title: Imaging cortical multiple sclerosis lesions with ultra-high field MRI

abstract:
BackgroundCortical lesions are abundant in multiple sclerosis (MS), yet difficult to visualize in vivo. Ultra-high field (UHF) MRI at 7T and above provides technological advances suited to optimize the detection of cortical lesions in MS.

PurposeTo provide a narrative and quantitative systematic review of the literature on UHF MRI of cortical lesions in MS.

MethodsA systematic search of all literature on UHF MRI of cortical lesions in MS published before September 2020. Quantitative outcome measures included cortical lesion numbers reported using 3T and 7T MRI and between 7T MRI sequences, along with sensitivity of UHF MRI towards cortical lesions verified by histopathology.

Results7T MRI detected on average 52{+/-}26% (mean {+/-} 95% confidence interval) more cortical lesions than the best performing image contrast at 3T, with the largest increase in type II-IV intracortical lesion detection. Across all studies, the mean cortical lesion number was 17{+/-}6/patient. In progressive MS cohorts, approximately four times more cortical lesions were reported than in CIS/early RRMS, and RRMS. Superiority of one MRI sequence over another could not be established from available data. Post-mortem lesion detection with UHF MRI agreed only modestly with pathological examinations. Mean pro- and retrospective sensitivity was 33{+/-}6% and 71{+/-}10%, respectively, with the highest sensitivity towards type I and type IV lesions.

ConclusionUHF MRI improves cortical lesion detection in MS considerably compared to 3T MRI, particularly for type II-IV lesions. Despite modest sensitivity, 7T MRI is still capable of visualizing all aspects of cortical lesion pathology and could potentially aid clinicians in diagnosing and monitoring MS, and progressive MS in particular. However, standardization of acquisition and segmentation protocols is needed.


title: The COVID-19 Yorkshire Rehabilitation Scale (C19-YRS): application and psychometric analysis in a post-COVID-19 syndrome cohort

abstract:
BackgroundAs our understanding of the nature and prevalence of Post-COVID-19 syndrome (PCS) is increasing, a measure of the impact of COVID-19 could provide valuable insights into patients perceptions in clinical trials and epidemiological studies, as well as routine clinical practice.

ObjectiveTo evaluate the clinical usefulness and psychometric properties of the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) in patients with PCS.

DesignA prospective, observational study of 187 consecutive patients attending a post-COVID-19 rehabilitation clinic. The C19-YRS was used to record patients symptoms, functioning and disability. A global health question was used to measure the overall impact of PCS on health. Classical psychometric methods (data quality, scaling assumptions, targeting, reliability and validity) were used to assess the C19-YRS.

ResultsFor the overall scale, missing data were low, scaling and targeting assumptions were satisfied, and internal consistency was high (Cronbachs alpha = 0.891). Relationships between perception of health and patients reports of symptoms, functioning and disability demonstrated good concordance.

ConclusionsThis is the first study to examine the psychometric properties of an outcome measure in patients with PCS. In this sample of patients, the C19-YRS was clinically useful and satisfied standard psychometric criteria, providing preliminary evidence of its suitability as a measure of PCS.

category: rehabilitation medicine and physical therapy


title: Racial/ethnic-based spirometry reference equations: Are they accurate for admixed populations?

abstract:
BACKGROUNDVariation in genetic ancestry among admixed racial/ethnic groups may influence the fit of guideline-recommended spirometry reference equations, which rely on self-identified race/ethnicity.

RESEARCH QUESTIONWhat is the influence of genetic ancestry on the fit of the guideline-recommended racial/ethnic-based spirometry reference equations in populations of genetically admixed children?

STUDY DESIGN AND METHODSCross-sectional fit of guideline-recommended racial/ethnic-based spirometry reference equations was evaluated in control subjects from case-control studies of asthma. Anthropometry, blood samples, and spirometric measurements were obtained in 599 healthy admixed children, aged 8 to 21-years. Genetic ancestry was estimated using genome-wide genotype data. Equation fit was determined as a mean z-score between -0.5 and 0.5 and assessed in self-identified African American (N = 275) and Puerto Rican (N = 324) children using the distribution to determine cut points of genetic ancestry.

RESULTSFor African American children, African American-derived equations fit for predicting FEV1 and FVC in those with an African ancestry above the median (81-100%), whereas composite equations for "other/mixed" populations fit for predicting FEV1 and FVC in those with an African ancestry below the median (31-81%). Among Puerto Rican children, White-derived equations fit for predicting FEV1, and the composite equations fit for predicting FVC for those with African ancestry above the median (21-88%). In contrast, in Puerto Rican children with African ancestry below the median (6-21%), only equations derived in Whites provide an adequate fit.

INTERPRETATIONGuideline-recommended spirometry reference equations yielded biased estimates of lung function in admixed populations with high variation of African ancestry. Spirometry is due for reference equations that incorporate genetic ancestry, either for more precise application of the current equations or the derivation and utilization of new equations.

category: respiratory medicine


title: Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy.

abstract: SARS-CoV-2 mRNA vaccination in healthy individuals generates effective immune protection against COVID-19. Little is known, however, about the SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses in patients with multiple sclerosis on anti-CD20 (MS-aCD20) monotherapy following SARS-CoV-2 mRNA vaccination. Treatment with aCD20 significantly reduced Spike and RBD specific antibody and memory B cell responses in most patients, an effect that was ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. In contrast, all MS-aCD20 patients generated antigen-specific CD4 and CD8 T-cell responses following vaccination. However, treatment with aCD20 skewed these responses compromising circulating Tfh responses and augmenting CD8 T cell induction, while largely preserving Th1 priming. These data also revealed underlying features of coordinated immune responses following mRNA vaccination. Specifically, the MS-aCD20 patients who failed to generate anti-RBD IgG had the most severe defect in cTfh cell responses and more robust CD8 T cell responses compared to those who generated anti-RBD IgG, whose T cell responses were more similar to healthy controls. These data define the nature of SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients, and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making, patient education and public health policy for patients treated with aCD20 and other immunosuppressed patients.

category: neurology


title: Different features of the cortical sensorimotor rhythms are uniquely linked to the severity of specific symptoms in Parkinson's disease

abstract:
Parkinsons disease (PD) is associated with functional changes in the neural activity within the brains sensorimotor network, which in turn are related to the characteristic motor symptoms in PD. The functional changes in PD are particularly prominent in terms of oscillatory neuronal activity in the characteristic sensorimotor alpha and beta rhythms. However, summaries in terms of alpha or beta power do not capture the full range of the complex dynamic nature of the signals from the somatosensory cortex. This raises the question of how to quantify and summarise the functional changes in such oscillatory features in a manner that captures the relevant disease- and symptom-related neural activity.

We investigated the role of spontaneous cortical somatosensory activity in the electrophysiological alpha and beta bands among a cohort of early- to mid-stage PD patients (N=78) and age- and gender-matched healthy controls (N=60) using source reconstructed resting-state magnetoencephalography (MEG) recordings. We quantified the oscillatory features of the neural time series by its oscillatory alpha power, beta power, and 1/f broadband characteristics using power spectral density, and additionally by characterising "burst" properties in the signals. We examined the relationship between the signal features and disease state, age, sex, and cortical thickness. Using multiple regression, we examined the relative contribution of the oscillatory features on the clinical manifestation of motor symptoms in the PD group.

Our results show that PD patients differ from healthy controls on several of the oscillatory features, showing higher beta-band power, higher burst amplitude, and steeper 1/f broadband characteristics compared to healthy controls, as well as a steeper age-related decrease in the bursts rate. While there was a high degree of correlation between some of the oscillatory features, several features also appeared functionally separated, showing independent feature-to-symptom relationships. For instance, oscillatory beta power increased with the severity of midline function symptoms, while burst rate decreased with the severity of bradykinesia.

Our study shows that quantification of distinct features within the oscillatory sensorimotor neural time series in PD captures different underlying mechanisms related to disease progression and symptom severity, which in turn has a potential for a more individualised and precision-based approach to assessing functional neural changes in PD.


title: Novelty-induced frontal-STN networks in Parkinson's disease

abstract: Novelty detection is a primitive subcomponent of cognitive control that is deficient in Parkinsons disease (PD) patients with cognitive dysfunction. Here, we studied novelty-response mechanisms in PD. In participants with PD, we recorded from cortical circuits with scalp-based electroencephalography (EEG) and from subcortical circuits using intraoperative neurophysiology during surgeries for implantation of deep-brain stimulation (DBS) electrodes. We report three major results. First, novel auditory stimuli triggered midfrontal low-frequency rhythms; of these, 1-4 Hz "delta" rhythms were linked to novelty-associated slowing whereas 4-7 Hz "theta" rhythms were specifically attenuated in PD. Second, 32% of subthalamic nucleus (STN) neurons were response-modulated; nearly all (94%) of these were also modulated by novel stimuli. Third, response-modulated STN neurons were coherent with midfrontal 1-4 Hz activity. These findings link scalp-based measurements of neural activity with neuronal activity in the STN. Our results provide insight into midfrontal cognitive control mechanisms and how purported hyperdirect fronto-basal ganglia circuits evaluate new information.


title: A Systematic Review: The Dimensions and Indicators utilized in the Performance Evaluation of Health Care Organizations- An Implication during COVID-19 Pandemic

abstract:
BackgroundThe balanced scorecard (BSC) has been implemented to evaluate the performance of health care organizations (HCOs). BSC proved to be effective in improving financial performance and patient satisfaction.

AimThis systematic review aims to identify key performance indicators (KPIs) and dimensions that are vital and most frequently used by health care managers in BSC implementations. Additionally, it attempts to analyze the resulting dimensions during the COVID-19 era.

MethodsThis systematic review adheres to PRISMA guidelines. The PubMed, Embase, Cochrane, and Google Scholar databases and Google search engine were inspected to find all implementations of BSC at HCO. The risk of bias was assessed using the nonrandomized intervention studies (ROBINS-I) tool to evaluate the quality of observational and quasi- experimental studies and the Cochrane (RoB 2) tool for randomized controlled trials (RCTs).

ResultsThere were 33 eligible studies, of which we identified 36 BSC implementations. The categorization and regrouping of the 797 KPIs resulted in 46 subdimensions. The reassembly of these subdimensions resulted in 13 major dimensions: financial, efficiency and effectiveness, availability and quality of supplies and services, managerial tasks, health care workers (HCW) scientific development error-free and safety, time, HCW-centeredness, patient-centeredness, technology, and information systems, community care and reputation, HCO building, and communication. On the other hand, this review detected that BSC design modification to include external and managerial perspectives was necessary for many BSC implementations.

ConclusionThis review solves the KPI categorization dilemma. It also guides researchers and health care managers in choosing dimensions for future BSC implementations and performance evaluations in general. Consequently, dimension uniformity will improve the data sharing and comparability among studies. Additionally, despite the pandemic negatively influencing many dimensions, the researchers observed a lack of comprehensive HCO performance evaluations. In the same vein, although some resulting dimensions were assessed separately during the pandemic, other dimensions still lack investigation. Lastly, BSC dimensions may play an essential role in tackling the COVID-19 pandemic. However, further research is required to investigate the BSC implementation effect in mitigating the pandemic consequences on HCO.

category: health systems and quality improvement


title: Resurgence of SARS-CoV-2 in India: Potential role of the B.1.617.2 (Delta) variant and delayed interventions

abstract:
India has seen a surge of SARS-CoV-2 infections and deaths in early part of 2021, despite having controlled the epidemic during 2020. Building on a two-strain, semi-mechanistic model that synthesizes mortality and genomic data, we find evidence that altered epidemiological properties of B.1.617.2 (Delta) variant play an important role in this resurgence in India. Under all scenarios of immune evasion, we find an increased transmissibility advantage for B.1617.2 against all previously circulating strains. Using an extended SIR model accounting for reinfections and wanning immunity, we produce evidence in support of how early public interventions in March 2021 would have helped to control transmission in the country. We argue that enhanced genomic surveillance along with constant assessment of risk associated with increased transmission is critical for pandemic responsiveness.

One Sentence SummaryAltered epidemiological characteristics of B.1.617.2 and delayed public health interventions contributed to the resurgence of SARS-CoV-2 in India from February to May 2021.

category: infectious diseases


title: In vivo kinetics of SARS-CoV-2 infection and its relationship with a person's infectiousness

abstract:
The within-host viral kinetics of SARS-CoV-2 infection and how they relate to a persons infectiousness are not well understood. This limits our ability to quantify the impact of interventions on viral transmission. Here, we develop data-driven viral dynamic models of SARS-CoV-2 infection and estimate key within-host parameters such as the infected cell half-life and the within-host reproductive number. We then develop a model linking VL to infectiousness, showing that a persons infectiousness increases sub-linearly with VL. We show that the logarithm of the VL in the upper respiratory tract (URT) is a better surrogate of infectiousness than the VL itself. Using data on VL and the predicted infectiousness, we further incorporated data on antigen and reverse transcription polymerase chain reaction (RT-PCR) tests and compared their usefulness in detecting infection and preventing transmission. We found that RT-PCR tests perform better than antigen tests assuming equal testing frequency; however, more frequent antigen testing may perform equally well with RT-PCR tests at a lower cost, but with many more false-negative tests. Overall, our models provide a quantitative framework for inferring the impact of therapeutics and vaccines that lower VL on the infectiousness of individuals and for evaluating rapid testing strategies.

SignificanceQuantifying the kinetics of SARS-CoV-2 infection and individual infectiousness is key to quantitatively understanding SARS-CoV-2 transmission and evaluating intervention strategies. Here we developed data-driven within-host models of SARS-CoV-2 infection and by fitting them to clinical data we estimated key within-host viral dynamic parameters. We also developed a mechanistic model for viral transmission and show that the logarithm of the viral load in the upper respiratory tract serves an appropriate surrogate for a persons infectiousness. Using data on how viral load changes during infection, we further evaluated the effectiveness of PCR and antigen-based testing strategies for averting transmission and identifying infected individuals.


title: Comparative of the Effectiveness of Different Objective Method for Infraclavicular Brachial Plexus Block Success; Which One of Them is A Reliable and Early Indicator?

abstract:
BACKGROUNDTraditional methods that evaluate the success of peripheral nerve block have been replaced by methods that allow objective evaluations over time. Multiple objective techniques for peripheral nerve block have been discussed in the literature.

OBJECTIVEThis study aims to investigate whether perfusion index (PI), non-invasive tissue hemoglobin monitoring (SpHb), tissue oxygen saturation (StO2), tissue hemoglobin index (THI) and body temperature are reliable and objective methods to evaluate the adequacy of infraclavicular blockage.

DESIGNA prospective observational study.

SETTINGSingle center, Department of Anesthesiology, Harran University Medical Faculty, Turkey, from February 2019 to December 2019.

PATIENTSA total of 100 patients scheduled to undergo forearm surgery.

INTERVENTIONUltrasound-guided infraclavicular block (ICB) in 100 patients undergoing forearm surgery.

MAIN OUTCOME MEASURESPI, SpHb, StO2, THI and Body Temperature measurements were recorded 5 min before the block procedure, right after the procedure, and until the 25th minute after the procedure at 5-min intervals. These values were compared between the blocked limbs and non-blocked limbs while being statistically compared between the successful and failed block groups.

RESULTSAlthough there were significant differences between the groups of blocked extremity and non-blocked extremity in terms of StO2 (P = 0.001), THI (P = 0.001), PI (P = 0.001) and body temperature (P = 0.001), there was no significant difference between these groups in terms of SpHb (P > 0.05). Moreover, a significant difference was detected between the groups of successful block and failed block in terms of StO2 (P = 0.002), PI (P = 0.002) and body temperature (P = 0.005), while there was no significant difference between these groups in terms of THI (P > 0.05) and SpHb (P > 0.05).

CONCLUSIONStO2, PI and body temperature measurements are the simple, objective, noninvasive techniques to be used to evaluate success of block procedures. According to The receiver operating characteristic (ROC) analysis, StO2 is the specific parameter with the highest sensitivity among these parameters.

TRIAL REGISTRATIONACTRN12621000588897

category: anesthesia


title: Age reporting in the Brazilian COVID-19 vaccination database: What can we learn from it?

abstract: Age is a key variable for sciences and public planning. The demographic consequences of not measuring age correctly are manifold, including errors in mortality rates and population estimates, particularly at older ages. It also affects public programs because target populations depend on reliable population age distributions. In Brazil, the start of the vaccination campaign against COVID-19 marked the collection of new administrative data. Every citizen must be registered and need to show an identity document to get vaccinated. The requirement of proof-of-age documentation provides a unique opportunity for measuring the elderly population using a different database. This article examines the reliability of age distributions of men and women 80 years and older. We calculate various demographic indicators using data from the vaccination registration system and compare them to those from the target population estimates of the National Vaccination Plan, censuses, and population projections for Brazil and countries with high-quality population data. We show that requiring proof-of-age, such as in the vaccination records, increases data quality, mainly through the reduction of age heaping and age exaggeration. However, I.D. cards cannot fully solve wrong birth dates that result from weak historical registration systems. Thus, one should be careful when using estimates of the old age population living in some of the Brazilian regions, particularly the North, Northeast, and Center-West. Also, our analysis reveals a mismatch between the projected population by age, sex, and region, which guided the vaccination plan, and the number of vaccinated at ages 80 and older. The methodology developed to adjust the mortality rates used in the demographic projections is probably the main factor behind the disparities found.

category: epidemiology


title: Minimizing the infected peak utilizing a single lockdown: a technical result regarding equal peaks

abstract: Due to the usage of social distancing as a means to control the spread of the novel coronavirus disease COVID-19, there has been a large amount of research into the dynamics of epidemiological models with time-varying transmission rates. Such studies attempt to capture population responses to differing levels of social distancing, and are used for designing policies which both inhibit disease spread but also allow for limited economic activity. One common criterion utilized for the recent pandemic is the peak of the infected population, a measure of the strain placed upon the health care system; protocols which reduce this peak are commonly said to  flatten the curve." In this work, we consider a very specialized distancing mandate, which consists of one period of fixed length of distancing, and addresses the question of optimal initiation time. We prove rigorously that this time is characterized by an equal peaks phenomenon: the optimal protocol will experience a rebound in the infected peak after distancing is relaxed, which is equal in size to the peak when distancing is commenced. In the case of a non-perfect lockdown (i.e. disease transmission is not completely suppressed), explicit formulas for the initiation time cannot be computed, but implicit relations are provided which can be pre-computed given the current state of the epidemic. Expected extensions to more general distancing policies are also hypothesized, which suggest designs for the optimal timing of non-overlapping lockdowns.


title: Carriage of ESBL-producing Enterobacterales in wastewater treatment plant workers and surrounding residents - The AWARE Study

abstract:
PurposeTo investigate whether wastewater treatment plant (WWTP) workers and residents living in close proximity to a WWTP have elevated carriage rates of ESBL-producing Enterobacterales, as compared to the general population.

MethodsFrom 2018 to 2020, we carried out a cross-sectional study in Germany, the Netherlands, and Romania among WWTP workers (N=344), nearby residents (living [≤] 300 meters away from WWTPs; N=431) and distant residents (living [≥] 1000 meters away = reference group; N=1165). We collected information on potential confounders via questionnaire. Culture of participants stool samples was performed with ChromID(R)-ESBL agar plates and species identification with MALDI-TOF-MS. We used logistic regression to estimate the odds ratio (OR) for carrying ESBL-producing E. coli (ESBL-EC). Sensitivity analyses included stratification by country and interaction models using country as secondary exposure.

ResultsPrevalence of ESBL-EC was 11% (workers), 29% (nearby residents), and 7% (distant residents), and higher in Romania (28%) than in Germany (7%) and the Netherlands (6%). Models stratified by country showed that within the Romanian population, WWTP workers are about twice as likely (aOR = 2.34, 95% CI: 1.22-4.5) and nearby residents about three times as likely (aOR = 3.17, 95% CI: 1.8-5.59) to be ESBL-EC carriers, when compared with distant residents.

ConclusionsIn stratified analyses by country, we found an increased risk for carriage of ESBL-EC in Romanian workers and nearby residents. This effect was higher for nearby residents than for workers, which suggests that, for nearby residents, factors other than the local WWTP could contribute to the increased carriage.


title: A systematic review of persistent symptoms and residual abnormal functioning following acute COVID-19: Ongoing symptomatic phase vs. post-COVID-19 syndrome

abstract:
ObjectiveTo compare the two phases of long COVID, namely ongoing symptomatic COVID-19 (OSC; signs and symptoms from 4 to 12 weeks from initial infection) and post-COVID-19 syndrome (PCS; signs and symptoms beyond 12 weeks) with respect to symptomatology, abnormal functioning, psychological burden, and quality of life.

DesignSystematic review.

Data SourcesElectronic search of EMBASE, MEDLINE, ProQuest Coronavirus Research Database, LitCOVID, and Google Scholar between January and April 2021, and manual search for relevant citations from review articles.

Eligibility CriteriaCross-sectional studies, cohort studies, randomised control trials, and case-control studies with participant data concerning long COVID symptomatology or abnormal functioning.

Data ExtractionStudies were screened and assessed for risk of bias by two independent reviewers, with conflicts resolved with a third reviewer. The AXIS tool was utilised to appraise the quality of the evidence. Data were extracted and collated using a data extraction tool in Microsoft Excel.

ResultsOf the 1,145 studies screened, 39 were included, all describing adult cohorts with long COVID and sample sizes ranging from 32 to 1,733. Studies included data pertaining to symptomatology, pulmonary functioning, chest imaging, cognitive functioning, psychological disorder, and/or quality of life. Fatigue presented as the most prevalent symptom during both OSC and PCS at 43% and 44%, respectively. Sleep disorder (36%; 33%), dyspnoea (31%; 40%), and cough (26%; 22%) followed in prevalence. Abnormal spirometry (FEV1 <80% predicted) was observed in 15% and 11%, and abnormal chest imaging observed in 34% and 28%, respectively. Cognitive impairments were also evident (20%; 15%), as well as anxiety (28%; 34%) and depression (25%; 32%). Decreased quality of life was reported by 40% of patients with OSC and 57% by those with PCS.

ConclusionsThe prevalences of OSC and PCS were highly variable. Reported symptoms covered a wide range of body systems, with general overlap in frequencies between the two phases. However, abnormalities in lung function and imaging seemed to be more common in OSC, whilst anxiety, depression, and poor quality of life seemed more frequent in PCS. In general, the quality of the evidence was moderate and further research is needed to better understand the complex interplay of somatic versus psychosocial drivers in long COVID.

Systematic Review RegistrationRegistered with PROSPERO with ID #CRD42021247846.


title: CYP2D6 Genotyping for Personalized Therapy of Tamoxifen in Indonesian Women with ER+ Breast Cancer

abstract: Tamoxifen is a Selective Estrogen-Receptor Modulator (SERM) commonly prescribed for standard of care in estrogen receptor positive (ER+) breast cancer as an adjuvant therapy. Tamoxifen is metabolized by CYP2D6 into its active metabolite, endoxifen, which has been known to play an important role in reducing risk of ER+ breast cancer recurrence. CYP2D6 is a highly polymorphic gene with more than 100 alleles. The phenotype of this gene is categorized into ultrarapid metabolizer (UM), normal metabolizer (NM), intermediate metabolizer (IM), and poor metabolizer (PM). Certain CYP2D6 polymorphisms may cause reduced activity of this enzyme. Studies have found that reduced CYP2D6 activity in IM and PM patients causes low efficacy of standard tamoxifen therapy. This study aims to observe the distribution of CYP2D6 alleles and its correlation with endoxifen levels in Indonesian ER+ breast cancer patients. 151 patients who have received tamoxifen therapy for at least eight weeks were recruited prospectively. DNA and blood samples were collected with buccal swab and finger-prick methods, respectively. Genotyping was performed using the qPCR method while metabolite level measurement was performed using high performance liquid chromatography tandem mass spectrometry. We found that 40.67% of ER+ breast cancer patients recruited were IM. CYP2D6*10 was the most abundant allele (0.288) in this population, and *10/*36 was the most frequently observed diplotype (0.236). Endoxifen levels between the NM-PM, NM-IM, and IM-PM were statistically significant (p-value = 6.26 x 10-5, 9.12 x 10-5, and 4.714 x 10-3, respectively), and dose increase of tamoxifen to 40 mg daily successfully increased endoxifen levels in IMs to a similar level with NMs at baseline. Given these findings, implementing pharmacogenomic testing of CYP2D6 on ER+ breast cancer women who are about to undergo tamoxifen therapy may be beneficial to increase the likelihood of achieving expected endoxifen levels, thus better treatment efficacy.

category: pharmacology and therapeutics


title: Microbiome profiles are associated with cognitive functioning in 45-month-old children

abstract:
Prenatal, perinatal, and postnatal factors have been shown to shape neurobiological functioning and alter the risk for mental disorders later in life. The gut microbiome is established early in life, and interacts with the brain via the brain-immune-gut axis. However, little is known about how the microbiome relates to early-life cognitive functioning in children. The present study, where the fecal microbiome of 380 children was characterized using 16s rDNA and metagenomic sequencing aimed to investigate the association between the microbiota and cognitive functioning of children at the age of 45 months measured with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III).

Overall the microbiome profile showed a significant association with cognitive functioning. A strong correlation was found between cognitive functioning and the relative abundance of an unidentified genus of the family Enterobacteriaceae. Follow-up mediation analyses revealed significant mediation effects of the level of this genus on the association of maternal smoking during pregnancy and current cigarette smoking with cognitive function. Metagenomic sequencing of a subset of these samples indicated that the identified genus was most closely related to Enterobacter asburiae. Analysis of metabolic potential showed a nominally significant association of cognitive functioning with the microbial norspermidine biosynthesis pathway.

Our results indicate that alteration of the gut microflora is associated with cognitive functioning in childhood. Furthermore, they suggest that the altered microflora might interact with other environmental factors such as maternal cigarette smoking. Interventions directed at altering the microbiome should be explored in terms of improving cognitive functioning in young children.

category: psychiatry and clinical psychology


title: Assessing physical fitness during pregnancy: validity and reliability of fitness tests, and relationship with maternal and neonatal health-related outcomes. A systematic review

abstract:
BackgroundPhysical fitness (PF) is a powerful marker of health throughout the lifespan. In pregnant women, higher PF is associated with better maternal and fetal health, better delivery outcomes and earlier postpartum recovery. The assessment of PF during pregnancy requires special considerations to preserve fetal and maternal health; thus, providing a compilation of the most frequently used fitness tests, and assessing their validity, reliability, and association with maternal and neonatal health-related outcomes is of scientific and clinical interest.

ObjectivesTo systematically review studies evaluating one or more components of PF in pregnant women, to answer two research questions: 1) What fitness tests have been previously employed in pregnant women? and 2) What is the validity and reliability of these tests and their relationship with health-related outcomes?

Data SourcesPubMed and Web of Science.

MethodsTwo independent reviewers systematically examined the articles in each database. The information from the included articles was summarized by a single researcher.

ResultsA total of 149 articles containing a sum of 191 fitness tests were included. Among the 191 fitness tests, 99 (i.e.,52%) assessed cardiorespiratory fitness through 75 different protocols, 28 (15%) assessed muscular fitness through 16 different protocols, 14 (7%) assessed flexibility through 13 different protocols, 45 (24%) assessed balance through 40 different protocols, 2 assessed speed with the same protocol and 3 were multidimensional tests using one protocol. A total of 19 articles with 23 tests (13%) assessed either validity (n=4), reliability (n=6), or the relationship of PF with maternal and neonatal health-related outcomes (n=16).

ConclusionPF during pregnancy has been assessed through a wide variety of protocols, mostly lacking validity and reliability data.

PROSPERO Registration Number: CRD42018117554

Key pointsO_LIPhysical Fitness during pregnancy has been assessed through a wide variety of tests (n=191) and different protocols (n=149).
C_LIO_LIWe found that cardiorespiratory fitness has been assessed with 75 different protocols (many of them made ad hoc), muscular fitness with 16 different protocols, flexibility with 13 different protocols, and balance with 40 different protocols.
C_LIO_LIMost of the protocols lacked validity and reliability data, which limits the confidence on the association of fitness with maternal and neonatal health-related outcomes, which is still scarce.
C_LIO_LIWe advocate for an expert consensus to be developed in the following years to achieve the goal of appropriate and effective PF assessment during pregnancy.
C_LI

Running HeadingAssessing physical fitness during pregnancy: validity, reliability and relationship with maternal and neonatal health-related outcomes.

category: sports medicine


title: Discharge prediction of critical patients with spinal cord injury: a machine learning study with 1485 cases

abstract:
ObjectivesPrognostication of spinal cord injury (SCI) is vital, especially for critical patients who need intensive care. The study aims to develop machine-learning (ML) classifiers for discharge prediction of SCI patients in the intensive care unit (ICU).

MethodsClinical data of patients diagnosed with SCI were extracted from the publicly available ICU database. A total of 105 ML classifiers were initially developed to predict the discharge destination (dead, further medical care, home), and then the top 3 classifiers with the best performance were stacked into an ensemble classifier (Esb-Clf). To balance the accuracy and the feasibility, the complete Esb-Clf was finally simplified with top 10 features (simplified Esb-Clf). The micro-average area under the curve (AUC) was used to compare the prediction performance of difference ML classifiers and 6 doctors artificial prediction.

ResultsA total of 1485 SCI patients were used for the early and the recent prediction of discharge destination. In the early prediction, the micro-average AUC of the Esb-Clf and the simplified Esb-Clf was 0.846 and 0.835 during the independent testing, respectively. While in the recent prediction, the micro-average AUC of the Esb-Clf and the simplified Esb-Clf was 0.898 and 0.892. Performance of both the Esb-Clf and the simplified Esb-Clf were superior to the doctors in the early and the recent prediction.

ConclusionsML classifiers can discriminate the discharge destination of SCI patients with high accuracy, feasibility and interpretability. Whether the simplified Esb-Clf as an online predictive tool is applicable to guiding clinical management needs further verification.


title: Relating in vitro neutralisation level and protection in the CVnCoV (CUREVAC) trial.

abstract: A recent study analysed the relationship between neutralising antibody response and protection from SARS-CoV-2 infection across eight vaccine platforms1. The efficacy results from a phase 2b/3 trial of a ninth vaccine candidate, CVnCoV (CUREVAC), was announced on 16 June 20212. The low efficacy of this new mRNA vaccine, which showed only 47% protection from symptomatic SARS-CoV-2 infection, was surprising given the high efficacy of two previous mRNA-based vaccines3,4. A number of factors have been suggested to play a role in the low efficacy in the CVnCoV study, particularly around the dose and immunogenicity of the vaccine (which uses an unmodified mRNA construct5,6) and the potential role of infection with SARS-CoV-2 variants (which were the dominant strains observed in the CVnCoV trial)2.


title: Dimeric IgA is a specific biomarker of recent SARS-CoV-2 infection

abstract: Current tests for SARS-CoV-2 antibodies (IgG, IgM, IgA) cannot differentiate recent and past infections. We describe a point of care, lateral flow assay for SARS-CoV-2 dIgA based on the highly selective binding of dIgA to a chimeric form of secretory component (CSC), that distinguishes dIgA from monomeric IgA. Detection of specific dIgA uses a complex of biotinylated SARS-CoV-2 receptor binding domain and streptavidin-colloidal gold. SARS-CoV-2-specific dIgA was measured both in 112 cross-sectional samples and a longitudinal panel of 362 plasma samples from 45 patients with PCR-confirmed SARS-CoV-2 infection, and 193 discrete pre-COVID-19 or PCR-negative patient samples. The assay demonstrated 100% sensitivity from 11 days post-symptom onset, and a specificity of 98.2%. With an estimated half-life of 6.3 days, dIgA provides a unique biomarker for the detection of recent SARS-CoV-2 infections with potential to enhance diagnosis and management of COVID-19 at point-of-care.


title: Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients

abstract: Infection with SARS-CoV-2 portends a broad range of outcomes, from a majority of asymptomatic cases or mild clinical courses to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty and co-morbidities such as obesity, diabetes or cardiovascular disease. A precise knowledge is still lacking of the molecular and biological mechanisms that may explain the association of severe disease with male sex. Here, we show that testosterone trajectories are highly accurate individual predictors (AUC of ROC = 0.928, p < 0.0001) of survival in male COVID-19 patients. Longitudinal determinations of blood levels of luteinizing hormone (LH) and androstenedione suggest an early modest inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by either full recovery in survivors or a peripheral failure in lethal cases. Moreover, failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and decrease of non-classical monocytes. The strong association of recovery or failure to reinstate testosterone levels with survival or death from COVID-19 in male patients is suggestive of a significant role of testosterone status in the immune responses to COVID-19.


title: Post COVID-19 sequelae: A prospective observational study from Northern India

abstract:
BackgroundLong COVID, or post-COVID-19 sequelae, is being seen in a growing number of patients reporting a constellation of symptoms, both pulmonary and extrapulmonary. Studies on COVID-19 recovered patients are scarce. Thus, there is a need to add granularity to our existing knowledge about the course and long-term effects of the infection.

AimTo describe the clinical details and risk factors of post-COVID sequelae in the North Indian population.

MethodThis prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 to February 2021. Patients aged >18 years with a confirmed COVID-19 disease were recruited after at least two weeks of diagnosis and interviewed for any post-COVID-19 symptoms.

ResultsOf 1234 patients recruited, who were followed up for a median duration of 91 days (IQR: 45-181 days), 495 (40.11%) patients had symptoms. In 223 (18.1%) patients, the symptoms resolved within four weeks, 150 (12.1%) patients had symptoms till twelve weeks, and 122 (9.9%) patients had symptoms beyond twelve weeks of diagnosis of COVID-19. Most common long COVID-19 symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), disturbed sleep (1.4%), mood disturbances (0.48%) and anxiety (0.6%). The major determinants of developing post-COVID-19 symptoms in the patients were hypothyroidism and the severity of the disease.

ConclusionMost often, patients complain of myalgias, fatigue, dyspnoea, cough and disturbed sleep. Patients who are hypothyroid or have recovered from moderate to severe COVID-19 are at higher risk of developing post-COVID sequelae. Therefore, a multidisciplinary approach is required to diagnose and manage COVID-19 recovered patients.


title: Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda

abstract:
BackgroundThe newly described SARS-CoV-2 lineage C.37 was recently classified as a variant of interest by the WHO (Lambda variant) based on its high circulation rates in South American countries and the presence of critical mutations in the spike protein. The impact of such mutations in infectivity and immune escape from neutralizing antibodies are entirely unknown.

MethodsWe performed a pseudotyped virus neutralization assay and determined the impact of the Lambda variant on infectivity and immune escape using plasma samples from healthcare workers (HCW) from two centers in Santiago, Chile who received the two-doses scheme of the inactivated virus vaccine CoronaVac.

ResultsWe observed an increased infectivity mediated by the Lambda spike protein that was even higher than that of the D614G (lineage B) or the Alpha and Gamma variants. Compared to the Wild type (lineage A), neutralization was decreased by 3.05-fold for the Lambda variant while it was 2.33-fold for the Gamma variant and 2.03-fold for the Alpha variant.

ConclusionsOur results indicate that mutations present in the spike protein of the Lambda variant of interest confer increased infectivity and immune escape from neutralizing antibodies elicited by CoronaVac. These data reinforce the idea that massive vaccination campaigns in countries with high SARS-CoV-2 circulation must be accompanied by strict genomic surveillance allowing the identification of new isolates carrying spike mutations and immunology studies aimed to determine the impact of these mutations in immune escape and vaccines breakthrough.


title: FGF21 defines a potential cardio-hepatic signaling circuit in human heart failure

abstract:
BackgroundExtrinsic control of cardiac contractility and ultrastructure via neurohormonal signaling is well established, but how other organs regulate cardiomyocyte metabolism is less well understood. Fibroblast growth factor-21 (FGF21) a hormonal regulator of metabolism mainly produced in the liver and adipose tissue, is a prime candidate for such signaling.

MethodsTo investigate this further, we examined blood and tissue obtained from human subjects with heart failure with reduced ejection fraction (HFrEF) at the time of left ventricular assist device (LVAD) implantation, and correlated serum FGF21 levels with cardiac gene expression, immunohistochemistry, and clinical parameters.

ResultsCirculating FGF21 levels were substantially elevated in HFrEF, compared to healthy subjects (HFrEF: 834.4 {+/-} 101.8 pg/mL, n = 40; controls: 145.9 {+/-} 28.6 pg/mL, n = 20, p = 5.5 x 10-8). There was clear FGF21 staining in diseased cardiomyocytes, and circulating FGF21 levels negatively correlated with the expression of cardiac genes involved in ketone metabolism, consistent with cardiac FGF21 signaling. FGF21 gene expression was low in failing and non-failing hearts, suggesting at least partial extracardiac production of the circulating hormone. Circulating FGF21 levels were correlated with BNP and total bilirubin, markers of chronic cardiac and hepatic congestion.

ConclusionsCirculating FGF21 levels are elevated in HFrEF. The liver is likely the main extracardiac source, and congestive hepatopathy, common in HFrEF, was likely the proximate signal leading to FGF21 elevations. This supports a model of venous congestion from cardiomyopathy driving hepatic FGF21 communication to diseased cardiomyocytes, defining a potential cardio-hepatic signaling circuit in human heart failure.

category: cardiovascular medicine


title: COVID-19 Has Long Term Effects on Chemosensory Functions

abstract: Several studies have revealed either self-reported chemosensory alterations in large groups or objective quantified chemosensory impairments in smaller populations of patients diagnosed with COVID-19. However, due to the great variability in published results regarding COVID-19-induced chemosensory impairments and their follow-up, prognosis for chemosensory functions in patients with such complaints remains unclear. Our objective is to describe the various chemosensory alterations associated with COVID-19 and their prevalence and evolution after infection. A cross-sectional study of 704 healthcare workers with a RT-PCR confirmed SARS-CoV-2 infection between 28/2/2020 and 14/6/2020 was conducted 3 to 7 months after onset of symptoms. Data were collected with an online questionnaire. Outcomes included differences in reported chemosensory self-assessment of olfactory, gustatory, and trigeminal functions across time points and Chemosensory Perception Test scores from an easy-to-use at-home self-administered chemosensory test. Among the 704 participants, 593 (84.2%) were women, the mean (SD) age was 42 (12) years, and the questionnaire was answered on average 4.8 (0.8) months after COVID-19. During COVID-19, a decrease in olfactory, gustatory, and trigeminal sensitivities were reported by 81.3%, 81.5% and 48.0% respectively. Three to seven months later, reduced sensitivity was still reported by 52.0%, 41.9% and 23.3% respectively. Chemosensory Perception Test scores indicate that 19.5% of participants had objective olfactory impairment. These data suggest a significant proportion of COVID-19 cases have persistent chemosensory impairments at 3 to 7 months after their infection but the majority of those who had completely lost their olfactory, gustatory, and trigeminal sensitivity have improved.

category: otolaryngology


title: Chemosensory dysfunctions induced by COVID-19 can persist up to 7 months: A study of over 700 healthcare workers


title: Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2 infection

abstract: Individuals with likely exposure to the highly infectious SARS-CoV-2 do not necessarily develop PCR or antibody positivity, suggesting some may clear sub-clinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections1-5. We hypothesised that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-26-12, would expand in vivo to mediate rapid viral control, potentially aborting infection. We studied T cells against the replication transcription complex (RTC) of SARS-CoV-2 since this is transcribed first in the viral life cycle13-15and should be highly conserved. We measured SARS-CoV-2-reactive T cells in a cohort of intensively monitored healthcare workers (HCW) who remained repeatedly negative by PCR, antibody binding, and neutralisation for SARS-CoV-2 (exposed seronegative, ES). 16-weeks post-recruitment, ES had memory T cells that were stronger and more multispecific than an unexposed pre-pandemic cohort, and more frequently directed against the RTC than the structural protein-dominated responses seen post-detectable infection (matched concurrent cohort). The postulate that HCW with the strongest RTC-specific T cells had an abortive infection was supported by a low-level increase in IFI27 transcript, a robust early innate signature of SARS-CoV-2 infection16. We showed that the RNA-polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and was preferentially targeted by T cells from UK and Singapore pre-pandemic cohorts and from ES. RTC epitope-specific T cells capable of cross-recognising HCoV variants were identified in ES. Longitudinal samples from ES and an additional validation cohort, showed pre-existing RNA-polymerase-specific T cells expanded in vivo following SARS-CoV-2 exposure, becoming enriched in the memory response of those with abortive compared to overt infection. In summary, we provide evidence of abortive seronegative SARS-CoV-2 infection with expansion of cross-reactive RTC-specific T cells, highlighting these highly conserved proteins as targets for future vaccines against endemic and emerging Coronaviridae.

category: allergy and immunology


title: Side Effects and Perceptions Following Sinopharm COVID-19 Vaccination

abstract:
BackgroundVaccines are one of the best interventions developed for eradicating COVID-19, the rapid creation of vaccinations was increased the risk of vaccine safety problems. The aim of this study to provide evidence on Sinopharm COVID-19 vaccine side effects which is approved by the United Arab Emirates (UAE).

MethodsA cross-sectional survey study was conducted between January and April 2021 to collect data on the effects of COVID-19 vaccine among individuals in the UAE. Demographic data, chronic conditions, side effects of the 1st and 2nd dose toward the vaccination, and the response of unwilling taking COVID-19 vaccine were reported.

ResultsThe most common side effects of post 1st dose vaccination among participants ([≤]49 years old vs >49 years) were normal injection site pain 42.2%, fatigue 12.2%, and headache 9.6%, while pain at the vaccination site 32.6%, fatigue16.3%, lethargy13.7%, headache10%, and tenderness 10% were the most side effects of the post 2nd dose of vaccination in both groups. All the side effects in both doses were more prevalent among the participants [≤] 49-year-old group.

Among two groups (females vs males), the study revealed the increase in the number of females that suffered from the vaccine side effects compared with males in both doses. The most prevalence adverse reactions of first dose in (females vs males) were fatigue (15.8% vs 3.75%), lethargy (12.6% vs 1.25%), headache (10.5% vs 7.5%), while in 2nd dose were fatigue (20% vs 7.5%), sever injection site pain (10.5% vs 2.5%). The most common reason of not willing to take the COVID-19 vaccine among the participants were the vaccines are not effective, and the participants were not authorized to take vaccine.

ConclusionThe 1st and 2nd dose post-vaccination side effects were mild, predictable, and there were no hospitalization cases, this data will help to reduce the vaccine hesitancy.


title: Community-Based Phenotypic Study of Safety, Tolerability, Reactogenicity and Immunogenicity of Emergency-Use-Authorized Vaccines Against COVID-19 and Viral Shedding Potential of Post-Vaccination Infections: Protocol for a prospective study

abstract:
1The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a global pandemic that disrupted and impacted lives in unprecedented ways. Within less than a year after the beginning of the COVID-19 pandemic, vaccines developed by several research teams were emergency-use authorized and made their way to distribution sites across the US and other countries. COVID-19 vaccines were tested in clinical trials with thousands of participants before authorization, and were administered to over a billion people across the globe in the following 6 months. Post-authorization safety monitoring was performed using pre-existing systems (such as the World Health Organizations platform VigiBase or US Vaccine Adverse Event Reporting System, VAERS) and newly developed post-vaccination health checkers (such as V-safe in the US). Vaccinated individuals were also posting their experiences on multiple social media groups created on Facebook, Reddit, Telegram and other platforms, but the groups were often removed as "proliferating false claims". These forms of reporting are susceptible to biases and misclassifications and do not reach all vaccinated individuals, raising questions about risks of exacerbating health inequalities as well as security and privacy vulnerabilities.

The objective of this paper is to present the protocol for a community-based participatory research approach enabling long-term monitoring of health effects, strengthening community participation via transparent messaging and support, and addressing challenges of transitioning to a new normal.


title: Community-Based Phenotypic Study of Safety, Tolerability, Reactogenicity and Immunogenicity of Emergency-Use-Authorized Vaccines Against COVID-19 and Viral Shedding Potential of Post-Vaccination Infections: Protocol for an Ambispective study


title: Completeness of reporting of clinical prediction models developed using supervised machine learning: A systematic review

abstract:
ObjectiveWhile many studies have consistently found incomplete reporting of regression-based prediction model studies, evidence is lacking for machine learning-based prediction model studies. We aim to systematically review the adherence of Machine Learning (ML)-based prediction model studies to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Statement.

Study design and settingWe included articles reporting on development or external validation of a multivariable prediction model (either diagnostic or prognostic) developed using supervised ML for individualized predictions across all medical fields (PROSPERO, CRD42019161764). We searched PubMed from 1 January 2018 to 31 December 2019. Data extraction was performed using the 22-item checklist for reporting of prediction model studies (www.TRIPOD-statement.org). We measured the overall adherence per article and per TRIPOD item.

ResultsOur search identified 24 814 articles, of which 152 articles were included: 94 (61.8%) prognostic and 58 (38.2%) diagnostic prediction model studies. Overall, articles adhered to a median of 38.7% (IQR 31.0-46.4) of TRIPOD items. No articles fully adhered to complete reporting of the abstract and very few reported the flow of participants (3.9%, 95% CI 1.8 to 8.3), appropriate title (4.6%, 95% CI 2.2 to 9.2), blinding of predictors (4.6%, 95% CI 2.2 to 9.2), model specification (5.2%, 95% CI 2.4 to 10.8), and models predictive performance (5.9%, 95% CI 3.1 to 10.9). There was often complete reporting of source of data (98.0%, 95% CI 94.4 to 99.3) and interpretation of the results (94.7%, 95% CI 90.0 to 97.3).

ConclusionSimilar to prediction model studies developed using conventional regression-based techniques, the completeness of reporting is poor. Essential information to decide to use the model (i.e. model specification and its performance) is rarely reported. However, some items and sub-items of TRIPOD might be less suitable for ML-based prediction model studies and thus, TRIPOD requires extensions. Overall, there is an urgent need to improve the reporting quality and usability of research to avoid research waste.

What is new?O_LIKey findings: Similar to prediction model studies developed using regression techniques, machine learning (ML)-based prediction model studies adhered poorly to the TRIPOD statement, the current standard reporting guideline.
C_LIO_LIWhat this adds to what is known? In addition to efforts to improve the completeness of reporting in ML-based prediction model studies, an extension of TRIPOD for these type of studies is needed.
C_LIO_LIWhat is the implication, what should change now? While TRIPOD-AI is under development, we urge authors to follow the recommendations of the TRIPOD statement to improve the completeness of reporting and reduce potential research waste of ML-based prediction model studies.
C_LI


title: Rotation-based schedules in elementary schools to prevent COVID-19 spread: A simulation study

abstract:
BackgroundRotations of schoolchildren on a weekly basis is one of the nonpharmaceutical interventions often considered in the covid-19 pandemic. This study aims to investigate the impact of different types of rotations in various testing contexts.

MethodsWe built an agent-based model of interactions among pupils and teachers based on an online survey in an elementary school in Prague, Czechia. This model contains 624 schoolchildren and 55 teachers (679 nodes) and about 27 thousands social contacts (edges) in 10 layers. The layers reflect different types of contacts (in classroom, cafeteria etc.) as described in the survey. On this multi-graph structure we run a modified SEIR model of the covid-19 dynamics. The parameters of the model are calibrated on data from the outbreak in the Czech Republic in the period March to June 2020.

FindingsThere are three main findings in our paper.

O_LIWeekly rotations of in-class and distance learning reduce the spread of covid-19 by 75-81% and thus represent an effective preventative measure in school setting.
C_LIO_LIRegular antigen testing twice a week, or weekly PCR testing, significantly reduces infections even when using tests with a lower sensitivity: tests with a 40% sensitivity reduce infections by more than 50 percent.
C_LIO_LIThe density of revealed contact graphs for older pupils is 1.5 times higher than the younger pupils graph, the teachers network is yet an order of magnitude denser. Consequently, the infection transmission between teachers is highly overproportional in our school. Moreover, teachers act as bridges connecting clusters of classes, especially in the secondary grade where they are responsible for 14-18% of infections, in comparison to 8-11% in primary grade.
C_LI

InterpretationWeekly rotations with regular testing are a highly effective non-pharmaceutical intervention for the prevention of covid-19 spread in schools and a way to keep schools open during an epidemic or to reopen them as the epidemiological situation improves.


title: OCD symptom severity and comorbid psychiatric diagnoses in a Swedish genetic epidemiological obsessive-compulsive disorder cohort

abstract:
BackgroundWe have established an epidemiological obsessive-compulsive disorder (OCD) cohort in Sweden. Individuals contributed DNA for genotyping and sequencing and also completed a Swedish translation of the Obsessive-Compulsive Inventory-Revised (OCI-R), a self-report questionnaire for assessing the severity and type of symptoms of OCD. This study made use of the OCI-R data to examine the severity and symptom dimensions of OCD as well as comorbidity with other psychiatric disorders.

MethodsOCI-R data for 1,134 individuals were available for this study, 1,010 diagnosed with OCD, and 124 diagnosed with chronic tic disorders without OCD used as a comparison group. We first evaluated the psychometric properties of the Swedish translation of the OCI-R. Then, we linked data from the Swedish national registries to access and analyze psychiatric comorbidities of OCD.

ResultsThe Swedish translation of OCI-R demonstrated internal consistency (Cronbachs  = 0.9) and clear agreement with the OCI-R six-factor model. The mean total OCI-R score for females was significantly higher than for males. The most comorbid psychiatric condition to OCD were anxiety disorders (13.6%) and major depression (12%). We observed that individuals with OCD frequently had additional comorbid psychiatric disorders and that the severity of OCD was significantly higher in individuals with at least one additional psychiatric comorbidity compared to individuals with no psychiatric comorbidity.

ConclusionWe showed that the Swedish translation of the OCI-R has appropriate psychometric properties. Using an epidemiological framework, we were able to assess the severity and symptom dimensions of OCD and comorbidity with other psychiatric disorders.


title: Reliability and Validity of Bifactor Models of Dimensional Psychopathology in Youth from three Continents

abstract:
Bifactor models are a promising strategy to parse general from specific aspects of psychopathology in youth. Currently, there are multiple configurations of bifactor models originating from different theoretical and empirical perspectives. Our aim is to identify and test the reliability, validity, measurement invariance, and the correlation of different bifactor models of psychopathology using the Child Behavior Checklist (CBCL). We used data from the Reproducible Brain Charts (RBC) initiative (N=7,011, ages 5 to 22 years, 40.2% females). Factor models were tested using the baseline data. To address our aim, we a) mapped the published bifactor models using the CBCL; b) tested their global model fit; c) calculated model-based reliability indices. d) tested associations with symptoms impact in everyday life; e) tested measurement invariance across many characteristics and f) analyzed the observed factor correlation across the models. We found 11 bifactor models ranging from 39 to 116 items. Their global model fit was broadly similar. Factor determinacy and H index were acceptable for the p-factors, internalizing, externalizing and somatic specific factors in most models. However, only p- and attention factors were predictors of symptoms impact in all models. Models were broadly invariant across different characteristics. P-factors were highly correlated across models (r = 0.88 to 0.99). Homotypic specific factors were also highly correlated. Regardless of item selection and strategy to compose CBCL bifactor models, results suggest that they all assess very similar constructs. Our results provide support for the robustness of the bifactor of psychopathology and distinct study characteristics.

General Scientific SummariesThis study supports the notion that models of psychopathology that separate what is general from what is specific in mental health problems have little impact from item selection and types of specific dimensions. The general dimensions are highly correlated among different models, valid to predict symptom impact in daily life and are not influenced by demographic and clinical characteristics, time and information.


title: Hospital Preparedness and Response Framework during infection pandemic.

abstract: Coronavirus disease 2019 (COVID-19) has put an unprecedented burden to world health, economy and social life with possible long-term consequences. The velocity and mass of this infection pandemic had already overwhelmed every robust health care system in the world. The evidence pertaining to this novel infection pandemic is evolving, so are the challenges in terms of adequate preparedness and response. In this review, we enumerate the strategic and operational domains and build a functional framework for the management of hospital mass infection incidents due to COVID-19 and similar future pandemics. This functional framework could assist health policy maker and health care worker to implement, innovate, and translate preparedness and response to save valuable life and resources.

category: public and global health


title: The Evolution of Young People's Mental Health during COVID-19: Evidence from four Low-and-Middle-Income-Countries

abstract:
BackgroundThough COVID-19 presents less risk to young people of serious morbidity or mortality, the resulting economic crisis has impacted their livelihoods. There is relatively little evidence on young peoples mental health in Low-and-Middle-Income-Countries (LMICs) as the pandemic has progressed.

MethodsTwo consecutive phone-surveys (August/October and November/December 2020) in Ethiopia, India, Peru and Vietnam interviewed around 9,000 participants of a 20-year cohort study who grew up in poverty (now aged 19 and 26). We investigate how young peoples mental health has evolved in the four countries during the pandemic. Rates of (at least mild) anxiety (depression) measured by GAD-7 (PHQ-8) were compared across countries; between males/females, and food secure/food insecure households.

ResultsOverall, rates of at least mild anxiety (depression) significantly decreased in all countries but Ethiopia as infection rates fell. However, young people in food insecure households report high rates of anxiety and depression and have not shown consistent improvements. Food insecure households are poorer, and have significantly more children (p<0.05) except in Ethiopia.

ConclusionsFood insecurity has increased during the COVID-19 pandemic and is negatively associated with young peoples mental health. Urgent support is needed for the most vulnerable.


title: Soft robotic steerable micro-catheter for the endovascular treatment of cerebral disorders

abstract: Catheters used for endovascular navigation in interventional procedures lack dexterity at the distal tip. Neurointerventionists, in particular, encounter challenges in up to 25% of aneurysm cases largely due to the inability to steer and navigate the tip of the micro-catheters through tortuous vasculature to access aneurysms. We overcome this problem with sub-millimeter diameter, hydraulically-actuated hyperelastic polymer devices at the distal tip of micro- catheters to enable active steerability. Controlled by hand, the devices offer complete 3D orientation of the tip. Using pressures up to 400 kPa (4 atm) we demonstrate guidewire-free navigation, access, and coil deployment in vivo, offering safety, ease of use, and design flexibility absent in other approaches to endovascular intervention. We demonstrate the ability of our device to navigate through vessels and to deliver embolization coils to the cerebral vessels in a live porcine model. This indicates the potential for microhydraulic soft robotics to solve difficult access and treatment problems in endovascular intervention.

category: surgery


title: Use of autologous platelet derivatives for secondary alveoloplasty in patients with cleft lip and palate: a protocol for a systematic review and meta-analysis

abstract:
ObjectiveTo assess the effectiveness and safety of autologous platelet derivatives, specifically platelet-rich plasma (PRP) or platelet-rich fibrin (PRF), for secondary alveoloplasty in patients with cleft lip and palate.

Eligibility criteriaWe will include randomized trials evaluating the effect of autologous platelet derivatives on newly bone formed after secondary alveoloplasty in cleft lip and palate patients. Two reviewers will independently screen each study for eligibility, data extraction, and bias assessment using the Cochrane "risk of bias "tool. We will pool the results using meta-analysis and apply the GRADE system to assess the certainty of the evidence for each outcome.

Data sourcesA comprehensive search will include all relevant randomized controlled trials (RCTs), the ongoing investigation reported in specialty congresses and trials regardless of language or publication status (published, unpublished, in press, and progress). We will conduct searches in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, Embase, and LILACS. We will screen trial registries and other sources in order to identify articles that might have been missed in the electronic searches.

Ethics and disseminationAs researchers will not access information that could identify an individual participant, obtaining ethical approval was waived.


title: Multi-Sequence Average Templates for Aging and Neurodegenerative Disease Populations

abstract:
Magnetic resonance image (MRI) processing pipelines use average templates to enable standardization of individual MRIs in a common space. MNI-ICBM152 is currently used as the standard template by most MRI processing tools. However, MNI-ICBM152 represents an average of 152 healthy young adult brains and is vastly different from brains of patients with neurodegenerative diseases. In those populations, extensive atrophy might cause inevitable registration errors when using an average template of young healthy individuals for standardization. Disease-specific templates that represent the anatomical characteristics of the populations can reduce such errors and improve downstream driven estimates.

We present multi-sequence average templates for Alzheimers Dementia (AD), Fronto-temporal Dementia (FTD), Lewy Body Dementia (LBD), Mild Cognitive Impairment (MCI), cognitively intact and impaired Parkinsons Disease patients (PD-CIE and PD-CI, respectively), individuals with Subjective Cognitive Impairment (SCI), AD with vascular contribution (V-AD), Vascular Mild Cognitive Impairment (V-MCI), Cognitively Intact Elderly (CIE) individuals, and a human phantom. We also provide separate templates for males and females to allow better representation of the diseases in each sex group.


title: A cross-sectional study of the association between frequency of telecommuting and unhealthy dietary habits among Japanese workers during the COVID-19 pandemic

abstract:
2.Abstract and keywordsO_ST_ABSObjectiveC_ST_ABSDue to the COVID-19 pandemic, telecommuting has become a new way of working that has not only changed individuals work, but also their health and lifestyle. We examined the relationship between telecommuting frequency and unhealthy dietary habits among Japanese workers.

MethodsA total of 33,302 workers completed an Internet survey about telecommuting and dietary habits. Data from 13,468 office workers who telecommuted were analyzed. Telecommuting frequency during the COVID-19 pandemic was extracted from a questionnaire. The odds ratios (ORs) of four types of dietary habits, namely, skipping breakfast, solitary eating, lower meal frequency, and meal substitution associated with telecommuting frequency were estimated using multilevel logistic regression nested in the prefecture of residence to control for differences in residential area.

ResultsThe multivariate OR of skipping breakfast was 1.15 (95% CI: 1.03-1.29, p=0.013) for participants who telecommuted in excess of four days per week compared to those who rarely telecommuted. Similarly, the OR of solitary eating, lower meal frequency and meal substitution were 1.44 (95%CI: 1.28-1.63, p<0.001), 2.39 (95%CI: 1.66-3.44, p<0.001), and 1.26 (95%CI: 1.04-1.51, p=0.015) for those who telecommuted in excess of four days per week compared to those who rarely telecommuted. There was a statistically significant increase in the dose-response trend in ORs of solitary eating (p for trend <0.001), lower meal frequency (p for trend <0.001), and meal substitution (p for trend =0.001) with increasing telecommuting frequency.

ConclusionTelecommuters may develop unhealthy dietary habits, indicating the need for strategies to help telecommuters manage their nutrition and diet.

category: occupational and environmental health


title: Familial Genetic Cancer Risk Assessment with respect to a Silent BRCA2 mutation

abstract: Male Breast Cancer (BC) is relatively rarer, accounting for less than 1% of cancers in men. MBC is hereditary in nature and mainly attributed to BRCA1/2 germline mutations. Accordingly, National Comprehensive Cancer Network (NCCN) guidelines advise genetic counselling and testing for all cases of MBCs and their unaffected family members. In this report, we present an uncommon case of male patient primarily diagnosed with pancreatic cancer who later developed asynchronous bilateral hormone positive breast cancer. We describe the genetic screening and clinical management protocol for the proband and family members. Genetic testing with next generation sequencing by uses of a multi-gene germline mutation panel revealed a likely pathogenic BRCA2 variant (c.8754G>A, p.E2918E). Subsequently, 34 members of the extended family of the proband were tested for the BRCA2 variant by Sanger sequencing. 6 of the family members were identified as carriers of this BRCA2 variant. Of these, three presented with hereditary breast cancer and 3 were unaffected healthy carriers. In silico analysis for mechanistic insights in underlying pathogenicity revealed that the silent BRCA2 mutation is a spliceogenic variant that is likely to create an aberrant mRNA transcript via alternative splicing of BRCA2 gene. Our study demonstrates the clinical relevance of this silent BRCA2 mutation and emphasizes the need for further experimental studies to elucidate its functional role in breast cancer pathology.

category: genetic and genomic medicine


title: The penetrance of age-related monogenic disease depends on ascertainment context

abstract:
BACKGROUNDAccurate penetrance of monogenic disorders is often unknown due to a phenotype-first approach to genetic testing. Here, we use a genotype-first approach in four large cohorts with different ascertainment contexts to accurately estimate penetrance of the three commonest causes of monogenic diabetes, Maturity Onset Diabetes of the Young (MODY). We contrast HNF1A-MODY / HNF4A-MODY which causes an age-related progressive diabetes and GCK-MODY, which causes life-long mild hyperglycaemia.

METHODSWe analysed clinical and genetic sequencing data from four different cohorts: 1742 probands referred for clinical MODY testing; 2194 family members of the MODY probands; 132,194 individuals from an American hospital-based cohort; and 198,748 individuals from a UK population-based cohort.

RESULTSAge-related penetrance of diabetes for pathogenic variants in HNF1A and HNF4A was substantially lower in the clinically unselected cohorts compared to clinically referred probands (ranging from 32% to 98% at age 40yrs for HNF1A, and 21% to 99% for HNF4A). The background rate of diabetes, but not clinical features or variant type, explained the reduced penetrance in the unselected cohorts. In contrast, penetrance of mild hyperglycaemia for pathogenic GCK variants was similarly high across cohorts (ranging from 89 to 97%) despite substantial variation in the background rates of diabetes.

CONCLUSIONSAscertainment context is crucial when interpreting the consequences of monogenic variants for age-related variably penetrant disorders. This finding has important implications for opportunistic screening during genomic testing.


title: Redefining tissue specificity of genetic regulation of gene expression in the presence of allelic heterogeneity

abstract: Understanding the mechanisms that underlie genetic regulation of gene expression is crucial to explaining the diversity that governs complex traits. Large scale expression quantitative trait locus (eQTL) studies have been instrumental in identifying genetic variants that influence the expression of target genes. However, a large fraction of disease-associated genetic variants have not been clearly explained by current eQTL data, frustrating attempts to use these data to comprehensively characterize disease loci. One notable observation from recent studies is that cis-eQTL effects are often shared across different cell types and tissues. This would suggest that common genetic variants impacting steady-state, adult gene expression are largely tolerated, shared across tissues, and less relevant to disease. However, allelic heterogeneity and complex patterns of linkage disequilibrium (LD) within each locus may skew the quantification of sharing of genetic effects between tissues, impede our ability to identify causal variants, and hinder the identification of regulatory effects for disease-associated genetic variants. Indeed, recent research suggests that multiple causal variants are often present in many eQTL and complex trait associated loci. Here, we re-analyze tissue-specificity of genetic effects in the presence of LD and allelic heterogeneity, proposing a novel method, CAFEH, that improves the identification of causal regulatory variants across tissues and their relationship to disease loci.


title: Global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection

abstract: We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (ACE2, TMPRSS2, DPP4, and LY6E). We analyzed novel data from 2,012 ethnically diverse Africans and 15,997 individuals of European and African ancestry with electronic health records, and integrated with global data from the 1000GP. At ACE2, we identified 41 non-synonymous variants that were rare in most populations, several of which impact protein function. However, three non-synonymous variants were common among Central African hunter-gatherers from Cameroon and are on haplotypes that exhibit signatures of positive selection. We identify strong signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2, we identified 13 amino acid changes that are adaptive and specific to the human lineage. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19.


title: Impact of natural selection on global patterns of genetic variation, and association with clinical phenotypes, at genes involved in SARS-CoV-2 infection.


title: The Gendered Implications of Energy Gaps in Health Care: A Comparative Analysis of Haiti, Senegal, and the Democratic Republic of Congo

abstract: The World Health Organization recently articulated a number of challenges faced by health systems due to unreliable access to energy services. Reliable energy availability at rural health facilities is understood to be an enabler of access to quality healthcare, owing to its potential impacts on medical services, health and safety, disease prevention and treatment, staff recruitment and retention, and administration and logistics. However, little is known empirically about the intersections of energy and healthcare, often due to the lack of availability of facility level data. Moreover, the gender implications of energy access (or lack thereof) for women as providers and seekers of primary healthcare have not been investigated. In this study, using a gender lens, we explore the linkages between energy and healthcare in three Francophone countries in the Caribbean and sub-Saharan Africa: Democratic Republic of the Congo (DRC), Haiti and Senegal. All three countries have faced serious challenges to the provision of quality health services, including infrastructure problems and specifically unreliable access to electricity. We use Demographic Health Survey data from all three countries to present detailed descriptions of the association between (a) the availability and reliability of electricity sources, and (b) availability of health services, equipment and medical personnel at different levels of the respective health systems. We find that the unavailability and unreliability of electricity is associated with lower availability of medical equipment and basic health services, especially among facilities at the primary care level in DRC and Haiti. Our findings highlight the opportunity to create more dependable and sustainable health systems by integrating decentralized clean energy technologies into health infrastructure, which can facilitate providers in female-dominated cadres such as nursing the ability to provide the care they are tasked with.


title: Navigating sample overlap, winner's curse and weak instrument bias in Mendelian randomization studies using the UK Biobank

abstract: We performed GWAS on 2514 complex traits from the UK Biobank using a linear mixed model, identifying 40,620 independent significant associations (p<5x10-8). We estimate that winners curse incurs substantial overestimation of effect sizes in a mean of 35% of discovered associations per trait. We use these results to estimate that the polygenicity of most complex traits is below 10000 common causal variants. We evaluated the impact of winners curse on causal effect estimation and hypothesis testing in Mendelian randomization analyses. We show that winners curse substantially amplifies the magnitude of weak instrument bias, though any inflation of false discovery rates tends to be low or modest. We designed a process of pseudo-replication within the UK Biobank data to generate GWAS estimates that minimise bias in MR studies using these data. Our resource is integrated into the OpenGWAS platform and enables a convenient framework for researchers to minimise bias or maximise precision of causal effect estimates.


title: Correlation between the environmental parameters with outbreak pattern of COVID-19: A district level investigation based on yearlong period in India

abstract: The present study has investigated the role of regional meteorology and air quality parameters in the outbreak pattern of COVID-19 pandemic in India. Using the remote sensing based dataset of 12 environmental variables we correlated infective case counts at a district level in India. Our investigation carried out on the circumstantial data from more than 300 major affected districts in India and found that air quality parameters are playing very crucial role in this outbreak. Among the air pollutants, O3 was better correlating with infection counts followed by AOD, CO, NO2, BC and SO2. We also observed that among the weather parameters air temperature, incoming shortwave radiation, wind speed are positively and significantly associate with outbreak pattern and precipitation and humidity are negatively correlated with confirmed cases; only cloud cover has no significant relation. We noted that coastal districts in the both coast of India and districts located in the plain and low-lying areas have experienced bitter situation during this pandemic. Our study suggests that improving air quality with proper strict regulations and complete lockdown during the peak of pandemic could reduce the misfortune in all over India.


title: Molecular pathways in post-colonoscopy versus detected colorectal cancers: results from a nested case-control study

abstract:
BackgroundPost-colonoscopy colorectal cancers (PCCRCs) pose a challenge in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. Specific features of lesions may contribute for this. In a nested case-control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs).

MethodsPCCRCs were defined according to the WEO 2018 classification, as cancers occurring after a complete index colonoscopy, which excluded CRC. CRCs in patients without colonoscopy or with colonoscopy >10 years before were defined as DCRCs. Whole genome chromosomal copy number changes and mutation status of genes commonly affected in CRC (including APC, KRAS, BRAF, FBXW7, PIK3CA, NRAS, SMAD4 and TP53) were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status were also determined.

ResultsIn total, 122 PCCRCs and 98 DCRCs with high quality DNA were examined. PCCRCs were more often located proximally in the colon (p<0.001), non-polypoid appearing (p=0.004), early stage (p=0.009), and poorly differentiated (p=0.006). PCCRCs showed similar patterns of DNA copy number changes typical of CRC, although significantly less 18q loss (FDR <0.2), compared to DCRCs. No significant differences in mutations were detected between PCCRCs and DCRCs. PCCRCs were more commonly CIMP-high (p=0.014) and MSI (p=0.029). After correction for tumour location, the only molecular difference between PCCRCs and DCRCs that remained significant was less frequent loss of 18q chromosome in PCCRCs (p=0.005).

ConclusionAlthough PCCRCs show molecular characteristics that are common to the canonical CIN, MSI and hypermethylation pathways, molecular features associated with the sessile serrated lesions (SSLs) and non-polypoid colorectal neoplasms (CRNs) are more commonly seen in PCCRCs than in DCRCs. This and the clinical features observed in PCCRCs support the hypothesis that sessile serrated lesions and non-polypoid CRNs are contributors to the development of these cancers. In order to further reduce the occurrence of PCCRCs, the focus should be directed at improving the detection, determination and endoscopic removal of these non-polypoid CRN and SSLs.

Clinical Trial RegistrationNTR3093 in the Dutch trial register (www.trialregister.nl)

category: gastroenterology


title: Polygenic risk for psychiatric disorder reveals distinct association profiles across social behaviour in the general population

abstract: Many complex psychiatric disorders are characterised by a spectrum of social difficulties. These symptoms lie on a behavioural dimension that is shared with social behaviour in the general population, with substantial contributions of genetic factors. However, shared genetic links may vary across psychiatric disorders and social symptoms. Here, we systematically investigate heterogeneity in shared genetic liabilities with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), bipolar disorder (BP), major depression (MD) and schizophrenia, across a spectrum of different social symptoms. Specifically, longitudinally assessed low-prosociality and peer-problem scores in two UK population-based/community-based cohorts (ALSPAC, N [≤] 6174, 4-17 years; TEDS, N [≤] 7112, 4-16 years; parent- and teacher-reports) were regressed on polygenic risk scores for ADHD, ASD, BP, MD, and schizophrenia, as informed by genome-wide summary statistics from large consortia, using negative binomial regression models. Across ALSPAC and TEDS, we replicated univariate polygenic associations between social behaviour and risk for ADHD, MD, and schizophrenia. Modelling univariate genetic effects across both cohorts with random-effect meta-regression revealed evidence for polygenic links between social behaviour and ADHD, ASD, MD, and schizophrenia risk, but not BP, where differences in age, reporter and social trait captured 45-88% in univariate effect variation. For ADHD, MD, and ASD polygenic risk, we identified stronger association with peer problems than low prosociality, while schizophrenia polygenic risk was solely associated with low prosociality. The identified association profiles suggest marked differences in the social genetic architecture underlying different psychiatric disorders when investigating population-based social symptoms across 13 years of child and adolescent development.


title: Mothers' hygiene experiences in confinement centres: a cohort study

abstract:
Ethnic Malaysian Chinese used to observe the 1-month postpartum confinement period at home and many families would engage a traditional postpartum carer (TPC) to help care for the mother and newborn. A recent trend has been the development of confinement centres (CCs) which are private non-healthcare establishments run by staff not trained in health care. Concerns about hygiene in CCs arose after infections were reported. We describe the practice of hand hygiene observed in CCs, the availability of resources for hygiene and to determine the prevalence of health related problems in CCs.

MethodsThis is a cohort study of ethnic Chinese mothers intending to breastfeed their healthy infants. They were recruited post-delivery along with a comparison group who planned to spend their confinement period at home, then all were telephone interviewed after their 1-month confinement period about their experience. To avoid any alteration in behaviour, mothers were not told at recruitment that they had to observe hygiene practices. Multiple logistic regression was used to assess the effect of place of confinement on rates of infant health problems.

ResultsOf 187 mothers, 88 (47%) went to 27 different CCs while 99 (53%) stayed at home. Response rates for the 1-month interviews were 88% (CC) versus 97% (home).

Mothers in CC group stayed in one to four-bedded rooms and 92% of them had their baby sleeping separately in a common nursery described to have up to 17 babies at a time; 74% of them spent less than six hours a day with their babies; 43% noticed that CC staff had inadequate hand hygiene practices; 66% reported no hand-basins in their rooms; 30% reported no soap at hand-basins; 28% reported inexperienced or inadequate staff and 4% reported baby item sharing.

Of mothers staying at home, 35% employed a TPC to care for her baby; 32% did not room-in with their babies, but only 11% spent less than 6 hours a day with their babies. 18% of mothers who employed TPCs reported that their TPC had unsatisfactory hand hygiene practices.

Health problems that were probably related to infection (HPRI) like fever and cough were similar between the groups: 14% (CC) versus 14% (home) (p=0.86). Multiple logistic regression did not show that CCs were a factor for HPRI: aOR 1.28 (95% CI 0.36 to 4.49). Three mothers reported events that could indicate transmission of infection in CCs.

ConclusionWe found unsatisfactory hygiene practices in CCs as reported by mothers who spent their confinement period there. Although we were not able to establish any direct evidence of infection transmission but based on reports given by the mothers in this study, it is likely to be happening. Therefore, future studies, including intervention studies, are urgently needed to establish an appropriate hygiene standard in CCs as well as the best method to implement this standard. Empowering CC staff with hygiene knowledge so that they can be involved and contribute to the development of the development of these standards would be important.


title: Doctors and Nurses Social Media Ads Reduced Holiday Travel and COVID-19 infections: A cluster randomized controlled trial in 13 States

abstract:
During the COVID-19 epidemic, many health professionals started using mass communication on social media to relay critical information and persuade individuals to adopt preventative health behaviors. Our group of clinicians and nurses developed and recorded short video messages to encourage viewers to stay home for the Thanksgiving and Christmas Holidays. We then conducted a two-stage clustered randomized controlled trial in 820 counties (covering 13 States) in the United States of a large-scale Facebook ad campaign disseminating these messages. In the first level of randomization, we randomly divided the counties into two groups: high intensity and low intensity. In the second level, we randomly assigned zip codes to either treatment or control such that 75% of zip codes in high intensity counties received the treatment, while 25% of zip codes in low intensity counties received the treatment. In each treated zip code, we sent the ad to as many Facebook subscribers as possible (11,954,109 users received at least one ad at Thanksgiving and 23,302,290 users received at least one ad at Christmas). The first primary outcome was aggregate holiday travel, measured using mobile phone location data, available at the county level: we find that average distance travelled in high-intensity counties decreased by -0.993 percentage points (95% CI -1.616, -0.371, p-value 0.002) the three days before each holiday. The second primary outcome was COVID-19 infection at the zip-code level: COVID-19 infections recorded in the two-week period starting five days post-holiday declined by 3.5 percent (adjusted 95% CI [-6.2 percent, -0.7 percent], p-value 0.013) in intervention zip codes compared to control zip codes.

One sentence summaryIn a large scale clustered randomized controlled trial, short messages recorded by health professionals before the winter holidays in the United States and sent as ads to social media users led to a significant reduction in holiday travel, and to a decrease in subsequent COVID-19 infection at the population level.

category: health policy


title: Real-time RT-PCR Allelic Discrimination Assay for Detection of N501Y Mutation in the Spike Protein of SARS-CoV-2 Associated with Variants of Concern

abstract:
The N501Y amino acid mutation caused by a single point substitution A23063T in the spike gene of SARS-CoV2 is possessed by the three most common variants of concern - B.1.1.7, B.1.351, and P.1. A rapid screening tool using this mutation is important for surveillance during the COVID-19 pandemic.

We developed and validated a single nucleotide polymorphism real-time reverse transcription polymerase chain reaction assay using allelic discrimination of the spike gene N501Ymutation to screen for potential variants of concern and differentiate them from wild-type SARS-CoV-2. A total of 160 clinical specimens positive for SARS-CoV-2 were characterized as mutant (N501Y) or wild-type by Sanger sequencing and were subsequently tested with the N501Y single nucleotide polymorphism real time reverse transcriptase polymerase chain reaction assay. Our assay compared to sequencing, the gold standard for SNP detection and lineage identification, demonstrated clinical sensitivity of 100% for all 57 specimens displaying N501Y mutant, which were confirmed by Sanger sequencing to be typed as A23063T, including one specimen with mixed signal for wildtype and mutant. Clinical specificity was 100% in all 103 specimens typed as wild-type, with A23063 identified as wild-type by Sanger sequencing. The identification of circulating SARS-CoV-2 lineages carrying an N501Y mutation is critical for surveillance purposes. Current identification methods rely primarily on Sanger sequencing or whole genome sequencing which are time-consuming, labor-intensive and costly. The assay described herein is an efficient tool for high-volume specimen screening for SARS-CoV-2 VOCs and for selecting specimens for confirmatory Sanger or whole genome sequencing.


title: Use of recently vaccinated individuals to detect bias in test-negative case-control studies of COVID-19 vaccine effectiveness

abstract: Post-authorization observational studies play a key role in understanding COVID-19 vaccine effectiveness following the demonstration of efficacy in clinical trials. While bias due to confounding, selection bias, and misclassification can be mitigated through careful study design, unmeasured confounding is likely to remain in these observational studies. Phase III trials of COVID-19 vaccines have shown that protection from vaccination does not occur immediately, meaning that COVID-19 risk should be similar in recently vaccinated and unvaccinated individuals, in the absence of confounding or other bias. Several studies have used the estimated effectiveness among recently vaccinated individuals as a negative control exposure to detect bias in vaccine effectiveness estimates. In this paper we introduce a theoretical framework to describe the interpretation of such a bias-indicator in test-negative studies, and outline assumptions that would allow the use of recently vaccinated individuals to correct bias due to unmeasured confounding.


title: The COVID-related mental health load of neonatal healthcare professionals: a multicentre study in Italy.

abstract:
BackgroundThe COVID-19 pandemic has dramatically affected healthcare professionals lives. We investigated the potential mental health risk faced by healthcare professionals working in neonatal units in a multicentre cross-sectional observational study.

MethodsWe included all healthcare personnel of 7 level-3 and 6 level-2 neonatal units in Tuscany, Italy. We measured the level of physical exposure to COVID-19 risk, self-reported COVID-related stress, and mental health load outcomes (anxiety, depression, burnout, psychosomatic, and post-traumatic symptoms) via validated, self-administered, on-line questionnaires.

ResultsWe analysed 314 complete answers. Scores above the clinical cutoff were reported by 91% of participants for anxious symptoms, 29% for post-traumatic symptoms, 13% for burnout, and 3% for depressive symptoms. Moreover, 50% of the participants reported at least one psychosomatic symptom. COVID-related stress (but not actual physical exposure) was significantly associated with all the measured mental health load outcomes, with a Risk Ratio of 3.33 (95% Confidence interval: 1.89, 5.85) for clinically relevant anxiety, 2.39 (1.69, 3.38) for post-traumatic symptoms, 1.79 (1.16, 2.75) for emotional exhaustion, and 2.51 (0.98, 6.44) for depression.

ConclusionsDespite a low clinical impact of COVID-19 in neonatology, neonatal professionals are a specific population at risk for psychological consequences during the pandemic.

KeynotesO_LIWe studied the mental health load (anxiety, post-traumatic, psychosomatic symptoms, burnout, depression) of healthcare professionals working in 13 neonatal units in Tuscany during the COVID-19 pandemic.
C_LIO_LIWe found very high levels of anxiety and psychosomatic symptoms, and moderate-high post-traumatic and burnout symptoms.
C_LIO_LIMental health load was higher in neonatal intensive (vs non-intensive) settings and in nurses (vs physicians). Mental health load outcomes were associated with COVID-related stress (rather than actual physical exposure to the virus).
C_LI

category: pediatrics