title: Bladder Cancer Immunotherapy by BCG is associated with a significantly reduced risk of Alzheimer disease

abstract:
IMPORTANCEDespite years of investigation and billions of dollars, there is no cure or even a disease-slowing remedy for Alzheimers disease (AD). Most studies thus far have focused on amyloid beta plaques (A{beta}) and neurofibrillary tangles as therapeutic targets, and only a few on modulating the associated inflammatory process.

OBJECTIVETo determine if exposure to Bacillus Calmette-Guerin (BCG) during treatment of non-muscle-invasive bladder cancer (NMIBC) is associated with a lower risk of developing AD.

DESIGN, SETTING AND PARTICIPANTSMulticenter retrospective study of 12,185 bladder cancer patients including 2301 BCG-treated patients between 2000 and 2019 meeting all inclusion criteria. Data was retrieved from two tertiary hospital systems in Israel and the United States, and the largest Israeli health provider database, with a median follow up of 3.5 to 7 years.

MAIN OUTCOMES AND MEASURESThe primary outcome was time to the first occurrence of AD/Dementia events following a diagnosis of bladder cancer by trans-urethral resection (TURBT) in BCG treated patients, and in bladder cancer patients not receiving BCG (control group).

RESULTSBCG treatment was associated with a significantly reduced risk of developing AD in bladder cancer patients of [≥]75 years following BCG treatment. A competing risk model using Cox Proportional-Hazard (PH) analysis applied to the largest medical records data showed a Hazard Ratio (HR) of 0.726 (95% CI: 0.529 - 0.996, P = 0.0473). The results were duplicated in analyzing NMIBC patients from a tertiary hospital with a HR of 0.416 (95% CI: 0.203 - 0.853, P = 0.017). A reduction in the risk (by 28%) for developing Parkinsons disease (PD) was also shown in bladder cancer patients subjected to BCG immunotherapy.

CONCLUSIONS AND RELEVANCEBCG treatment for bladder cancer patients was associated with a significantly reduced risk for developing AD and PD in the elderly population (>75 years), and in NMIBC patients from a tertiary hospital. Prospective studies in elderly inoculated with intradermic BCG should be initiated to evaluate the potential protective effect of BCG against AD and PD.

KEY POINTSO_ST_ABSQuestionC_ST_ABSWhether bladder cancer patients treated with BCG immunotherapy have a lower risk to develop AD than bladder cancer patients that do not receive such treatment.

FindingsIn a multicenter retrospective study composed of three cohorts covering >12,000 bladder cancer patients, those receiving intravesical BCG immunotherapy had a significantly lower risk of developing AD.

MeaningIntradermal inoculation of BCG to elderly people should be tested as a potential preventive approach against AD.


title: Glutamate levels across deep brain structures in patients with a psychotic disorder and its relation with cognitive functioning

abstract: Patients with psychotic disorders often show prominent cognitive impairment. Glutamate seems to play a prominent role, but knowledge on its role in deep gray matter regions is limited and previous studies have yielded heterogeneous results. The aim was to evaluate glutamate levels within deep gray matter structures in patients with a psychotic disorder in relation to cognitive functioning, using advanced spectroscopic acquisition, reconstruction and post-processing techniques. A 7 tesla MRI scanner combined with a unique lipid suppression coil and subject specific water signal suppression pulses were used to acquire high-resolution magnetic resonance spectroscopic imaging data. Anatomical scans were used to perform tissue fraction correction and registration to a standard brain for group comparison in specifically delineated brain regions. The brief assessment of cognition in schizophrenia was used to evaluate cognitive status. Average glutamate levels across deep gray matter structures (i.e. caudate, pallidum, putamen, and thalamus) in patients with a psychotic disorder (n=16, 4 females) were lower compared to healthy controls (n=23, 7 females). Stratified analyses showed lower glutamate levels in the caudate and putamen but not in the pallidum or thalamus. Average glutamate levels across deep gray matter structures were positively correlated with cognition, particularly to psychomotor speed. We find reduced glutamate levels across deep brain structures such as the caudate and putamen in patients with a psychotic disorder that are linked to psychomotor speed. Our results underscore the potential role of detailed in vivo glutamate assessments to understand cognitive deficits in patients with psychotic disorders.

category: radiology and imaging


title: Neurofilament light protein as a blood biomarker for Huntington's disease in children

abstract: Juvenile-onset Huntingtons disease (JoHD) is a rare, particularly devastating form of Huntingtons Disease (HD) for which clinical diagnosis is challenging and robust outcome measures are lacking. Neurofilament light protein (NfL) in plasma has emerged as a prognostic biomarker for adult-onset HD. We report that plasma NfL is elevated in JoHD and premanifest HD mutation-carrying children. Quantifying plasma NfL may improve clinical diagnosis and therapeutic trial design in the pediatric population.

category: neurology


title: The effect of Alzheimer's disease-associated genetic variants on longevity

abstract:
The genetics underlying human longevity is influenced by the genetic risk to develop -or escape- age-related diseases. As Alzheimers disease (AD) represents one of the most common conditions at old age, an interplay between genetic factors for AD and longevity is expected.

We explored this interplay by studying the prevalence of 38 AD-associated single-nucleotide-polymorphisms (SNPs) identified in AD-GWAS, in self-reported cognitively healthy centenarians, and we replicated findings in the largest GWAS on parental-longevity.

We found that 28/38 SNPs identified to associate with increased AD-risk also associated with decreased odds of longevity. For each SNP, we express the imbalance between AD- and longevity-risk as an effect-size distribution. When grouping the SNPs based on these distributions, we found three groups: 17 variants increased AD-risk more than they decreased the risk of longevity (AD-group): these variants were functionally enriched for {beta}-amyloid metabolism and immune signaling, and they were enriched in microglia. 11 variants reported a larger effect on longevity as compared to their AD-effect (Longevity-group): these variants were enriched for endocytosis/immune signaling, and at the cell-type level were enriched in microglia and endothelial cells. Next to AD, these variants were previously associated with other aging-related diseases, including cardiovascular and autoimmune diseases, and cancer. Unexpectedly, 10 variants associated with an increased risk of both AD and longevity (Unexpected-group). The effect of the SNPs in AD- and Longevity-groups replicated in the largest GWAS on parental-longevity, while the effects on longevity of the SNPs in the Unexpected-group could not be replicated, suggesting that these effects may not be robust across different studies.

Our study shows that some AD-associated variants negatively affect longevity primarily by their increased risk of AD, while other variants negatively affect longevity through an increased risk of multiple age-related diseases, including AD.

category: genetic and genomic medicine


title: BurnNet: An Efficient Deep Learning Framework for Accurate Dermal Burn Classification

abstract: AO_SCPLOWBSTRACTC_SCPLOWBurns are the fourth most prevalent unintentional injury around the world, and when left untreated can become permanent and sometimes fatal. An important aspect of treating burn injuries is accurate and efficient diagnosis. Classifying the three primary types of burns - superficial dermal, deep dermal, and full thickness - is essential in determining the necessity of surgery, which is often critical to the afflicted patients survival. Unfortunately, reconstructive burn surgeons and dermatologists are merely able to diagnose these types of burns with approximately 50-75% accuracy. As a result, we propose the use of an eight-layer convolutional neural network, BurnNet, for rapid and precise burn classification with 99.87% accuracy. We applied affine transformations to artificially augment our dataset and found that our model attained near perfect metrics across the board, demonstrating the high propensity of deep learning architectures in burn classification.

category: health informatics


title: Point-of-care evaluation of a rapid antigen test (CLINITEST Rapid COVID-19 Antigen Test) for diagnosis of SARS-CoV-2 infection in symptomatic and asymptomatic individuals

abstract: Rapid antigen assays (RAD) based on lateral flow immunochromatography (LFIC) technology have emerged as a valuable tool for the control of COVID-19 pandemic. Manufacturer{square}independent, real{square}world evaluation of these assays is crucial given the considerable heterogeneity reported in their clinical and analytical performances. Here, we report for the first time on the point-of-care performance of the CLINITEST(R) Rapid COVID-19 Antigen Test (Siemens, Healthineers, Erlangen, Germany) to detect SARS-CoV-2 infection in presumptive COVID-19 cases or asymptomatic close contacts of COVID-19 patients. When compared to RT-PCR, the overall sensitivity of the assay was 80.2 (95% CI, 70.9-87.1) for symptomatic patients sampled (nasopharyngeal specimens) within five days after the onset of symptoms and 60% (95% CI, 40.7-76.6%) for asymptomatic participants. The overall specificity was 100% in both population groups.

category: infectious diseases


title: The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS):Rationale, Objectives, and Design

abstract:
BackgroundInfluenza viruses pose significant disease burdens through annual seasonal outbreaks and unpredictable pandemics. Existing influenza surveillance programs have relied heavily on reporting of medically attended influenza (MAI). Continuously monitoring cause-specific school absenteeism may identify local acceleration of seasonal influenza activity. The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS; Oregon, WI) implements daily school-based monitoring of influenza-like illness-specific student absenteeism (a-ILI) in pre-kindergarten through grade 12 schools and assesses this approach for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities.

MethodsStarting in September 2014, ORCHARDS combined automated reporting of daily absenteeism within 6 schools and home visits to school children with acute respiratory infections (ARI). Demographic, epidemiological, and symptom data are collected along with respiratory specimens. Specimens are tested for influenza and other respiratory viruses. Household members can opt into a supplementary household transmission study. Community comparisons are possible using a pre-existing, long-standing, and highly effective influenza surveillance program, based on MAI at 5 primary care clinics in the same geographical area.

ResultsOver the first 5 years, a-ILI occurred on 6,634 (0.20%) of 3,260,461 student school days. Viral pathogens were detected in 64.5% of the 1,728 children with ARI who received a home visit. Influenza was the most commonly detected virus, noted in 23.3% of ill students. Influenza (p<0.001) and adenovirus (P=0.004) were significantly associated with a-ILI.

ConclusionORCHARDS uses a community-based design to detect influenza trends over multiple seasons and to evaluate the utility of absenteeism for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. Initial findings suggest the study design is succeeding in collecting appropriate data to achieve study objectives.


title: PRINCIPLE trial demonstrates scope for in-pandemic improvement in primary care antibiotic stewardship

abstract:
BackgroundThe Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE) trial has provided in-pandemic evidence of what does not work in the early primary care management of coronavirus-2019 disease (COVID-19). PRINCIPLEs first finding was that azithromycin and doxycycline were not effective.

AimTo explore the extent to which azithromycin and doxycycline were being used in-pandemic, and the scope for trial findings impacting on practice.

Design and SettingWe compared crude rates of prescribing and respiratory tract infections (RTI) in 2020, the pandemic year, with 2019, using the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC).

MethodsWe used a negative binomial model including age-band, gender, socioeconomic status, and NHS region to compare azithromycin and doxycycline lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), and influenza-like-illness (ILI) in 2020 with 2019; reporting incident rate ratios (IRR) between years and 95% confidence intervals (95%CI).

ResultsAzithromycin prescriptions increased 7% in 2020 compared to 2019, whereas doxycycline decreased by 7%. Concurrently, LRTI and URTI incidence fell by over half (58.3% and 54.4% respectively) while ILI rose slightly (6.4%). The overall percentage of RTI prescribed azithromycin rose by 42.1% between 2019 and 2020, doxycycline increased by 33%.

Our adjusted IRR showed azithromycin prescribing was 22% higher in 2020 (IRR=1.22, 95%CI:1.19-1.26, p<0.0001), for every unit rise in confirmed COVID there was an associated 3% rise in prescription (IRR=1.026, 95%CI 1.024-1.0285, p<0.0001); whereas these measures were static for doxycycline.

ConclusionPRINCIPLE trial flags scope for improvement in antimicrobial stewardship.

category: primary care research


title: Role of Inflammation in Depression and Anxiety: Tests for Disorder Specificity, Linearity and Potential Causality of Association in the UK Biobank

abstract:
BackgroundConcentrations of C-reactive protein (CRP), interleukin 6 (IL-6) and other inflammatory markers are elevated in people with depression and anxiety compared to controls, but evidence for disorder-specificity, linearity and potential causality is sparse.

MethodsUsing data from up to 144,890 UK Biobank cohort participants, we tested associations of circulating CRP concentrations with depression and anxiety symptom scores and probable diagnosis, including tests for linearity, disorder-specificity and sex difference. We examined potential causality using 1-sample and 2-sample Mendelian randomisation (MR) analyses testing associations of genetically-predicted CRP concentration and IL-6 activity with depression and anxiety.

FindingsCRP concentration was associated with depressive and anxiety symptom scores and with probable diagnoses of depression and generalised anxiety disorder (GAD) in a dose-response fashion. These associations were stronger for depression than for anxiety, and for women than for men although less consistently. MR analyses provided consistent results suggesting that genetically predicted higher IL-6 activity was associated with increased risk for depressive symptoms, while genetically-predicted higher CRP concentration was associated with decreased risks of depressive and anxiety symptoms.

InterpretationAltered activity of the IL-6/IL-6R pathway could be causally linked to depression. The field now requires experimental studies of IL-6 modulation in humans and animal models to further examine causality, mechanisms and treatment potential. Such studies are also needed to elucidate mechanisms for divergent associations of genetically-predicted higher IL-6 activity (risk increasing) and higher CRP concentrations (protective) with depression/anxiety.

FundingMQ (MQDS17/40); Wellcome Trust (201486/Z/16/Z).

category: psychiatry and clinical psychology


title: Usability of saliva collection devices for SARS-CoV-2 diagnostics

abstract: There is an urgent need to expand testing for SARS-CoV-2 and other respiratory pathogens as the global community struggles to control the COVID-19 pandemic. Current diagnostic methods can be affected by supply chain bottlenecks and require the assistance of medical professionals, impeding the implementation of large-scale testing. Self-collection of saliva may solve these problems, as it can be completed without specialized training and uses generic materials. In this study, we observed thirty individuals who self-collected saliva using four different collection devices and analyzed their feedback. Two of these devices, a funnel and bulb pipette, were used to evaluate at-home saliva collection by 60 individuals. All devices enabled the safe, unsupervised self-collection of saliva. The quantity and quality of the samples received were acceptable for SARS-CoV-2 diagnostic testing, as determined by RNase P detection. Here, we demonstrate inexpensive, generic, buffer free collection devices suitable for unsupervised and home saliva self-collection.

category: public and global health


title: Evaluation of saliva self-collection devices for SARS-CoV-2 diagnostics


title: Estimation of infection rate and the population size potentially exposed to SARS-CoV-2 in Japan during 2020

abstract:
BackgroundThe infectious respiratory disease COVID-19, caused novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reached pandemic status during 2020. The primary statistic data are important to survey the actual circumstances of COVID-19. Here, we report the analysis of the primary data of COVID-19 in Japan during 2020.

MethodsData were collected and released systematically under Japan domestic law. Machine learning was conducted to estimate the positive rate in Japan and four prefectures (Tokyo, Osaka, Chiba, and Fukuoka).

ResultsPrimary data analysis revealed there were at least two peaks of infection in Japan; the first one was during April 2020 and the second one started from November 1, 2020. Estimating the positive rate in Japan as well as in the four prefectures reinforced the above observations. The positive rate in Japan during 2020 was estimated to be around 6% to 8%. We also estimated that 1.95 million people were possibly exposed to the novel virus on October 31, 2020. The numbers of related deaths were over 3,000 people at the end of 2020.

ConclusionWe estimated the infection rate of SARS-CoV-2 in Japan to be 6-8% in 2020. We also concluded that Japan had at least two infection-spreading periods, the first one being from Jan 19, 2020 until May 2020, and the second one beginning from November 1, 2020. Importantly, our analysis supports the need for clear definition of the criteria for conducting confirmation tests before embarking on data analysis.


title: Performance of a Computational Phenotyping Algorithm for Sarcoidosis Using Diagnostic Codes in Electronic Medical Records: A Pilot Study from Two Veterans Affairs Medical Centers

abstract:
BackgroundThe accuracy of identifying sarcoidosis cases in electronic medical records (EMR) using diagnostic codes is unknown.

MethodsTo estimate the statistical performance of using diagnostic codes, ICD-9 and ICD-10 diagnostic codes in identifying sarcoidosis cases in EMR, we searched the San Francisco and Palo Alto Veterans Affairs (VA) medical centers EMR and randomly selected 200 patients coded as sarcoidosis. To further improve diagnostic accuracy, we developed an "index of suspicion" algorithm to identify probable sarcoidosis cases based on clinical and radiographic features. We then determined the positive predictive value (PPV) of diagnosing sarcoidosis by two computational methods using ICD only and ICD plus the "index of suspicion" against the gold standard developed through manual chart review based on the American Thoracic Society (ATS) practice guideline. Finally, we determined healthcare providers adherence to the guidelines using a new scoring system.

ResultsThe PPV of identifying sarcoidosis cases in VA EMR using ICD codes only was 71% (95%CI=64.7%-77.3%). The inclusion of our construct of "index of suspicion" along with the ICD codes significantly increased the PPV to 90% (95%CI=85.2%-94.6%). The care of sarcoidosis patients was more likely to be classified as "Fully" or "Substantially" adherent with the ATS practice guideline if their managing provider was a specialist (45% of primary care providers vs. 74% of specialists; P=0.008).

ConclusionsAlthough ICD codes can be used as reasonable classifiers to identify sarcoidosis cases within EMR, using computational algorithms to extract clinical and radiographic information ("index of suspicion") from unstructured data could significantly improve case identification accuracy.

HighlightsO_LIIdentifying sarcoidosis cases using diagnostic codes in EMR has low accuracy.
C_LIO_LI"Unstructured data" contain information useful in identifying cases of sarcoidosis.
C_LIO_LIComputational algorithms could improve the accuracy and efficiency of case identification in EMR.
C_LIO_LIWe introduce a new scoring system for assessing healthcare providers compliance with the American Thoracic Society (ATS) practice guideline.
C_LIO_LICompliance scoring could help automatically assess sarcoidosis patients care delivery.
C_LI

category: respiratory medicine


title: Trends in Technology Usage for Parkinson's Disease Assessment: A Systematic Review

abstract:
Parkinsons disease (PD) is a neurological disorder with complicated and disabling motor and non-motor symptoms. The complexity of PD pathology is amplified further due to its dependency on patient diaries and the neurologists subjective assessment of clinical scales. This challenge can be addressed by the advances in mobile technology, which can enable objective, accurate, and continuous patient monitoring. Indeed, a significant amount of recent work explores new cost-effective and subjective assessment methods of PD symptoms. For example, smart technologies, such as wearable sensors, have been used to analyze a PD patients symptoms to assess their disease progression and even to detect signs in their nascent stage for early diagnosis of PD.

This review focuses on the use of modern wearable and mobile equipment for PD applications in the last decade. Four significant fields of research were identified: Assistance to Diagnosis, Prognosis or Monitoring of Symptoms and their Severity, Predicting Response to Treatment, and Assistance to Therapy or Rehabilitation. This study starts with 31,940 articles published between January 2008 and December 2019 in the following four databases: Pubmed Central, Science Direct, IEEE Xplore and MDPI. A total of 976 papers are manually investigated and included in this review after removing unrelated articles, duplicate entries, publications in languages other than English, and other articles that did not fulfill the selection criteria. Our analysis shows that the numbers of published papers every year has increased at a constant rate from 2008 to 2015, while the rate of increase has significantly grown from 2016 to 2019. Majority of the papers (62%) were published in the last four years, and 21% papers in just 2019. In terms of the symptoms, gait and tremor are two major ones that researchers have focused on. The trend shows the growing interest in assessing Parkinsons Disease with wearable devices in the last decade, particularly in the last 4 years. Our automated script makes the review easily reproducible for publications published in the future.


title: Salivary profiles of 11 oxygenated androgens follow a diurnal rhythm in patients with congenital adrenal hyperplasia

abstract:
ContextSeveral studies have highlighted the importance of the 11-oxygenated 19-carbon (11oxC19) adrenal-derived steroids as potential biomarkers for monitoring patients with 21-hydroxylase deficiency (21OHD).

ObjectiveTo analyze circadian rhythmicity of 11oxC19 steroids in saliva profiles and evaluate their relevance as potential monitoring parameters in 21OHD.

Design, Setting, and ParticipantsCross-sectional single center study including 34 patients with classic 21OHD (men=14; women=20) and 32 BMI- and age-matched controls (men=15; women=17).

Outcome MeasuresSalivary concentrations of the following steroids were analyzed by LC-MS/MS: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11{beta}-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT).

ResultsSimilar to the previously described rhythmicity of 17OHP, 11OHA4 and 11KT concentrations followed a distinct diurnal rhythm in both patients and controls with highest concentrations in the early morning and declining throughout the day (11-OHA4: male patients {Delta}mean = 79 %; male controls {Delta}mean = 81%; female patients {Delta}mean = 33 %; female controls {Delta}mean = 91 %; 11KT: male patients {Delta}mean = 64 %; male controls {Delta}mean = 60 %; female patients {Delta}mean = 49 %; female controls {Delta}mean = 81 %). Significant correlations between the area under the curve (AUC) for 17OHP and 11KT (r(p)male = 0.741**; r(p)female = 0.842****), and 11OHA4 (r(p)male = 0.385n.s.; r(p)female = 0.527*) were observed in patients but not in controls.

ConclusionsAdrenal 11oxC19 androgens are secreted following a diurnal pattern. This should be considered when evaluating their utility for monitoring treatment control.

category: endocrinology


title: Using a household structured branching process to analyse contact tracing in the SARS-CoV-2 pandemic

abstract: We explore strategies of contact tracing, case isolation and quarantine of exposed contacts to control the SARS-CoV-2 epidemic using a branching process model with household structure. This structure reflects higher transmission risks among household members than among non-household members, and is also the level at which physical distancing policies have been applied. We explore implementation choices that make use of household structure, and investigate strategies including two-step tracing, backwards tracing, smartphone tracing and tracing upon symptom report rather than test results. The primary model outcome is the effect on the growth rate of the epidemic under contact tracing in combination with different levels of physical distancing, and we investigate epidemic extinction times to indicate the time period over which interventions must be sustained. We consider effects of non-uptake of isolation/quarantine, non-adherence, and declining recall of contacts over time. We find that compared to self-isolation of cases but no contact tracing, a household-based contact tracing strategy allows for some relaxation of physical distancing measures; however, it is unable to completely control the epidemic in the absence of other measures. Even assuming no imported cases and sustainment of moderate distancing, testing and tracing efforts, the time to bring the epidemic to extinction could be in the order of months to years.

category: epidemiology


title: Could the new COVID-19 mutant strain undermine vaccination efforts? A mathematical modelling approach for estimating the spread of the UK mutant strain using Ontario, Canada, as a case study

abstract:
BackgroundInfections represent highly dynamic processes, characterized by evolutionary changes and events that involve both the pathogen and the host. Among infectious agents, viruses, such as the "Severe Acute Respiratory Syndrome-related Coronavirus type 2" (SARS-CoV-2), the infectious agent responsible for the currently ongoing "Coronavirus disease 2019" (COVID-2019) pandemic, have a particularly high mutation rate. Taking into account the mutational landscape of an infectious agent, it is important to shed light on its evolution capability over time. As new, more infectious strains of COVID-19 emerge around the world, it is imperative to estimate when these new strains may overtake the wild-type strain in different populations. Therefore, we developed a general-purpose framework to estimate the time at which a mutant variant is able to takeover a wild-type strain during an emerging infectious diseases outbreak. In this study, we used COVID-19 as a case-study, but the model is adaptable to any emerging pathogens.

Methods and findingsWe devise a two-strain mathematical framework, to model a wild- and a mutant-type viral population and fit cumulative case data to parameterize the model, using Ontario as a case study. We found that, in the context of under-reporting and the current case levels, a variant strain is unlikely to dominate until March/April 2021. Current non-pharmaceutical interventions in Ontario need to be kept in place longer even with vaccination in order to prevent another outbreak. The spread of a variant strain in Ontario will mostly likely be observed by a widened peak of the daily reported cases. If vaccine efficacy is maintained across strains, then it is still possible to have an immune population by end of 2021.

ConclusionsOur findings have important practical implications in terms of public health as policy-and decision-makers are equipped with a mathematical tool that can enable the estimation of the take-over of a mutant strain of an emerging infectious disease.


title: Estimating the Population Benefits of Blood Pressure Lowering: A Wide-Angled Mendelian Randomization Study in UK Biobank

abstract:
BackgroundThe causal relevance of elevated blood pressure for several cardiovascular diseases is uncertain, as is the population impact of blood pressure lowering on risk of cardiovascular diseases more broadly. This study systematically assesses evidence of causality for various cardiovascular diseases in a two-sample Mendelian randomization framework, and estimates the potential reduction in the prevalence of these diseases attributable to long-term population shifts in the distribution of systolic blood pressure (SBP).

Methods and ResultsWe investigated associations of genetically-predicted SBP as predicted by 256 genetic variants with 21 cardiovascular diseases in UK Biobank, a population-based cohort of UK residents. The sample consisted of 376,703 participants of European ancestry aged 40-69 years at baseline. Genetically-predicted SBP was positively associated with 14 of the outcomes (p<0.002), including dilated cardiomyopathy, endocarditis, peripheral vascular disease, and rheumatic heart disease. Using genetic variation to estimate the long-term impact of blood pressure lowering on disease, population reductions in SBP were predicted to result in an overall 16.9% (95% confidence interval (CI): 12.2-21.3%) decrease in morbidity for a 5 mmHg decrease from a population mean of 137.7 mmHg, 30.8% (95% CI: 22.8-38.0%) for a 10 mmHg decrease, and 56.2% (95% CI: 43.7-65.9%) decrease for a 22.7 mmHg decrease in SBP (22.7 mmHg represents a shift from the current mean SBP to 115 mmHg).

ConclusionsRisk of many cardiovascular diseases is influenced by long-term differences in SBP. The burden of a broad range of CVDs could be substantially reduced by long-term population-wide reductions in the distribution of blood pressure.


title: Quantifying transmissibility of COVID-19 and impact of intervention within long-term health care facilities

abstract: Estimates of the basic reproduction number (R0) for Coronavirus disease 2019 (COVID-19) are particularly variable in the context of transmission within locations such as long-term health care (LTHC) facilities. We sought to characterise the heterogeneity of R0 across known outbreaks within these facilities. We used a unique comprehensive dataset of all outbreaks that have occurred within LTHC facilities in British Columbia, Canada. We estimated R0 with a Bayesian hierarchical dynamic model of susceptible, exposed, infected, and recovered individuals, that incorporates heterogeneity of R0 between facilities. We further compared these estimates to those obtained with standard methods that utilize the exponential growth rate and maximum likelihood. The total size of an outbreak varied dramatically, with a range of attack rates of 2%-86%. The Bayesian analysis provides more constrained overall estimates of R0 = 2.19 (90% CrI [credible interval] 0.19-6.69) than standard methods, with a range within facilities of 0.48-10.08. We further estimated that intervention led to 57% (47%-66%) of all cases being averted within the LTHC facilities, or 73% (63%-78%) when using a model with multi-level intervention effect. Understanding the risks and impact of intervention are essential in planning during the ongoing global pandemic, particularly in high-risk environments such as LTHC facilities.


title: Mental Health, Substance Use, and Suicidal Ideation Among Unpaid Caregivers in the United States During the COVID-19 Pandemic: Relationships to Age, Race/Ethnicity, Employment, and Caregiver Intensity

abstract:
ObjectivesTo estimate the prevalence of unpaid caregiving during the coronavirus disease 2019 (COVID-19) pandemic, and to identify factors associated with adverse mental health symptoms, substance use, and suicidal ideation in this population, which provides critical support in health care systems by providing care to older adults and those with chronic conditions.

MethodsIn June 2020, Internet-based surveys with questions about demographics, caregiving responsibilities, and mental health were administered to US adults aged [≥]18 years. Demographic quota sampling and survey weighting to improve cross-sectional sample representativeness of age, gender, and race/ethnicity. Prevalence ratios for adverse mental health symptoms were estimated using multivariable Poisson regressions.

ResultsOf 9,896 eligible invited adults, 5,412 (54.7%) completed surveys; 5,011 (92.6%) respondents met screening criteria and were analysed, including 1,362 (27.2%) caregivers. Caregivers had higher prevalences of adverse mental health symptoms than non-caregivers, including anxiety or depressive disorder symptoms (57.6% vs 21.5%, respectively, p<0.0001) having recently seriously considered suicide (33.4% vs 3.7%, p<0.0001). Symptoms were more common among caregivers who were young vs older adults (e.g., aged 18-24 vs [≥]65 years, aPR 2.75, 95% CI 1.95-3.88, p<0.0001), Hispanic or Latino vs non-Hispanic White (1.14, 1.04-1.25, p=0.0044), living with vs without disabilities (1.18, 1.10-1.26, p<0.0001), and with moderate and high vs low Caregiver Intensity Index scores (2.31, 1.65-3.23; 2.81, 2.00-3.94; both p<0.0001). Suicidal ideation was more prevalent among non-Hispanic Black vs non-Hispanic White caregivers (1.48, 1.15-1.90, p=0.0022).

ConclusionsCaregivers, who accounted for one in four US adult respondents in this nationally representative sample, more commonly reported adverse mental health symptoms than non-caregivers. Increased visibility of and access to mental health care resources are urgently needed to address mental health challenges of caregiving.


title: Estimating vaccine confidence levels among future healthcare workers and their trainers: A quantitative study protocol

abstract:
IntroductionThe outbreak of novel coronavirus disease 2019 (COVID-19) caught the world off guard in the first quarter of the year 2020. To stem the tide of this pandemic, the development, testing, and pre-licensure approval for emergency use of some COVID 19 vaccine candidates were accelerated. This led to raised public concern about their safety and efficacy, compounding the challenges of vaccine hesitancy which was already declared one of the top ten threats to global health in the year 2019. The onus of managing and administering these vaccines to a skeptical populace when they do become available rests mostly on the shoulders of healthcare workers (HCWs). Therefore, the vaccine confidence levels of HCWs becomes critical to the success of vaccination endeavors, especially COVID 19 vaccination. This proposed study aims to estimate the level of vaccine confidence and the intention to receive a COVID 19 vaccine among future HCWs and their trainers at a specific university in Cape Town, South Africa, and to identify any vaccination concerns early for targeted intervention.

Methods and analysisAn online survey will be distributed to current staff and students of an academic institution for HCWs. The survey questionnaire will consist of a demographic questions section consisting of six items and a vaccine confidence section comprising six items in Likert scale format.

A multinomial logistic regression model will be employed to identify factors associated with vaccine confidence and intention. The strength of association will be assessed using odds ratio and its 95% confidence interval. Statistical significance will be defined at a p-value <0.05.

Ethics and disseminationEthics approval has been obtained for the study from Stellenbosch University (HREC Reference # S19/01/014 (PhD)). The results will be shared with relevant health authorities, presented at conferences, and published in a peer-reviewed journal.

ARTICLE SUMMARYO_ST_ABSStrengths and limitations of this studyC_ST_ABS{blacktriangleright} The proposed study will generate baseline knowledge of the vaccine confidence among future healthcare workers and their trainers in its specific context.
{blacktriangleright}It will contribute to addressing the knowledge gap about the intention to receive a COVID 19 vaccine among health care workers in Africa.
{blacktriangleright}It will enable the early identification of vaccine concerns of healthcare workers while they are still in training and assist in informing tailored measures to address them.
{blacktriangleright}A limitation of the study is the possibility of a low response rate which is an inherent challenge of online surveys.


title: HYDROXYCHLOROQUINE FOR THE TREATMENT OF SEVERE RESPIRATORY INFECTION BY COVID-19: A RANDOMIZED CONTROLLED TRIAL

abstract:
The novel coronavirus pandemic (COVID-19) represents a major public health problem due to its rapid spread and its ability to generate severe pneumonia. Thus, it is essential to find a treatment that reduces mortality. Our objective was to estimate whether treatment with 400 mg/day of Hydroxychloroquine for 10 days reduces in-hospital mortality in subjects with severe respiratory disease due to COVID-19 compared with placebo.

Material and methodsA double-blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of Hydroxychloroquine for the treatment of severe disease by COVID-19 through an intention-to-treat analysis. Eligible for the study were adults aged more than 18 years with COVID-19 confirmed by RT-PCR and lung injury requiring hospitalization with or without mechanical ventilation. Primary outcome was 30-day mortality. Secondary outcomes: days of mechanical ventilation, days of hospitalization and cumulative incidence of serious adverse events.

ResultsA total of 214 patients with COVID-19 were recruited, randomized and analyzed. They were hypoxemic with a mean SpO2 of 65% {+/-} 20, tachycardic (pulse rate 108{+/-}17 min-1) and tachypneic (32 {+/-}10 min-1); 162 were under mechanical ventilation at randomization. Thirty-day mortality was similar in both groups (38% in Hydroxychloroquine vs. 41% in placebo, hazard ratio [HR] 0.88, 95% Confidence Interval [95%CI] 0.51-1.53). In the surviving participants, no significant difference was found in secondary outcomes.

ConclusionNo beneficial effect or significant harm could be demonstrated in our randomized controlled trial including 214 patients, using relatively low doses of Hydroxychloroquine compared with placebo in hospitalized patients with severe COVID-19.

CONSORT GUIDELINES

O_TBL View this table:
org.highwire.dtl.DTLVardef@c46418org.highwire.dtl.DTLVardef@1877269org.highwire.dtl.DTLVardef@1685cb1org.highwire.dtl.DTLVardef@9d8b09org.highwire.dtl.DTLVardef@11339bc_HPS_FORMAT_FIGEXP  M_TBL C_TBL


title: Multi-centre Epilepsy Lesion Detection (MELD) Project: Predictors of lesion location and postsurgical seizure freedom in focal cortical dysplasia

abstract:
Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome.

The Multi-centre Epilepsy Lesion Detection (MELD) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centres worldwide. MRI-based maps of individual FCDs with accompanying demographic, clinical and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom.

FCDs were non-uniformly distributed, concentrating in the superior frontal sulcus, frontal pole and temporal pole. Epilepsy onset was typically before age 10. Earlier epilepsy onset was associated with lesions in primary sensory areas while later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%.

FCD location is an important determinant of its size, the age of epilepsy onset and the likelihood of seizure freedom post-surgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data-driven atlases and predictive models are essential for evidence-based, precision medicine and risk counselling in neurology.


title: MELD Project: Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia


title: Parental lifespan and polygenic risk score of longevity are associated with white matter hyperintensities

abstract: Human longevity is moderately heritable and is hence influenced by both genetic and environmental factors. However, there remains considerable uncertainty regarding its relationship with brain ageing. In this study, we investigated the associations of parental lifespan (parental age at death) and polygenic risk score for longevity (longevity-PRS) with structural magnetic resource imaging (MRI) brain metrics considered to reflect the brain ageing process. We used a discovery sample (N = 19136) from the UK Biobank and a replication sample (N =809) from the Sydney Memory and Ageing Study and the Older Australian Twins Study. We found lower cerebral white matter hyperintensity (WMH) volumes to be significantly associated with longer parental lifespan in the discovery and replication samples and higher longevity-PRS in the discovery sample and a similar trend in the replication sample. The association of longevity-PRS with WMH remained significant after removing the influence of the apolipoprotein E locus. Additionally, the effects of longevity-PRS on the association were more prominent in males, especially in the older-male group. Our findings suggest that human longevity-related genes may have an influence on WMH burden, suggesting WMH volume may be a biomarker for longevity and an ageing endophenotype.


title: Concentrations and immunostimulatory potential of cell-free circulating membrane-bound and -unbound mitochondrial DNA in preeclampsia

abstract: Cell-free circulating mitochondrial DNA (CFCmtDNA) is a damage-associated molecular pattern (DAMP) that can activate Toll-like receptor 9 (TLR-9). The main objectives of this case-control study were 1) to determine absolute concentrations and immunostimulatory capacity of CFCmtDNA, in membrane-bound and -unbound states, in cases with preeclampsia and healthy controls and 2) to implement a bootstrapped penalized regression analysis to establish the contribution of CFCmtDNA to preeclampsia diagnosis and its interaction with commonly collected patient characteristics. To determine the contribution of membrane-bound and -unbound CFCmtDNA in preeclampsia, DNA from plasma samples was exctracted with lysis buffer (membrane-unbound) and without lysis buffer (membrane-bound). CFCmtDNA, quantified using absolute PCR quantification protocol, was reduced in preeclampsia compared to healthy controls (P[≤]0.02). While the pattern of reduced CFCmtDNA in preeclampsia was similar between methods of DNA extraction, DNA isolation with membrane lysis buffer resulted in 1,000-fold higher CFCmtDNA quantification in the preeclampsia group (P=0.0014) and 430-fold higher CFCmtDNA quantification in the control group (P<0.0001). Even though CFCmtDNA concentrations were reduced, plasma from women with preeclampsia induced greater TLR-9 activation than plasma from gestational age matched controls (P[≤]0.01) as monitored using SEAP reporter 293 cells expressing human TLR-9. Penalized regression analysis showed that women with preeclampsia are strongly likely to have high concentrations of nDNA and DNase I along with a prior history of preeclampsia. Low concentrations of CFCmtDNA and mode of delivery were also associated with preeclampsia. In conclusion, our data demonstrate increases in the immunostimulatory potential of CFCmtDNA and upregulation of DNA degradation mechanisms in women with preeclampsia at the third trimester.

category: obstetrics and gynecology


title: Antibiotic Resistance in Wastewater Treatment Plants and Transmission Risks for Employees and Residents: The Concept of the AWARE Study

abstract:
BackgroundAntibiotic resistance has become a serious global health threat. Wastewater treatment plants (WWTPs) may become unintentional collection points for bacteria resistant to antimicrobials. Little is known about the transmission of antibiotic resistance from wastewater treatment plants to humans, most importantly to WWTP workers and residents living in the vicinity. We aim to deliver precise information about the methods used in the AWARE (Antibiotic Resistance in Wastewater: Transmission Risks for Employees and Residents around Waste Water Treatment Plants) study.

Methods/DesignWithin the AWARE study, we gather data on the prevalence of two antibiotic resistance phenotypes, ESBL-producing E.coli (ESBL-EC) and carbapenemase-producing Enterobacteriaceae (CPE) as well as on their corresponding antibiotic resistance genes (ARGs) isolated from air, water, and sewage samples taken from inside and outside of different WWTPs in Germany, Netherlands and Romania. Additionally, we analyse stool samples of WWTP workers, nearby residents and members of a comparison group living [≥]1,000 m away from the closest WWTP.

DiscussionThe study results will enable the assessment of the potential health impact of exposure to ESBL-EC, CPE and ARGs in and around WWTPs. Quantifying the contribution of different wastewater treatment processes to the ESBL-EC, CPE and ARGs removal efficiency will provide us with evidence-based support for possible mitigation strategies.

category: occupational and environmental health


title: Protocol for a nationwide Internet-based health survey in workers during the COVID-19 pandemic in 2020

abstract: The ever-changing social implications of the COVID-19 pandemic have resulted in an urgent need to understand the working environments and health status of workers. We conducted a nationwide Internet-based health survey in Japanese workers in December 2020, in the midst the countrys "third wave" of COVID-19 infection. Of 33,087 surveys collected, 6,051 were determined to have invalid responses. The 27,036 surveys included in the study were balanced in terms of geographical area, participant sex, and type of work, according to the sampling plan. Men were more likely than women to have telecommuted, while women were more likely to have resigned since April 2020. Moreover, 40% and 9.1% of respondents had a K6 score of 5 or higher and 13 or higher, respectively, they did not exhibit extremely poor health. The present study describes the protocol used to conduct an Internet-based health survey in workers and a summary of its results during a period when COVID-19 was spreading rapidly in Japan. In the future, we plan to use this survey to examine the impact of COVID-19 on workers work styles and health.


title: Impact of personal protective equipment use on health care workers physical health during the COVID-19 pandemic: a systematic review and meta-analysis

abstract:
BackgroundDuring the COVID-19 pandemic, health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) in high-risk clinical settings have been obliged to wear personal protective equipment (PPE).

AimTo assess the impact of PPE use on HCWs physical health during the COVID-19 pandemic. Also, we examined factors related with a greater risk of adverse events among HCWs due to PPE use.

MethodsWe applied the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and the Cochrane criteria for this systematic review and meta-analysis. We searched PubMed, Medline, Scopus, ProQuest, CINAHL and pre-print services (medRxiv) from January 1, 2020 to December 27, 2020.

FindingsOur review included 14 studies with 11,746 HCWs from 16 countries. The estimated overall prevalence of adverse events among HCWs was 78% (95% CI: 66.7-87.5%) with a range from 42.8% to 95.1% among studies. The prevalence of adverse events was higher for the studies with poor quality compared to those with moderate quality (83.5% vs. 67.1%), while increased sample size was related with decreased prevalence (p<0.001). The most frequent adverse events were headache (55.9%), dry skin (54.4%), dyspnoea (53.4%), pressure injuries (40.4%), itching (39.8%), hyperhidrosis (38.5%), and dermatitis (31.0%). Among others, the following factors were related with the risk of adverse events among HCWs due to PPE use: female gender, younger age, obesity, diabetes mellitus, smoking pre-existing headache, longer duration of shifts wearing PPE, increased consecutive days with PPE, and increased exposure to confirmed or suspected COVID-19 patients.

ConclusionThe frequency of adverse events amongst HCWs due to PPE use is very high. Further studies should be conducted since the limitations of this review do not allow us to infer conclusive results especially in case of risk factors for the occurrence of adverse events. Healthcare facilities should take the necessary precautions and change the working conditions during the COVID-19 pandemic to prevent adverse events associated with PPE use and minimize harm to HCWs.


title: HEALTHCARE WORKERS PSYCHOLOGICAL DISTRESS At EARLY PHASE OF THE COVID-19 PANDEMIC IN MOROCCO

abstract:
IntroductionThe mental being of healthcare workers with the COVID 19 pandemic is a determinant of their resilience. We investigated the psychological impact of health workers during early phase of Covid 19 pandemic in Morocco.

MethodsThis was a cross-sectional study based on a survey of health workers of the Rabat University Hospital Ibn-Sina in Morocco. Data were collected during the first week of health emergency state -between 23 and 30 march-related to the covid-19 pandemic declaration in Morocco. Sociodemographic, health characteristics and professional characteristics of each health worker were collected. We also evaluated the knowledge of health workers concerning the protective measures against COVID 19. The mental health status of the health workers was investigated using the Arabic validated version of HADS 14 items, evaluating hospital anxiety and depression

ResultsTwo hundred eighty-seven health workers were included.The mean age was 34.4{+/-}12.18 year; and 64.5% were female, 54% have been trained regarding protection procedures, and 94.8% declared that they are aware of individual protection measures. The incidence of anxiety and depression was respectively 77.4% and 73.9%. High degree of anxiety and depression was associated with female gender. However, Higher degree of anxiety was also related to function, specialty of practice, and knowledge of the protective measures against COVID-19.

ConclusionWe reported the result of the first evaluation of psychological burden of health worker during early period of COVID-19 pandemic in a developing country. The study showed high frequency of anxiety and depression among Moroccan health worker in a hospital faced to COVID-19 patient management.


title: Network analysis identifies DAPK3 as a potential biomarker for lymphovascular invasion and prognosis of colon adenocarcinoma

abstract: Adenocarcinoma of the colon is the fourth most common malignancy worldwide with significant rates of mortality. Hence, the identification of novel molecular biomarkers with prognostic significance is of particular importance for improvements in treatment and patient outcome. Clinical traits and RNA-Seq data of 551 patient samples and 18,205 genes in the UCSC Toil Recompute Compendium of TCGA TARGET and GTEx datasets (restricted to |Primary_site| = colon) were obtained from the Xena platform. Weighted gene co-expression network analysis was completed, and 24 unique modules were assembled to specifically examine the association between gene networks and cancer cell invasion. One module, containing 151 genes, was significantly correlated with lymphatic invasion, a histopathological feature of higher-risk colon cancer. Search tool for the retrieval of interacting genes/proteins (STRING) and gene ontology (GO) analyses identified the module to be enriched in genes related to cytoskeletal organization and apoptotic signaling, suggesting involvement in tumor cell survival and migration along with epithelial-mesenchymal transformation. Of genes that were differentially expressed and significant for overall survival, DAPK3 (death-associated protein kinase 3) was revealed as the pseudo-hub of the module. Although DAPK3 expression was reduced in colon cancer patients, survival analysis revealed that high expression of DAPK3 was significantly correlated with greater lymphovascular invasion and poor overall survival.

category: oncology


title: Convalescent Plasma and Improved Survival in Patients with Hematologic Malignancies and COVID-19

abstract: Convalescent plasma may benefit immunocompromised individuals with COVID-19, including those with hematologic malignancy. We evaluated the association of convalescent plasma treatment with 30-day mortality in hospitalized adults with hematologic malignancy and COVID-19 from a multi-institutional cohort. 143 treated patients were compared to 823 untreated controls. After adjustment for potential confounding factors, convalescent plasma treatment was associated with improved 30-day mortality (hazard ratio, 0.60; 95% CI, 0.37-0.97). This association remained significant after propensity-score matching (hazard ratio, 0.52; 95% CI, 0.29-0.92). These findings suggest a potential survival benefit in the administration of convalescent plasma to patients with hematologic malignancy and COVID-19.


title: Predicting clinical endocrine response in advanced breast cancers using a reproducible low-dimensional biomarker

abstract: Endocrine therapy remains the primary treatment for advanced and metastatic estrogen receptor-positive (ER+) breast cancers. Patients who progress on endocrine therapy may benefit from add-on treatment targeting the PI3K/MTOR signaling pathways or by switching to chemotherapy. However, these options are only available after progression on first-line treatment with endocrine therapy. In the absence of reliable prognostic tests for advanced ER+ breast cancers, it is currently not possible to stratify patients into pertinent treatment arms at the baseline. To address this, we have developed a low-dimensional endocrine response signature (ENDORSE) model for advanced ER+ breast cancers. The ENDORSE model was developed using the baseline tumor transcriptomes and long-term survival outcomes of >800 invasive ER+ breast cancers and predicts the risk of death on endocrine therapy. ENDORSE was validated in multiple clinical trial datasets for endocrine therapy response in metastatic ER+ breast cancers and demonstrated superior predictive performance over clinical factors and published gene signatures. Our results show that ENDORSE is a reproducible and accurate prognostic model for endocrine therapy response in advanced and metastatic ER+ breast cancers.


title: ENDORSE: a prognostic model for endocrine therapy response in advanced estrogen-receptor positive breast cancers


title: Incorporating the Laplacian Filter with a Three-Stream Multi-Channel Convolutional Neural Network for Improved Abnormality Detection in Knee MRIs

abstract: AO_SCPLOWBSTRACTC_SCPLOWDespite ACL and meniscus tears being among the most common movement induced injuries, they are often the most difficult to diagnose due to the variable severity with which these tears occur. Typically, magnetic resonance imaging (MRI) scans are used for diagnosing ligament tears, but performing and analyzing these scans is time consuming and expensive due to the necessitation of a radiologist or professional orthopedic specialist. Consequently, we developed a custom three-stream convolutional neural network (CNN) architecture that contains multiple channels to automate the diagnosis of ACL and meniscus tears from MRI scans. Our algorithm utilizes the sagittal, coronal, and axial slices to maximize feature extraction. Furthermore, we apply the Laplace Operator on the MRI scan images to evaluate and compare its propensity in different medical imaging modalities. The algorithm attained an accuracy of 92.80%, significantly higher than that of orthopedic diagnosis accuracy. Our results point towards the feasibility of shallow, multi-channel CNNs and the ability of the Laplace Operator to improve performance metrics for MRI scan diagnosis.


title: Association between Median Household Income, State Medicaid Expansion Status, and COVID-19 Outcomes Across US Counties

abstract:
ObjectiveThe relationship between socioeconomic status and its interaction with States Medicaid-expansion policies on COVID-19 outcomes across United States (US) counties are uncertain. To determine the association between median-household-income and its interaction with State Medicaid-expansion status on COVID-19 incidence and mortality in US counties

MethodsLongitudinal, retrospective analysis of 3142 US counties (including District of Columbia) to study the relationship between County-level median-household-income (defined by US Census Bureaus Small-Area-Income-and-Poverty-Estimates) and COVID-19 incidence and mortality per 100000 of the population in US counties from January 20, 2020 through December 6, 2020. County median-household-income was log-transformed and stratified by quartiles. Medicaid-expansion status was defined by US States Medicaid-expansion adoption as of first reported US COVID-19 infection, January 20, 2020. Multilevel mixed-effects generalized-linear-model with negative binomial distribution and log link function compared quartiles of median-household-income and COVID-19 incidence and mortality, reported as incidence-risk-ratio (IRR) and mortality-risk-ratio (MRR), respectively. Models adjusted for county socio-demographic and comorbidity conditions, population density, and hospitals, with a random intercept for states. Multiplicative interaction tested for Medicaid-expansion*income quartiles on COVID-19 incidence and mortality.

ResultsThere was no significant difference in COVID-19 incidence across counties by income quartiles or by Medicaid expansion status. Conversely, significant differences exist between COVID-19 mortality by income quartiles and by Medicaid expansion status. The association between income quartiles and COVID-19 mortality was significant only in counties from non-Medicaid-expansion states but not significant in counties from Medicaid-expansion states (P<0.01 for interaction). For non-Medicaid-expansion states, counties in the lowest income quartile had a 41% increase in COVID-19 mortality compared to counties in the highest income quartile (MRR 1.41, 95% CI: 1.25-1.59).

Conclusions and RelevanceMedian-household-income was not related to COVID-19 incidence but negatively related to COVID-19 mortality in US counties of states without Medicaid-expansion. It was unrelated to COVID-19 mortality in counties of states that adopted Medicaid-expansion. These findings suggest that expanded healthcare coverage should be investigated further to attenuate the excessive COVID-19 mortality risk associated with low-income communities.

Key FindingsO_ST_ABSQuestionC_ST_ABSIs there a relationship between COVID-19 outcomes (incidence and mortality) and household income and status of Medicaid expansion of US counties?

FindingsIn this longitudinal, retrospective analysis of 3142 US counties, we found no significant difference in COVID-19 incidence across US counties by quartiles of household income. However, counties with lower median household income had a higher risk of COVID-19 mortality, but only in non-Medicaid expansion states. This relationship was not significant in Medicaid expansion states.

MeaningExpanded healthcare coverage through Medicaid expansion should be investigated as an avenue to attenuate the excessive COVID-19 mortality risk associated with low-income communities.

category: health policy


title: Impact of Vaccination and Testing in an Urban Campus model for the SARS-CoV-2 Pandemic

abstract:
The crisis induced by the Coronavirus pandemic has severely impacted educational institutes. Even with vaccination efforts underway, it is not clear that sufficient confidence will be achieved for schools to reopen soon.

This paper considers the impact of vaccination rates and testing rates to reduce infections and hospitalizations and evaluates strategies that will allow educational institute in urban settings to reopen. These strategies are also applicable to businesses and would help plan reopening in order to help the economy.

Our analysis is based on a graph model where nodes represent population groups and edges represent population exchanges due to commuting populations. The commuting population is associated with edges and is associated with one of the end nodes of the edge during part of the time period and with the other node during the remainder of the time period. The progression of the disease at each node is determined via compartment models, that include vaccination rates and testing to place infected people in quarantine along with consideration of asymptomatic and symptomatic populations. Applying this to a university population in Chicago with a substantial commuter population, chosen to be 80% as an illustration, provides an analysis which specifies benefits of testing and vaccination strategies over a time period of 150 days.


title: Antibiotic stewardship in Norway: are strategies for rational use of antibiotics followed in Norwegian healthcare system?

abstract: This manuscript has been withdrawn by medRxiv as it was submitted and made public without the full consent of all the authors. If you have any questions, please contact the corresponding author.

category: health systems and quality improvement


title: Age-related heterogeneity in Neutralising antibody responses to SARS-CoV-2 following BNT162b2 vaccination

abstract: Two dose mRNA vaccination provides excellent protection against SARS-CoV-2. However, there are few data on vaccine efficacy in elderly individuals above the age of 801. Additionally, new variants of concern (VOC) with reduced sensitivity to neutralising antibodies have raised fears for vulnerable groups. Here we assessed humoral and cellular immune responses following vaccination with mRNA vaccine BNT162b22 in elderly participants prospectively recruited from the community and younger health care workers. Median age was 72 years and 51% were females amongst 140 participants. Neutralising antibody responses after the first vaccine dose diminished with increasing age, with a marked drop in participants over 80 years old. Sera from participants below and above 80 showed significantly lower neutralisation potency against B.1.1.7, B.1.351 and P.1. variants of concern as compared to wild type. Those over 80 were more likely to lack any neutralisation against VOC compared to younger participants following first dose. The adjusted odds ratio for inadequate neutralisation activity against the B.1.1.7, P.1 and B.1.351 variant in the older versus younger age group was 4.3 (95% CI 2.0-9.3, p<0.001), 6.7 (95% CI 1.7-26.3, p=0.008) and 1.7 (95% CI 0.5-5.7, p=0.41). Binding IgG and IgA antibodies were lower in the elderly, as was the frequency of SARS-CoV-2 Spike specific B-memory cells. We observed a trend towards lower somatic hypermutation in participants with suboptimal neutralisation, and elderly participants demonstrated clear reduction in class switched somatic hypermutation, driven by the IgA1/2 isotype. SARS-CoV-2 Spike specific T-cell IFN{gamma} and IL-2 responses fell with increasing age, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high risk population that warrant specific measures in order to mitigate against vaccine failure, particularly where variants of concern are circulating.


title: Age-related heterogeneity in neutralising antibody responses to SARS-CoV-2 following BNT162b2 vaccination


title: Risk Factors for Infection and Health Impacts of the COVID-19 Pandemic in People with Autoimmune Diseases

abstract:
BackgroundPeople with autoimmune or inflammatory conditions who take immunomodulatory/suppressive medications may have a higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences.

ObjectiveAssess whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterize pandemic-associated changes to care.

DesignLongitudinal registry study

Participants4666 individuals with autoimmune or inflammatory conditions followed by specialists in neurology, rheumatology, cardiology, pulmonology or gastroenterology at Johns Hopkins

MeasurementsPeriodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare

ResultsA total of 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medication exposure) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in multivariable models incorporating behavior and other potential confounders (OR: 1.43; 95%CI: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95%CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95%CI: 1.24, 2.28), and chronic kidney disease (OR: 1.76; 95%CI: 1.04, 2.97) were each associated with higher odds of COVID-19. Pandemic-related disruption to care was common. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions. Individuals experiencing changes to employment or income were at highest odds of care disruption.

LimitationsResults may not be generalizable to all patients with autoimmune or inflammatory conditions. Information was self-reported.

ConclusionsExposure to glucocorticoids may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.


title: Increased SAR-CoV-2 shedding associated with reduced disease severity despite continually emerging genetic variants

abstract: Since the first report of SARS-CoV-2 in December 2019, genetic variants have continued to emerge, complicating strategies for mitigating the disease burden of COVID-19. Positive SARS-CoV-2 nasopharyngeal swabs (n=8,735) were collected from Missouri, USA, from March-October 2020, and viral genomes (n=178) were sequenced. Hospitalization status and length of stay were extracted from medical charts of 1,335 patients and integrated with emerging genetic variants and viral shedding analyses for assessment of clinical impacts. Multiple introductions of SARS-CoV-2 into Missouri, primarily from Australia, Europe, and domestic states, were observed. Four local lineages rapidly emerged and spread across urban and rural regions in Missouri. While the majority of Missouri viruses harbored Spike-D614G mutations, a large number of unreported mutations were identified among Missouri viruses, including seven in the RNA-dependent RNA polymerase complex and Spike protein that were positively selected. A 15.6-fold increase in viral RNA levels in swab samples occurred from March to May and remained elevated. Accounting for other comorbidities, individuals test-positive for COVID-19 with high viral loads were less likely to be hospitalized (odds ratio=0.39, 95% confidence interval [CI]=0.20, 0.77) and had shorter hospital stays (hazard ratio=0.34, p=0.003) than those with low viral loads. Overall, the first eight months of the pandemic in Missouri saw multiple locally acquired mutants emerge and dominate in urban and rural locations. Although we were unable to find associations between specific variants and greater disease severity, Missouri COVID-positive individuals that presented with increased viral shedding had less severe disease by several measures.


title: Antibody responses boosted in seropositive healthcare workers after single dose of SARS-CoV-2 mRNA vaccine

abstract: Current guidelines recommend that individuals who have had COVID-19 should receive the identical vaccine regimen as those who have not had the infection. This includes two doses of the mRNA platform vaccines (BNT162b2/Pfizer; mRNA-1273/Moderna) that are approved for use in the United States. In this brief report, we show that after a single dose of the Pfizer SARS-CoV-2 vaccine, individuals that had prior SARS-CoV-2 infection had significantly higher antibody levels than individuals that had no history of infection. This provides the rationale for changing vaccination policy to deliver only a single dose to individuals with recent SARS-CoV-2 infection that may free up additional doses for individuals that have no preexisting immunity to the virus. Future study of other immune parameters such as T cell response and durability of immune response should be rapidly undertaken in individuals that had COVID-19 prior to vaccination.


title: IgA autoantibodies target pulmonary surfactant in patients with severe COVID-19

abstract: Complications affecting the lung are hallmarks of severe coronavirus disease 2019 (COVID-19). While there is evidence for autoimmunity in severe COVID-19, the exact mechanisms remain unknown. Here, we established a prospective observational cohort to study lung specific autoantibodies (auto-Abs). Incubation of plasma from severe COVID-19 patients with healthy human lung tissue revealed the presence of IgA antibodies binding to surfactant-producing pneumocytes. Enzyme-linked immunosorbent assays (ELISA) and protein pull-downs using porcine surfactant confirmed the presence of auto-Abs binding to surfactant proteins in severe COVID-19 patients. Mass spectrometry and ELISAs with recombinant proteins identified IgA auto-Abs that target human surfactant proteins B and C. In line with these findings, lungs of deceased COVID-19 patients showed reduced pulmonary surfactant. Our data suggest that IgA-driven autoimmunity against surfactant may result in disease progression of COVID-19.


title: Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant

abstract: Antibody responses against the SARS-CoV-2 Spike protein correlate with protection against COVID-19. Serum neutralizing antibodies appear early after symptom onset following SARS-CoV-2 infection and can last for several months. Similarly, the messenger RNA vaccine, mRNA-1273, generates serum neutralizing antibodies that are detected through at least day 119. However, the recent emergence of the B.1.1.7 variant has raised significant concerns about the breadth of these neutralizing antibody responses. In this study, we used a live virus neutralization assay to compare the neutralization potency of sera from infected and vaccinated individuals against a panel of SARS-CoV-2 variants, including SARS-CoV-2 B.1.1.7. We found that both infection- and vaccine-induced antibodies were effective at neutralizing the SARS-CoV-2 B.1.1.7 variant. These findings support the notion that in the context of the UK variant, vaccine-induced immunity can provide protection against COVID-19. As additional SARS-CoV-2 viral variants continue to emerge, it is crucial to monitor their impact on neutralizing antibody responses following infection and vaccination.


title: SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection

abstract: SARS-CoV-2 infection of children leads to a mild illness and the immunological differences with adults remains unclear. We quantified the SARS-CoV-2 specific T cell responses in adults and children (<13 years of age) with RT-PCR confirmed asymptomatic and symptomatic infection for long-term memory, phenotype and polyfunctional cytokines. Acute and memory CD4+ T cell responses to structural SARS-CoV-2 proteins significantly increased with age, whilst CD8+ T cell responses increased with time post infection. Infected children had significantly lower CD4+ and CD8+ T cell responses to SARS-CoV-2 structural and ORF1ab proteins compared to infected adults. SARS-CoV-2-specific CD8+ T cell responses were comparable in magnitude to uninfected negative adult controls. In infected adults CD4+ T cell specificity was skewed towards structural peptides, whilst children had increased contribution of ORF1ab responses. This may reflect differing T cell compartmentalisation for antigen processing during antigen exposure or lower recruitment of memory populations. T cell polyfunctional cytokine production was comparable between children and adults, but children had a lower proportion of SARS-CoV-2 CD4+ T cell effector memory. Compared to adults, children had significantly lower levels of antibodies to {beta}-coronaviruses, indicating differing baseline immunity. Total T follicular helper responses was increased in children during acute infection indicating rapid co-ordination of the T and B cell responses. However total monocyte responses were reduced in children which may be reflective of differing levels of inflammation between children and adults. Therefore, reduced prior {beta}-coronavirus immunity and reduced activation and recruitment of de novo responses in children may drive milder COVID-19 pathogenesis.


title: Impact of systemic corticosteroids on hospitalized patients with COVID-19: January 2021 Meta-analysis of randomized controlled trials

abstract:
BackgroundThe COVID-19 pandemic has stimulated worldwide investigation into a myriad of potential therapeutic agents, including corticosteroids. The first RCT reporting results on the impact of systemic corticosteroids on COVID-19 in a peer reviewed journal was the RECOVERY trial published in July, 2020. The RECOVERY trial showed a reduced risk of 28-day mortality in patients who received oral or intravenous dexamethasone for 10 days.

This study is a meta-analysis of peer reviewed RCTs aims to estimate the association of systemic corticosteroid therapy compared to the usual care or placebo on all-cause mortality in hospitalized patients with COVID-19. Software based tools to accelerate the analysis process.

MethodsMeta-analysis of peer reviewed RCTs comparing systemic corticosteroids to usual care or placebo.

ResultsFive English language RCTs were identified, including data from 7645 hospitalized patients worldwide using systemic dexamethasone, hydrocortisone and methylprednisolone in COVID-19 positive patients. Three RCTs were discontinued when preliminary results from the RECOVERY trial became available.

Meta-analysis of all identified RCTs showed no difference in survival in patients who received systemic corticosteroid therapy compared to usual care or placebo (Odds ratio 0.82, 95% CI 0.64-1.05, p = 0.09). Subgroup analysis from the 1967 critically ill patients in the identified RCTs showed improved survival in patients who received systemic corticosteroid therapy (Odds ratio 0.67, 95% CI 0.51-0.87, p = 0.01).

ConclusionsThis meta-analysis of randomized controlled trials published in peer-reviewed literature by January 1, 2021 showed reduced mortality in critically ill patients but not all hospitalized patients with COVID-19 who received systemic corticosteroids. The early termination of three of the included RCTs because of the preliminary results of the RECOVERY trial is likely to have dramatically influenced the results of this meta-analysis. Further research is needed to clarify the role of systemic corticosteroid therapy in the management of COVID-19.


title: Arabic validation and cross-cultural adaptation of the 5C scale for assessment of COVID-19 vaccines psychological antecedents

abstract:
BackgroundIn the Arab countries, there has not been yet a specific validated questionnaire that can assess the psychological antecedents of COVID-19 vaccine among the general population. This study, therefore, aimed to translate, culturally adapt, and validate the 5C scale into the Arabic language.

MethodsThe 5C scale was translated into Arabic by two independent bilingual co-authors, and then subsequently translated back into English. After reconciling translation disparities, the final Arabic questionnaire was disseminated into four randomly selected Arabic countries (Egypt, Libya, United Arab Emirates (UAE), and Saudi Arabia). Data from 350 Arabic speaking adults (aged [≥]18 years) were included in the final analysis. Convergent, discriminant, exploratory and confirmatory factor analyses were carried out. Internal consistency was assessed by Cronbach alpha.

ResultsAge of participants ranged between 18 to 73 years; 57.14% were females, 37.43% from Egypt, 36.86%, from UAE, and 30% were healthcare workers. The 5 sub-scales of the questionnaire met the criterion of internal consistency (Cronbach alpha [≥]0.7). Convergent validity was identified by the significant inter-item and item-total correlation (P<0.001). Discriminant validity was reported as inter-factor correlation matrix (<0.7). Exploratory factor analysis indicated that the 15 items of the questionnaire could be summarized into five factors. Confirmatory factor analysis confirmed that the hypothesized five-factor model of the 15-item questionnaire was satisfied with adequate psychometric properties and fit with observed data (RMSEA=0.060,GFI=0.924, CFI=0.957, TLI=0.937, SRMR=0.076 & NFI=906).

Conclusionthe Arabic version of the 5C scale is a valid and reliable tool to assess the psychological antecedents of COVID-19 vaccine among Arab population.


title: Bronchoscopy in COVID19 ARDS patients on mechanical ventilation: a prospective study

abstract:
BackgroundBronchoscopy has been done sparingly in COVID19 patients due to the risk of aerosol generation, with few reports describing its clinical utility. We describe a study on bronchoscopy in mechanically ventilated (MV) COVID-19 patients outlining the procedural, clinical, utilitarian and safety aspects.

MethodsBedside bronchoscopy was performed in suspected or confirmed COVID-19 cases on MV; only positive cases were included in the study. Demographic, clinical, bronchoscopic and laboratory findings were noted and analysed.

Results98 procedures were performed on 61 patients, mean age of 62.1 years, 51 (83.6%) males. 42 patients (69%) had at least 1 co-morbidity. Major indications for bronchoscopy were new radiographic infiltrates with clinical deterioration, increased endotracheal tube (ETT) secretions and haemorrhagic secretions/hemoptysis. Common findings were copious secretions in 87 (88.8%), purulent in 61%, mucoid in 18%, haemorrhagic in 7% and frothy in 14% cases. Morphologically, hyperaemic airways were seen in 85 (86.7%) cases, ranging from mild (61%) to moderate-severe (39%). On the management front, antibiotics were changed in 31 (31.6%) cases based on bronchoscopic findings. Other significant changes included reduction or stopping of steroids and anticoagulation, fluid, and diuretic adjustment and ETT repositioning. The incidence of bacterial superinfection was also high (54% culture positivity for various bacteria), a significant number (94%) with multi-drug resistant organisms. Fungi were seen in 7 cases (7.1%). Pneumocystis jiroveci was not seen and cytology did not show any viral inclusions. Therapeutic mucus plug removal was done in 30 cases (30.6%), and hemoptysis control in 4% cases. The procedures were safe with no complications, and none of the HCW developed any COVID19 infection.

ConclusionBronchoscopy in critically ill MV COVID-19 patients contributes on both diagnostic and therapeutic fronts and can significantly influence management decisions. With adequate precautions and standard protocols, it is safe for both HCW and patients.


title: Human mobility and COVID-19 transmission: a systematic review and future directions

abstract: Without a widely distributed vaccine, controlling human mobility has been identified and promoted as the primary strategy to mitigate the transmission of COVID-19. Many studies have reported the relationship between human mobility and COVID-19 transmission by utilizing the spatial-temporal information of mobility data from various sources. To better understand the role of human mobility in the pandemic, we conducted a systematic review of articles that measure the relationship between human mobility and COVID-19 in terms of their data sources, statistical models, and key findings. Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we selected 47 articles from Web of Science Core Collection up to September 2020. Restricting human mobility reduced the transmission of COVID-19 spatially, although the effectiveness and stringency of policy implementation vary temporally and spatially across different stages of the pandemic. We call for prompt and sustainable measures to control the pandemic. We also recommend researchers 1) to enhance multi-disciplinary collaboration; 2) to adjust the implementation and stringency of mobility-control policies in corresponding to the rapid change of the pandemic; 3) to improve statistical models used in analyzing, simulating, and predicting the transmission of the disease; and 4) to enrich the source of mobility data to ensure data accuracy and suability.


title: Efficacy of Ivermectin in COVID-19 Patients with Mild to Moderate Disease

abstract:
ObjectiveTo evaluate the efficacy of ivermectin (IVM) as an addition to the standard of care (SOC) treatment in COVID-19 patients with mild and moderate disease

Materials and MethodsA randomized clinical trial (Trial registration # NCT04392713) was carried out at Combined Military Hospital Lahore from March 15, 2020, to June 15, 2020. Eighty-six patients with reverse transcriptase-polymerase chain reaction (RT-PCR) proven SARS-CoV-2 infection completed the trial protocol. Patients were stratified via the lottery method into two groups. Group A was administered standard of care (SOC) treatment as per existing hospital guidelines whereas group B was given ivermectin (single dose of 12 milligrams) along with SOC treatment. PCR was repeated at 72 hours, 7th day, and at 14th day of admission for both the groups and the point at which the PCR became negative was noted. Complete blood counts, liver function tests and renal function tests were done at recruitment, 7th day, and 14th day. The primary outcome was the viral clearance, measured as days to achieve PCR negativity. The secondary outcome was the development of any adverse side effects pertinent to ivermectin or derangement in baseline laboratory parameters.

ResultsIn group A, 36 (80%) participants were males, and 9 (20%) were females, whereas in group B, 37 (90.2%) were males and 4 (9.8%) were females. Mean age was 39.0{+/-} 12.6 and 42.2 {+/-} 12.0 years for groups A and B, respectively (p= 0.394). There was early viral clearance in group B as compared to group A (p=0.001). No adverse reaction or derangements in laboratory parameters was noted in the intervention arm during the trial period.

ConclusionIn the intervention arm, early viral clearance was observed and no side effects were documented. Therefore ivermectin is a potential addition to the standard care of treatment in COVID-19 patients.


title: A Comparison of Methylprednisolone and Dexamethasone in Intensive Care Patients with COVID-19

abstract:
OBJECTIVESThis study retrospectively compares the effectiveness of methylprednisolone to dexamethasone in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) requiring ICU care.

DESIGNThis is an institutional review board approved cohort study in patients with COVID-19 requiring intensive care unit admission. Patients admitted and requiring oxygen supplementation were treated with either methylprednisolone or dexamethasone.

SETTINGThis study takes place in the intensive care units at a large, tertiary, public teaching hospital serving a primarily low-income community in urban Los Angeles.

PATIENTSAll eligible patients admitted to the intensive care unit for COVID-19 respiratory failure from March 1 to July 31, 2020 were included in this study.

INTERVENTIONSA total of 262 patients were grouped as receiving usual care (n=75), methylprednisolone dosed at least at 1mg/kg/day for [≥] 3 days (n=104), or dexamethasone dosed at least at 6 mg for [≥] 7 days (n=83).

MEASUREMENTS and MAIN RESULTSAll-cause mortality within 50 days of initial corticosteroid treatment as compared to usual care was calculated. The mortality effect was then stratified based on levels of respiratory support received by the patient.

In this cohort of 262 patients with severe COVID-19, all-cause mortalities in the usual care, methylprednisolone, and dexamethasone groups were 41.3%, 16.4% and 26.5% at 50 days (p <0.01) respectively. In patients requiring mechanical ventilation, mortality was 42% lower in the methylprednisolone group than in the dexamethasone group (hazard ratio 0.48, 95% CI: 0.235-0.956, p=0.0385).

CONCLUSIONSIn COVID-19 patients requiring mechanical ventilation, sufficiently dosed methylprednisolone can lead to a further decreased mortality as compared to dexamethasone.

category: intensive care and critical care medicine


title: A Dynamic Bayesian Model for Identifying High-Mortality Risk in Hospitalized COVID-19 Patients

abstract:
IntroductionAs COVID-19 hospitalization rates remain high, there is an urgent need to identify prognostic factors to improve treatment. Our analysis, to our knowledge, is one of the first to quantify the risk associated with dynamic clinical measurements taken throughout the course of hospitalization.

MethodsWe collected data for 553 PCR-positive COVID-19 patients admitted to hospital whose eventual outcomes were known. The data collected for the patients included demographics, comorbidities and laboratory values taken at admission and throughout the course of hospitalization. We trained multivariate Markov prognostic models to identify high-risk patients at admission along with a dynamic measure of risk incorporating time-dependent changes in patients laboratory values.

ResultsFrom the set of factors available upon admission, the Markov model determined that age >80 years, history of coronary artery disease and chronic obstructive pulmonary disease increased mortality risk. The lab values upon admission most associated with mortality included neutrophil percentage, RBC, RDW, protein levels, platelets count, albumin levels and MCHC. Incorporating dynamic changes in lab values throughout hospitalization lead to dramatic gains in the predictive accuracy of the model and indicated a catalogue of variables for determining high-risk patients including eosinophil percentage, WBC, platelets, pCO2, RDW, LUC count, alkaline phosphatase and albumin.

ConclusionOur prognostic model highlights the nuance of determining risk for COVID-19 patients and indicates that, rather than a single variable, a range of factors (at different points in hospitalization) are needed for effective risk stratification.


title: Prophylactic post-operative high flow nasal oxygen versus conventional oxygen therapy in obese patients undergoing bariatric surgery (OXYBAR study): a pilot randomised controlled trial

abstract: Obesity has become a global pandemic, as a result surgical intervention for weight loss has increased in popularity. Obese patients undergoing operative intervention pose several challenges in respect of their peri-operative care. A prominent feature is the alteration in respiratory mechanics and physiology evident in the obese. These combine to predispose individuals to a reduction in end expiratory lung volume (EELV) and atelectasis after anaesthesia. Consequently, the incidence of post-operative pulmonary complications (PPC) in this cohort has been reported to be in excess of 35%. High flow nasal oxygen (HFNO) has been suggested as a means of increasing EELV in post-operative patients, reducing the likelihood of PPC. We conducted a single centre, pilot, randomised controlled trial (RCT) of conventional oxygen therapy versus HFNO in patients after bariatric surgery. The aim of the study was to investigate the feasibility of using Electrical Impedance Tomography (EIT) as a means of assessing respiratory mechanics and to inform the design of larger, definitive RCT. Fifty patients were randomised during a 10-month period (conventional O2 n=25 vs. HFNO n = 25). One patient crossed over from conventional O2 to HFNO. There was no loss to follow-up. and analyses were performed on an intention-to-treat basis. Delta EELI was higher at 1 hour in patients receiving HFNO (mean difference = 831 Au (95% CI -1636 - 3298), p = 0.5). Continuous EIT beyond 1 hour was poorly tolerated. At 6 hours, there were no differences in PaO2/FiO2 ratio or PaCO2. ICU and hospital LOS were comparable. Only one patient developed a PPC (in the HFNO group). In a secondary analysis, delta EELI was positively correlated with increasing BMI. These data suggest that a large-scale randomised controlled trial of HFNO after bariatric surgery in an  all-comers population is likely infeasible. Furthermore, while EIT is a useful tool for assessing respiratory mechanics in this group it could not be considered a patient-centred outcome in a larger study. Similarly, the infrequency of PPC precludes its use as a primary outcome in a definitive trial. Future studies should focus on identifying patients most at risk for post-operative pulmonary complications and those in whom HFNO is likely to confer greatest benefit.


title: Exponential increase in neutralizing and spike specific antibodies following vaccination of COVID-19 convalescent plasma donors

abstract:
BackgroundWith the recent approval of COVID-19 vaccines, recovered COVID-19 subjects who are vaccinated may be ideal candidates to donate COVID-19 convalescent plasma (CCP).

Case SeriesThree recovered COVID-19 patients were screened to donate CCP. All had molecularly confirmed COVID-19, and all were antibody positive by chemiluminescence immunoassay (DiaSorin) prior to vaccination. All were tested again for antibodies 11 to 21 days after they received the first dose of the vaccine (Pfizer). All showed dramatic increases ([~]50 fold) in spike-specific antibody levels and had at least a 20-fold increase in the IC50 neutralizing antibody titer based on plaque reduction neutralization testing (PRNT). The spike-specific antibody levels following vaccination were significantly higher than those seen in any non-vaccinated COVID-19 subjects tested to date at our facility.

ConclusionSpike-specific and neutralizing antibodies demonstrated dramatic increases following a single vaccination post COVID-19 infection which significantly exceeded values seen with COVID-19 infection alone. Recovered COVID-19 subjects who are vaccinated may make ideal candidates for CCP donation.

category: allergy and immunology


title: Deep Learning Prediction of Biomarkers from Echocardiogram Videos

abstract: Laboratory blood testing is routinely used to assay biomarkers to provide information on physiologic state beyond what clinicians can evaluate from interpreting medical imaging. We hypothesized that deep learning interpretation of echocardiogram videos can provide additional value in understanding disease states and can predict common biomarkers results. Using 70,066 echocardiograms and associated biomarker results from 39,460 patients, we developed EchoNet-Labs, a video-based deep learning algorithm to predict anemia, elevated B-type natriuretic peptide (BNP), troponin I, and blood urea nitrogen (BUN), and abnormal levels in ten additional lab tests. On held-out test data across different healthcare systems, EchoNet-Labs achieved an area under the curve (AUC) of 0.80 in predicting anemia, 0.82 in predicting elevated BNP, 0.75 in predicting elevated troponin I, and 0.69 in predicting elevated BUN. We further demonstrate the utility of the model in predicting abnormalities in 10 additional lab tests. We investigate the features necessary for EchoNet-Labs to make successful predictions and identify potential prediction mechanisms for each biomarker using well-known and novel explainability techniques. These results show that deep learning applied to diagnostic imaging can provide additional clinical value and identify phenotypic information beyond current imaging interpretation methods.

category: cardiovascular medicine


title: COVID-19 infection and subsequent thromboembolism: A self-controlled case series analysis of a population cohort

abstract:
ObjectiveAn unexpectedly large number of people infected with Covid-19 had experienced a thrombotic event. This study aims to assess the associations between Covid-19 infection and thromboembolism including myocardial infarction (MI), ischaemic stroke, deep-vein thrombosis (DVT), and pulmonary embolism (PE).

Patients and MethodsA self-controlled case-series study was conducted covering the whole of Scotlands general population. The study population comprised individuals with confirmed (positive test) Covid-19 and at least one thromboembolic event between March 2018 and October 2020. Their incidence rates during the risk interval (5 days before to 56 days after the positive test) and the control interval (the remaining periods) were compared intra-personally.

ResultsAcross Scotland, 1,449 individuals tested positive for Covid-19 and experienced a thromboembolic event. The risk of thromboembolism was significantly elevated over the whole risk period but highest in the 7 days following the positive test (IRR 12.01, 95% CI 9.91-14.56) in all included individuals. The association was also present in individuals not originally hospitalised for Covid-19 (IRR 4.07, 95% CI 2.83-5.85). Risk of MI, stroke, PE and DVT were all significantly higher in the week following a positive test. The risk of PE and DVT was particularly high and remained significantly elevated even 56 days following the test.

ConclusionConfirmed Covid-19 infection was associated with early elevations in risk with MI, ischaemic stroke, and substantially stronger and prolonged elevations with DVT and PE both in hospital and community settings. Clinicians should consider thromboembolism, especially PE, among people with Covid-19 in the community.


title: Thromboembolic risk in hospitalised and non-hospitalised Covid-19 patients: A self-controlled case series analysis of a nation-wide cohort


title: Risk factors of uncontrolled hypertension in urban slums of Central India : A Community health worker based two-year follow up

abstract:
BackgroundHypertension is a leading cause of cardiovascular diseases its control is poor. There exists heterogeneity in levels of blood-pressure control among various population sub-groups. Present study conducted in framework of National Program for prevention and control of cancer, diabetes, cardiovascular diseases and stroke (NPCDCS) in India, aims to estimate proportion of optimal blood pressure control and identify potential risk factors pertaining uncontrolled hypertension consequent to initial screening.

MethodsWe conceived a cohort of individuals with hypertension confirmed in a baseline screening in sixteen urban slum clusters of Bhopal (2017-2018). Sixteen Accredited Social Health Activists (ASHAs) were trained from within these urban slum communities. Individuals with hypertension were linked to primary care providers and followed-up for next two years. Obtaining optimal blood-pressure control (defined as SBP< 140 and DBP<90 mm of Hg) was a key outcome. Role of baseline anthropometric, and CVD risk factors was evaluated as predictors of blood-pressure control on univariate and multivariate analysis.

ResultsOf a total of 6174 individuals, 1571 (25.4%) had hypertension, of which 813 were previously known and 758 were newly detected during baseline survey. Two year follow up was completed for 1177 (74.9%). Blood-pressure was optimally controlled in 301 (26%) at baseline, and in 442 (38%) individuals at two years (absolute increase of 12%; 95% CI 10.2-13.9). Older age, physical-inactivity, higher BMI and newly diagnosed hypertension were significantly associated with uncontrolled blood-pressure.

ConclusionsIn the current study we found about six of every ten individuals with hypertension were on-treatment, and about four were optimally controlled. These findings provide a benchmark for NPCDCS, in terms of achievable goals within short periods of follow-up.