title: Minority and Rural Coronavirus Insights Study (MRCIS): The Need for Targeted COVID-19 Vaccination Efforts in Minority Populations

abstract:
ImportanceRacial and ethnic minority populations have been disproportionately affected in terms of hospitalizations and deaths during the COVID-19 pandemic. Vaccine uptake remains a barrier to full population inoculation against this highly infectious disease.

ObjectiveThe purpose of this report is to describe SARS-CoV-2 vaccine interest rates in a racially, geographically, and ethnically diverse study cohort and characterize vaccine interest across a racially, ethnically, and geographically diverse study population.

DesignThis report describes responses to a survey administered between November 2020 and May 2021 using a community convenience sample through a partnership between the National Minority Quality Forum (NMQF) and Federally Qualified Health Centers (FQHCs) as part of the Minority and Rural Coronavirus Insights Study (MRCIS). Analysis of survey responses from 3,624 participants are provided.

ResultsEarly data from the MRCIS cohort suggest that "SARS-CoV-2 vaccine hesitancy" is more prevalent in Black versus Non-Hispanic Whites survey respondents, and the Hispanic community has positive interest in the vaccine, to a similar degree as Whites. The persistent presence of "vaccine undecideds" across different sites and racial/ethnic groups uncovers the need for more public health efforts to influence positive views about vaccination.

ConclusionThese findings highlights the urgent need for interventional educational campaigns targeted at populations at risk of low vaccine interest. Focused efforts are needed to combat misinformation and explain the vaccines safety and effectiveness to promote its uptake and avoid low inoculation rates. Public health communication must consider differences in population groups, regions, and social determinants of health to fully address vaccine uptake disparities and overcome alleged hesitancy.

Key PointsO_LIWillingness to receive the SARS CoV-2 varies among minority populations.
C_LIO_LI"SARS-CoV-2 vaccine hesitancy" is more prevalent in the non-Hispanic Black population than the non-Hispanic White and Hispanic populations.
C_LIO_LIPublic health infrastructure is needed in underserved communities for efficient assessment and targeted communication of public health priorities such as the SARS CoV-2 vaccination.
C_LI


title: Characterizing the spatiotemporal heterogeneity of the COVID-19 vaccination landscape

abstract: It is critical that we maximize vaccination coverage across the United States so that SARS-CoV-2 transmission can be suppressed, and we can sustain the recent reopening of the nation. Maximizing vaccination requires that we track vaccination patterns to measure the progress of the vaccination campaign and target locations that may be undervaccinated. To improve efforts to track and characterize COVID-19 vaccination progress in the United States, we integrate CDC and state-provided vaccination data, identifying and rectifying discrepancies between these data sources. We find that COVID-19 vaccination coverage in the US exhibits significant spatial heterogeneity at the county level and statistically identify spatial clusters of undervaccination, all with foci in the southern US. Vaccination progress at the county level is also variable; many counties stalled in vaccination into June 2021 and few recovered by July, with transmission of the Delta variant rapidly rising. Using a comparison with a mechanistic growth model fitted to our integrated data, we classify vaccination dynamics across time at the county scale. Our findings underline the importance of curating accurate, fine-scale vaccination data and the continued need for widespread vaccination in the US, especially in the wake of the highly transmissible Delta variant.

category: public and global health


title: Time trends in social contacts before and during the COVID-19 pandemic: the CONNECT study

abstract:
BackgroundSince the beginning of the COVID-19 pandemic, many countries, including Canada, have adopted unprecedented physical distancing measures such as closure of schools and non-essential businesses, and restrictions on gatherings and household visits. We described time trends in social contacts for the pre-pandemic and pandemic periods in Quebec, Canada.

MethodsCONNECT is a population-based study of social contacts conducted shortly before (2018/2019) and during the COVID-19 pandemic (April 2020 - February 2021), using the same methodology for both periods. We recruited participants by random-digit-dialing and collected data by self-administered web-based questionnaires. Questionnaires documented socio-demographic characteristics and social contacts for two assigned days. A contact was defined as a two-way conversation at a distance [≤]2 meters or as a physical contact, irrespective of masking. We used weighted generalized linear models with a Poisson distribution and robust variance (taking possible overdispersion into account) to compare the mean number of social contacts over time by characteristics.

ResultsA total of 1291 and 5516 Quebecers completed the study before and during the pandemic, respectively. Contacts significantly decreased from a mean of 8 contacts/day prior to the pandemic to 3 contacts/day during the spring 2020 lockdown. Contacts remained lower than the pre-COVID period thereafter (lowest=3 contacts/day during the Christmas 2020/2021 holidays, highest=5 in September 2020). Contacts at work, during leisure activities/other locations, and at home with visitors showed the greatest decreases since the beginning of the pandemic. All sociodemographic subgroups showed significant decreases of contacts since the beginning of the pandemic. The mixing matrices illustrated the impact of public health measures (e.g. school closure, gathering restrictions) with fewer contacts between children/teenagers and fewer contacts outside of the three main diagonals of contacts between same-age partners/siblings and between children and their parents.

ConclusionPhysical distancing measures in Quebec significantly decreased social contacts, which most likely mitigated the spread of COVID-19.


title: Beyond the limits of circadian entrainment: Non-24-hour sleep-wake disorder, shift work, and social jet lag

abstract: AO_SCPLOWBSTRACTC_SCPLOWWhile the vast majority of humans are able to entrain their circadian rhythm to the 24-hour light-dark cycle, there are numerous individuals who are not able to do so due to disease or societal reasons. We use computational and mathematical methods to analyze a well-established model of human circadian rhythms to address cases where individuals do not entrain to the 24-hour light-dark cycle, leading to misalignment of their circadian phase. For each case, we provide a mathematically justified strategy for how to minimize circadian misalignment. In the case of non-24-hour sleep-wake disorder, we show why appropriately timed bright light therapy induces entrainment. With regard to shift work, we explain why reentrainment times following transitions between day and night shifts are asymmetric, and how higher light intensity enables unusually rapid reentrainment after certain transitions. Finally, with regard to teenagers who engage in compensatory catch-up sleep on weekends, we propose a rule of thumb for sleep and wake onset times that minimizes circadian misalignment due to this type of social jet lag. In all cases, the primary mathematical approach involves understanding the dynamics of entrainment maps that measure the phase of the entrained rhythm with respect to the daily onset of lights.


title: Feasibility and acceptability of daily testing at school as an alternative to self-isolation following close contact with a confirmed case of COVID-19: A qualitative analysis

abstract:
BackgroundDaily testing using a rapid Lateral Flow Device (LFD) has been suggested as an alternative to self-isolation. A randomised trial comparing daily contact testing (DCT) in schools with self-isolation found that SARS-CoV-2 transmission within school was comparable and low in both groups. However, if this approach is to be adopted widely, it is critical that we understand the perspective of those who will be delivering and receiving DCT. The aim of this qualitative process study embedded in the randomised controlled trial (RCT) was to improve understanding of a range of behavioural factors that could influence implementation.

MethodsInterviews were conducted with 63 participants, including staff, students, and parents of students who had been identified as being in close contact with someone with COVID-19. The topic guide explored perceptions of daily testing, understanding of positive and negative test results, and adherence to guidance. Data were analysed using an inductive thematic approach.

ResultsResults were organised under three main headings: (1) factors influencing daily testing (2) interpretation of test results (3) behaviour during testing period. Participants recognized that daily testing may allow students to remain in school, which was viewed as necessary for both education and social needs. Whilst some felt safer as a result of daily testing, others raised concerns about safety. Participants did not always understand how to interpret and respond to test results, and although participants reported high levels of adherence to the guidance, improved communications were desired.

ConclusionDaily testing may be a feasible and acceptable alternative to self-isolation among close contacts of people who test positive. However, improved communications are needed to ensure that all students and parents have a good understanding of the rationale for testing, what test results mean, how test results should be acted on, and how likely students are to test positive following close contact. Support is needed for students and parents of students who have to self-isolate and for those who have concerns about the safety of daily testing.


title: A twelve-month projection to September 2022 of the Covid-19 epidemic in the UK using a Dynamic Causal Model

abstract:
ObjectivesPredicting the future UK Covid-19 epidemic allows other countries to compare their epidemic with one unfolding without public health measures except a vaccine programme.

MethodsA Dynamic Causal Model (DCM) is used to estimate the model parameters of the epidemic such as vaccine effectiveness and increased transmissibility of alpha and delta variants, the vaccine programme roll-out and changes in contact rates. The model predicts the future trends in infections, long-Covid, hospital admissions and deaths.

ResultsTwo dose vaccination given to 66% of the UK population prevents transmission following infection by 44%, serious illness by 86% and death by 93%. Despite this, with no other public health measures used, cases will increase from 37 million to 61 million, hospital admission from 536,000 to 684,000 and deaths from 136,000 to 142,000 over twelve months.

DiscussionVaccination alone will not control the epidemic. Relaxation of mitigating public health measures carries several risks - overwhelming the health services, the creation of vaccine resistant variants and the economic cost of huge numbers of acute and chronic cases.


title: ToKSA - Tokenized Key Sentence Annotation - a Novel Method for Rapid Approximation of Ground Truth for Natural Language Processing

abstract:
ObjectiveIdentifying phenotypes and pathology from free text is an essential task for clinical work and research. Natural language processing (NLP) is a key tool for processing free text at scale. Developing and validating NLP models requires labelled data. Labels are generated through time-consuming and repetitive manual annotation and are hard to obtain for sensitive clinical data. The objective of this paper is to describe a novel approach for annotating radiology reports.

Materials and MethodsWe implemented tokenized key sentence-specific annotation (ToKSA) for annotating clinical data. We demonstrate ToKSA using 180,050 abdominal ultrasound reports with labels generated for symptom status, gallstone status and cholecystectomy status. Firstly, individual sentences are grouped together into a term-frequency matrix. Annotation of key (i.e. the most frequently occurring) sentences is then used to generate labels for multiple reports simultaneously. We compared ToKSA-derived labels to those generated by annotating full reports. We used ToKSA-derived labels to train a document classifier using convolutional neural networks. We compared performance of the classifier to a separate classifier trained on labels based on the full reports.

ResultsBy annotating only 2,000 frequent sentences, we were able to generate labels for symptom status for 70,000 reports (accuracy 98.4%), gallstone status for 85,177 reports (accuracy 99.2%) and cholecystectomy status for 85,177 reports (accuracy 100%). The accuracy of the document classifier trained on ToKSA labels was similar (0.1-1.1% more accurate) to the document classifier trained on full report labels.

ConclusionToKSA offers an accurate and efficient method for annotating free text clinical data.

category: radiology and imaging


title: Personalizing deep brain stimulation using advanced imaging sequences

abstract:
ObjectiveWith a growing appreciation for interindividual anatomical variability and patient-specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their broad implementation in clinical practice.

MethodsUsing fast gray matter acquisition T1 inversion recovery (FGATIR) sequences, the present study identified a thalamic hypointensity that holds promise as a visual marker in DBS. To validate the clinical utility of the identified hypointensity we retrospectively analyzed 65 patients (26 female, mean age: 69.1{+/-}12.7 years) who underwent DBS in the treatment of essential tremor. We characterized its neuroanatomical substrates and evaluated the hypointensitys ability to predict clinical outcome using stimulation volume modeling and voxel-wise mapping. Finally, we determined whether the hypointensity marker could predict symptom improvement on a patient-specific level.

ResultsAnatomical characterization suggested that the identified hypointensity constituted the terminal part of the dentato-rubro-thalamic tract. Overlap between DBS stimulation volumes and the hypointensity in common space significantly correlated with tremor improvement (R2=0.16, p=0.017) and distance to hotspots previously reported in the literature (R2=0.49, p=7.9e-4). In contrast, the amount of variance explained by other anatomical atlas structures was reduced. When accounting for interindividual neuroanatomical variability, the predictive power of the hypointensity increased further (R2=0.37, p=0.002).

InterpretationOur findings introduce and validate a novel imaging-based marker attainable from FGATIR sequences that has the potential to personalize and inform targeting and programming in DBS for essential tremor.


title: Single-Molecule Detection of SARS-CoV-2 by Plasmonic Sensing of Isothermally Amplified Nucleic Acids

abstract:
Single-molecule detection of pathogens such as SARS-CoV-2 is key to combat infectious diseases outbreak and pandemic. Currently colorimetric sensing with loop-mediated isothermal amplification (LAMP) provides simple readouts but suffers from intrinsic non-template amplification. Herein, we report that plasmonic sensing of LAMP amplicons via DNA hybridization allows highly specific and single-molecule detection of SARS-CoV-2 RNA. Our work has two important advances. First, we develop gold and silver alloy (Au-Ag) nanoshells as plasmonic sensors that have 4-times stronger extinction in the visible wavelengths and give 20-times lower detection limit for oligonucleotides than Au nanoparticles. Second, we demonstrate that the diagnostic method allows cutting the complex LAMP amplicons into short repeats that are amendable for hybridization with oligonucleotide-functionalized nanoshells. This additional sequence identification eliminates the contamination from non-template amplification. The detection method is a simple and single-molecule diagnostic platform for virus testing at its early representation.

Table of Content

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category: respiratory medicine


title: The Effect of Headgear Use on Concussion Injury Rates in Girls' High School Lacrosse

abstract:
ObjectivesThe use of headgear is a controversial issue in girls lacrosse. We compared concussion rates among high school lacrosse players wearing versus not wearing lacrosse headgear.

MethodsStudy participants included a sample of convenience of high schools with girls lacrosse from across the United States. Certified athletic trainers reported athlete exposure and injury data via the National Athletic Treatment, Injury and Outcomes Network during the 2019 through 2021 seasons. The Headgear cohort was inclusive of high schools from the state of Florida, which mandate the use of ASTM standard F3137 headgear, while the Non-Headgear cohort was inclusive of the remaining states, none of which have headgear mandates. Incidence Rate Ratios (IRR) and 95% Confidence Intervals (CI) were calculated. IRRs with corresponding CIs that excluded 1.00 were deemed statistically significant.

Results141 concussions (Headgear: 25; Non-Headgear: 116) and 357,225 Athlete Exposures (AE) were reported (Headgear: 91,074AE; Non-Headgear: 266,151AE) across all games and practices. Overall, the concussion injury rate per 1000AE was significantly higher in the Non-Headgear cohort (0.44) than the Headgear Cohort (0.27) (IRR=1.59, 95% CI:1.03 - 2.45). The IRR was significantly higher for the Non-Headgear cohort during games (1.74, 95% CI: 1.00, 3.02) but not for practices (1.42, 95% CI: 0.71, 2.83).

ConclusionsThese findings indicate that concussion rates among high school girls lacrosse players not wearing headgear were 59% higher than those wearing headgear. These data support the use of protective headgear to reduce the risk of concussion among high school female lacrosse athletes.

SummaryO_ST_ABSWhat are the new findingsC_ST_ABSO_LIThe use of lacrosse headgear meeting the ASTM F3137 standard was associated with a lower risk of experiencing a concussion injury among high school girls lacrosse players.
C_LI

How might these findings impact clinical practice in the future?O_LILacrosse headgear may be warranted for use for concussion risk mitigation among high school girls lacrosse players.
C_LIO_LILacrosse headgear may be considered for concussion risk mitigation at other levels of play such as the youth or collegiate levels; further study is warranted.
C_LI

category: sports medicine


title: Enhancing Tele-Simulation during OSCE: Incorporating Feedback from Standardized Patients

abstract:
BackgroundAs COVID-19 impacted universities across the globe for over one year, the organization of OSCEs also demanded change. The traditional OSCEs had to transition to Tele simulation OSCEs. As the pandemic continues, there is possibility that this approach may continue for some time, it is imminent to capture feedback from the simulated patients so that we can explore ways to improve in future.

ObjectivesTo gather feedback from standardized patients doing Tele Simulation in OSCEs, To develop plans to improve Tele Simulation involving Standardized Patients based on the feedback gathered.

MethodData were collected immediately after Tele simulation OSCE during debriefing from 18 Simulated Patients. This was followed up with an open-ended questionnaire and gathered additional information.

ResultsThe feedback from SPs included their feelings when they were introduced to Tele simulation OSCE, Tele simulation versus Face to Face OSCE and areas of improvement.

ConclusionTele simulation OSCE was a quick adaptation during COVID-19 pandemic. But the lessons learned, and the feedback received are pearls for future innovative approaches to assessments. It is encouraged to collect verbal and written feedback for the improvement of Tele simulation.

category: medical education


title: Changes in ischemic stroke presentations and associated workflow during the first wave of the COVID-19 pandemic: A population study in Alberta, Canada

abstract:
BackgroundPandemics may promote hospital avoidance among patients with emergencies, and added precautions may exacerbate treatment delays. There is a paucity of population-based data on these phenomena for stroke. We examined the effect of the COVID-19 pandemic on the presentation and treatment of ischemic stroke in an entire population.

MethodsWe used linked provincial administrative data and data from the Quality Improvement and Clinical Research Alberta Stroke Program - a registry capturing stroke-related data on the entire population of Alberta(4.3 million)- to identify all patients presenting with stroke in the pre-pandemic(1-January-2016 to 27-February-2020, n=19,531) and pandemic(28-February-2020 to 30-August-2020, n=2,255) periods. We examined changes in thrombolysis and endovascular therapy(EVT) rates, workflow, and in-hospital outcomes.

ResultsHospitalizations/presentations for ischemic stroke dropped (weekly adjusted-incidence-rate-ratio[aIRR]:0.48, 95%CI:0.46-0.50, adjusted for age, sex, comorbidities, pre-admission care needs), as did population-level incidence of thrombolysis(aIRR:0.49,0.44-0.56) or EVT(aIRR:0.59,0.49-0.69). However, the proportions of presenting patients receiving acute therapies did not decline (e.g. thrombolysis:11.7% pre-pandemic vs 13.1% during-pandemic, aOR:1.02,0.75-1.38). Onset-to-door times were prolonged; EVT recipients experienced longer door-to-reperfusion times (median door-to-reperfusion:110-minutes, IQR:77-156 pre-pandemic vs 132.5-minutes, 99-179 during-pandemic; adjusted-coefficient:18.7-minutes, 95%CI:1.45-36.0). Hospitalizations were shorter but stroke severity and in-hospital mortality did not differ.

InterpretationThe first COVID-19 wave was associated with a halving of presentations and acute therapy utilization for ischemic stroke at a population level, and greater pre-hospital and in-hospital treatment delays. Our data can inform public health messaging and stroke care in current and future waves. Messaging should encourage attendance for emergencies and stroke systems should re-examine "code stroke" protocols to mitigate inefficiencies.

category: neurology


title: Correlation between leukocyte phenotypes and prognosis of amyotrophic lateral sclerosis: a longitudinal cohort study

abstract:
BackgroundImmune response changes have been reported in amyotrophic lateral sclerosis (ALS), but their clinical relevance remains undetermined. Therefore, we aim to evaluate the relationships between blood leukocyte subpopulations and prognosis of ALS.

MethodsA longitudinal cohort of 288 ALS patients with up to 5 years of follow-up during 2015-2020 were recruited at the only tertiary referral center for ALS in Stockholm, Sweden. Routine differential leukocyte counts, and determination of lymphocyte subpopulations including an extended T cell panel with flow cytometry, collected at diagnosis and at regular intervals thereafter. The primary outcome was risk of death (alternatively use of invasive ventilation) after diagnosis of ALS. The secondary outcomes included repeatedly measured functional status - through Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) score and disease progression rate. Cox model was used to evaluate the associations between leukocytes and risk of death. Generalized estimating equation model (GEE) was used to assess the correlation between leukocytes and ALSFRS-R score and disease progression rate.

ResultsThe counts of leukocytes, neutrophils and monocytes increased gradually over time since diagnosis and were negatively correlated with ALSFRS-R score, but not associated with risk of death or disease progression rate. Focusing on lymphocyte subpopulations, increasing counts of natural killer (NK) cells (HR=0.61, 95% CI= [0.42-0.88] per SD increase) and proportions of Th2-diffrentiated CD4+ central memory (CM) T cells (HR=0.64, 95% CI= [0.48-0.85] per SD increase) were correlated with a lower risk of death. Increasing proportions of CD4+ effector memory cells re-expressing CD45RA (EMRA) T cells (HR=1.39, 95% CI= [1.01-1.92] per SD increase) and CD8+ T cells (HR=1.38, 95% CI= [1.03-1.86] per SD increase) were associated with a higher risk of death. None of the lymphocyte subpopulations was correlated with ALSFRS-R score or disease progression rate.

ConclusionOur findings suggest a dual role of immune responses in ALS prognosis, where neutrophils and monocytes primarily reflect functional status whereas NK cells and different T lymphocyte populations act as prognostic markers for survival. The findings also provide insights for cell-specific treatment for ALS.

FundingThis work was supported by the European Research Council (ERC) Starting Grant (MegaALS, No. 802091), the Swedish Research Council (No. 2019-01088), Karolinska Institutet (Strategic Research Area in Epidemiology and Senior Researcher Award), and China Scholarship Council.


title: Prenatal maternal distress during the COVID-19 pandemic and its effects on the infant brain

abstract: The COVID-19 pandemic has caused elevated distress in pregnant individuals, which has the potential to impact the developing infant. In this study, we examined anxiety and depression symptoms during the pandemic in a large sample of pregnant individuals (n=8602). For a sub-sample of participants, their infants underwent magnetic resonance imaging (MRI) at 3-months of age to examine whether this prenatal maternal distress was associated with infant brain changes. We found significantly elevated prenatal maternal distress compared to pre-pandemic rates, with 47% and 33% of participants reporting clinically significant symptoms of anxiety and depression, respectively. Importantly, we identified social support as a protective factor for clinically elevated prenatal maternal distress. We found significant relationships between prenatal maternal distress and infant amygdala-prefrontal microstructural and functional connectivity and demonstrate for the first time that social support moderates this relationship. Our findings suggest a potentially long-lasting impact of the COVID-19 pandemic on children and show that social support acts as a protective factor not just for pregnant individuals, but also for their developing infants. These findings provide timely evidence to inform clinical practice and policy surrounding the care of pregnant individuals and highlight the importance of social support.


title: Transcriptomic analysis of frontotemporal lobar degeneration with TDP-43 pathology reveals cellular alterations across multiple brain regions

abstract: Frontotemporal lobar degeneration (FTLD) is a group of heterogeneous neurodegenerative disorders affecting the frontal and temporal lobes of the brain. Nuclear loss and cytoplasmic aggregation of the RNA-binding protein TDP-43 represents the major FTLD pathology, known as FTLD-TDP. To date, there is no effective treatment for FTLD-TDP due to an incomplete understanding of the molecular mechanisms underlying disease development. Here we compared post-mortem tissue RNA-seq transcriptomes from the frontal cortex, temporal cortex and cerebellum between 28 controls and 30 FTLD-TDP patients to profile changes in cell-type composition, gene expression and transcript usage. We observed downregulation of neuronal markers in all three regions of the brain, accompanied by upregulation of microglia, astrocytes, and oligodendrocytes, as well as endothelial cells and pericytes, suggesting shifts in both immune activation and within the vasculature. We validate our estimates of neuronal loss using neuropathological atrophy scores and show that neuronal loss in the cortex can be mainly attributed to excitatory neurons, and that increases in microglial and endothelial cell expression are highly correlated with neuronal loss. All our analyses identified a strong involvement of the cerebellum in the neurodegenerative process of FTLD-TDP. Altogether, our data provides a detailed landscape of gene expression alterations to help unravel relevant disease mechanisms in FTLD.


title: Information, Involvement, Self-care and Support - The Needs of Caregivers of People with Stroke: A Grounded Theory Approach

abstract:
BackgroundGlobally, stroke is a leading cause of death and disability, with most care undertaken by caregivers who are generally family and friends without prior experience of care. The lack of experience or unpreparedness results in feelings of uncertainty, burnout, anxiety, burden, etc. Hence, it is necessary to identify the needs of caregivers to support them in their caregiving journey better and improve the quality of care delivered.

MethodsThe study employed a grounded theory methodology that utilizes information gathered from literature reviews and social media to represent the needs and create a storyline visually. The storyline is further refined and evaluated using an online survey of 72 participants recruited through online stroke caregiving communities.

ResultsThe study identified four core categories of needs, i.e., information, involvement, self-care and support that need to be delivered at appropriate times to ensure the caregivers feel prepared to assume their role of care and are supported throughout the care trajectory.

ConclusionsThere is a need to create a caregiver-centered approach in stroke recovery to ensure limited obstruction to care and reduced uncertainty in recovery. Moreover, through the inclusion of caregivers in the recovery process, it may be possible to reduce the burden of care to the caregiver and ensure the satisfaction of the healthcare system throughout recovery.

category: nursing


title: Red cell folate status among a subset of Canadian children with Down Syndrome post-fortification.

abstract:
BackgroundTrisomy 21 or Down Syndrome (DS) is associated with altered methylation pathways. Children with DS may therefore represent a population subgroup with vulnerability to increased exposures to folic acid, which is involved in one-carbon metabolism. Folic acid (FA) fortification of flour and maternal FA supplementation are intended to reduce neural tube defects related to folate deficiency. The interventions have been widely successful in Canada. Emerging evidence suggests that higher FA exposures may also have potential negative consequences, including implications for DNA methylation. This retrospective chart review provides insight on the RBC folate status of a subset of Canadian children and infants with DS, post-fortification.

MethodChildren with DS in 2 Canadian provinces were assessed in the community. Access to RBC folate testing was variable, limiting sample size to 39 (n=27 for children [≤] 6 years; n=12 for children 6-18 years). All children with DS and an RBC folate result were included. Use of FA-containing supplements and formula was documented.

ResultsAmong children 6-18 years, 100% had RBC folates > 1000 nmol/L, 50% were > 2000 nmol/L and 25% had levels above the reporting limit. Among the younger children (< 6 years), 52 % had RBC folates >2000 nmol and 2 children exceeded 3000 nmol/L. Among exclusively breast-fed infants (<12 months), 100% had RBC folates > 1000 nmol/L and 50% had levels > 2000 nmol/L, suggestive of in-utero or maternal exposures. RBC folate status among this subset of Canadian children with DS is higher than documented for the larger Canadian population, and higher than among US children with DS.

ConclusionsYoung Canadian children with DS demonstrated high post-fortification RBC folate status. RBC folate status was higher than reported for the larger Canadian population, and higher than for US children with Down Syndrome. Consumption of folic acid-containing formula and/or supplements was relatively low among these Canadian children with DS, suggesting maternal FA supplements and/or FA-fortified foods may be important etiological factors. A larger, prospective study is needed to validate these results, and to explore potential health implications among this vulnerable population.

category: nutrition


title: A clinical trial to evaluate the dayzz smartphone app on employee sleep, health, and productivity at a large US employer

abstract: Sleep deficiency is a hidden cost of our 24-7 society, with 70% of adults in the US admitting that they routinely obtain insufficient sleep. Further, it is estimated that 50-70 million adults in the US have a sleep disorder. Undiagnosed and untreated sleep disorders are associated with diminished health for the individual and increased costs for the employer. Research has shown that adverse impacts on employees and employers can be mitigated through sleep health education and sleep disorder screening and treatment programs. Smartphone applications (app) are increasingly commonplace and represent promising, scalable modalities for such programs. The dayzz app is a personalized sleep training program that incorporates assessment of sleep disorders and offers a personalized comprehensive sleep improvement solution. Using a sample of day workers affiliated with a large institution of higher education, we will conduct a single-site, parallel-group, randomized, waitlist control trial. Participants will be randomly assigned to either use the dayzz app throughout the study or receive the dayzz app at the end of the study. We will collect data on feasibility and acceptability of the dayzz app; employee sleep, including sleep behavioral changes, sleep duration, regularity, and quality; employee presenteeism, absenteeism, and performance; employee mood; adverse and safety outcomes; and healthcare utilization on a monthly basis throughout the study, as well as collect more granular daily data from the employee during pre-specified intervals. Our results will illuminate whether a personalized smartphone app is a viable approach for improving employee sleep, health, and productivity.

category: occupational and environmental health


title: Detecting respiratory chain deficiency in osteoblasts of older patients

abstract:
Mitochondria contain their own genome which encodes 13 essential mitochondrial proteins and accumulates somatic variants at up to 10 times the rate of the nuclear genome. These mitochondrial genome variants lead to respiratory chain deficiency and cellular dysfunction. Work with the PolgAmut/PolgAmut mouse model, which has a high mitochondrial DNA mutation rate, showed enhanced levels of age related osteoporosis in affected mice along with respiratory chain deficiency in osteoblasts. To explore whether respiratory chain deficiency is also seen in human osteoblasts with age, we developed a protocol and analysis framework for imaging mass cytometry (IMC) in bone tissue sections to analyse osteoblasts in situ. We have demonstrated significant increases in complex I deficiency with age in human osteoblasts. This work is consistent with findings from the PolgAmut/PolgAmut mouse model and suggests that respiratory chain deficiency, as a consequence of the accumulation of age related mitochondrial DNA mutations, may have a significant role to play in the pathogenesis of human age related osteoporosis.

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category: orthopedics


title: A gender-bias-mitigated, data-driven precision medicine system to assist in the selection of biological treatments of grade 3 and 4 knee osteoarthritis: development and preliminary validation of precisionKNEE

abstract:
IntroductionOsteoarthritis is a leading cause of global disability and is set to worsen with the concurrent rise in rates of obesity and an ageing population [1]. Current clinical solutions are sub-optimal with regards to their invasiveness and outcomes. Orthopaedic biologics is an emerging field that offers alternative and parallel treatment options to address this problem. Determining which patients will benefit most from these novel treatments is key in developing clinical pathways.

MethodsOur dataset included 329 patients treated with microfragmented fat injection (MFAT) over a 2 year period. Clinico-demographic data was recorded as well as 1-year Oxford Knee Score (OKS). The data was modelled to predict OKS 1-year response using Random Forest Regressors. Gender-bias was mitigated and outliers were hidden from the training model. The model was validated on raw test data and on a subset of patients with Kellgren-Lawrence grade 3 and 4 radiological evidence of arthritis, age greater than 64, preoperative OKS less than or equal to 27 and idiopathic aetiology of arthritis.

ResultsThe mean age and mean body mass index (BMI) of patients in our dataset was 66.4 years, 26.9 respectively. 53.5% of patients had Kellgren-Lawrence grade 4 arthritis.

The final models RMSE was 6.72, MAE was 5.38 and r-squared was 0.23 on raw test data. An RMSE of 9.77 and MAE of 7.81 was achieved when validating the model on our subset of patients. Wilcoxon signed rank tests found no evidence of predicted results being statistically significantly different to ground truth values (p {inverted question} 0.05).

Preoperative OKS and Kellgren-Lawrence arthritis grade was the most important feature in our model.

DiscussionOur model is performant and able to predict 1 year OKS response outcome within our set of patients. We have found key features of prediction and would recommend these are researched further to improve model performance.

Our dataset does not compare outcomes with other standard treatments. We also dont compare outcomes with other biologic treatments.

Ultimately, this research can be used as a tool to benefit both patients and clinicians in a combined decision-making process.


title: Estimating the Efficacy of Common Treatments in Children and Young Adults Diagnosed with Cerebral Palsy Using Three Machine Learning Algorithms

abstract:
BackgroundOrthopedic and neurological deformity are often treated in children and young adults with cerebral palsy (CP). Due to challenges arising from combinatorics, research funding priorities, and medical practicalities, the efficacy of these treatments is not well studied.

ObjectivesOur goal was to estimate the efficacy of 13 common orthopedic and neurological treatments at four different levels of outcome in children and young adults diagnosed with CP. The outcome levels considered were anatomy and physiology, gait parameter, overall gait pattern, and function.

MethodsWe used three well-establish causal inference approaches (direct matching, virtual twins, and Bayesian causal forests) and a large clinical gait analysis database to estimate the average treatment effect on the treated (ATT). We then examined the efficacy across treatments, methods, and outcome levels.

ResultsThe median ATT of 13 common treatments in children and young adults with CP, measured as Cohens D, bordered on medium at the anatomy and physiology level (median [IQR] = 0.42 [.05, .60]) and became smaller as we moved along the causal chain through gait parameter (0.21 [.01, .33]), overall gait pattern (0.09 [.03, .19]), and function (-0.01 [-.06, .13]).

ConclusionsCurrent treatments have medium effects on anatomy and physiology, but modest to minimal efficacy on gait and function. Further work is needed to understand the source of heterogeneous treatment effects, which are large in this patient population. Replication or refutation of these findings by other centers will be valuable to establish the generalizability of these results and for benchmarking of best practices.


title: Exploring the clinical consequences and genetic aetiology of adult weight trajectories

abstract:
BackgroundLongitudinal weight trajectories may reflect individual health status. We examined the genetic aetiology and clinical consequences of adult weight trajectories in males and females leveraging genetic and phenotypic data in the electronic health records (EHR) of the BioMe Biobank.

MethodsWe constructed four longitudinal weight trajectories using annual EHR-recorded weights (stable weight, weight gain, weight loss, or weight cycle) (n=21,487). After validating the accuracy of the trajectories (n=100), we conducted a hypothesis-free phenome-wide association study (PheWAS), including sex-stratified PheWAS, to identify diseases associated with each weight trajectory. We then performed a hypothesis-driven polygenic risk score (PRS) analysis on these weight trajectories, focusing on anorexia nervosa (AN) and depression--both commonly associated with weight changes.

FindingsWeight trajectory classification was highly accurate (accuracy, sensitivity, and specificity > 97% for all four trajectories). Hypothesis-free PheWAS analyses identified a significant association between depression and weight cycle (OR=1.4, p[≤]7.7x10-16) after Bonferroni correction, but not with weight gain or loss. Compared to other weight trajectories, we also observed a significant association of osteoporosis-related phecodes with weight loss in females only (ORfemale=1.4, pfemale[≤] 1.4x10-7, ORmale=0.8, pmale[≥] 0.18). AN-PRS was positively associated with weight loss trajectory among individuals without eating disorder diagnoses (ORtop vs. bottom 10% PRS=1.95, p=0.00035). Consistent effect direction was observed across three ancestry groups. The AN-PRS-weight loss association was not attenuated by obesity-PRS (ORtop vs. bottom 10% PRS=1.94).

InterpretationAdult weight trajectory is associated with disease both phenotypically and genetically. Our PheWAS reveals unique relationships between diseases and weight trajectory patterns, including the association of depression and weight cycle trajectory in both males and females, and osteoporosis-weight loss trajectory association in females only. In addition, our PRS analysis suggests that adults with higher AN genetic risk are more likely to have a weight loss trajectory, and this association may be independent of BMI/obesity-related genetic pathways.

FundingKlarman Family Foundation, NIMH.

Research in Context PanelO_ST_ABSEvidence before this studyC_ST_ABSWe used PubMed and medRxiv to search for phenome-wide association studies (PheWAS) of BMI/weight that have been published and/or are currently in preprint. For the weight PheWAS, we used search terms: "(phewas[tiab] OR phenome wide[tiab]) AND (weight[tiab] OR BMI[tiab] OR body mass index[tiab])" on PubMed, and "phewas weight", "phewas BMI", "phewas body mass index", "phenome weight", "phenome BMI", or "phenome body mass index" for abstract or title search on medRxiv (up to March 17, 2021). The literature search identified 45 studies in total. From title screening, 13 of the studies were further reviewed, and 5 studies were ultimately included as relevant evidence of PheWAS on weight or BMI. These five PheWAS included four studies of adult populations of European ancestry, and one study conducted in children (ALSPAC). The weight-related exposure variables used in these studies were genetic variants of the obesity-associated FTO gene, BMI-associated SNPs, BMI PRS, BMI value, and obesity status. Through using BMI/obesity-related exposures, these published PheWAS identified comorbidities associated with obesity, including type 2 diabetes, sleep apnea, hypertension, edema, liver disease, asthma, bronchitis, and earlier age of puberty in at least two of the PheWAS. The childhood PheWAS found positive associations of BMI PRS with multiple biomarkers, including leptin, C-reactive protein, IL6, triglyceride, very low-density lipoprotein, and a negative association with high density lipoprotein. One BMI PheWAS published in 2020 observed that hyperlipidemia and gastroesophageal reflux disease were only significantly associated with BMI on a phenotypic level, but not on a genetic level (e.g., BMI or obesity SNPs), likely due to the small genetic effect of single genetic variants.

Regarding the impact of anorexia nervosa (AN) and depression genetic risk on weight trajectory, we searched "anorexia nervosa[title] AND (weight[title] OR BMI[title] OR body mass index[title]) AND (genetic[tiab])" or "depression[title] AND (weight[title] OR BMI[title] OR body mass index[title]) AND (genetic[tiab])" on PubMed, and "anorexia polygenic weight" or "anorexia polygenic BMI" or "anorexia polygenic body mass index" or "depression polygenic weight" or "depression BMI" or "depression body mass index" for abstract or title search on medRxiv (up to March 17, 2021). The literature search identified 36 studies in total, and 21 were further reviewed through the title screening. No studies were identified that examined the effect of depression genetic risk on BMI or weight, and only two were included as relevant evidence of AN genetic risk on BMI and weight. Of these two studies, one was cross-sectional in a small adult sample (age 18-59, n=380), and the other was longitudinal in a children/young adult population in the ALSPAC cohort (age 10-24, n=8,654). BMI PRS was found to be associated with lower BMI cross-sectionally, and with weight loss over time only in females.

Added value of this studyIn this study, we create a novel inflection-point based method to classify longitudinal weight trajectory using weights recorded in the EHR in a hospital-based biobank (Mount Sinai BioMe Biobank), with an accuracy of 98% or higher through our validation study (n=100).

With this validated phenotype of weight pattern over time (i.e., weight trajectory), our PheWAS analysis afforded us the opportunity to examine comorbidity across the weight spectrum and across time. We identified 143 diseases associated with weight cycle (e.g., depression, anemias, renal failure),13 diseases positively associated with weight gain trajectory (e.g., obesity, obstructive sleep apnea, edema), and 36 with weight loss (e.g., protein-calorie malnutrition, gastrointestinal complication, end stage renal disease), after Bonferroni correction, using 5% as the cutoff for clinically relevant weight change. All diseases were negatively associated with a stable weight trajectory. Furthermore, we performed, to our knowledge, the first sex-stratified PheWAS related to weight trajectory, and identified eight sex-stratified associations with weight gain (e.g., obstructive sleep apnea), eight with weight loss (e.g., osteoporosis), and ten with weight cycle (e.g., vitamin B-complex deficiencies).

On a genetic level, our study fills in the gap of the impact of AN genetic risk on longitudinal weight changes in the adult population. Unlike the finding in adolescents in the ALSPAC study, which found an AN-PRS-weight loss trajectory association only in females, we found an association of higher AN genetic risk with weight loss trajectory in both men and women, with consistent effect direction observed across individuals with European, African, and Hispanic ancestry in the BioMe Biobank. Additionally, this association of AN genetics with weight loss was independent of the influence of obesity/BMI related genetic variants on weight.

Implications of all the available evidencePheWAS is an excellent tool for exploring comorbidities associated across the weight spectrum. Our PheWAS findings identify diseases with different weight patterns (e.g., depression and weight cycle), which may reflect characteristics of these diseases, including age of onset, progression pattern, severity, and chronicity (e.g., the episodic nature of depression with the weight cycle pattern). In addition, our sex-stratified PheWAS implicates the important role of sex in weight regulation in the presence of disease. Certain sub-populations may be at greater risk of weight loss in some disease states (e.g., women with osteoporosis) and may need targeted treatment to address nutritional needs and to prevent further weight loss.

Our study also suggests that people who have high AN genetic risk are at greater risk of displaying a weight loss trajectory during adulthood. However, given the limited amount of variation in the outcome of interest (e.g., weight loss) explained by the AN-PRS, the PRS may have to be jointly modeled with other risk factors to predict weight loss more accurately, or to identify subgroups at risk of weight loss. In addition, given our finding that the effect of AN genetics on weight loss was minimally affected by the obesity-related genetics, and the previously reported low genetic correlation of -0.22 between AN and obesity in the 2019 AN GWAS, this may indicate that AN- and obesity-related weight changes might have unique genetic underpinnings. Future studies that assess the pathway-specific genetic risk on weight pattern will further our understanding of the genetic architecture of longitudinal weight trajectory.

category: genetic and genomic medicine


title: Variation in influenza vaccine assessment, receipt, and refusal by the concentration of Medicare Advantage enrollees in U.S. nursing homes

abstract:
BackgroundMore older adults enrolled in Medicare Advantage (MA) are entering nursing homes (NHs), and MA concentration could affect vaccination rates through shifts in resident characteristics and/or payer related influences on preventive services use. We investigated whether rates of influenza vaccination and refusal differ across NHs with varying concentrations of MA-enrolled residents.

MethodsWe analyzed 2014-2015 Medicare enrollment data and Minimum Data Set clinical assessments linked to NH-level characteristics, star ratings, and county-level MA penetration rates. The independent variable was the percentage of residents enrolled in MA at admission and categorized into three groups. We examined three NH-level outcomes: percentage of residents assessed and appropriately provided the influenza vaccine, receiving influenza vaccine, and refusing influenza vaccine.

ResultsThere were 936,513 long-stay residents in 12,384 NHs. Categories for the prevalence of MA enrollment in NHs were low (0% to 3.3%; n=4131 NHs), moderate (3.4% to 18.6%; n=4127 NHs) and high (>18.6%; n=4126 NHs). Adjusting for covariates, influenza vaccination rates among long-stay residents were higher in NHs with moderate (1.7%, P<0.0001), or high (3.1%, P<0.0001) MA versus the lowest prevalence of MA. Influenza vaccine refusal was lower in NHs with moderate (-3.1%, P<0.0001), or high (-4.6% P<0.0001) MA compared with NHs with the lowest prevalence of MA. Among 753,616 short-stay residents in 12,205 NHs, there was no association between MA concentration and influenza vaccination receipt but vaccine refusal was greater in NHs with higher MA prevalence (high or moderate vs. low MA: 5.2%, P<0.0001).

ConclusionThe relationship between MA concentration and influenza vaccination measures varied among post-acute and long-term NH residents. As MA takes a larger role in the Medicare program, and more MA beneficiaries enter NHs, there is need to consider how managed care can be leveraged to improve the delivery of preventive services such as influenza vaccinations in NH settings.

category: geriatric medicine


title: Correlation of Long-Term Care Facility Influenza Vaccination Practices between Seasons and Resident Types

abstract:
ObjectivesInfluenza vaccination varies widely across LTCFs due to staff behaviors, LTCF practices, and patient factors. It is unclear how seasonal LTCF vaccination varies between cohabitating but distinct short-stay and long-stay residents. Thus, we assessed the correlation of LTCF vaccination between these populations and across seasons.

DesignNational retrospective cohort using Medicare and Minimum Data Set (MDS) data.

Setting and ParticipantsU.S. LTCFs. Short-stay and long-stay Medicare-enrolled residents age [≥]65 in U.S. LTCFs from a source population of residents during October 1st-March 31st in 2013-2014 (3,042,881 residents; 15,683 LTCFs) and 2014-2015 (3,143,174, residents; 15,667 LTCFs).

MethodsMDS-assessed influenza vaccination was the outcome. Pearson correlation coefficients were estimated to assess seasonal correlations between short-stay and long-stay resident vaccination within LTCFs.

ResultsThe median proportion of short-stay residents vaccinated across LTCFs was 70.4% (IQR, 50.0-82.7%) in 2013-2014 and 69.6% (IQR, 50.0-81.6%) in 2014-2015. The median proportion of long-stay residents vaccinated across LTCFs was 85.5% (IQR, 78.0-90.9%) in 2013-2014 and 84.6% (IQR, 76.6-90.3%) in 2014-2015. Within LTCFs, there was a moderate correlation between short-stay and long-stay vaccination in 2013-2014 (r=0.50, 95%CI: 0.49-0.51) and 2014-2015 (r=0.53, 95%CI: 0.51-0.54). Across seasons, there was a moderate correlation for LTCFs with short-stay residents (r=0.54, 95%CI: 0.53-0.55) and a strong correlation for those with long-stay residents (r=0.68, 95%CI: 0.67-0.69).

Conclusion and ImplicationsIn LTCFs with inconsistent influenza vaccination across seasons or between populations, targeted vaccination protocols for all residents, regardless of stay type, may improve successful vaccination in this vulnerable patient population.

Brief summaryIn LTCFs, influenza vaccination was moderately correlated across all residents, but varied across seasons. Inconsistent vaccination among cohabitating residents may increase infection risk in LTCFs.


title: Solving the "right" problems for effective machine learning driven in vitro fertilization

abstract:
Automated live embryo imaging has transformed in-vitro fertilization (IVF) into a data-intensive field. Unlike clinicians who rank embryos from the same IVF cycle cohort based on the embryos visual quality and determine how many embryos to transfer based on clinical factors, machine learning solutions usually combine these steps by optimizing for implantation prediction and using the same model for ranking the embryos within a cohort. Here we establish that this strategy can lead to sub-optimal selection of embryos. We reveal that despite enhancing implantation prediction, inclusion of clinical properties hampers ranking. Moreover, we find that ambiguous labels of failed implantations, due to either low quality embryos or poor clinical factors, confound both the optimal ranking and even implantation prediction. To overcome these limitations, we propose conceptual and practical steps to enhance machine-learning driven IVF solutions. These consist of separating the optimizing of implantation from ranking by focusing on visual properties for ranking, and reducing label ambiguity.

Lay SummaryO_ST_ABSBackgroundC_ST_ABSIn vitro fertilization (IVF) is the process where a cohort of embryos are developed in a laboratory followed by selecting a few to transfer in the patients uterus. After approximately forty years of low-throughput, automated live embryo imaging has transformed IVF into a data-intensive field leading to the development of unbiased and automated methods that rely on machine learning for embryo assessment. These advances are now revolutionizing the field with recent retrospective papers demonstrating computational models comparable and even exceeding clinicians performance, startups and medical companies are securing significant funds and at advanced stages of regulatory approvals. Traditionally, embryo selection is performed by clinicians ranking cohort embryos based solely on their visual qualities to estimate implantation potential, and then using non-visual clinical properties that are common to all cohort embryos to decide how many embryos to transfer. Machine learning solutions usually combine these two steps by optimizing for implantation prediction and using the same model for ranking the embryos within a cohort under the implicit assumption that training to predict implantation potential also optimizes a solution to the problem of ranking embryos from a specific cohort.

ResultsIn this multi-center retrospective study we analyzed over 48,000 live imaged embryos to provide evidence that the common machine-learning scheme of training a model to predict implantation and using the same model for embryo ranking is wrong. We made this point by explicitly decoupling the problems of embryo implantation prediction and ranking with a set of computational analyses. We demonstrated that: (1) Using clinical cohort-related information (oocyte age) improves embryo implantation prediction but deteriorates ranking, and that (2) The label ambiguity of the embryos that failed to implant (it is not known whether the embryo or the external factors were the reason for failure) deteriorates embryo ranking and even the ability to accurately predict implantation. Our study provides a quantitative mapping of the tradeoffs between data volume, label ambiguity and embryo quality. In a key result, we reveal that considering embryos that were excluded based on their poor visual appearance (called discarded embryos), although commonly thought as trivially discriminated from high quality embryos, enhances embryo ranking by reducing the ambiguity in their (negative) labels. These results establish the benefit of harnessing the availability of extensive data and reliable labels in discarded embryos to improve embryo ranking and implantation prediction.

OutlookWe make two practical recommendations for devising machine learning solutions to embryo selection that will open the door for future advancements by data scientists and IVF technology developers. Namely, training models for embryo ranking should: (1) focus exclusively on embryo intrinsic features. (2) include less ambiguous negative labels, such as discarded embryos. In the era of machine learning, these guidelines will shift back the traditional two-step process of optimizing embryo ranking and implantation prediction independently under the appropriate assumptions - an approach better reflecting the clinicians decision that involves the evaluation of all the embryos in the context of its cohort.

category: health informatics


title: Covid-19 vaccine perceptions in Senegal and in Mali: a mixed approach

abstract: This paper presents the results of two qualitative surveys in Senegal and in Mali, which include questions about hesitancy to the COVID-19 vaccine between April and June 2021. It took place within a larger 2-year research project involving researchers in Senegal, Mali and Canada which examines the uses of artificial intelligence technologies in the fight against COVID-19. The study involved 1000 respondents in Senegal and 555 in Mali. The researchers found that overall, 55% of respondents in Senegal and 52% of respondents in Mali did not plan to be vaccinated. Hesitancy was much higher in youth aged 15-35 in both cases, with 70% of youth in Senegal and 57% of youth in Mali not planning to be vaccinated, compared to only 42% of elderly in Senegal and 37% of elderly in Mali. The researchers did not find disparities between male and female respondents in Senegal but found some in Mali. They also found that those who had a member of the family with chronic disease (diabetes or hypertension) were slightly more likely to want to be vaccinated. Reasons for vaccine hesitancy fell in several categories, including fear of vaccine side-effects, disbelief in vaccine efficacy or usefulness, and general distrust in the public health system.


title: Suboptimal HIV status ascertainment at antenatal clinics and the impact on HIV prevalence estimates.

abstract:
IntroductionHIV prevalence estimates is a key indicator to inform the coverage and effectiveness of HIV prevention measures. Many countries including Kenya transitioned from sentinel surveillance to the use of routine antenatal care data to estimate the burden of HIV. Countries in Sub Saharan Africa reported several challenges of this transition, including low uptake of HIV testing and sub national / site-level differences in HIV prevalence estimates.

MethodsWe examine routine data from Kwale County, Kenya, for the period January 2015 to December 2019 and predict HIV prevalence among women attending antenatal care (ANC) at 100% HIV status ascertainment. We estimate the bias in HIV prevalence estimates as a result of imperfect uptake of HIV testing and make recommendations to improve the utility of ANC routine data for HIV surveillance. We used a generalized estimating equation with binomial distribution to model the observed HIV prevalence as explained by HIV status ascertainment and region (Sub County). We then used marginal standardization to predict the HIV prevalence at 100% HIV status ascertainment.

ResultsHIV testing at ANC was at 91.3%, slightly above the global target of 90%. If there was 100% HIV status ascertainment at ANC, the HIV prevalence would be 2.7% (95% CI 2.3-3.2). This was 0.3% lower than the observed prevalence. Similar trends were observed with yearly predictions except for 2018 where the HIV prevalence was underestimated with an absolute bias of -0.2%. This implies missed opportunities for identifying new HIV infections in the year 2018.

ConclusionsImperfect HIV status ascertainment at ANC overestimates HIV prevalence among women attending ANC in Kwale County. However, the use of ANC routine data may underestimate the true population prevalence. There is need to address both community level and health facility level barriers to the uptake of ANC services.

Key questionsO_ST_ABSWhat is already known?C_ST_ABS{blacksquare} HIV surveillance estimates from antenatal clinics (ANC) can serve as a useful proxy for HIV prevalence trends in the general female population.
{blacksquare}Kenya has conducted multiple studies which have shown that national HIV prevalence estimates from sentinel surveillance and those from routine program data to be similar.
{blacksquare}However, these studies have also revealed ongoing challenges to the suitability of using routine data as compared to sentinel surveillance including sub optimal uptake of HIV testing and sub national/ site-level differences in HIV prevalence estimates.

What are the new findings?{blacksquare} HIV positive pregnant women are more likely to be tested at ANC as compared to HIV negative women, leading to higher HIV prevalence estimates among women attending ANC.
{blacksquare}Health facility level HIV prevalence estimates are lower than that of the general population.

What do the new findings imply?{blacksquare} HIV positive women are underrepresented in antenatal clinics.
{blacksquare}In Kwale County (and similar contexts), use of routine ANC data is still not a reliable method to estimate HIV prevalence, both at facility and community level.

category: hiv aids


title: Higher Hospitalization and Mortality Rates Among SARS-CoV-2 infected Persons in Rural America

abstract:
IMPORTANCERural communities are among the most underserved and resource-scarce populations in the United States (US), yet there are limited data on COVID-19 mortality in rural America. Furthermore, rural data are rarely centralized, precluding comparability across urban and rural regions.

OBJECTIVEThe purpose of this study is to assess hospitalization rates and all-cause inpatient mortality among persons with definitive COVID-19 diagnoses residing in rural and urban areas.

DESIGN, SETTINGS, AND PARTICIPANTSThis retrospective cohort study from the National COVID Cohort Collaborative (N3C) examines a cohort of 573,018 patients from 27 US hospital systems presenting with SARS-CoV-2 infection between January 2020 and March 2021, of whom 117,897 were hospitalized. A sample of 450,725 hospitalized persons without COVID-19 diagnoses was identified for comparison.

EXPOSURESZIP Codes provided by source hospital systems were classified by urban-rural gradient through a crosswalk to the US Department of Agriculture Rural-Urban Commuting Area Codes.

MAIN OUTCOMES AND MEASURESPrimary outcomes were hospitalization and all-cause mortality among hospitalized patients. Kaplan-Meier analysis and mixed effects logistic regression were used to estimate 30-day survival in hospitalized patients and associations between rurality, hospitalization, and inpatient mortality while controlling for major risk factors.

RESULTSRural patients were more likely to be older, white, have higher body mass index, and diagnosed with SARS-CoV-2 later in the pandemic compared with their urban counterparts. Rural compared with urban inhabitants had higher rates of hospitalization (23% vs. 19%) and all-cause mortality among hospitalized patients (16% vs. 11%). After adjustment for demographic and baseline differences, rural residents (both urban adjacent and non-adjacent) with COVID-19 were more likely to be hospitalized (Adjusted Odds Ratio (AOR) 1.41, 95% Confidence Interval (CI), 1.37-1.45 and AOR 1.42, CI 1.35-1.50) and to die or be transferred to hospice (AOR 1.62, CI 1.30-1.49 and 1.38, CI 1.30-1.49), respectively. Similar differences in mortality were noted for hospitalized patients without SARS-CoV-2 infection.

CONCLUSIONSHospitalization and inpatient mortality are higher among rural compared with urban persons with COVID-19, even after adjusting for several factors, including age and comorbidities. Further research is needed to understand the factors that drive health disparities in rural populations.

KEY POINTSO_ST_ABSQUESTIONC_ST_ABSDo mortality and hospitalization rates among rural SARS-CoV-2 infected patients in the United States differ from that of their urban counterparts?

FINDINGSHospitalization and mortality rates were significantly greater among rural compared with urban patients, even after adjusting for rural-urban differences including age and comorbidities. Similarly, in persons without SARS-CoV-2 infection, mortality rates were also higher among rural patients.

MEANINGThese findings demonstrate a pervasive rural-urban discrepancy in all-cause inpatient mortality among rural individuals in the U.S. infected with SARS-COV-2 as well as among those who were uninfected. Further research is needed to understand factors driving health disparities among rural populations.

category: infectious diseases


title: Neutralizing antibodies against SARS-CoV-2 variants of concern elicited by the Comirnaty COVID-19 vaccine in nursing home residents

abstract: Immunosenescence may impact the functionality and breadth of vaccine-elicited humoral immune responses. The ability of sera to neutralize the SARS-CoV-2 spike protein (S) from Beta, Gamma, Delta, and Epsilon variants of concern (VOCs) relative to the ancestral Wuhan-Hu-1 strain was compared in Comirnaty(R) COVID-19-vaccinated elderly nursing home residents (n=30) or younger individuals (n=18) and non-vaccinated individuals who recovered from severe COVID-19 (n=19). In all groups, some participants lacked NtAb against one or more VOCs, mainly the Beta variant (15-20%). Serum NtAb titers were lowest against the Beta variant followed by Gamma, Epsilon, and Delta variants. Fold change reduction in NtAb titers relative to the ancestral strain was greatest for the Beta variant (6.7-18.8) followed by Gamma (3.6-6.2), Epsilon (2.9-5.8), and Delta (3.5-4.3) variants, regardless of the study group considered. In summary, older age, frailty, and concurrence of co-morbidities had no impact on the serum NtAb activity profile against SARS-CoV-2 VOCs.


title: Seropositivity to Nucleoprotein to detect SARS-CoV-2 infections: a tool to detect breakthrough infections after COVID-19 vaccination

abstract:
BackgroundWith COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination.

MethodsMultiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) with a primary infection and no vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech).

ResultsThe sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80-90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50-81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 [≥]14 days after the first dose as compared to those unexposed to SARS-CoV-2 at [≥]7 days after the second dose (p=0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in naive participants.

ConclusionsSerological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history.


title: Rotational worker vaccination provides indirect protection to vulnerable groups in regions with low COVID-19 prevalence

abstract: As COVID-19 vaccines become available, different model-based approach have been developed to evaluate strategic priorities for vaccine allocation to reduce severe illness. One strategy is to directly prioritize groups that are likely to experience medical complications due to COVID-19, such as older adults. A second strategy is to limit community spread by reducing importations, for example by vaccinating members of the mobile labour force, such as rotational workers. This second strategy may be appropriate for regions with low disease prevalence, where importations are a substantial fraction of all cases and reducing the importation rate reduces the risk of community outbreaks, which can provide significant indirect protection for vulnerable individuals. Current studies have focused on comparing vaccination strategies in the absence of importations, and have not considered allocating vaccines to reduce the importation rate. Here, we provide an analytical criteria to compare the reduction in the risk of hospitalization and intensive care unit (ICU) admission over four months when either older adults or rotational workers are prioritized for vaccination. Vaccinating rotational workers (assumed to be 6,000 individuals and about 1% of the Newfoundland and Labrador (NL) population) could reduce the average risk of hospitalization and ICU admission by 42%, if no community spread is observed at the time of vaccination, because epidemic spread is reduced and vulnerable individuals are indirectly protected. In contrast, vaccinating all individuals aged 75 and older (about 43,300 individuals, or 8% of the NL population) would lead to a 24% reduction in the average risk of hospitalization, and to a 45% reduction in the average risk of ICU admission, because a large number of individuals at high risk from COVID-19 are now vaccinated. Therefore, reducing the risk of hospitalization and ICU admission of the susceptible population by reducing case importations would require a significantly lower number of vaccines. Benefits of vaccinating rotational workers decrease with increasing infection prevalence in the community. Prioritizing members of the mobile labour force should be considered as an efficient strategy to indirectly protect vulnerable groups from COVID-19 exposure in regions with low disease prevalence.


title: Gut microbial communities modulate efficacy of albendazole-ivermectin against soil-transmitted helminthiases

abstract:
BackgroundSoil-transmitted helminth infections represent a large burden across the globe with over a quarter of the worlds population at risk. The outcome of available treatments is species-specific with a large proportion of unexplained treatment failure. Administration of albendazole is the standard of care, but because of low cure rates (CR) observed in treating Trichuris trichiura infections, a significantly more efficacious alternative therapy combining albendazole and ivermectin is being investigated.

Methods80 patients from the village of Pak-Khan, in Laos, with confirmed STH infections (Trichuris trichiura and hookworms), received either albendazole (400 mg) or albendazole (400 mg) and ivermectin (200 {micro}g/kg) together. A pre-treatment stool sample was collected as well as daily post-treatment stool samples for up to 28 days to measure treatment efficacy. Taxonomic profiling of pre-treatment stool samples was conducted using 16S rRNA gene sequencing, target-specific and total bacteria qPCR, as well as shotgun sequencing.

ResultsThree bacterial communities, or enterotypes (ET) 1-3, were identified. No association with pre-treatment enterotype and treatment outcome of both Trichuris trichiura and hookworm were found in the monotherapy arm with overall cure rates (CR) of 7.5% and 50%, respectively. Pre-treatment enterotype was strongly associated with efficacy of the combination therapy for both, T. trichiura (CRoverall = 33.3%; CRET1 = 5.8%; CRET2 = 16.6%; CRET3 = 68.5%) and hookworm (CRoverall = 47.2%; CRET1 = 31.2%; CRET2 = 16.6%; CRET3 = 78.5%) infections. Daily post-treatment egg per gram of stool counts recapitulated these observations and faster and increased egg reduction was observed in ET3 when compared to failure-associated ET1 and ET2. Species-level comparisons of these enterotypes highlighted a set of ten differentially enriched bacterial species.

ConclusionTaxonomically distinct gut microbiota communities were found in this setting in terms of both, relative and absolute abundances, of specific bacterial taxa. Pre-treatment enterotype was relevant for treatment outcome of the combination therapy, albendazole and ivermectin, for T. trichiura as well as for hookworm infections. These observations indicate that pre-treatment microbial composition of stool samples should be monitored to ensure evidence-based administration of albendazole-ivermectin to treat these diseases.


title: Postvaccination SARS-CoV-2 infection among healthcare workers: A Systematic Review and meta-analysis

abstract:
INTRODUCTIONHealthcare workers (HCWs) remain on the front line of the battle against SARS-CoV-2 and COVID-19 infection, and are among the highest groups at risk of infection during this raging pandemic. We conducted a systematic review and meta-analysis to assess incidence of postvaccination SARS-CoV-2 infection among vaccinated HCWs.

METHODSWe searched multiple databases from inception through August 2021 to identify studies that reported on incidence of postvaccination SARS-CoV-2 infection among HCWs. Meta-analysis was performed to determine pooled proportions of COVID-19 infection in partially and fully vaccinated individuals.

RESULTSEighteen studies with 228,873 HCWs were included in the final analysis. Total number of partially vaccinated, fully vaccinated, and unvaccinated HCWs were 132,922, 155,673 and 17505, respectively. Overall pooled proportion of COVID-19 infections among partially/fully vaccinated and unvaccinated HCWs was 2.1% (95% CI 1.2-3.5). Among partially vaccinated, fully vaccinated and unvaccinated HCWs, pooled proportion of COVID-19 infections was 3.7% (95% CI 1.8-7.3), 1.3% (95% CI 0.6-2.9), and 10.1% (95% CI 4.5-19.5), respectively.

DISCUSSIONOur analysis shows the risk of COVID-19 infection in both partially and fully vaccinated HCWs remains exceedingly low when compared to unvaccinated individuals. There remains an urgent need for all frontline HCWs to be vaccinated against SARS-CoV-2 infection.


title: Is the infection of the SARS-CoV-2 Delta variant associated with the outcomes of COVID-19 patients?

abstract:
BackgroundSARS-CoV-2 Delta variant (B.1.617.2) has been responsible for the current increase in COVID-19 infectivity rate worldwide. We compared the impact of the Delta variant and non-Delta variant on the COVID-19 outcomes in patients from Yogyakarta and Central Java provinces, Indonesia.

MethodsWe ascertained 161 patients, 69 with the Delta variant and 92 with the non-Delta variant. The Illumina MiSeq next-generation sequencer was used to perform the whole genome sequences of SARS-CoV-2.

ResultsThe mean age of patients with Delta and the non-Delta variant was 27.3 {+/-} 20.0 and 43.0 {+/-} 20.9 (p=3x10-6). The patients with Delta variant consisted of 23 males and 46 females, while the patients with the non-Delta variant involved 56 males and 36 females (p=0.001). The Ct value of the Delta variant (18.4 {+/-} 2.9) was significantly lower than the non-Delta variant (19.5 {+/-} 3.8) (p=0.043). There was no significant difference in the hospitalization and mortality of patients with Delta and non-Delta variants (p=0.80 and 0.29, respectively). None of the prognostic factors was associated with the hospitalization, except diabetes with an OR of 3.6 (95% CI=1.02-12.5; p=0.036). Moreover, the patients with the following factors have been associated with higher mortality rate than patients without the factors: age [≥]65 years, obesity, diabetes, hypertension, and cardiovascular disease with the OR of 11 (95% CI=3.4-36; p=8x10-5), 27 (95% CI=6.1-118; p=1x10-5), 15.6 (95% CI=5.3-46; p=6x10-7), 12 (95% CI=4-35.3; p=1.2x10-5), and 6.8 (95% CI=2.1-22.1; p=0.003), respectively. Multivariate analysis showed that age [≥]65 years, obesity, diabetes, and hypertension were the strong prognostic factors for the mortality of COVID-19 patients with the OR of 3.6 (95% CI=0.58-21.9; p=0.028), 16.6 (95% CI=2.5-107.1; p=0.003), 5.5 (95% CI=1.3-23.7; p=0.021), and 5.8 (95% CI=1.02-32.8; p=0.047), respectively.

ConclusionsWe show that the patients infected by the SARS-CoV-2 Delta variant have a lower Ct value than the patients infected by the non-Delta variant, implying that the Delta variant has a higher viral load, which might cause a more transmissible virus among humans. However, the Delta variant does not affect the COVID-19 outcomes in our patients. Our study also confirms the older age and comorbidity increase the mortality rate of COVID-19 patients.


title: An assessment of a rapid SARS-CoV-2 antigen test in Bangladesh

abstract: Early detection of SARS-CoV-2 infection is crucial to prevent the spread of the virus. In this study, we evaluated the performance of a commercial rapid antigen detection test, BD Veritor, and compared this (and another rapid test, Standard Q) against a gold-standard of nasopharyngeal (NP) swab tested by reverse transcription-polymerase chain reaction (RT-PCR) in prospectively-recruited adults in Dhaka, Bangladesh. We compared the sensitivity and specificity of the two rapid antigen tests against RT-PCR results in 130 symptomatic and 130 asymptomatic adults. In addition, we evaluated the suitability and ease-of-use of the BD Veritor test in a subsample of study participants (n=42) and implementers (n=5). The sensitivity of the BD Veritor rapid antigen test was 70% in symptomatic (95% confidence interval [CI]: 51-85%) and 87% (95% CI: 69-96%) in asymptomatic individuals with positive SARSCoV-2 RT-PCR, for overall sensitivity of 78% (95% CI: 66-88%). The sensitivity of the Standard Q rapid antigen test was 63% (95% CI: 44-80%) in symptomatic and 73% (95% CI: 54-87%) in asymptomatic individuals. One false positive in BD Veritor test (specificity 99.5) and no false positive in Standard Q tests were observed (specificity 100%). The BD Veritor rapid antigen test was 78% sensitive when compared with RT-PCR irrespective of the cycle threshold (Ct) levels in this evaluation in Bangladesh. The implementation evaluation data showed good acceptability in the field settings. This warrants large field evaluation as well as use of the rapid antigen test for quick assessment of SARS-CoV-2 for containment of epidemics in the country.


title: Comparison of antibody immune responses between BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in naive and previously infected individuals

abstract: Two mRNA vaccines, Pfizer-BNT162b2 and Moderna-mRNA-1273, were granted the US Food and Drug Administration Emergency Use Authorization for preventing COVID-19. However, little is known about the difference in antibody responses induced by the two mRNA vaccines in naive and individuals with a previous history of infections (PI group). Therefore, we investigated the levels of anti-S-RBD total antibodies (IgM, IgA, and IgG), anti-S-RBD IgG, and anti-S-RBD IgA in these two groups 1-13 (median=6) weeks following administration of two doses of mRNA-1273 or BNT162b2 vaccines. Results showed that in naive-vaccinated group, the mRNA-1327 vaccine induces significantly higher levels of S-RBD total antibodies (3.5-fold; p<0.001), S-RBD IgG (2-fold-p<0.01), and S-IgA (2.1-fold, p<0.001) than the BNT162b2 vaccine. In the PI-vaccinated group, both vaccines produce significantly higher S-RBD total antibodies level than those of the naive-vaccinated group. The PI group produced a higher level of S-RBD IgG than the naive-BNT162b2 (p=0.05) but not more than the naive-mRNA-1273 (p=0.9) group. Interestingly, the PI-vaccinated group produced a comparable level of IgA ratio to the naive-mRNA-1273 group but significantly higher than the naive-BNT162b2 group (1.6-fold, p<0.001). Our results showed that the mRNA-1327 vaccine is more immunogenic and induces a greater antibody response than the BNT162b2 vaccine.


title: Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus

abstract: The Rhesus D antigen (RhD) has been associated with susceptibility to several viral infections. Reports suggest that RhD-negative individuals are better protected against infectious diseases and have overall better health. However, potential mechanisms contributing to these associations have not yet been defined. Here, we used transcriptomic and genomic data from the Milieu Interieur cohort of 1000 healthy individuals to explore the effect of RhD on immune responses. We used the rs590787 SNP in the RHD gene to classify the 1000 donors as either RhD-positive or -negative. Whole blood was stimulated with LPS, polyIC, and the live influenza A virus and the NanoString human immunology panel of 560 genes used to assess donor immune response and to investigate sex specific effects. Using regression analysis, we observed no significant differences in responses to polyIC or LPS between RhD-positive and - negative individuals. However, upon sex-specific analysis, we observed over 30 differentially expressed genes (DEGs) between RhD-positive (n=401) and RhD-negative males (n=78). Interestingly these Rhesus-associated differences were not seen in females. Further investigation, using gene set enrichment analysis, revealed enhanced IFN{gamma} signalling in RhD-negative males. This amplified IFN{gamma} signalling axis may explain the increased viral resistance previously described in RhD-negative individuals.

category: allergy and immunology


title: Serum but not mucosal antibody responses are predicted by pre-existing SARS-CoV-2 spike cross-reactive CD4+ T cells following BNT162b2 vaccination in the elderly

abstract: Advanced age is a main risk factor for severe COVID-19. However, low vaccination efficacy and accelerated waning immunity have been reported in this age group. To elucidate age-related differences in immunogenicity, we analysed human cellular, serological and salivary SARS-CoV-2 spike glycoprotein-specific immune responses to BNT162b2 COVID-19 vaccine in old (69-92 years) and middle-aged (24-57 years) vaccinees compared to natural infection (COVID-19 convalescents, 21-55 years). Serological humoral responses to vaccination exceeded those of convalescents but salivary anti-spike subunit 1 (S1) IgA and neutralizing capacity were less durable in vaccinees. In old vaccinees, we observed that pre-existing spike-specific CD4+ T cells are associated with efficient induction of anti-S1 IgG and neutralizing capacity in serum but not saliva. Our results suggest pre-existing SARS-CoV-2 cross-reactive CD4+ T cells as predictor of an efficient COVID-19 vaccine-induced humoral immune response in old individuals.


title: Serum but not mucosal antibody responses are associated with pre-existing SARS-CoV-2 spike cross-reactive CD4+ T cells following BNT162b2 vaccination in the elderly


title: Comparison of MIS-C Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine related Myocarditis in Children

abstract:
BackgroundAlthough rare, myocarditis in the pediatric population is a disease process that carries significant morbidity and mortality. Prior to the SARS-CoV-2 related (COVID-19) pandemic, enteroviruses were the most common cause of classic myocarditis. However, since 2020, myocarditis linked to multisystem inflammatory syndrome in children (MIS-C) is now common. In recent months, myocarditis related to COVID-19 vaccines has also been described. This study aims to compare these three different types of myocarditis with regards to clinical presentation, course, and outcomes.

MethodsIn this retrospective cohort study, we included all patients <21 years of age hospitalized at our institution with classic viral myocarditis from 2015-2019, MIS-C myocarditis from 3/2020-2/2021 and COVID-19 vaccine-related myocarditis from 5/2021-6/2021. We compared demographics, initial symptomatology, treatment, laboratory data, and echocardiogram findings.

ResultsOf 201 total participants, 43 patients had classic myocarditis, 149 had MIS-C myocarditis, and 9 had COVID-19 vaccine-related myocarditis. Peak troponin was highest in the classic myocarditis group, whereas the MIS-C myocarditis group had the highest recorded brain natriuretic peptide (BNP). There were significant differences in time to recovery of normal left ventricular ejection fraction (LVEF) for the three groups: nearly all patients with MIS-C myocarditis (n=139, 93%) and all patients with COVID-19 vaccine-related myocarditis (n=9, 100%) had normal LVEF at the time of discharge, but a lower proportion of the classic myocarditis group (n=30, 70%) had a normal LVEF at discharge (p<0.001). Three months post-discharge, 18 of 40 children (45%) in the classic myocarditis group still required heart failure treatment, whereas only one of the MIS-C myocarditis patients and none of the COVID-19 vaccine-associated myocarditis patients did.

ConclusionsCompared to those with classic myocarditis, those with MIS-C myocarditis had more significant hematologic derangements and worse inflammation at presentation, but had better clinical outcomes, including rapid recovery of cardiac function. Patients with COVID-19 vaccine-related myocarditis had similar clinical presentation to patients with classic myocarditis, but their pattern of recovery was similar to those with MIS-C, with prompt resolution of symptoms and improvement of cardiac function. Long-term follow-up should focus on cardiac and non-cardiac consequences of myocarditis associated with COVID-19 illness and vaccination.

category: cardiovascular medicine


title: Procedural time reduction associated with active esophageal cooling during pulmonary vein isolation

abstract:
BackgroundActive esophageal cooling is increasingly utilized as an alternative to luminal esophageal temperature (LET) monitoring for protection against thermal injury during pulmonary vein isolation (PVI) when treating atrial fibrillation (AF). Published data demonstrate the efficacy of active cooling in reducing thermal injury, but impacts on procedural efficiency are not as well characterized. LET monitoring compels pauses in ablation due to heat stacking and temperature overheating alarms that in turn delay progress of the PVI procedure, whereas active esophageal cooling allows avoidance of this phenomenon.

ObjectiveMeasure the change in PVI procedure duration after implementation of active esophageal cooling as a protective measure against esophageal injury.

MethodsWe performed a retrospective review under IRB approval of patients with AF undergoing PVI between January 2018 to February 2020. For each patient, we recorded age, gender, and total procedure time. We then compared procedure times before and after the implementation of active esophageal cooling as a replacement for LET monitoring.

ResultsA total of 373 patients received PVI over the study period. LET monitoring using a multi-sensor probe was performed in 198 patients, and active esophageal cooling using a dedicated device was performed in 175 patients. Patient characteristics did not significantly differ between groups (mean age of 67 years, and gender 37.4% female). Mean procedure time was 146 minutes in the LET monitored patients, and 110 minutes in the actively cooled patients, representing a reduction of 36 minutes, or 24.7% (p<.001). Median procedure time was 141 minutes in the LET monitored patients and 100 minutes in the actively cooled patients, for a reduction of 41 minutes, or 29.1% (p<.001).

ConclusionsImplementation of active esophageal cooling for protection against esophageal injury during PVI was associated with a significantly large reduction in procedure duration.


title: Deep Learning Model for Mortality Prediction of ICU Patients with Paralytic Ileus

abstract:
BackgroundParalytic Ileus (PI) patients in the Intensive Care Unit (ICU) are at a significant risk of death. Prediction of at-risk patients for mortality after 24 hours of admission of ICU PI patients is important to increase the life expectancy of PI patients.

Methods and ResultsThe proposed framework, DLMP (Deep Learning Model for Mortality Prediction of ICU Patients with PI) is a powerful deep learning model consisting of six total unique clinical lab items and two demographics as inputs to a Neural Network(NN) of only two neuron layers. Using the Medical Information Mart for Intensive Care III (MIMIC-III) dataset of 1,017 ICU PI patients, the DLMP resulted in the best prediction performance with an AUC score of 0.866.

ConclusionThe proposed approach is capable of modeling the mortality of ICU patients after 24 hours admission using only six unique total clinical data and two demographics with a simple NN architecture. DLMP framework significantly improves the outcome prediction compared to the process mining and machine learning models. The proposed DLMP has the potential of allowing clinicians to create targeted interventions that reduce mortality for PI patients in an ICU setting.

category: endocrinology


title: Characterizing the effective reproduction number during the COVID-19 epidemic: Insights from Qatar experience

abstract:
BackgroundThe effective reproduction number, Rt, is a tool to track and understand epidemic dynamics. This investigation of Rt estimations was conducted to guide the national COVID-19 response in Qatar, from the onset of the epidemic until August 18, 2021.

MethodsReal-time "empirical" [Formula] was estimated using five methods, including the Robert Koch Institute, Cislaghi, Systrom-Bettencourt and Ribeiro, Wallinga and Teunis, and Cori et al. methods. R was also estimated using a transmission dynamics model [Formula]. Uncertainty and sensitivity analyses were conducted. Agreements between different Rt estimates were assessed by calculating correlation coefficients.

Results[Formula] captured the evolution of the epidemic through three waves, public health response landmarks, effects of major social events, transient fluctuations coinciding with significant clusters of infection, and introduction and expansion of the B.1.1.7 variant. The various estimation methods produced consistent and overall comparable [Formula] estimates with generally large correlation coefficients. The Wallinga and Teunis method was the fastest at detecting changes in epidemic dynamics. [Formula] estimates were consistent whether using time series of symptomatic PCR-confirmed cases, all PCR-confirmed cases, acute-care hospital admissions, or ICU-care hospital admissions, to proxy trends in true infection incidence. [Formula] correlated strongly with [Formula] and provided an average [Formula].

ConclusionsRt estimations were robust and generated consistent results regardless of the data source or the method of estimation. Findings affirmed an influential role for Rt estimations in guiding national responses to the COVID-19 pandemic, even in resource-limited settings.

category: epidemiology


title: Burden of five healthcare associated infections in Australia

abstract: Healthcare associated infections (HAIs) are associated with increased morbidity and mortality, but there are few data that quantify the burden of infection nationally in Australia. We used data from an Australian national point prevalence survey to estimate the burden of HAIs amongst adults in Australian public hospitals. The incidence based appropach, introduced by the ECDC Burden of Comunicable Diseases in Europe was used. We estimate that 170,574 HAIs occur in adults admitted to public hospitals in Australia annually, resulting in 7583 deaths. Hospital acquired pneumonia is the most frequent HAI, followed by surgical site infections, and urinary tract infections. We find that blood stream infections contribute a small percentage of HAIs, but contribute the highest number of deaths (3512), more than twice that of the second largest, while pneumonia has the highert impact on years lived with disability. This study is the first time the national burden of HAIs has been estimated for Australia from point prevalence data. The estimated burden is high, and highlights the need for continued investment in HAI prevention.


title: Comparative transmissibility of SARS-CoV-2 variants Delta and Alpha in New England, USA

abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant quickly rose to dominance in mid-2021, displacing other variants, including Alpha. Studies using data from the United Kingdom and India estimated that Delta was 40-80% more transmissible than Alpha, allowing Delta to become the globally dominant variant. However, it was unclear if the ostensible difference in relative transmissibility was due mostly to innate properties of Deltas infectiousness or differences in the study populations. To investigate, we formed a partnership with SARS-CoV-2 genomic surveillance programs from all six New England US states. By comparing logistic growth rates, we found that Delta emerged 37-163% faster than Alpha in early 2021 (37% Massachusetts, 75% New Hampshire, 95% Maine, 98% Rhode Island, 151% Connecticut, and 163% Vermont). We next computed variant-specific effective reproductive numbers and estimated that Delta was 58-120% more transmissible than Alpha across New England (58% New Hampshire, 68% Massachusetts, 76% Connecticut, 85% Rhode Island, 98% Maine, and 120% Vermont). Finally, using RT-PCR data, we estimated that Delta infections generate on average [~]6 times more viral RNA copies per mL than Alpha infections. Overall, our evidence indicates that Deltas enhanced transmissibility could be attributed to its innate ability to increase infectiousness, but its epidemiological dynamics may vary depending on the underlying immunity and behavior of distinct populations.


title: Adiposity and risk of prostate cancer death: a prospective analysis in UK Biobank and meta-analysis of published studies

abstract:
IntroductionThe association of adiposity with prostate cancer specific mortality remains unclear. We examined how adiposity and its distribution relates to fatal prostate cancer by analysing data from UK Biobank, and conducting a dose-response meta-analysis to integrate existing prospective evidence. We also described the cross-sectional associations in UK Biobank of commonly used adiposity measurements with indices of adiposity estimated by imaging.

Methods218,246 men from UK Biobank who were free from cancer at baseline were included and participants were followed-up via linkage to health administrative datasets. Body mass index (BMI), total body fat percentage (using bioimpedance), waist circumference (WC) and waist-to-hip ratio (WHR) were collected at recruitment. Risk of dying from prostate cancer (primary cause) by the different adiposity measurements was estimated using multivariable-adjusted Cox proportional hazards models. Results from this and other prospective cohort studies were combined in a dose-response meta-analysis.

ResultsIn UK Biobank, 631 men died from prostate cancer over a mean follow-up of 11.5 years. The hazard ratios (HR) for prostate cancer death were 1.10 (95% confidence interval=1.00-1.21) per 5 kg/m2 higher BMI, 1.03 (0.96-1.11) per 5% increase in total body fat percentage, 1.09 (1.02-1.18) per 10 cm increase in WC, and 1.09 (1.02-1.16) per 0.05 increase in WHR. Our meta-analyses of prospective studies included 22,106 prostate cancer deaths for BMI, 642 for body fat percentage, 3,153 for WC and 1,611 for WHR, and the combined HRs for dying from prostate cancer for the increments above were 1.10 (1.08-1.13), 1.03 (0.96-1.11), 1.08 (1.04-1.12), and 1.07 (1.02-1.12), respectively. In up to 4,800 UK Biobank participants with magnetic resonance imaging and dual-energy X-ray absorptiometry, BMI and WC were strongly associated with imaging estimations of total and central adiposity (e.g. visceral fat, trunk fat), with associations marginally larger for WC. There might be [~]1000 fewer prostate cancer deaths per year in the UK if the mean BMI in men was reduced by 5 kg/m2.

ConclusionOverall, we found that men with higher total and central adiposity had similarly higher risks of prostate cancer death, which may be biologically driven or due to differences in detection. In either case, these findings provide further reasons for men to maintain a healthy body weight.