2.

category: nephrology


title: The impact of COVID-19 on the oncologic outcomes of 3236 patients undergoing ColoRectal Cancer surgery in Northern Italy in 2019 and 2020 (COVID-CRC): results of a multicentric comparative cohort study.

abstract:
ObjectiveThis study compared all patients undergoing surgery for colorectal cancer in 20 hospitals of Northern Italy in 2019 versus 2020, in order to evaluate whether COVID-19-related delays in the execution of colorectal cancer screening resulted in more advanced cancers at diagnosis and worse clinical outcomes.

DesignA retrospective multicentric cohort analysis of patients who underwent surgery for colorectal cancer in March-December 2019 (2019) versus March-December 2020 (2020). The independent predictors of disease stage (oncologic stage, associated symptoms, clinical T4 stage, metastasis) and postoperative outcome (surgical complications, palliative surgery, 30-day death) were evaluated using logistic regression.

ResultsThe sample consisted of 1755 patients operated in 2019, and 1481 in 2020 (both mean ages 69.6 years). The proportions of cancers with symptoms, clinical T4 stage, liver and lung metastases in 2019 and 2020 were, respectively: 80.8% vs 84.5%; 6.2% vs 8.7%; 10.2% vs 10.3%; and 3.0% vs 4.4%. The proportions of surgical complications, palliative surgery, and death in 2019 and 2020 were, respectively: 34.4%vs 31.9%; 5.0% vs 7.5%; and 1.7% vs 2.4%. At multivariate analysis, as compared with 2019, cancers in 2020 were significantly more likely to be symptomatic (Odds Ratio - OR: 1.36, 95% Confidence Interval - CI: 1.09-1.69), in clinical T4 stage (OR: 1.38; 1.03-1.85), with multiple liver metastases (OR: 2.21; 1.24-3.94), but less likely to cause surgical complications (OR: 0.79; 0.68-0.93).

ConclusionsColorectal cancer patients who had surgery between March and December 2020 had an increased risk of more advanced disease in terms of associated symptoms, cancer location, clinical T4 stage, and number of liver metastases.

SHORT SUMMARY BOX

What is already known about this subject?A specific search regarding the correlation between colorectal cancer oncologic outcomes and COVID-19 showed a few modeling studies which reported the predictions of the potential impact of the diagnostic delays (due to the reduction of the screening programs) on the survival of patients affected by colorectal cancer. However, no study reported any real-life evidence regarding the correlation between the COVID-19 outbreak and the deteriorations of the oncologic outcomes of patients with colorectal cancer.

What are the new findings?The present study showed that patients who had surgery for colorectal cancer between March and December 2020 had an increased risk of more advanced disease in terms of associated symptoms, cancer location, clinical T4 stage, and number of liver metastases, than patients who had surgery between March and December 2019.

How might it impact on clinical practice in the foreseeable future?The present study confirmed that the backlogs of the screening programs have had, and probably will have, detrimental effects on the oncologic outcomes of patients affected by colorectal cancer. Increased resources should be placed in order to reactivate and enhance the screening programs, and to reduce the risk of colorectal cancer patients to be diagnosed with advanced cancer in the next future.

category: oncology


title: Frequency of variants of hereditary cancer risk syndrome in 1682 Brazilian patients genotyped by next-generation sequencing

abstract: Hereditary cancer risk syndromes are caused by germline variants. Most studies on hereditary cancer have been conducted in white populations. We report the largest study in Brazilian individuals with multiple ethnicities. We genotyped 1682 individuals from all regions of the country with Next-generation sequencing (NGS) panels. Most were women with personal/family history of cancer, mostly breast and ovarian. We identified 321 pathogenic/likely pathogenic (P/LP) variants in 305 people (18.1%) distributed among 32 genes. Most were on BRCA1 and BRCA2 (129 patients, 26.2% and 14.3% of all P/LP, respectively), MUTYH (42 monoallelic patients, 13.1%), PALB2 (25, 7.8%), Lynch syndrome genes (17, 5.3%), and TP53 (17, 5.3%). Transheterozygosity prevalence in our sample was 0.89% (15/1682). BRCA1/BRCA2 double heterozygosity rate was 0.78% (1/129) for BRCA variants carriers and 0.06% (1/1682) overall. We evaluated the performance of the genetic testing criteria by NCCN and Brazilian National Health Agency (ANS). We observed false negative rates of 17.3% and 44.2%, meaning that both failed to detect a substantial part of P/LP positive patients. Our results add knowledge on the Brazilian spectrum of cancer risk germline variants, demonstrate that large multigene panels have high rates of positivity, and indicate that Brazilian testing guidelines should be improved.

category: genetic and genomic medicine


title: The genetics of hereditary cancer risk syndromes in Brazil: a comprehensive analysis of 1682 patients


title: Estimating the effect of mobility on SARS-CoV-2 transmission during the first and second wave of the COVID-19 epidemic in Switzerland: a population-based study

abstract: The effect of mobility and its value for surveillance in different waves of the COVID-19 epidemic is still unclear. In this study, we compared the role of mobility during the first and second epidemic wave in Switzerland by analysing the link between daily travel distances and the effective reproduction number Rt of SARS-CoV-2. Here we used aggregated mobile phone data from a representative panel survey of the Swiss population to measure human mobility. We estimated the effects of reductions in daily travel distance on Rt via a regression model. We compared mobility effects between the first wave (March 2-April 7, 2020) and the second wave (October 1-December 10, 2020) across mode of transport, travel purpose, sociodemographic subgroup and movement radius. We found that human mobility was associated with the effective reproduction number of SARS-CoV-2 during both the first and second epidemic wave in Switzerland. The estimated relative effects of mobility were similar in both waves for all modes of transport, travel purposes, and sociodemographic subgroups but differed by movement radius. Moreover, smaller mobility reductions in the second wave translated into smaller overall reductions of Rt. Mobility data from mobile phones have a continued potential to support real-time surveillance of COVID-19 during epidemic waves.

category: health policy


title: The impact of COVID-19 pandemic on AMI and Stroke mortality in Lombardy: Evidence from the epicenter of the pandemic

abstract:
BackgroundThe Covid-19 pandemic has enormously impacted the delivery of clinical healthcare and hospital management practices in most of the hospitals around the world for both Covid and no-Covid patients. In this context, it is extremely important to assess whether the clinical management of no-Covid cases has not seriously been compromised during the first epidemic outbreak. Among no-Covid cases, patients with acute myocardial infarction (AMI) and stroke need non-deferrable emergency care and are the natural candidates as no-Covid patients to be studied. Preliminary evidence suggests that i) the time from onset of symptoms to emergency department (ED) presentation has increased in Covid-19 times as well 30-day mortality during the pandemic has been higher. We aimed to complement this evidence assessing if the additional stress due to the high inflow of Covid-19 patients at hospital level has modified AMI and Stroke admission criteria and related mortality rates in a causal inference framework.

MethodsTo study the impact of Covid pandemic on mortality rates for AMI and Stroke we adopt two quasi-experimental approaches, regression-discontinuity design (RDD) and difference-in-regression-discontinuity (DRD) designs by which we identify the plausible causal effect on mortality of the Covid-19-related hospital stress due to the introduction of State of Emergency restrictions.

FindingsWe check the causal effect of the Covid-19 pandemic on mortality rates of AMI and stroke over several time-windows of 15-days around the implementation date of the State of Emergency restrictions for COVID-19 (March, 9th). Despite the potential adverse effect on expected mortality due to a longer time to hospitalization, the AMI and Stroke mortality rates are overall not statistically different from the one observed in the control group. The obtained results provided by RDD and DRD models are robust also when we account for seasonality and unobserved factors.

InterpretationIn a quasi-experimental setting we assessed the causal impact of the hospital and staff extra-burden generated by the first wave of Covid-19 patients on mortality rates of no-Covid non-deferrable urgent cases (AMI and Stroke) hospitalized at Spedali Civili of Brescia, one of the most hit provinces in Italy by Covid-19 during March and May 2020. We find a non-statistically significant impact on mortality rates for AMI and Stroke patients providing evidence of the hospital ability to manage - with the implementation of a double track organization-the simultaneously delivery of high quality cares to both Covid and no-Covid patients. Availability of similar data for the regional context as a whole is needed to further substantiate the findings and explore existing differences in efficacy of different managerial settings implemented in Lombardy hospitals.

FundingAll authors - except for Stefano Verzillo-acknowledge financial support from the Region of Lombardy, project 2014IT16RFOP012  Misura a sostegno dello sviluppo di collaborazioni per lidentificazione di terapie e sistemi di diagnostica, protezione e analisi per contrastare lemergenza Coronavirus e altre emergenze virali del futuro. Stefano Verzillo has participated as external econometrician from European Commission, Joint Research Center to this project without receiving any funding or financial support, in compliance with EC rules. His contribution has been offered in the Conceptualization and Writing and Editing stages.

Role of the Funding sourceThe founder had no roles in our study design, data collection and analysis, decision to publish and preparation of the manuscript.

category: health systems and quality improvement


title: Unlocking low- and middle-income countries to detect SARS-CoV-2

abstract:
Low- and middle-income countries (LMICs) are significantly affected by SARS-CoV-2, partially due to their limited capacity for local development of molecular testing and accentuated by the international supply shortage. Here, we describe a molecular toolkit that can be readily produced and deployed in LMICs using minimal laboratory equipment. Our results show that mid-scale production of enzymes and nucleic acids can supply thousand tests per production batch. One-step RT-PCR was optimized for two SARS-CoV-2 loci and coupled to CRISPR/Cas12a detection. The clinical validation indicated a sensitivity near 100% for mid and high viral load samples (Cq [≤] 33). The specificity was around 100% regardless of viral load. The toolkit was used with the mobile laboratory BentoLab, potentially unlocking LMICs to implement detection services in unattended regions. Altogether, we provide detailed methods and performance evidence of molecular tools aiming to aid LMICs to deploy molecular testing for current or future pathogenic outbreaks.

One Sentence SummaryWe describe a molecular toolkit for the detection of SARS-CoV-2 that is compatible with available facilities in low- and middle-income countries (LMICs).


title: Self-collected oral, nasal and saliva samples yield sensitivity comparable to professional-collected oro-nasopharyngeal swabs in SARS-CoV-2 diagnosis

abstract:
Summary/AbstractO_ST_ABSIntroductionC_ST_ABSContainment of the COVID-19 pandemic requires broad-scale testing. Laboratory capacities for real-time-PCR were increased, and are complemented by Ag-tests. However, sample-collection still requires qualified personnel and protective equipement, may produce transmission to others during conduct and travel, and is perceived uncomfortable. We tested sensitivity of three simplified self-sampling techniques compared to professional-collected combined oro-nasopharyngeal samples (cOP/NP).

MethodsFrom 62 symptomatic COVID-19 outpatients, we obtained simultaneously three self- and one professional-collected sample after initial confirmation in a testing centre: (i) combination swab (tongue, cheek, both nasal vestibula, MS, (ii) saliva sponge combined with both nasal vestibula, SN, and (iii) gargled tap water, GW, (iv) professionally-collected cOP/NP (standard). We compared the results of SARS-CoV-2 PCR-assays detecting E-gene and ORF1ab for the different sample types and performed bivariate statistical analysis to determine the variables reducing sensitivity of the self-collecting procedures.

ResultsSARS-CoV-2 RNA was detected in all 62 professionally-collected cOP/NP. MS and SN samples showed a sensitivity of 95.2% (95%CI 86.5-99.0) and GW samples of 88.7% (78.1-95.3). Compared to the median ct-values of cOP/NP samples for E-gene (20.7) and ORF1ab (20.2) these were higher for MS (22.6 and 21.8), SN (23.3 and 22.3), and for GW (30.3 and 29.8).

For MS and SN samples but not for GW specimens, false negativity in bivariate analysis was associated with non-German mother-tongue, number of sampling errors, and with symptom duration. For symptom duration of [≤]8 days, test sensitivity for SN samples was 98.2% (95%CI 90.4-100.0) and for MS 96.4% (95%CI 87.7-99.6) and drops after day 8 below 90%.

DiscussionThe study is limited to sensitivity of self-collection in symptomatic patients. Still, in this group, self-collected oral/nasal/saliva samples are reliable alternatives to professional-collected cOP/NP samples, if symptom duration does not exceed eight days and operational errors are minimized. Self-sampling could contribute to up-scaling of safe and efficient testing.


title: Evaluation of seven different rapid methods for nucleic acid detection of SARS-COV-2 virus

abstract:
BackgroundIn the current COVID-19 pandemic there is mass screening of SARS-CoV-2 happening round the world due to the extensive spread of the infections. There is a high demand for rapid diagnostic tests to expedite identification of cases and to facilitate early isolation and control spread. Hence this study evaluates seven different rapid nucleic acid detection assays that are commercially available for SARS-CoV-2 virus detection.

MethodsNasopharyngeal samples were collected from 4859 participants and were tested for SARS-CoV-2 virus by the gold standard RT-PCR method along with one of these seven rapid methods of detection. Evaluation of the rapid nucleic acid detection assays was done by comparing the results of these rapid methods with the gold standard RT-qPCR results for SARS-COV-2 detection.

ResultsAQ-TOP had the highest sensitivity (98%) and strong kappa value of 0.943 followed by Genechecker and Abbot ID NOW. The POCKIT (ii RT-PCR) assay had the highest test accuracy of 99.29% followed by Genechecker and Cobas Liat. Atila iAMP showed the highest percentage of invalid reports (35.5%) followed by AQ-TOP with 6% and POCKIT with 3.7% of invalid reports.

ConclusionGenechecker system, Abbott ID NOW and Cobas Liat, were found to have best performance and agreement when compared to the standard RT-PCR for COVID-19 detection. With further research, these rapid tests have the potential to be employed in large scale screening of COVID-19.


title: Survival analysis methods for analysis of hospitalization data: Application to COVID-19 patient hospitalization experience

abstract: During most of 2020, the COVID-19 pandemic gave rise to considerable and growing numbers of hospitalizations across most of the U.S. Typical COVID-19 hospitalization data, including length of stay, intensive care unit (ICU) use, mechanical ventilation (Vent), and in-hospital mortality provide clearly interpretable health care endpoints that can be compared across population strata. They capture the resources consumed for the care of COVID-19 patients, and analysis of these endpoints can be used for resource planning at the local level. Yet, hospitalization data embody novel features that require careful statistical treatment to be useful in this context. Specifically, statistical models must meet three goals: (i) They should mesh with and inform mathematical epidemiologic or agent-based models of the COVID-19 experience in the population. (ii) They need to handle administrative censoring of hospitalization experience when data are extracted and downloaded for a given patient before that patients hospitalization experience has terminated. And, (iii) models need to handle risks for competing events, the occurrence of one blocking the possibility of the other(s). For example, live discharge from the hospital "competes with" (i.e., blocks) in-hospital mortality. We have adapted approaches from the survival analysis literature to address these challenges in order to better understand and quantify the population experience in hospital with respect to length of stay, ICU, Vent use and so on. Using hospitalization data from a large U.S. metropolitan region, in this report, we show how standard techniques from survival analysis can be brought to bear to address these challenges and yield interpretable results. In the breakout/discussion, we will discuss formulation, estimation and inference, and interpretation of competing risks models.


title: The Amortization of Funding Gene Therapies: Making the 'Intangibles' Tangible for Patients

abstract: Gene replacement therapies (GRTs) are increasingly expected to reach the market. Current healthcare systems are struggling to fund such valuable, costly therapies. GRTs are highly valuable as they extend life through sustained, long-term efficacy or by saving on the costs of a current high-cost standard of care. Some payers have implemented payment models, which do not address the budget impact on the year of acquisition or administration of costly GRTs. This study aims to (1) introduce amortization as an accounting tool within the context of healthcare, specifically for GRTs, (2) present a systematic literature review (SLR) on the amortization or depreciation of pharmaceuticals and medical devices, (3) assess the rationale and feasibility as well as the pros and cons of the amortization of GRTs, and (4) provide recommendations for future steps for the introduction of amortization for GRTs. The limited literature, identified in the SLR, has proposed amortization as a solution for costly, highly valuable GRT funding, but did not fully investigate and detail amortization and its feasibility. This paper further details and illustrates amortization as a promising method for these GRTs by facilitating market and patient access. Current accounting principles and guidelines must evolve to apply amortization to GRTs.

category: health economics


title: ODACH: A One-shot Distributed Algorithm for Cox model with Heterogeneous Multi-center Data

abstract:
ObjectiveWe developed and evaluated a privacy-preserving One-shot Distributed Algorithm for Cox model to analyze multi-center time-to-event data without sharing patient-level information across sites, while accounting for heterogeneity across sites by allowing site-specific baseline hazard functions and feature distributions.

Materials and MethodsWe constructed a surrogate likelihood function to approximate the Cox log partial likelihood function which is stratified by site, using patient-level data from a single site and aggregated information from other sites. The ODAC estimator was obtained by maximizing the surrogate likelihood function. We evaluated and compare the performance of ODACH with meta-analysis by extensive numerical studies.

ResultsThe simulation study showed that ODACH provided estimates close to the pooled estimator, which is obtained by directly analyzing patient-level data from all sites via a stratified Cox model. The relative bias was <1% across all scenarios. As a comparison, the meta-analysis estimator, which was obtained by the inverse variance weighted average of the site-specific estimates, had substantial bias when the event rate is <5%, with the relative bias reaching 12% when the event rate is 1%.

ConclusionsODACH is a privacy-preserving and communication-efficient method for analyzing multi-center time-to-event data, which allows the baseline hazard functions as well as the distribution of covariate variables to vary across sites. It provides estimates that is close to the pooled estimator and substantially outperforms the meta-analysis estimator when the event is rare. It is thus extremely suitable for studying rare events with heterogeneous baseline hazards across sites in a distributed manner.

category: health informatics


title: COVID-19 Vaccine Prioritisation in Japan and South Korea

abstract:
BackgroundDue to a limited initial supply of COVID-19 vaccines, the prioritisation of individuals for vaccination is of utmost importance for public health. Here, we provide the optimal allocation strategy for COVID-19 vaccines according to age in Japan and South Korea.

MethodsCombining national case reports, age-specific contact matrices, and observed periods between each stages of infection (Susceptible-Exposed-Infectious-Quarantined), we constructed a compartmental model. We estimated the age-stratified probability of transmission given contact (qi) using Bayesian inference method and simulated different vaccination scenarios to reduce either case numbers or death toll. We also performed sensitivity analyses on the proportion of asymptomatic cases and vaccine efficacy.

FindingsThe model inferred age-stratified probability of transmission given contact (qi) showed similar age-dependent increase in Japan and South Korea. Assuming the reported COVID-19 vaccine efficacy, our results indicate that Japan and South Korea need to prioritise individuals aged 20-35 years and individuals aged over 60 years, respectively, to minimise case numbers. To minimise the death toll, both countries need to prioritise individuals aged over 75 years. These trends were not changed by proportions of asymptomatic cases and varying vaccine efficacy on individuals under 20 years.

InterpretationWe presented the optimal vaccination strategy for Japan and South Korea. Comparing the results of these countries demonstrates that not only the effective contact rates containing qi but also the age-demographics of current epidemic in Japan (dominance in 20s) and South Korea (dominant cases over 50s) affect vaccine allocation strategy.


title: Rapid detection of SARS CoV-2 N501Y mutation in clinical samples

abstract: Severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) variants poses major threats in increasing infectivity, transmission, mortality of Coronavirus Disease 2019 (Covid-19). Additionally, SARS CoV-2 variants resist antibody neutralizations or may abolish vaccine efficacies. Researches to develop economical and fast methods will support the developing or poor countries to challenge the Covid-19 pandemic via tracking common mutations that may help to deploy the vaccination programs and control the virus. Current study has developed a novel low-cost rapid technique, exploiting real time PCR probes and conventional PCR specific primers, to identify N501Y mutation, which was independently emerged in the UK, South African and Brazilian variants. Currently, these variants tend to spread to all over the world and seem to be more infectious, transmissible and fatal. This study helps tracking the N501Y mutation for understanding its clinical and epidemiological characteristics, in those countries where sequencing facilities are lacking or expensive. Further study should focus on other common mutations in the variants of concerns of SARS CoV-2.


title: Analyzing the effect of relaxing restriction on the COVID-19 outbreak for some US states

abstract: The ongoing pandemic disease COVID-19 has caused worldwide social and financial disruption. As many countries are engaged in designing vaccines, the harmful second and third waves of COVID-19 have already appeared in many countries. To investigate changes in transmission rates and the effect of social distancing in the USA, we formulate a system of ordinary differential equations using data of confirmed cases and deaths in these states: California, Texas, Florida, Georgia, Illinois, Louisiana, Michigan, and Missouri in the USA to be able to investigate changes in transmission rates of the outbreak and effect of social distancing. Our models and the corresponding parameter estimations show social distancing reduces the transmission by 60% to 90%, and thus obeying the movement restriction rules plays a crucial rule to reduce the magnitudes of the outbreak waves. Our analysis shows the current management restrictions do not sufficiently slow the disease propagation.


title: Is coagulation-protein consumption upon admission linked to COVID-19 severity and mortality?

abstract: The link between coagulation system disorders and COVID-19 has not yet been fully elucidated. With the aim of evaluating the association of several coagulation proteins with COVID-19 severity and mortality, we performed a cross-sectional study in 134 patients classified according to the highest disease severity reached during the disease. We found higher levels of antithrombin, prothrombin, factor XI, factor XII and factor XIII in asymptomatic/mild and moderate COVID-19 patients than healthy individuals. Interestingly, decreased levels of antithrombin, factor XI, XII and XIII were observed in those patients who eventually developed severe illness. Additionally, survival models showed us that patients with lower levels of these coagulation proteins had an increased risk of death. In conclusion, COVID-19 provokes early increments of some specific coagulation proteins in most patients. However, lower levels of these proteins at diagnosis might "paradoxically" imply a higher risk of progression to severe disease and COVID-19-related mortality.


title: Thromboembolism risk is higher among patients with diabetes and COVID-19 and is associated to poor clinical outcome

abstract:
AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSPurposeC_ST_ABSIndividuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications.

MethodsWe prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia.

ResultsAmong 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p=0.001), fasting blood glucose (HR 4.32, p<0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p=0.01) or fasting blood glucose [≥] 7 mmol/l (HR 3.07, p=0.015).

ConclusionsThromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen.

category: endocrinology


title: Thromboembolism risk among patients with diabetes/stress hyperglycemia and COVID-19


title: The Mental Health Under the COVID-19 Crisis in Africa: A Systematic Review and Meta-Analysis

abstract:
ObjectiveIn this paper, we aim to provide a systematic review and meta-analysis on the prevalence rates of mental health symptoms of anxiety, depression, and insomnia among the major populations during the COVID-19 pandemic in Africa.

DesignA systematic review and meta-analysis.

Data sourcesWe search and include articles using PubMed, Embase, Web of Science, PsycINFO, and medRxiv databases between Feb 202 and Feb 6th, 2021.

Eligibility criteria and data analysisThe meta-analysis targets the prevalence rates of mental health symptoms of major populations including frontline/general healthcare workers (HCWs), the general adult population, and medical students during the COVID-19 pandemic in Africa. To estimate the prevalence rates of anxiety, depression, and insomnia, we pooled data using random-effects meta-analyses.

ResultsIn this meta-analysis, we identify and include 28 studies and 32 independent samples from 12 countries with a total of 15,072 participants in Africa. Ethiopia (7) and Egypt (6) had the largest number of studies. While many countries including, but not limited to, Algeria, Kenya, and Ghana had a high number of COVID-19 cases, as many as three quarters of African countries have no studies. The pooled prevalence of anxiety in 27 studies was 37% (95%CI: 31-43%, I2 = 99.0%) and that of depression in 24 studies was 45% (95%CI: 36-51%, I2 = 99.5%) and that of insomnia in 9 studies was 28% (95%CI: 20-41%, I2 = 99.2%). The pooled prevalence rates of anxiety, depression, and insomnia in North Africa (44%, 55%, and 31%, respectively) are higher than the rates in Sub-Saharan Africa (31%, 30%, and 24%, respectively). Our analysis indicated high heterogeneity and varying prevalence rates of mental health symptoms during the COVID-19 pandemic in Africa.

DiscussionWe discuss our findings that a) a scarcity of studies in several African countries with a high number of COVID-19 cases, b) high heterogeneity among the studies, c) the extent of prevalence of mental health symptoms in Africa to be high, and d) the pattern of mental health symptoms in Africa differs from elsewhere, i.e., more African adults suffer from depression rather than anxiety and insomnia during COVID 19 compared to adult population in other countries or regions. Hence, our findings carry crucial implications for healthcare organizations and future research to enable evidence-based medicine in Africa. Our findings also call for increased scholarly attention on Africa, the least studied continent with a limited amount of research on mental health symptoms under the COVID 19 pandemic.

Trial registrationCRD42020224458

category: psychiatry and clinical psychology


title: Rare coding variants in five DNA damage repair genes associate with timing of natural menopause

abstract: The age of menopause is associated with fertility and disease risk, and its genetic control is of great interest. We used whole-exome sequences from 119,992 women in the UK Biobank to test for associations between rare damaging variants and age at natural menopause. Rare damaging variants in three genes significantly associated with menopause: CHEK2 (p = 6.2 x 10-51) and DCLRE1A (p = 1.2 x 10-12) with later menopause and TOP3A (p = 8.8 x 10-8) with earlier menopause. Two additional genes were suggestive: RAD54L (p = 2.3 x 10-6) with later menopause and HROB (p = 2.7 x 10-6) with earlier menopause. In a follow-up analysis of repeated questionnaires in women who were initially pre-menopausal, CHEK2, TOP3A, and RAD54L genotype associated with subsequent menopause. Consistent with previous GWAS, all five genes are involved in the DNA-damage repair pathway. Phenome-wide scans across 363,977 men and women revealed that in addition to known associations with cancers and blood cell counts, rare variants in CHEK2 also associated with increased risk of uterine fibroids, polycystic ovary syndrome, and prostate hypertrophy; these associations are not shared with higher-penetrance breast cancer genes. Causal mediation analysis suggests that approximately 8% of the breast cancer risk conferred by CHEK2 pathogenic variants after menopause is mediated through delayed menopause.

category: sexual and reproductive health


title: Clarivate listed nursing journals in 2020: what they publish and how they measure use of social media

abstract:
ObjectivesTo investigate what the most common types of articles that nursing journals purport to publish are and what they actually publish? And to investigate the extent to which academic nursing journals listed by Clarivate track alternative metrics?

MethodsJournals included in the nursing Journal Citation Report journal category in 2019 described as nursing were identified and considered suitable for inclusion in the analysis. Instructions for authors were reviewed online and mention of each type of article identified. The tables of contents of each issue of each journal published during 2019 was examined and the types of articles published were extracted to a spreadsheet into permitted article types and published articles. Likewise, the use of alternative metrics by each journal was extracted to a spreadsheet. Pearsons and Spearmans correlation analysis was applied to investigate the relationship between articles permitted and articles published.

ResultsIn the 2020 Journal Citation Report, 123 journals were listed. The most common article type permitted was original research (n=117), followed by review papers (n=116) and discussion papers (n=63). Original research (n=7045); review papers (n=1268); discussion papers (n=1225); editorials (n=793) and commentaries (n=776) were the most commonly published categories of article. Of journals examined, 108 (96.8%) tracked mentions on social media and the Altmetric score was the most commonly use (75%). There was a strong correlation (r=0.73; p=0,002) between the numbers of article permitted and published and a strong correlation (rho=0.86; p<0.001) in terms of the rankings of the permitted and published articles.

ConclusionsThere is a relationship between the most frequently permitted article types and those published, especially for the most frequent categories of both. Original articles, review papers and discussion papers are the backbone of academic publishing in nursing with original articles vastly outweighing review and discussion papers. Most Clarivate listed journals now use some method of tracking alternative metrics indicating how seriously publishers take their social media profiles.

category: nursing


title: A cross-sectional study of workplace measures against COVID-19 and psychological distress among Japanese workers

abstract:
ObjectivesThis study examined the relationship between the status of infection control efforts against COVID-19 in the workplace and workers mental health using a large-scale Internet-based study.

MethodsThis cross-sectional study was based on an Internet monitoring survey conducted during the third wave of the COVID-19 epidemic in Japan. Of the 33,302 people who participated in the survey, 27,036 were included in the analyses. Participants answered whether or not each of 10 different infection control measures were in place at their workplace (e.g. wearing masks at all times during working hours). A Kessler 6 (K6) score of [≥]13 was defined as mild psychological distress. The odds ratios (ORs) of psychological distress associated with infection control measures at the workplace were estimated using a multilevel logistic model nested in the prefectures of residence.

ResultsThe OR of subjects working at facilities with 4 or 5 infection control measures for psychological distress was 1.19 (95% confidence interval [CI]: 1.05-1.34, p=0.010), that in facilities with 2 or 3 infection control measures was 1.43 (95% CI: 1.25-1.64, p<0.001), and that in facilities with 1 or no infection control measures was 1.87 (95% CI: 1.63-2.14, p<0.001) compared to subjects whose workplaces had [≥]6 infection control measures.

ConclusionOur findings suggest that proactive COVID-19 infection control measures can influence the mental health of workers.

category: occupational and environmental health


title: A cross-sectional study of infection control measures against COVID-19 and psychological distress among Japanese workers


title: A Tool for Translating Polygenic Scores onto the Absolute Scale Using Summary Statistics

abstract:
BackgroundThere is growing interest in the clinical application of polygenic scores as their predictive utility increases for a range of health-related phenotypes. However, providing polygenic score predictions on the absolute scale is an important step for their safe interpretation. Currently, polygenic scores can only be converted to the absolute scale when a validation sample is available, presenting a major limitation in the interpretability and clinical utility of polygenic scores.

MethodsWe have developed a method to convert polygenic scores to the absolute scale for binary and normally distributed phenotypes. This method uses summary statistics, requiring only the area-under-the-ROC curve (AUC) or variance explained (R2) by the polygenic score, and the prevalence of binary phenotypes, or mean and standard deviation of normally distributed phenotypes. Polygenic scores are converted using normal distribution theory. Given the AUC/R2 of polygenic scores may be unknown, we also evaluate two methods (AVENGEME, lassosum) for estimating these values from genome-wide association study (GWAS) summary statistics alone. We validate the absolute risk conversion and AUC/R2 estimation using data for eight binary and three continuous phenotypes in the UK Biobank sample.

ResultsWhen the AUC/R2 of the polygenic score is known, the observed and estimated absolute values were highly concordant. Across binary phenotypes, the mean absolute difference between the observed and estimated proportion of cases was 5%. For continuous phenotypes, the mean absolute difference between observed and estimated means was <0.3%. Estimates of AUC/R2 from the lassosum pseudovalidation method were most similar to the observed AUC/R2 values, though estimated values deviated substantially from the observed for autoimmune disorders.

ConclusionThis study enables accurate interpretation of polygenic scores using only summary statistics, providing a useful tool for educational and clinical purposes. Furthermore, we have created interactive webtools implementing the conversion to the absolute scale for binary and normally distributed phenotypes (https://opain.github.io/GenoPred/PRS_to_Abs_tool.html). Several further barriers must be addressed before clinical implementation of polygenic scores, such as ensuring target individuals are well represented by the GWAS sample.


title: Genetic variation in activating clopidogrel: longer-term outcomes in a large community cohort

abstract:
BackgroundThe antiplatelet drug clopidogrel is commonly prescribed for stroke and myocardial infarction (MI) prevention. Clopidogrel prodrug is predominantly activated by liver enzyme CYP2C19. CYP2C19 Loss-of-function (LoF) genetic variants have been linked to excess morbidity mainly in patients hospitalized for acute ischemic events and related interventions. Little is known about the magnitude of impact of LoF variants in family practice, especially over long periods of exposure. We aimed to determine whether CYP2C19 LoF alleles increase risk of ischemic stroke and MI in primary care patients prescribed clopidogrel for up to 18 years.

MethodsRetrospective cohort analysis of 7,483 European-ancestry adults from the UK Biobank study with genetic and linked primary care data, aged 36 to 79 years at first clopidogrel prescription. We examined CYP2C19 LoF variant (*2-*8) associations with incident hospital-diagnosed ischemic stroke and MI in patients prescribed clopidogrel for at least 2 months using time-to-event models, with secondary analysis of the *17 gain of function variant.

Results28.7% (n=2,144/7,483) of included subjects (mean age 63 years at first clopidogrel prescription) carried at least one CYP2C19 intermediate or low metabolizer LoF variant. 1.9% of LoF variant carriers had an incident ischemic stroke whilst prescribed clopidogrel (mean 2.6 years, range 2 months to 18 years), versus 1.3% without the variants (0.6% absolute excess: Hazard Ratio 1.53: 95% CI 1.04 to 2.26, p=0.031). Additionally, 26.4% of CYP2C19 LoF variant carriers had an incident MI versus 24.1% (HR 1.14: 1.04 to 1.26, p=.008). Adjustment for aspirin co-prescription produced similar estimates. In lifetables using observed incidence rates, 22.5% (95% CI 14.4% to 34.0%) of CYP2C19 LoF carriers on clopidogrel were projected to develop an ischemic stroke by age 79 (the oldest age in the study), compared with 15.4% (95% CI 11.4% to 20.5%) in non-carriers: the absolute excess stroke incidence with LoF variants was 7.1% by age 79.

ConclusionIn family practice patients on clopidogrel, CYP2C19 LoF variants are associated with substantially higher incidence of ischemic events. Genotype-guided (or routine) prescription of antiplatelet medications unaffected by CYP2C19 variants may improve outcomes in patients for whom clopidogrel is currently indicated.


title: CovidEnvelope: A Fast Automated Approach to Diagnose COVID-19 from Cough Signals

abstract: The COVID-19 pandemic has a devastating impact on the health and well-being of global population. Cough audio signals classification showed potential as a screening approach for diagnosing people, infected with COVID-19. Recent approaches need costly deep learning algorithms or sophisticated methods to extract informative features from cough audio signals. In this paper, we propose a low-cost envelope approach, called CovidEnvelope, which can classify COVID-19 positive and negative cases from raw data by avoiding above disadvantages. This automated approach can pre-process cough audio signals by filter-out back-ground noises, generate an envelope around the audio signal, and finally provide outcomes by computing area enclosed by the envelope. It has been seen that reliable datasets are also important for achieving high performance. Our approach proves that human verbal confirmation is not a reliable source of information. Finally, the approach reaches highest sensitivity, specificity, accuracy, and AUC of 0.92, 0.87, 0.89, and 0.89 respectively. The automatic approach only takes 1.8 to 3.9 minutes to compute these performances. Overall, this approach is fast and sensitive to diagnose the people living with COVID-19, regardless of having COVID-19 related symptoms or not, and thus have vast applicability in human well-being by designing HCI devices incorporating this approach.


title: A data-driven pipeline to extract potential side effects through co-prescription analysis: application to a cohort study of 2,010 patients taking hydroxychloroquine with an 11-year follow-up

abstract:
ContextReal-life data consist of exhaustive and unbiased data to study drug-safety profiles but are underused because of their complex temporality (i.e., safety depends on the dose, timing, and duration of treatment) and the considerable number of potential side effects to study. We aimed to create a pipeline that manages the complex temporality of real-life data using a data-driven strategy (i.e., without any hypothesis on the potential side effects to search for) to highlight the safety profile of a given drug. We used hydroxychloroquine (HCQ) and its co-prescription in a real-life database to illustrate this pipeline.

MethodsWe incorporated a weighted cumulative exposure statistical model into a data-driven strategy. This pipeline makes it possible to highlight both long-term and short-term side effects, while avoiding false positives due to the natural course of the underlying disease. We applied the proposed pipeline to a cohort of 2,010 patients with a prescription of HCQ and used their drug prescription as the source of data to highlight the HCQ safety profile.

ResultsThe proposed pipeline introduces a bootstrap strategy into weighted cumulative-exposure statistics estimates to highlight significant drug signals. As applied to HCQ, the proposed pipeline showed nine drugs to be significantly associated with HCQ exposure. Of note, one of them has therapeutic indications for known HCQ side effects. Other associations could be explained by therapeutic indications linked to conditions associated with HCQ indications in France.

ConclusionWe propose a data-driven pipeline that makes it possible to provide a broad picture of the side effects of a given drug. It would be informative to pursue the development of this pipeline using other sources of data.


title: Coupling machine learning and high throughput multiplex digital PCR enables accurate detection of carbapenem-resistant genes in clinical isolates

abstract:
Rapid and accurate identification of patients colonised with carbapenemase-producing organisms (CPOs) is essential to adopt prompt prevention measures to reduce the risk of transmission. Recent studies have demonstrated the ability to combine machine learning (ML) algorithms with real-time digital PCR (dPCR) instruments to increase classification accuracy of multiplex PCR assays when using synthetic DNA templates. We sought to determine if this novel methodology could be applied to improve identification of the five major carbapenem-resistant genes in clinical CPO-isolates, which would represent a leap forward in the use of PCR-based data-driven diagnostics for clinical applications.

We collected 253 clinical isolates (including 221 CPO-positive samples) and developed a novel 5-plex PCR assay for detection of blaIMP, blaKPC, blaNDM, blaOXA-48 and blaVIM. Combining the recently reported ML method  Amplification and Melting Curve Analysis (AMCA) with the abovementioned multiplex assay, we assessed the performance of the AMCA methodology in detecting these genes. The improved classification accuracy of AMCA relies on the usage of real-time data from a single-fluorescent channel and benefits from the kinetic/thermodynamic information encoded in the thousands of amplification events produced by high throughput real-time dPCR.

The 5-plex showed a lower limit of detection of 10 DNA copies per reaction for each primer set and no cross-reactivity with other carbapenemase genes. The AMCA classifier demonstrated excellent predictive performance with 99.6% (CI 97.8-99.9%) accuracy (only one misclassified sample out of the 253, with a total of 160,041 positive amplification events), which represents a 7.9% increase (p-value < 0.05) compared to conventional melting curve analysis.

This work demonstrates the use of the AMCA method to increase the throughput and performance of state-of-the-art molecular diagnostic platforms, without hardware modifications and additional costs, thus potentially providing substantial clinical utility on screening patients for CPO carriage.

category: infectious diseases


title: Skin imprints to provide noninvasive metabolic profiling of COVID-19 patients

abstract: As the current COVID-19 pandemic progresses, more symptoms and signals related to how the disease manifests in the human body arise in the literature. Skin lesions and coagulopathies may be confounding factors on routine care and patient management. We analyzed the metabolic and lipidic profile of the skin from COVID-19 patients using imprints in silica plates as a non-invasive alternative, in order to better understand the biochemical disturbances caused by SARS-CoV-2 in the skin. One hundred and one patients (64 COVID-19 positive patients and 37 control patients) were enrolled in this cross-sectional study from April 2020 to June 2020 during the first wave of COVID-19 in Sao Paulo, Brazil. Fourteen biomarkers were identified related to COVID-19 infection (7 increased and 7 decreased in COVID-19 patients). Remarkably, oleamide has shown promising performance, providing 79.0% of sensitivity on a receiver operating characteristic curve model. Species related to coagulation and immune system maintenance such as phosphatidylserines were decreased in COVID-19 patients; on the other hand, cytokine storm and immunomodulation may be affected by molecules increased in the COVID-19 group, particularly primary fatty acid amides and N-acylethanolamines, which are part of the endocannabinoid system. Our results show that skin imprints may be a useful, noninvasive strategy for COVID-19 screening, by electing a pool of biomarkers with diagnostic potential.


title: Association between Influenza-like illness and acute myocardial infarction patients: A case-control study

abstract: Seasonal Influenza can cause cardiovascular complications. Therefore, this study aimed to investigate recent influenza-like illnesses (ILI) in acute myocardial infarction (AMI) patients compared to other hospitalized patients as the control group during the cold season in the north of Iran. This retrospective case-control study included 300 patients (150 AMI patients and 150 controls) aged [≥] 50 years hospitalized for acute myocardial infarction (AMI) or other conditions between September 22, 2019, and March 15, 2020. Patients in each group were frequency-matched for gender and age range. The primary exposure was a recent ILI (fever [≥] 37.8{degrees}C, cough, and sore throat) in the past month. The patients mean age was 64.42 {+/-} 9.47 years, with a range of 50-94 years. Forty-five (15%) patients had diseases that met the ILI criteria. The AMI group patients significantly reported more ILI than controls (adjusted OR: 3.04, 95% CI: 1.02 to 9.09, p < 0.001). On the other hand, patients who received the influenza vaccine were significantly less likely to have an acute myocardial infarction than those who did not receive the vaccine (adjusted OR: 0.02, 95% CI: 0.001 to 0.38, p = 0.006). In conclusion, the present study demonstrates that ILI can significantly increase the risk of AMI. Also, it was confirmed that Influenza vaccination could significantly reduce the risk of AMI.


title: Influenza outbreak, disease transmission rate and mortality risk in the United States (2021 to 2050 Projection)

abstract: Influenza and COVID-19 pandemics are among the deadliest respiratory diseases recorded in the history of humanity. Influenza infections are difficult to diagnose and nearly impossible to predict because the disease symptoms changes as the pathogen(s) evolve. The U.S. was the case study for this research (Latitude: 37.0902{degrees}N and Longitude: 95.7129{degrees}W). The principle employed in the design of the influenza forecast model was "The Integrated Independent System of Disease Prediction (IISDP)", where the functionality of one forecast model depends on the predictive capacity of one or more forecast models. It was predicted that 49,734,427 individuals will be infected in 2021 out of the current estimation of 322,900.000 U.S. citizens (only about 1.5% of the total population). The situation was estimated by Etaware-Pred-2021 to worsen in 2050 (300,803,433 infected individuals out of the estimated 400,000,000 U.S. citizens), with a geometric increase in the ratio of infected individuals from 1.5% (in 2021) to 75.2% (in 2050), if necessary health precautions fail. unless there are potent influenza vaccines in circulation, total compliance to influenza vaccination and a high level of personal hygiene among U.S. citizens, influenza infection will become a global threat to humanity. These situations can be averted if the U.S. citizens act accordingly.


title: Differences in estimates for ten-year risk of cardiovascular disease in Black versus white persons with identical risk factor profiles using pooled cohort equations

abstract:
BackgroundSex- and race-specific pooled cohort equations (PCE) are recommended for estimating the 10-year risk of cardiovascular disease (CVD), with an absolute risk >7.5% indicating a clinical decision threshold.

MethodsWe generated in silico 30,565 risk profiles in men and 29,515 in women by combining numerical (age, total and high-density lipoprotein cholesterol, systolic blood pressure) and binary risk factors (smoking, diabetes, antihypertensive treatment). We compared PCE-estimated 10-year CVD risk in Black versus white individuals with identical risk profiles. We performed similar comparisons in participants in the Framingham Third Generation cohort and the National Health and Nutrition Examination Survey 2017-2018.

ResultsThere were 6357 risk profiles associated with 10-year CVD risk >7.5% for Black but not for white men (median risk difference [RD] 6.25%, range 0.15-22.8%; median relative risk [RR] 2.40, range 1.02-12.6). There were 391 profiles with 10-year CVD risk >7.5% for white but not for Black men (median RD 2.68%, range 0.07-16.9%; median RR 1.42, range 1.01-3.57). There were 6543 risk profiles associated with 10-year estimated CVD risk >7.5% for Black but not for white women (median RD 6.14%, range 0.35-26.8%; median RR 2.29, range 1.05-12.6). There were 318 profiles with 10-year CVD risk >7.5% for white but not for Black women (median RD 3.71%, range 0.22-20.1%; median RR 1.66, range 1.03-5.46). The population-based samples demonstrated similar risk differences.

ConclusionsThe PCE may generate substantially divergent CVD risk estimates for Black versus white individuals with identical risk profiles, which could introduce race-related variations in clinical recommendations for CVD prevention.

category: cardiovascular medicine


title: Exaggerated Right Ventricular Dysfunction in Females with Group 3 Pulmonary Hypertension

abstract: Group 3 pulmonary hypertension (PH) patients have disproportionate right ventricular dysfunction (RVD) as compared to pulmonary arterial hypertension (PAH) patients, but the cause of the divergent RV phenotypes is unknown. One potential mechanism may be biological sex as females have better RV function than males. However, the combined effects of PH type and sex on RV function are unexplored. Therefore, we evaluated how sex and PH etiology modulated RVD in a single-center cohort study. Male sex was not associated with significant differences in RV function when comparing PH etiologies. However, female Group 3 patients had more pronounced RVD than female PAH patients. In particular, Group 3 females had marked reduction in RV function when pulmonary vascular resistance was matched. Group 3 females were older than PAH females, but the exaggerated RVD was still observed in postmenopausal (age[≥]55) Group 3 females. This suggests lung disease exacerbates RVD in Group 3 females.


title: Silver diamine fluoride, atraumatic restorations, and oral health-related quality of life: Results from the CariedAway cluster randomized trial

abstract:
ObjectiveSilver diamine fluoride (SDF) is a non-surgical treatment for the arrest and prevention of dental caries that results in irreversible black staining of dental decay. The objective of this study was to evaluate the impact of SDF treatment on oral health-related quality of life (OHRQoL) relative to a standard package of glass ionomer sealants and atraumatic restorative treatment.

MethodsCariedAway is a pragmatic, longitudinal, cluster-randomized non-inferiority trial of non-surgical interventions for caries. Secondary study outcomes included OHRQoL and academic performance. Oral health-related quality of life was measured at each study visit using the Child Oral Health Impact Profile. Change in OHRQoL was assessed using linear regression and non-inferiority was determined using t-tests.

ResultsUntreated decay at baseline was associated with signifcantly worse ORHQoL and treatment in both groups resulted in incremental improvement. Quality of life in children receiving silver diamine fluoride was non-inferior to those receiving sealants and ART at least six months post-treatment. Additionally, change in OHRQoL did not depend on the severity of baseline decay.

ConclusionsORHQoL is related to untreated dental caries, however no appreciable change was observed following SDF treatment relative to standard preventive therapies.

category: dentistry and oral medicine


title: Health effects of European colonization: An investigation of skeletal remains from 19th to early 20th-century migrant settlers in South Australia

abstract: Nineteenth century medical understanding of human metabolism was limited, therefore, the incidence of metabolic deficiencies was not fully recorded. In addition, the transition from agricultural based mode of life to the industrial one significantly changed the pattern of these metabolic deficiencies. They were further altered by colonisation of distant continents. Palaeopathological study of skeletal remains from the early industrialised colonial era allowed light to be shed on the metabolic stresses produced by this new mode of life. Aims of this study were to investigate manifestations of disease in skeletal remains from 65 (20 adults, 45 sub-adults) migrant settlers buried in the "free ground" of St Marys Anglican Church Cemetery (1847 to 1927). An area allocated for burials paid for by the South Australian Government. Skeletal manifestations were determined and interpreted in terms of their multiple aetiologies. Findings were compared with those published for two 19th century British samples. Skeletal manifestations, commonly related to metabolic deficiencies, were observed. Areas of abnormal porosity of bone cortices were seen in 9 adults and 12 sub-adults, flaring of metaphyses was seen in one sub-adult, flaring of costochondral junctions of the ribs was seen in one sub-adult. Porous lesions of orbital roof bones (Types 3 to 5) were seen on three sub-adults. Micro-CT scans of tooth samples located interglobular dentine in three individuals. Comparison of St Marys findings with St Martins, Birmingham, and St Peters, Wolverhampton, UK, showed more individuals from St Marys had areas of abnormal porosity of bone cortices possibly related to vitamin C deficiency. However, St Marys sample displayed fewer changes attributable to vitamin D deficiency as expected in a country with greater UV irradiation. This indicates that, although the early industrialisation produced metabolic stresses, change of the environment through colonisation of new continents altered the distribution of metabolic deficiencies.

category: pathology


title: Aberrant Activation of the Mentalizing Brain System During Eye Gaze Discrimination in Bipolar Disorder

abstract:
Bipolar disorder (BD) is associated with a range of social cognitive deficits. This study investigated the functioning of the mentalizing brain system in BD probed by an eye gaze perception task during fMRI. Compared with healthy controls (n = 21), BD participants (n = 14) showed reduced preferential activation for self-directed gaze discrimination in the medial prefrontal cortex (mPFC) and temporo-parietal junction (TPJ), which was associated with poorer cognitive and social functioning. Aberrant functions of the mentalizing system should be further investigated as marker of social dysfunction and treatment targets.

HighlightsO_LISocial dysfunction in bipolar disorder (BD) may be due to altered mentalizing.
C_LIO_LIIndividuals with BD showed reduced activation in the mentalizing brain system.
C_LIO_LIAberrant activity of the mentalizing system was associated with poorer functioning.
C_LI


title: Assessing the Mortality Impact of the COVID-19 Pandemic in Florida State Prisons

abstract:
BackgroundThe increased risk of COVID-19 infection among incarcerated individuals due to environmental hazards is well known and recent studies have highlighted the higher rates of infection and mortality prisoners in the United States face due to COVID-19. However, the impact of COVID-19 on all-cause mortality rates in incarcerated populations has not been studied.

MethodsUsing data reported by the Florida Department of Corrections on prison populations and mortality events we conducted a retrospective cohort study of all individuals incarcerated in Florida state prisons between 2015 and 2020. We calculated excess deaths by estimating age-specific expected deaths from mortality trends in 2015 through 2019 and taking the difference between observed and expected deaths during the pandemic period. We calculated life table measures using standard demographic techniques and assessed significant yearly changes using bootstrapping.

FindingsThe Florida Department of Corrections reported 510 total deaths from March 1, 2020 to December 31, 2020 among the state prison population. This was 42% higher (rate ratio 1.42, 95% CI 1.15 to 1.89) than the expected number of deaths in light of mortality rates for previous years. Reported COVID-19 deaths in a month were positively correlated with estimated excess deaths (80.4%, p <.01). Using age-specific mortality estimates, we found that life expectancy at age 20 declined by 4 years (95% CI 2.06-6.57) between 2019 and 2020 for the Florida prison population.

InterpretationThe Florida prison population saw a significant increase in all-cause mortality during the COVID-19 pandemic period, leading to a decrease in life expectancy of more than four years. Life years lost by the Florida prison population were likely far greater than those lost by the general United States population, as reported by other studies. This difference in years lost highlights the need for increased interventions to protect vulnerable incarcerated populations during pandemics.

FundingVital Projects Fund, Arnold Ventures, US Centers for Disease Control, Eunice Kennedy Shriver National Institute of Child Health and Human Development

category: public and global health