title: A Web-based Tool for Automatically linking Clinical Trials to their Publications

abstract:
ObjectiveEvidence synthesis teams, physicians, policy makers, and patients and their families all have an interest in following the outcomes of clinical trials and would benefit from being able to evaluate both the results posted in trial registries and in the publications that arise from them. Manual searching for publications arising from a given trial is a laborious and uncertain process. We sought to create a statistical model to automatically identify PubMed articles likely to report clinical outcome results from each registered trial in ClinicalTrials.gov.

Materials and MethodsA machine learning-based model was trained on pairs (publications linked to specific registered trials). Multiple features were constructed based on the degree of matching between the PubMed article metadata and specific fields of the trial registry, as well as matching with the set of publications already known to be linked to that trial.

ResultsEvaluation of the model using NCT-linked articles as gold standard showed that they tend to be top ranked (median best rank = 1.0), and 91% of them are ranked in the top ten.

DiscussionBased on this model, we have created a free, public web based tool at http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/TrialPubLinking/trial_pub_link_start.cgithat, given any registered trial in ClinicalTrials.gov, presents a ranked list of the PubMed articles in order of estimated probability that they report clinical outcome data from that trial. The tool should greatly facilitate studies of trial outcome results and their relation to the original trial designs.


title: The impact of changing smoking habits and smoke-free legislation on orofacial cleft incidence in the United Kingdom: evidence from two time-series studies

abstract:
ObjectivesTo analyse the association between active and passive cigarette smoking and the incidence of children born with a cleft lip and/or palate within the United Kingdom.

DesignFirst, a longitudinal time-series study was conducted with routinely collected smoking prevalence data for females over 16 years of age. Second, an interrupted time-series design was used as a natural experiment to assess the impact of smoke-free legislation using segmented Poisson regression.

SettingUnited Kingdom.

PopulationAll children born between 2000 and 2018 and their mothers.

Main outcome measuresOrofacial cleft incidence, reported annually for England, Wales and Northern Ireland and separately for Scotland.

ResultsOver the study period, the annual incidence of orofacial cleft per 10,000 live births ranged from 14.2-16.2 in England, Wales and Northern Ireland and 13.4-18.8 in Scotland. The proportion of active smokers amongst females in the United Kingdom declined by 37% during the study period. Adjusted regression analysis did not show a correlation between the proportion of active smokers and orofacial cleft incidence in either dataset, although we were unable to exclude a modest effect of the magnitude seen in individual-level observational studies. The data in England, Wales and Northern Ireland suggested an 8% reduction in orofacial cleft incidence (95%CI 1% to 14%; P=0.026) following the implementation of smoke-free legislation. In Scotland, there was weak evidence for an increase in orofacial cleft incidence following smoke-free legislation.

ConclusionThese two ecological studies offer a novel insight into the influence of smoking in orofacial cleft aetiology, adding to the evidence base from individual-level studies. Our results suggest that smoke-free legislation may have reduced orofacial cleft incidence in England, Wales and Northern Ireland.

SUMMARY BOXO_ST_ABSSection 1: What is already known on this topicC_ST_ABSO_LIAn association between maternal active and passive smoking and orofacial cleft has been previously reported in conventional individual-level observational studies
C_LIO_LIEcological and natural experiment time-series designs have been successfully used to demonstrate the association between population-level exposures and other non-cleft health outcomes
C_LI

Section 2: What this study addsO_LIEcological studies within a single country with complete cleft registration data are unlikely to be sufficiently powered to detect a relationship between time-series population level trends in active smoking and the number of children born with orofacial cleft each year.
C_LIO_LIIn England, Wales and Northern Ireland our natural experiment study showed a reduction in the proportion of children born with an orofacial cleft following the implementation of smoke-free legislation, but this was not replicated in Scotland.
C_LIO_LIThis study exploits the systematic collection of population data in the UK and adds to our understanding of the role of smoking in orofacial clefting as well as demonstrating the impact of public health interventions.
C_LI

category: health policy


title: A spectrum of HRCT chest findings in RT-PCR positive asymptomatic COVID-19 patients at a COVID designated hospital in Nepal

abstract:
IntroductionCOVID-19 pandemic is grappling the world with the surge of infection time and again. Clinicians are trying to justify the ethics of public health care. Asymptomatic COVID-19 cases are going undocumented and most of them practice self-isolation. Studies have revealed significant radiological changes among RT-PCR positive asymptomatic COVID-19 cases.

ObjectiveThe aim of this cross-sectional study is to characterized chest CT findings of asymptomatic RT-PCR-positive patients in one of the COVID-designated hospitals in Nepal.

ResultsOut of 43, 26 (60.5%) participants had positive Chest CT scan findings consistent with COVID pneumonia. 65% had bilateral and 77% had multifocal lesions. The ground-glass opacities (92%), mixed (ground-glass opacities and consolidation) pattern (30.7%), and consolidation only (34.6%) were common chest CT findings. The median CT score was 3.5 (Interquartile range; 2-6).

ConclusionThe majority of the RT-PCR positive asymptomatic patient present with CT scan changes of lungs which are important to determine clinical status, prognosis, and long-term sequel in those cohorts.

category: infectious diseases


title: Projecting the impact of SARS-CoV-2 variants on the COVID-19 epidemic and social restoration in the United States: a mathematical modelling study

abstract:
BackgroundThe SARS-CoV-2 Alpha variant B.1.1.7 became prevalent in the United States (US). We aimed to evaluate the impact of vaccination scale-up and potential reduction in the vaccination effectiveness on the COVID-19 epidemic and social restoration in the US.

MethodsWe extended a published compartmental model and calibrated the model to the latest US COVID-19 data. We estimated the vaccine effectiveness against B.1.1.7 and evaluated the impact of a potential reduction in vaccine effectiveness on future epidemics. We projected the epidemic trends under different levels of social restoration.

ResultsWe estimated the overall existing vaccine effectiveness against B.1.1.7 to be 88.5% (95%CI: 87.4-89.5%) and vaccination coverage would reach 70% by the end of August, 2021. With this vaccine effectiveness and coverage, we anticipated 498,972 (109,998-885,947) cumulative infections and 15,443 (3,828-27,057) deaths nationwide over the next 12 months, of which 95.0% infections and 93.3% deaths were caused by B.1.1.7. Complete social restoration at 70% vaccination coverage would only slightly increase cumulative infections and deaths to 511,159 (110,578-911,740) and 15,739 (3,841-27,638), respectively. However, if the vaccine effectiveness were reduced to 75%, 50% or 25% due to new SARS-CoV-2 variants, we predicted 667,075 (130,682-1,203,468), 1.7m (0.2-3.2m), 19.0m (5.3-32.7m) new infections and 19,249 (4,281-34,217), 42,265 (5,081-79,448), 426,860 (117,229-736,490) cumulative deaths to occur over the next 12 months. Further, social restoration at a lower vaccination coverage would lead to even greater future outbreaks.

ConclusionCurrent COVID-19 vaccines remain effective against the B.1.1.7 variant, and 70% vaccination coverage would be sufficient to restore social activities to a pre-pandemic level. Further reduction in vaccine effectiveness against SARS-CoV-2 variants would result in a potential surge of the epidemic in the future.


title: Increased LPS levels coexist with systemic inflammation and result in monocyte activation in severe COVID-19 patients.

abstract: This study aimed to evaluate the link between microbial translocation markers and systemic inflammation at the earliest time-point after hospitalization and at the last 72 h of hospitalization in survivors and non-survivors COVID-19 patients. Sixty-six SARS-CoV-2 RT-PCR+ infected patients and nine non-COVID-19 pneumonia controls were admitted in this study. Blood samples were collected at hospital admission (T1) (Controls and COVID-19+ patients) and 0-72 h before hospital discharge (T2, alive or dead) to analyze systemic cytokines and chemokines, LPS concentrations and soluble CD14 (sCD14) levels. THP-1 human monocytic cell line was incubated with plasma from survivors and non-survivors COVID-19 patients and their phenotype, activation status, TLR4, and chemokine receptors were analyzed by flow cytometry. COVID-19 patients presented higher IL-6, IFN-{gamma}, TNF-, TGF-{beta}1, CCL2/MCP-1, CCL4/MIP-1{beta}, and CCL5/RANTES levels than controls. Moreover, LPS and sCD14 were higher at hospital admission in SARS-CoV-2-infected patients. Non-survivors COVID-19 patients had increased LPS levels concomitant with higher IL-6, TNF-, CCL2/MCP-1, and CCL5/RANTES levels at T2. Increased expression of CD16 and CCR5 were identified in THP-1 cells incubated with the plasma of survivor patients obtained at T2. The incubation of THP-1 with T2 plasma of non-survivors COVID-19 leads to higher TLR4, CCR2, CCR5, CCR7, and CD69 expression. In conclusion, increased microbial translocation during hospitalization coexist with the inflammatory condition of SARS-CoV-2 infection and could lead to higher monocyte activation in non-survivors COVID-19 patients.


title: Differential excretion of urinary complement fragments in kidney diseases: a potential link to complement activation?

abstract: Defective complement activation has been associated with various types of kidney disease. This led to the hypothesis that specific urine complement fragments may be associated with kidney disease etiologies, and disease progression may be reflected by changes in these complement fragments. We investigated the occurrence of complement fragments in urine, their association with kidney function, proteinuria and disease etiology. Mass spectrometry based peptidomics data from the Human Urinary Proteome/Peptidome Database were extracted and the distribution of complement peptides in the different kidney disease etiologies and controls was investigated. All datasets with informations on disease/health status and detectable complement peptides were included (n=16027). Twenty-three different urinary peptides derived from complement proteins could be identified, originating from the complement proteins C3, C4 and complement factor B. For most C3-derived peptides an inverse association with eGFR was observed, while the majority of peptides derived from CFB demonstrated positive association with eGFR. Highest levels of significant C3 excretion relative to controls were seen in minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), lupus nephritis (LN), diabetic kidney disease (DKD), IgAN, membranoproliferative glomerulonephritis (MPGN), and C3-glomerulonephritis. In conclusion, several peptides derived from the complement proteins C3, C4 and factor B are significantly associated with specific kidney disease etiologies. These peptides may depict disease-specific complement activation, as well as damage to the glomerular basement membrane. Further targeted investigation of these peptides may provide new insight into disease pathophysiology and could possibly guide therapeutic decisions, especially when targeting complement factors.


title: Molecular mapping of urinary complement peptides in kidney diseases


title: Exceedingly high proportions of Plasmodium-infected Anopheles funestus mosquitoes in two villages in the Kilombero valley, south-eastern Tanzania

abstract:
BackgroundIn south-eastern Tanzania where insecticide-treated nets have been widely used for more than 20 years, malaria transmission has greatly reduced but remains highly heterogenous over small distances. This study investigated the seasonal prevalence of Plasmodium sporozoite infections in the two main malaria vector species, Anopheles funestus and Anopheles arabiensis for 34 months, starting January 2018 to November 2020.

MethodsAdult mosquitoes were collected using CDC-light traps and Prokopack aspirators inside local houses in Igumbiro and Sululu villages, where earlier surveys had found very high densities of An. funestus. Collected females were sorted by taxa, and the samples examined using ELISA assays for detecting Plasmodium circumsporozoite protein in their salivary glands.

ResultsOf 7,859 An. funestus tested, 4.6% (n = 365) were positive for Pf sporozoites in the salivary glands. On the contrary, only 0.4% (n = 9) of the 2,382 An. arabiensis tested were positive. The sporozoite prevalence did not vary significantly between the villages or seasons. Similarly, the proportions of parous females of either species were not significantly different between the two villages (p > 0.05) but was slightly higher in An. funestus (0.50) than in An. arabiensis (0.42). Analysis of the 2020 data determined that An. funestus contributed 97.7% of all malaria transmitted in households in these two villages.

ConclusionsIn contexts where individual vector species mediate most of the pathogen transmission, it may be most appropriate to pursue a species-specific approach to better understand the ecology of the dominant vectors and target them with effective interventions to suppress transmission. Despite the widespread use and overall impact of insecticide-treated nets over the past two decades in the two study villages, there is still persistently high Plasmodium infection prevalence in local populations of An. funestus, which now carry [~]97% of all malaria infections and mediates intense year-round transmission. Further reduction in malaria burden in these or other similar settings requires effective targeting of An. funestus.


title: Persistently high proportions of Plasmodium-infected Anopheles funestus mosquitoes in two villages in the Kilombero valley, south-eastern Tanzania


title: A proteomic survival predictor for COVID-19 patients in intensive care

abstract:
Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Comprehensively capturing the host physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index and APACHE II score were poor predictors of survival. Plasma proteomics instead identified 14 proteins that showed concentration trajectories different between survivors and non-survivors. A proteomic predictor trained on single samples obtained at the first time point at maximum treatment level (i.e. WHO grade 7) and weeks before the outcome, achieved accurate classification of survivors in an exploratory (AUROC 0.81) as well as in the independent validation cohort (AUROC of 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that predictors derived from plasma protein levels have the potential to substantially outperform current prognostic markers in intensive care.

Trial registrationGerman Clinical Trials Register DRKS00021688


title: Fusion of Fully Integrated Analog Machine Learning Classifier with Electronic Medical Records for Real-Time Prediction of Sepsis Onset

abstract: The objective of this work is to develop a fusion artificial intelligence (AI) model that combines patient electronic medical record (EMR) and physiological sensor data to accurately predict early risk of sepsis. The fusion AI model has two components - an on-chip AI model that continuously analyzes patient electrocardiogram (ECG) data and a cloud AI model that combines EMR and prediction scores from on-chip AI model to predict fusion sepsis onset score. The on-chip AI model is designed using analog circuits for sepsis prediction with high energy efficiency for integration with resource constrained wearable device. Combination of EMR and sensor physiological data improves prediction performance compared to EMR or physiological data alone, and the late fusion model has an accuracy of 93% in predicting sepsis 4 hours before onset. The key differentiation of this work over existing sepsis prediction literature is the use of single modality patient vital (ECG) and simple demographic information, instead of comprehensive laboratory test results and multiple vital signs. Such simple configuration and high accuracy makes our solution favorable for real-time, at-home use for self-monitoring.

category: intensive care and critical care medicine


title: On multifactorial drivers for malaria rebound in Brazil: a spatio-temporal analysis

abstract:
BackgroundMalaria incidence in Brazil reversed its decreasing trend when cases from recent years, as recent as 2015, exhibited an increase in the Brazilian Amazon basin, the area with highest transmission of Plasmodium vivax and Plasmodium falciparum. In fact, an increase of more than 20% in the years 2016 and 2017 revealed possible vulnerabilities in the national malaria-control program.

MethodsWe studied factors that are potentially associated with this reversal, including migration, economical activities, and deforestation, and weakening of investment in control programs. We analyze past incidences of malaria cases due to Plasmodium vivax and Plasmodium falciparum with a spatio-temporal Bayesian model using more than 5 million individual records of malaria cases from January of 2003 to December of 2018 in the Brazilian Amazon to establish the municipalities with unexpected increases in cases.

ResultsWe observe an increase in imported cases from border countries in Roraima state and found small effects due to deforestation and change of occupations. Also, an overall funding reduction from 2013 to 2016 happened before an increase in malaria cases in five regions in Amazon basin, markedly for P. vivax incidence and especially, in Para and Roraima States.

ConclusionUrban developments, discontinued funding for control programs, migration from border areas, deforestation activities, and different economic activities such as mining and agriculture appear linked to the rebound on malaria incidence. These multifactorial drivers show that malaria control programs require permanent attention towards elimination.

category: epidemiology


title: Test negative designs with uncertainty, sensitivity, and specificity

abstract: Test-negative designs (TNDs) can be used to estimate vaccine effectiveness by comparing the relative rates of the target disease and symptomatically similar diseases among vaccinated and unvaccinated populations. However, the diagnostic tests used to identify the target disease typically suffer from imperfect sensitivity and specificity, leading to biased vaccine effectiveness estimates. Here we present a solution to this problem via a Bayesian statistical model which can either incorporate point estimates of test sensitivity and specificity, or can jointly infer them directly from laboratory validation data. This approach enables uncertainties in the performance characteristics of the diagnostic test to be correctly propagated to estimates, avoiding both bias and false precision in vaccine effectiveness. By further incorporating individual covariates of study participants, and by allowing data streams from multiple diagnostic test types to be rigorously combined, our approach provides a flexible model for the analysis of TNDs with explicitly stated assumptions.


title: COVID-19 infection and subsequent psychiatric morbidity, sleep problems and fatigue: analysis of an English primary care cohort of 226,521 positive patients

abstract:
ObjectivesThe primary hypothesis was that the risk of incident or repeat psychiatric illness, fatigue and sleep problems increased following COVID-19 infection. The analysis plan was pre-registered (https://osf.io/n2k34/).

DesignMatched cohorts were assembled using a UK primary care registry (the CPRD-Aurum database). Patients were followed-up for up to 10 months, from 1st February 2020 to 9th December 2020.

SettingPrimary care database of 11,923,499 adults ([≥]16 years).

ParticipantsFrom 232,780 adults with a positive COVID-19 test (after excluding those with <2 years historical data or <1 week follow-up), 86,922 without prior mental illness, 19,020 with anxiety or depression, 1,036 with psychosis, 4,152 with fatigue and 4,539 with sleep problems were matched to up to four controls based on gender, general practice and year of birth. A negative control used patients who tested negative for COVID-19 and patients negative for COVID with an influenza diagnosis.

Main Outcomes and MeasuresCox proportional hazard models estimated the association between a COVID-19 positive test and subsequent psychiatric morbidity (depression, anxiety, psychosis, or self-harm), sleep problems, fatigue or psychotropic prescribing. Models adjusted for comorbidities, ethnicity, smoking and BMI.

ResultsAfter adjusting for observed confounders, there was an association between testing positive for COVID-19 and almost all markers of psychiatric morbidity, fatigue and sleep problems. The adjusted hazard ratio (aHR) for incident psychiatric morbidity was 1.75 (95% CI 1.56-1.96). However, there was a similar risk of incident psychiatric morbidity for those with a negative COVID-19 test (aHR 1.57, 95% CI 1.51-1.63) and a larger increase associated with influenza (aHR 2.97, 95% CI 1.36-6.48).

ConclusionsThere is consistent evidence that COVID-19 infection elevates risk of fatigue and sleep problems, however the results from the negative control analysis suggests that residual confounding may be responsible for at least some of the association between COVID-19 and psychiatric morbidity.


title: Early warning signals predict emergence of COVID-19 waves

abstract: Early warning signals (EWSs) aim to predict changes in complex systems from phenomenological signals in time series data. These signals have recently been shown to precede the initial emergence of disease outbreaks, offering hope that policy makers can make predictive rather than reactive management decisions. Here, using daily COVID-19 case data in combination with a novel, sequential analysis, we show that composite EWSs consisting of variance, autocorrelation, and return rate not only pre-empt the initial emergence of COVID-19 in the UK by 14 to 29 days, but also the following wave six months later. We also predict there is a high likelihood of a third wave as of the data available on 9th June 2021. Our work suggests that in highly monitored disease time series such as COVID-19, EWSs offer the opportunity for policy makers to improve the accuracy of time critical decisions based solely upon surveillance data.


title: Monitoring SARS-CoV-2 Populations in Wastewater by Amplicon Sequencing and Using the Novel Program SAM Refiner

abstract: Sequencing SARS-CoV-2 from wastewater has become a useful tool in monitoring the spread of variants. We use a novel computation workflow with SARS-CoV-2 amplicon sequencing in order to track wastewater populations of the virus. As part of this workflow, we developed a program for both variant reporting and removal of PCR generated chimeric sequences. With these methods, we are able to track viral population dynamics over time. We observe the emergence of the variants of concern B.1.1.7 and P.1, and their displacement of the D614G B.1 variant.


title: Technology in Palliative Care (TIP): the identification of digital priorities for palliative care research using a modified Delphi method

abstract:
BackgroundDevelopments in digital health (describing technologies which use computing platforms, connectivity, software, and sensors for health care and related purposes) has the potential to transform the delivery of health and social care to help citizens manage their own health. Currently, we lack consensus about digital health research priorities in palliative care and lack theories about how these technologies might improve care outcomes. Global palliative care need is expected to increase due to the consequences of an ageing population; therefore, it is important for healthcare leaders to identify innovations to ensure that an increasingly frail population have appropriate access to palliative care services. Consequently, it is important to articulate research priorities as the first step to determine how we should allocate finite resources to a field saturated with rapidly developing innovations.

AimsTo identify research priority areas for digital health in palliative care.

MethodsWe selected the digital health trends, most relevant to palliative care, from a list of emerging trends reported by the  Future Today Institute. We conducted a modified Delphi process and consensus meeting with palliative care experts to identify research priorities. We used the views of public representatives to gain their perspectives of the agreed priorities.

ResultsOne hundred and three experts (representing 11 countries) participated in the 1st Delphi round. Fifty-five participated in the 2nd round (53% of 1st round). Eleven experts attended the final consensus meeting. We identified 16 priorities areas, which were summarised into eight themes. These themes were: big data, mobile devices, telehealth and telemedicine, virtual reality, artificial intelligence, the smart home, biotechnology and digital legacy.

ConclusionsThe identified priorities in this paper represent a wide range of important emerging areas in field of digital health, personalised medicine, and data science. Human-centred design and robust governance systems should be considered in future research. It is important that the barriers and risks of using these technologies in palliative care are properly addressed to ensure that these tools are used meaningfully, wisely and safely and that do not cause unintentional harm.

category: palliative medicine


title: Differentials in the characteristics of COVID-19 cases in Wave-1 and Wave-2 admitted to a network of hospitals in North India

abstract:
Second wave of COVID-19 pandemic in India came with unexpected quick speed and intensity, creating an acute shortage of beds, ventilators, and oxygen at the peak of occurrence. This may have been partly caused by emergence of new variant delta. Clinical experience with the cases admitted to hospitals suggested that it is not merely a steep rise in cases but also possibly the case-profile is different. This study was taken up to investigate the differentials in the characteristics of the cases admitted in the second wave versus those admitted in the first wave.

Records of a total of 14398 cases admitted in the first wave (2020) to our network of hospitals in north India and 5454 cases admitted in the second wave (2021) were retrieved, making it the largest study of this kind in India. Their demographic profile, clinical features, management, and outcome was studied.

Age-sex distribution of the cases in the second wave was not much different from those admitted in the first wave but the patients with comorbidities and those with greater severity had larger share. Level of inflammatory markers was more adverse. More patients needed oxygen and invasive ventilation. ICU admission rate remained nearly the same. On the positive side, readmissions were lower, and the duration of hospitalization was slightly less. Usage of drugs like remdesivir and IVIG was higher while that of favipiravir and tocilizumab was lower. Steroid and anticoagulant use remained high and almost same during the two waves. More patients had secondary bacterial and fungal infections in Wave-2. Mortality increased by almost 40% in Wave-2, particularly in the younger patients of age less than 45 years. Higher mortality was observed in those admitted in wards, ICU, with or without ventilator support and those who received convalescent plasma.

No significant demographic differences in the cases in these two waves, indicates the role of other factors such as delta variant and late admissions in higher severity and more deaths. Comorbidity and higher secondary bacterial and fungal infections may have contributed to increased mortality.


title: More complaints than findings - Long-term pulmonary function in children and adolescents after COVID-19

abstract:
BackgroundThe frequency of persistent symptoms after coronavirus disease 2019 (COVID-19) in adults varies from 4.5% to 87%. Pulmonary function can also show long-term impairment in adults: 10% of hospitalised adults had reduced spirometry values, and 24% had decreased diffusion capacity. To date, only preliminary evidence is available on persistent respiratory sequelae in children and adolescents, therefore our objective was to examine the long-term effects of COVID-19 on pulmonary function in this age group.

MethodsMultiple-breath washout, body plethysmography, and diffusion capacity testing were performed after an average of 2.6 months (range 0.4-6.0) following COVID-19 in 73 children and adolescents (age 5-18 years) with different disease severity. Cases were compared to 45 controls with and without infection within six months prior to assessment after exclusion of severe acute respiratory coronavirus-2 infection (SARS-CoV-2).

ResultsOf the 19 patients (27.1%) who complained about persistent or newly emerged symptoms since COVID-19, 8 (11.4%) reported respiratory symptoms. Comparing patients with COVID-19 to controls, no significant differences were detected in frequency of abnormal pulmonary function (COVID-19: 12, 16.4%; controls: 12, 27.7%; OR 0.54, 95% CI 0.22-1.34). Only two patients with persistent respiratory symptoms showed abnormal pulmonary function. Multivariate analysis revealed reduced forced vital capacity (p=0.045) in patients with severe infection regardless of SARS-CoV-2 infection.

DiscussionPulmonary function is rarely impaired in children and adolescents after COVID-19, except of those with severe infection. The discrepancy between persistent respiratory symptoms and normal pulmonary function suggests a different underlying pathology such as dysfunctional breathing.

category: pediatrics


title: Hospital profiling using Bayesian decision theory

abstract:
BackgroundFor evaluating the quality of care provided by hospitals, special interest lies in the identification of performance outliers. We study a setting where the decision to classify hospitals as performance outliers or non-outliers is based on the observed result of a single binary quality indicator.

MethodsWe propose to embed the classification of providers into a Bayesian decision theoretical framework which enables the derivation of optimal decision rules with respect to the expected decision consequences. We argue that these consequences depend upon for which pathway to quality improvement the profiling of hospitals takes place. We propose paradigmatic utility functions for the two pathways external reporting and change in care delivery and compare the resulting optimal decision rules with regard to their threshold values, sensitivity and specificity. We further apply them to the area of hip replacement surgeries by analyzing data from the mandatory German hospital profiling program. Based on five quality indicators, we re-evaluate the performance of 1,277 hospitals which treated over 180,000 patients for hip-replacement surgeries during 2017.

ResultsBased on the utilities we assigned to the classification decisions, the decision rule for change in care delivery classifies more high-volume providers as outliers compared to the decision rule for external reporting, with consequences for both sensitivity and specificity. The re-evaluation of the five quality indicators illustrates that classification decisions are highly dependent upon the underlying utilities.

ConclusionAnalyzing the classification of hospitals as a decision theoretic problem and considering pathway-specific consequences of decisions can help to derive an appropriate decision rule. Contrasting decision rules with regard to their underlying assumptions about the utilities of classification consequences can be helpful to make implicit assumptions transparent and justifiable.

category: health systems and quality improvement


title: Deciphering how early life adiposity influences breast cancer risk using Mendelian randomization

abstract:
Studies suggest that adiposity in childhood may reduce the risk of breast cancer in later life. The biological mechanism underlying this effect is unclear but is likely to be independent of body size in adulthood. Using a Mendelian randomization framework, we investigated 18 hypothesised mediators of the protective effect of childhood adiposity on later-life breast cancer, including hormonal, reproductive, physical, and glycaemic traits.

Our results indicate that, while most of the hypothesised mediators are affected by childhood body size, only IGF-1, testosterone, age at menarche and age at menopause influenced breast cancer risk. However, accounting for those traits in multivariable Mendelian randomization showed that the protective effect of childhood body size still remained. This suggests either a direct effect of childhood body size on breast cancer risk or mediation via other pathways not considered.

Our work presents a framework for the systematic exploration of potential biological mediators of disease in Mendelian randomization analysis.


title: GWAS meta-analysis and gene expression data link reproductive tract development, immune response and cellular proliferation/apoptosis with cervical cancer and clarify overlap with other cervical phenotypes

abstract: Genome-wide association studies (GWAS) have successfully identified associations for cervical cancer, but the underlying mechanisms of cervical biology and pathology remain uncharacterised. Our GWAS meta-analyses fill this gap, as we characterise the genetic architecture of cervical phenotypes, including up to 9,229 cases and 490,304 controls for cervical cancer from diverse ancestries. We prioritise PAX8/PAX8-AS1, LINC00339, CDC42, CLPTM1L, HLA-DRB1, and GSDMB as the most likely candidate genes for cervical cancer signals, providing insights into cervical cancer pathogenesis and supporting the involvement of reproductive tract development, immune response, and cellular proliferation/apoptosis. We construct a GRS that associates with cervical cancer (HR=3.7 for top 5% vs lowest 5%), and with other HPV- and immune-system related diagnoses in a PheWAS analysis. Our results propose valuable leads for further functional studies and the presented GRS offers an additional opportunity for risk stratification together with conventional screening strategies.

category: genetic and genomic medicine


title: The evaluation of factors affecting antibody response after administration of the BNT162b2 vaccine: A prospective study in Japan

abstract:
The aim of this study was to evaluate the antibody reaction after administration of the BNT162b2 vaccine, and to reveal the factors that affect antibody production. This prospective study was carried out in the Association of EISEIKAI Medical and Healthcare Corporation Minamitama Hospital, in Tokyo, Japan, from April 15, 2021 to June 09, 2021. All our hospitals workers who were administered the BNT162b2 vaccine as part of a routine program were included in this study.

We calculated the anti-SARS-CoV-2 spike-specific antibody titter 1) before vaccination, 2) seven to twenty days after the first vaccination, and 3) seven to twenty days after the second vaccination.

The low-antibody titer group (LABG) was defined as the group having less than 25 percentiles of antibody titer. Univariate and Multivariate logistic regression analysis were performed to ascertain the effects of factors on the likelihood of LABG. 374 participants were eventually included in our study, and they were divided into 94 LABG and 280 non-LABG. All samples showed significant antibody elevation in the second antibody test, with a mean value of 3476 U/mL. When comparing the LABG and non-LABG groups, the median age, blood sugar, and HbA1c were significantly higher in the LABG group. The rates of participants with low BMI (<18.5) and high BMI (>30) were significantly higher in the LABG group. The proportion of chronic lung disease, hypertension, diabetes, dyslipidemia, autoimmune disease, and cancer were significantly higher in the LABG group. Although there was no significant difference confirmed with respect to the exercise hours per day, the proportion of participants that did not perform outdoor activities was significantly higher in the LABG group. The time interval between the second vaccination and the second antibody test, and between the first and the second vaccination was significantly longer in the non-LABG group.

Our logistic regression analysis revealed that the age, obesity, hypertension, diabetes, dyslipidemia, antihypertensive drug, antilipid drug, {gamma}-GT, BS, HbA1c, and lack of outdoor activity were significant suppressors of antibody reaction, whereas maintaining the appropriate time interval between the first and the second vaccination could promote a significant antibody response. In the multivariate logistic regression analysis, age, obesity, and lack of outdoor activities were significant suppressors of antibody reaction, whereas the length of days from the first to the second vaccination promoted a significant antibody response.

Our single-center study demonstrates that age, obesity, and lack of outdoor activities were significant suppressors of antibody response, whereas maintaining the appropriate time interval between the first and the second vaccination could promote a significant antibody response. Evidence from multi-center studies is needed to develop further vaccination strategies.


title: Effectiveness of Face Masks in Blocking the Transmission of SARS-CoV-2: a Preliminary Evaluation of Masks Used by SARS-CoV-2-Infected Individuals

abstract: In 2019, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is transmitted via airborne route, caused a new pandemic namely, "coronavirus disease 2019" (COVID-19). Although it is still debated whether the use of masks can prevent the transmission of SARS-CoV-2, no study has evaluated the virus-blocking efficacy of masks used by patients. We aimed to evaluate this efficacy of masks used by SARS-CoV-2-infected individuals. Data, masks used, and nasopharyngeal swab samples were obtained from these patients. Forty-five paired samples of nasopharyngeal swabs and masks were obtained and processed; the majority of masks were woven. Viral RNAs were amplified using quantitative reverse-transcription polymerase chain reaction and detected only on the inner parts of masks. Median cycle threshold (Ct) values of swabs and masks were 28.41 and 37.95, respectively. Statistically, there was a difference of approximately 10 Ct values between swabs and masks and no significant difference in Ct values among different types of masks. There were statistically significant differences in Ct values between men and women and symptomatic and asymptomatic patients. Our findings suggest the blocking of the transmission of viruses by different types of masks and reinforce the use of masks by both infected and non-infected individuals.


title: Taiwan on track to end third COVID-19 community outbreak

abstract: Since the start of the COVID-19 pandemic on December 31st, 2019, with the World Health Organization being notified of pneumonia of unknown cause in Wuhan (China), Taiwan has successfully ended two COVID-19 community outbreaks. For 19 days, the third community outbreak has now been successfully suppressed, putting Taiwan on path to end it too around Aug. 16th based on our forecast using an exponential model. Since May 28th the 7-day average of reported confirmed infected, which peaked at 593, has been falling to 204 on June 16th and the 7-day average of reported suspected and excluded cases increased to above 25 000. Resulting in a decrease in the ratio of the 7-day average of local & unknown confirmed to suspected cases-the identified control variable-to less than one third of its peak value. The later is a hallmark of working contact tracing, which together with testing and isolation of infected are the keys to ending the community outbreak.


title: Enhancing Parental Knowledge of Child Safety: An Interventional Educational Campaign

abstract:
BackgroundSafeguarding children from unintentional injuries is a significant concern for parents and caregivers. With children staying more at home during the COVID-19 pandemic, more educational tools and valid educational programs are warranted to improve parental knowledge and awareness about childrens safety. This study aims to explore the effectiveness of child safety campaigns on parents knowledge and attitude towards preventable childhood injuries.

MethodsThis was a pre-post experimental study, in which the pre-designed assessments were used as an evaluation tool before and after attending a Child Safety Campaign. The Pre - Post assessment question included questions to evaluate the socio-demographic status, followed by knowledge questions in line with the current child safety campaign. The outcomes of interest were assessed before and after attending the campaigns stations.

ResultsThree hundred and eight parents volunteered to participate in this study. Their knowledge score improved from 36.2 (SD 17.7) to 79.3 (SD 15.6) after attending the Child Safety Campaign (t-value= 34.6, p<0.001). Both, perceptions on the preventability of accidents and the parents perceived usefulness of educational campaigns showed improvements, with (t-value =6.3, p<0.001) and (t-value= 3.097, p<0.001), respectively.

ConclusionThe educational child safety campaign for caregivers in Saudi Arabia resulted in a significant increase in the overall knowledge and attitudes towards childrens safety. As children are currently staying at home more, additional educational tools and programs are warranted to promote childhood safe practices among parents and caregivers.


title: Association between preference and e-learning readiness among the Bangladeshi female nursing students in the Covid-19 pandemic: a cross-sectional study

abstract:
BackgroundThe COVID-19 pandemic jeopardized the traditional academic learning calendars due to the closing of all educational institutions across the globe. To keep up with the flow of learning, most of the educational institutions shifted toward e-learning. However, the students e-learning preference for various subdomains of e-learning readiness did not identify, particularly among the female nursing students for a developing country like Bangladesh, where those domains pose serious challenges.

ResultsA cross-sectional study was conducted among the female nursing students perceived e-learning readiness in subdomains of readiness; availability, technology use, self-confidence, and acceptance. The findings of the study revealed that the prevalence of preference for e-learning was 43.46%. The students did not prefer e-learning compared to  prefer group has significantly less availability of technology ({beta} = -3.01, 95% CI: -4.46, -1.56), less use of technology ({beta} = - 3.08, 95% CI: -5.11, -1.06), less self-confidence ({beta} = -4.50, 95% CI: -7.02, -1.98), less acceptance ({beta} = -5.96, 95% CI: -7.76, -4.16) and less training need ({beta} = -1.86, 95% CI: -2.67, - 1.06). The age, degree, residence, parents highest education, having a single room, having any eye problems were significantly associated with the variation of availability of technology, use of technology, self-confidence, acceptance, and training need of e-learning.

ConclusionsThe outcomes of the study could be helpful while developing an effective and productive e-learning infrastructure regarding the preparedness of nursing colleges for the continuation of academia in any adverse circumstances like the COVID-19 pandemic.

category: public and global health


title: A randomized crossover trial of short versus conventional pulse width DBS in Parkinsons Disease

abstract:
BackgroundSubthalamic nucleus deep brain stimulation is a well-established treatment for patients with Parkinsons disease. Previous acute challenge studies suggested that short pulse widths might increase the therapeutic window while maintaining motor symptom control.

ObjectivesTo investigate in patients with Parkinsons disease and nucleus subthalamicus deep brain stimulation (STN-DBS) whether short pulse width stimulation with 30{micro}s maintains equal motor control as conventional 60{micro}s stimulation over a period of 4 weeks.

MethodsIn this monocentric, double-blinded, randomized crossover trial, 30 patients with Parkinsons disease and STN-DBS were enrolled and assigned to 4 weeks of stimulation with 30{micro}s and 4 weeks of stimulation with 60{micro}s in randomized order (German Clinical Trials Register No. DRKS00017528). The primary outcome was the difference in motor symptom control as assessed by a motor diary. Secondary outcomes included energy consumption measures, non-motor effects, side-effects, and quality of life.

ResultsA total of 24 patients were included in the final analysis. There was no difference in motor symptom control between the two treatment conditions. Concerning secondary outcomes there was no difference in energy consumption, non-motor symptoms, side-effects, or quality of life. On the individual level, patients preferring 30{micro}s tended to be more dyskinetic in the 60{micro}s setting, whereas patients preferring 60{micro}s experienced more off-time in the 30{micro}s setting.

ConclusionsShort pulse width settings (30{micro}s) provide equal motor symptom control as conventional (60{micro}s) stimulation without significant differences in energy consumption. Future studies are warranted to evaluate a potential benefit of short pulse width settings in patients with pronounced dyskinesia.

category: neurology


title: Risk of dementia after hospitalization due to traumatic brain injury: a longitudinal, population-based study

abstract:
ObjectiveTraumatic brain injury (TBI) is considered a potential modifiable dementia risk factor. We aimed to determine whether TBI actually increases the risk of dementia when adjusting for other relevant dementia risk factors.

MethodsNational prospective longitudinal cohort study that included 32,385 participants aged 25-64 during 1992-2012. Of these, 288 suffered from a major TBI (diagnosis of traumatic intracranial hemorrhage and hospital length of stay (LOS) [≥]3 days) and 406 from a minor TBI (concussion diagnosis and hospital LOS [≤]1 day). Dementia was defined as any first hospital contact with a diagnosis of dementia; first use of an anti-dementia drug; and dementia as an underlying or contributing cause of death. Follow-up until the end of 2017 yielded a total of 1,010 incident dementia cases.

ResultsAfter adjusting for age and sex, hospitalization due to major TBI (hazard ratio [HR] 1.51, 95% CI 1.03-2.22), but not minor TBI, increased the risk of dementia. After additional adjustment for educational status, smoking status, alcohol consumption, physical activity, and hypertension, the association between major TBI and dementia weakened (HR 1.30, 95% CI 0.86-1.97). The risk factors most strongly attenuating the association between major TBI and dementia were alcohol consumption and physical activity.

ConclusionThere was an association between major TBI and incident dementia. The association was attenuated after adjusting for confounders, especially alcohol consumption and physical activity. Minor TBI was not associated with an increased risk of dementia.


title: Seroconversion panels demonstrate anti-SARS-CoV-2 antibody development after administration of the mRNA-1273 vaccine

abstract: Seroconversion panels are an important tool for investigating antibody responses in acute and chronic phases of disease and development of serological assays for viral diseases including COVID-19. Globally it is anticipated that vaccines against SARS-CoV-2 will facilitate control of the current pandemic. The two COVID-19 seroconversion panels analyzed in this study were obtained from consenting donors with samples collected before vaccination with the mRNA-1273 vaccine (Moderna) and after the first and second doses of the vaccine. Panel samples were tested for antibodies to SARS-CoV-2 (IgG). Individual subjects with a positive response for anti-SARS-CoV2 IgG in their pre-vaccination samples showed a significantly enhanced response to the first vaccination. In older subjects, weaker immunological responses to the first injection were observed, which were overcome by the second injection. All subjects in the study were positive for anti-SARS-CoV-2 IgG after the second dose of vaccine.


title: Rapid, large-scale wastewater surveillance and automated reporting system enabled early detection of nearly 85% of COVID-19 cases on a University campus

abstract:
Wastewater based surveillance has gained prominence and come to the forefront as a leading indicator of forecasting COVID-19 infection dynamics owing to its cost-effectiveness and its ability to inform early public health interventions. A university campus could especially benefit from wastewater surveillance as they are characterized by largely asymptomatic populations and are potential hotspots for transmission that necessitate frequent diagnostic testing. In this study, we employed a large-scale GIS (Geographic information systems) enabled building-level wastewater monitoring system associated with the on-campus residences of 7614 individuals. Sixty-eight automated wastewater samplers were deployed to monitor 239 campus buildings with a focus on residential buildings. Time-weighted composite samples were collected on a daily basis and analyzed within the same day. Sample processing was streamlined significantly through automation, reducing the turnaround time by 20-fold and exceeding the scale of similar surveillance programs by 10 to 100-fold, thereby overcoming one of the biggest bottlenecks in wastewater surveillance. An automated wastewater notification system was developed to alert residents to a positive wastewater sample associated with their residence and to encourage uptake of campus-provided asymptomatic testing at no charge. This system, integrated with the rest of the "Return to Learn" program at UC San Diego-led to the early diagnosis of nearly 85% of all COVID-19 cases on campus. Covid-19 testing rates increased by 1.9-13X following wastewater notifications. Our study shows the potential for a robust, efficient wastewater surveillance system to greatly reduce infection risk as college campuses and other high-risk environments reopen.

IMPORTANCEWastewater based epidemiology can be particularly valuable at University campuses where high-resolution spatial sampling in a well-controlled context could not only provide insight into what affects campus community as well as how those inferences can be extended to a broader city/county context. In the present study, a large-scale wastewater surveillance was successfully implemented on a large university campus enabling early detection of 85% of COVID-19 cases thereby averting potential outbreaks. The highly automated sample processing to reporting system enabled dramatically reduced the turnaround time to 5h (sample to result time) for 96 samples. Furthermore, miniaturization of the sample processing pipeline brought down the processing cost significantly ($13/sample). Taken together, these results show that such a system could greatly ameliorate long-term surveillance on such communities as they look to reopen.


title: DNA methylation changes in glial cells of the normal-appearing white matter in Multiple Sclerosis patients

abstract:
BackgroundMultiple Sclerosis (MS), the leading cause of non-traumatic neurological disability in young adults, is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). Due to the poor accessibility to the target organ, CNS-confined processes underpinning the later progressive form of MS remain elusive thereby limiting treatment options. We aim to examine DNA methylation, a stable epigenetic mark of genome activity, in glial cells to capture relevant molecular changes underlying MS neuropathology.

MethodsWe profiled DNA methylation in nuclei of glial cells, isolated from 38 post-mortem normal-appearing white matter (NAWM) specimens of MS patients (n=8) in comparison to white matter of control individuals (n=14), using Infinium MethylationEPIC BeadChip.

FindingsWe identified 1,226 significant (genome-wide adjusted P-value < 0.05) differentially methylated positions (DMPs) between MS patients and controls. Functional annotation of the altered DMP-genes uncovered alterations of processes related to cellular motility, cytoskeleton dynamics, metabolic processes, synaptic support, neuroinflammation and signaling, such as Wnt and TGF-{beta} pathways. A fraction of the affected genes displayed transcriptional differences in the brain of MS patients, as reported by publically available transcriptomic data. Cell type-restricted annotation of DMP-genes attributed alteration of cytoskeleton rearrangement and extracellular matrix remodelling to all glial cell types, while some processes, including ion transport, Wnt/TGF-{beta} signaling and immune processes were more specifically linked to oligodendrocytes, astrocytes and microglial cells, respectively.

ConclusionOur findings strongly suggest that NAWM glial cells are highly altered, even in the absence of lesional insult, collectively exhibiting a multicellular reaction in response to diffuse inflammation.


title: Rapid protocols to support Covid-19 clinical diagnosis based on hematological parameters

abstract:
PurposeIn December 2019, the Covid-19 pandemic began in the world. To reduce mortality, in addiction to mass vaccination, it is necessary to massify and accelerate clinical diagnosis, as well as creating new ways of monitoring patients that can help in the construction of specific treatments for the disease.

ObjectiveIn this work, we propose rapid protocols for clinical diagnosis of Covid-19 through the automatic analysis of hematological parameters using Evolutionary Computing and Machine Learning. These hematological parameters are obtained from blood tests common in clinical practice.

MethodWe investigated the best classifier architectures. Then, we applied the particle swarm optimization algorithm (PSO) to select the most relevant attributes: serum glucose, troponin, partial thromboplastin time, ferritin, D-dimer, lactic dehydrogenase, and indirect bilirubin. Finally, we used decision trees to build four rapid protocols for Covid-19 clinical diagnosis.

ResultsWe developed a web system for Covid-19 diagnosis support. Using a 100-tree Random Forest, we obtained results for accuracy, sensitivity and specificity superior to 99

ConclusionBy using a reduced set of hematological parameters common in clinical practice, it was possible to achieve results of accuracy, sensitivity and specificity comparable to those obtained with RT-PCR. It was also possible to automatically generate clinical decision protocols, allowing relatively accurate clinical diagnosis even without the aid of the web decision support system.

category: health informatics


title: The impact of National Centralized Drug Procurement policy on the use of policy-related original and generic drugs in public medical institutions in China: A difference-in-difference analysis based on national database

abstract:
ObjectiveTo evaluate the impact of the first round of the National Centralized Drug Procurement (NCDP) pilot (referred to as "4+7" policy) on the use of policy-related original and generic drugs.

MethodsDrug purchase data from the China Drug Supply Information Platform (CDSIP) database were used, involving nine "4+7" pilot cities and 12 non-pilot provinces in China. "4+7" policy-related drugs were included, which consisted of 25 "4+7" List drugs and 97 alternative drugs that have an alternative relationship with "4+7" List drugs in clinical use. "4+7" List drugs were divided into bid-winning and non-winning products according to the bidding results. Purchase volume, purchase expenditures, daily costs were selected as outcome variables, and were measured using Defined Daily Doses (DDDs), Chinese Yuan (CNY), and Defined Daily Drug cost (DDDc), respectively. Difference-in-Difference (DID) method was employed to estimate the net effect of policy impact.

ResultsAfter policy intervention, the DDDs of original drugs among "4+7" List drugs significantly reduced by 124.59%, while generic drugs increased by 52.12% (all p-values <0.01). 17.08% of the original drugs in DDDs were substituted by generic drugs. Prominent reductions of 121.69% and 80.54% were observed in the expenditure of original and generic drugs, with a total cost-saving of 5036.78 million CNY for "4+7" List drugs. The DDDc of bid-winning original and generic drugs, as well as non-winning original drugs, significantly decreased by 33.20%, 75.74%, and 5.35% (all p-values <0.01), while the DDDc of non-winning generic drugs significantly increased by 73.66% (p<0.001). The use proportion of bid-winning products and non-winning original drugs raised prominently from 39.66% to 91.93%

Conclusions"4+7" policy promoted the substitution use of generic drugs against original drugs, which conducive to drug costs saving. The overall quality level of drug use of public medical institutions significantly increased after "4+7" policy, especially in primary medical institutions.

Strengths and limitations of this study[tpltrtarr] The "4+7" policy is the first policy attempt of volume-based drug procurement work at the national level in China, and is a pioneering work in the reform of Drug Supply and Guarantee System in China. This study aimed to explored the effect of this policy on original and generic drug use in China.
[tpltrtarr]This study used data of national database - China Drug Supply Information Platform (CDSIP). The monthly drug purchase data of nine pilot cities and twelve non-pilot provinces in mainland China were analyzed.
[tpltrtarr]This study used Difference-in-Difference analysis to evaluate the policy effect.
[tpltrtarr]The findings based on drug purchase data rather than drug use data in the present study might limit the interpretation and extrapolation of research results.


title: Emergence of immune escape at dominant SARS-CoV-2 killer T-cell epitope

abstract:
The adaptive immune system protects against infection via selection of specific antigen receptors on B-cells and T-cells. We studied the prevalent CD8  killer T-cell response mounted against SARS-CoV-2 Spike269-277 epitope YLQPRTFLL via the most frequent Human Leukocyte Antigen (HLA) class I worldwide, HLA A*02. The widespread Spike P272L mutation has arisen in at least 14 different SARS-CoV-2 lineages to date, including in lineages identified as variants of concern. P272L was common in the B.1.177 lineage associated with establishing the  second wave in Europe. The large CD8 T-cell response seen across a cohort of HLA A*02+ convalescent patients, comprising of over 120 different TCRs, failed to respond to the P272L. Sizable populations (0.01%-0.2%) of total CD8 T-cells from individuals vaccinated against SARS-CoV-2 stained with HLA A*02-YLQPRTFLL multimers but failed to bind to the P272L reagent. Viral escape at prevalent T-cell epitopes restricted by high frequency HLA may be particularly problematic when vaccine immunity is focussed on a single protein such as SARS-CoV-2 Spike and provides a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlights the urgent need for monitoring T-cell escape in new SARS-CoV-2 variants.

New in Version 2O_LIUpdated as P272L now seen in 14 different SARS-CoV-2 lineages including the B.1.1.7/Alpha (UK variant) lineage
C_LIO_LIAtomic structures of HLA A*02-YLQPRTFLL and HLA A*02-YLQLRTFLL added
C_LIO_LIPierre Rizkallah added as an author and author list changed to reflect the contributions of Aaron Wall and Anna Fuller to the newly added datasets
C_LI


title: Development and validation of blood-based prognostic biomarkers for severity of COVID disease outcome using EpiSwitch 3D genomic regulatory immuno-genetic profiling.

abstract: The COVID-19 pandemic has raised several global public health challenges to which the international medical community have responded. Diagnostic testing and the development of vaccines against the SARS-CoV-2 virus have made remarkable progress to date. As the population is now faced with the complex lifestyle and medical decisions that come with living in a pandemic, a forward-looking understanding of how a COVID-19 diagnosis may affect the health of an individual represents a pressing need. Previously we used whole genome microarray to identify 200 3D genomic marker leads that could predict mild or severe COVID-19 disease outcomes from blood samples in a multinational cohort of COVID-19 patients. Here, we focus on the development and validation of a qPCR assay to accurately predict severe COVID-19 disease requiring intensive care unit (ICU) support and/or mechanical ventilation. From 200 original biomarker leads we established a classification model containing six markers. The markers were qualified and validated on 38 COVID-19 patients from an independent cohort. Overall, the six-marker model obtained a positive predictive value of 93% and balanced accuracy of 88% across 116 patients for the prognosis of COVID-19 severity requiring ICU care/ventilation support. The six-marker signature identifies individuals at the highest risk of developing severe complications in COVID-19 with high predictive accuracy and can assist in patient prognosis and clinical management decisions.


title: Detection of B.1.351 and B.1.1.7 SARS-CoV-2 variants in Monterrey metropolitan area in Northeast Mexico

abstract:
SARS-CoV-2 variants of concern (VOC) have spread throughout the world. In Mexico, VOC B.1.351 has been detected on one occasion and B.1.1.7 several times. We detected lineages B.1.351 and B.1.1.7 in patients who traveled to USA and B.1.1.7 in a patient with no travel history.

Article summary lineIntroduction of B.1.351 and B.1.1.7 S ARS-CoV-2 variants in Monterrey, Mexico.


title: A novel cell type negatively associated with secondary autoimmunity in alemtuzumab-treated patients is revealed through single-cell longitudinal analysis of clinical trial samples

abstract:
Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is an approved treatment for relapsing forms of multiple sclerosis (RMS). While its efficacy has been demonstrated in clinical studies, its use is associated with unpredictable non-MS autoimmunity manifesting months or years after treatment. Approximately 40% of treated patients present with autoimmune thyroid events, 2% with platelet deficiency (immune thrombocytopenia; ITP)1, and 0.34% with autoimmune nephropathies2. The lack of predictive biomarkers necessitates careful monitoring in clinical practice with a Risk Management Plan or Risk Evaluation and Mitigation Strategy (RMP/REMS) in place for early detection of these autoimmune events. We carried out a longitudinal single-cell analysis of PBMCs in a small subset of alemtuzumab-treated patients from the phase 3 CARE-MS I (CAMMS323) study3 and identified a novel platelet lineage cell negatively associated with thyroid autoimmunity. This discovery raises the possibility that a shared underlying mechanism may contribute to the incidence of thyroid autoimmunity and ITP in alemtuzumab-treated patients.

HighlightsO_LIA novel platelet-lineage cell type present in peripheral blood is uncovered and characterized
C_LIO_LIDepletion and/or transcriptomic changes in this cell type are associated with increased incidence of secondary autoimmunity in MS patients on Alemtuzumab.
C_LIO_LIRetrospective single-cell analysis studies can uncover novel insights and lead to future biomarker development
C_LI

category: allergy and immunology


title: The development and usability testing of digital knowledge translation tools for parents of children with bronchiolitis

abstract:
Bronchiolitis is an acute infection of the lower respiratory tract that predominantly affects children less than two years old. Although self-limiting, symptoms of bronchiolitis can be distressing for young children. Research has demonstrated that parents may not have the necessary information to be able to identify bronchiolitis symptoms, resulting in emergency department (ED) visits and hospitalizations. Parents have expressed that they feel unprepared, afraid, and that they lack information on their childs condition. Digital knowledge translation (KT) tools have the potential to convey complex health information to parents to support their healthcare decision-making needs.

We worked with parents of children with bronchiolitis to develop and evaluate three digital tools on bronchiolitis (whiteboard animation video, infographic, and e-Book). Following prototype completion, usability testing was conducted using iPads in two Alberta ED waiting rooms. Parents were randomized to one out of the three tools. Overall, the tools were highly rated, suggesting that arts-based digital tools are useful in delivering complex health information to parents.


title: The development and usability testing of two digital knowledge translation tools for parents of children with urinary tract infections

abstract:
Urinary tract infections (UTI) are a common source of acute illness for infants and children. Approximately 7-8% of girls and 2% of boys will experience a UTI before they are 8 years old. UTIs may be difficult to identify and treat as symptoms in children are different from expected adult symptoms. A previously conducted systematic review identified four common information needs expressed by parents. More specifically, the research identified that parents had difficulty recognizing signs and symptoms of UTIs, felt disappointed by health care providers responses, needed timely and relevant information, and feared the unknown due to lack of UTI knowledge. This demonstrates that more effective knowledge translation tools are needed to satisfy parent information needs.

The purpose of this research was to work with parents to develop and test the usability of an interactive infographic and video about UTIs in children. Prototypes were evaluated by parents through usability testing in two Alberta emergency department waiting rooms. Results were positive and overall, the tools were highly rated across all usability items, suggesting that arts-based digital tools are useful mediums for sharing health information with parents.


title: Effects of pharmacogenomic (PGx) testing on clinical pain management prescriptions, a retrospective study.

abstract:
Current deficits in effectively utilizing PGx testing in clinical practice include limited awareness and training of healthcare professionals, routine ordering of assays investigating up to 5 genes and lack of concise reporting of dosing guidelines and drug-drug-interactions. A novel deep sequencing (>1000X) PGx panel is described encompassing 23 genes and 141 SNPs or indels combined with PGx dosing guidance, drug-gene-interaction (DGI) and drug-drug-interaction (DDI) reporting to prevent adverse drug reaction events. During a 2-year period, patients (n = 171) were monitored in a pain management clinic. Urine toxicology, PGx reports, and progress notes were studied retrospectively for changes in prescription regimens before and after the PGx report was made available to the provider.

Among patient PGx reports with medication lists provided (n = 146) 57.5% showed one or more moderate and 5.5% at least one serious pharmacogenetic interaction. 66% of patients showed at least one moderate and 15% one or more serious drug-gene or drug-drug-interaction. A significant number of active changes in prescriptions based on the PGx reports provided was observed for 85 patients (83%) for which a specific drug was either discontinued, switched within the defined drug classes of the report or a new drug added.

Preventative action was observed for all serious interactions and only moderate interactions were tolerated for lack of other alternatives. This study demonstrates a successful implementation of PGx testing utilizing an extended PGx panel combined with a customized, informational report to help improve clinical outcomes.

category: pharmacology and therapeutics


title: Meta-analytical evidence on mental disorder symptoms during the COVID-19 pandemic in Latin America

abstract:
ObjectiveThere is a lack of evidence related to the prevalence of mental disorder symptoms as well as their heterogeneities during the COVID-19 pandemic in Latin America, a continent across the equators. The current study aims to provide meta-analytical evidence on mental disorder symptoms during COVID-19 among frontline healthcare workers, general healthcare workers, the general population, and university students in Latin America.

MethodsBibliographical databases, such as PubMed, Embase, Web of Sciences, PsycINFO, and medRxiv, were systematically searched to identify pertinent studies up to Februry 6, 2021. Two coders performed the screening using predefined eligibility criteria. Studies were assigned quality scores using the Mixed Methods Appraisal Tool. The double data extraction method was used to minimize data entry errors.

ResultsA total of 33 studies with 101,772 participants in Latin America were identified. The pooled prevalence of anxiety, depression, distress, and insomnia was 32%, 27%, 32%, and 35%, respectively. There was a higher prevalence of mental health symptoms in South America compared to Central America (33% vs. 27%, p <0.001). The pooled prevalence of mental health symptoms in the general population, general healthcare workers, frontline healthcare workers, and students in Latin America was 33%, 31%, 37%, and 36%, respectively.

ConclusionThe high yet heterogenous level of prevalence of mental disorder symptoms emphasizes the need for appropriate identification of psychological interventions in Latin America.


title: Changes in mobility pre and post first SARS-CoV-2 vaccination: findings from a prospective community cohort study including GPS movement tracking in England and Wales (Virus Watch)

abstract:
BackgroundSome evidence suggests that individuals may change adherence to public health policies aimed at reducing contact, transmission and spread of the SARS-CoV-2 virus after they receive their first SARS-CoV-2 vaccination. In this study, we aim to estimate the rate of change in average daily travel distance from a participants registered address before and after SARS-CoV-2 vaccination.

MethodParticipants were recruited into Virus Watch starting in June 2020. Weekly surveys were sent out to participants and vaccination status was collected from January 2021 onwards. Between September 2020 and February 2021, we invited 13,120 adult Virus Watch participants to contribute towards our tracker sub-cohort which uses the Global Positioning System (GPS) to collect data on movement. We used segmented linear regression to estimate the median daily travel distance before and after the first self-reported SARS-CoV-2 vaccine dose.

ResultsWe analysed the daily travel distance of 228 vaccinated adults. Between 157 days prior to vaccination until the day before vaccination, the median daily travel distance travelled was 8.9km (IQR: 3.50km, 24.17km). Between the day of vaccination and 100 days after vaccination, the median daily travel distance travelled was 10.30km (IQR: 4.11, 27.53km). Between 157 days prior to vaccination and the vaccination date, there was a daily median decrease in mobility of 40m (95%CI: -51m, -31m, p-value <0.001) per day. After the removal of outlier data, and between the vaccination date and 99 days after vaccination, there was a median daily increase in movement of 45.0m (95%CI: 25m, 65m, p-value = <0.001). Restricting the analysis to the 3rd national lockdown (4th of January 2021 to the 5th of April 2021), we found a median daily movement increase of 9m (95%CI: -25m, 45m, p = 0.57) in the 30 days prior to vaccination and the vaccination date, and a median daily movement increase of 10m (95%CI: -60m, 94m, p-value = 0.69) in the 30 days after vaccination.

ConclusionsOur study demonstrates the feasibility of collecting high volume geolocation data as part of research projects, and the utility of these for understanding public health issues. Our results are consistent with both an increase and decrease in movement after vaccination and suggest that, amongst Virus Watch participants, any changes in movement distances post-vaccination are small.


title: Assessment and clinical utility of a non-Next Generation Sequencing based Non-Invasive Prenatal Testing technology

abstract:
BackgroundRolling circle replication (RCR) is a novel technology that has not been applied to cell-free DNA (cfDNA) testing until recently. Given the cost and simplicity advantages of this technology compared to other platforms currently used in cfDNA analysis, an assessment of RCR in clinical laboratories was performed. Here, we present the first validation study from clinical laboratories utilizing RCR technology.

Methods831 samples from spontaneously pregnant women carrying a singleton fetus and 25 synthetic samples were analyzed for the fetal risk of Trisomy 21, Trisomy 18 and Trisomy 13 by three laboratories on three continents. All women who provided the samples were followed to birth, where evaluation for fetal aneuploidies was performed using newborn examinations and any suspected aneuploidies were confirmed with karyotyping.

ResultsThe study found rolling circle replication to be a highly viable technology for clinical assessment of fetal aneuploidies with 100% sensitivity for T21 (95% CI:82.35% - 100.00%); 100.00% sensitivity for T18 (71.51% - 100.00%) and 100.00% sensitivity for T13 analyses (66.37% - 100.00%). The specificities were >99% for each trisomies [99.7% (99.01% - 99.97%) for T21; 99.5% (98.62% - 99.85%) for T18; 99.7% (99.03% - 99.97%) for T13], along with a first pass no-call rate of 0.93%.

ConclusionsThe study showed that using a rolling circle replication-based cfDNA system for the evaluation of the common aneuploidies would provide greater accuracy and clinical utility compared to conventional biochemical screening and comparable results to other reported cfDNA methodologies.


title: Is Second dose of vaccination useful in previously SARS-CoV-2 infected Health Care Workers?

abstract: SummaryVaccines are the most important public health measure to protect people from COVID-19 worldwide. In addition, healthcare workers account for a large number of infected people. Then, protecting this population from COVID-19 seems crucial in the preservation of healthcare systems. In a context of few doses available, serological assays could be useful to decide whether one or two doses are needed. Our results show that a first dose of BNT162b2 mRNA vaccine seems to act as a boost after SARS-CoV-2 infection in healthcare workers with a previous SARS-CoV-2 infection and a second dose might not be required.


title: Long Term Health Consequences of COVID-19 in Hospitalized Patients from North India: A follow up study of upto 12 months

abstract:
BackgroundLong-COVID syndrome is now a real and pressing public health concern. We cannot reliably predict who will recover quickly or suffer with mild debilitating long COVID-19 symptoms or battle life-threatening complications. In order to address some of these questions, we studied the presence of symptoms and various correlates in COVID-19 patients who were discharged from hospital, 3 months and up to 12 months after acute COVID-19 illness.

MethodsThis is an observational follow-up study of RT-PCR confirmed COVID-19 patients admitted at 3 hospitals in north India between April - August 2020. Patients were interviewed telephonically using a questionnaire regarding the post-COVID symptoms. The first tele-calling was done in the month of September 2020, which corresponded to 4-16 weeks after disease onset. All those who reported presence of long COVID symptoms, were followed-up with a second call, in the month of March 2021, corresponding to around 9-12 months after the onset of disease.

ResultsOf 990 patients who responded to the first call, 615 (62.2%) had mild illness, 227 (22.9%) had moderate and 148 (15.0%) had severe COVID-19 illness at the time of admission. Nearly 40% (399) of these 990 patients reported at least one symptom at that time. Of these 399 long-COVID patients, 311 (almost 78%) responded to the second follow-up. Nearly 8% reported ongoing symptomatic COVID, lasting 1-3 months and 32% patients having post-COVID phase with symptoms lasting 3-12 months. Nearly 11% patients continued to have at least one symptom even at the time of the second interview (9-12 months after the disease onset). Overall, we observed Long-COVID in almost 40% of our study group. Incidence of the symptoms in both the follow-ups remained almost same across age-groups, gender, severity of illness at admission and presence of comorbidity, with no significant association with any of them. Most common symptoms experienced in long COVID phase in our cohort were fatigue, myalgia, neuro-psychiatric symptoms like depression, anxiety, "brain fog" and sleep disorder, and breathlessness. Fatigue was found to be significantly more often reported in the elderly population and in those patients who had a severe COVID-19 illness at the time of admission. Persistence of breathlessness was also reported significantly more often in those who had severe disease at the onset. The overall median duration of long COVID symptoms was 16.9 weeks with inter-quartile range of 12.4 to 35.6 weeks. The duration of symptom resolution was not associated with age, gender or comorbidity but was significantly associated with severity of illness at the time of admission (P=0.006).

ConclusionsLong-COVID is now being recognized as a new disease entity, which includes a constellation of symptoms. Long-COVID was in almost 40% of our study group with no correlation to age, gender, comorbidities or to the disease severity. The duration of symptom resolution was significantly associated with severity of illness at the time of admission (P = 0.006). In our study, all patients reported minor symptoms such as fatigue, myalgia, neuro-psychiatric symptoms like depression, anxiety, "brain fog" and sleep disorder and persistence of breathlessness. Severe organ damage was not reported by our subjects. This might be the longest post-COVID follow-up study on a sample of nearly 1000 cases from India.


title: Effectiveness of vaccination against SARS-CoV-2 infection and Covid-19 hospitalization among Finnish elderly and chronically ill - An interim analysis of a nationwide cohort study

abstract:
BackgroundIn Finland, both mRNA and adenovirus vector (AdV) Covid-19 vaccines have been used after the vaccination campaign started on December 27, 2020. Vaccination of the elderly and chronically ill was prioritized and the interval between doses set to 12 weeks. The objective of this interim analysis was to evaluate first and second dose vaccine effectiveness (VE) in a real-world setting.

MethodsDuring the first 5 months of the campaign, a register-based cohort study was conducted in the Finnish elderly aged 70+ years and those aged 16-69 years with medical conditions predisposing to severe Covid-19 (chronically ill). Using Cox regression, VE against SARS-CoV-2 infection and Covid-19 hospitalization was estimated comparing the hazard in the vaccinated with that in the unvaccinated.

ResultsThe cohorts included 901092 elderly (89% vaccinated) and 774526 chronically ill (69% vaccinated) individuals. Three weeks after the first dose, mRNA VE against infection was 45% (95% confidence interval, 36-53%) and 40% (26-51%) in elderly and chronically ill; mRNA VE against hospitalization was 63% (49-74%) and 82% (56-93%). In chronically ill, AdV VE was 42% (32-50) and 62% (42- 75%) against infection and hospitalization, respectively. One week after the second dose, mRNA VE against infection was 75% (65-82%) and 77% (65-85%) in elderly and chronically ill; mRNA VE against hospitalization was 93% (70-98%) and 90% (29-99%).

ConclusionsCovid-19 vaccines protect against SARS-CoV-2 infection and Covid-19 hospitalization. A single dose provides moderate protection in elderly and chronically ill, although 2 doses are clearly superior.

summaryThis register-based cohort study demonstrates that Covid-19 vaccines protect against SARS-CoV-2 infection and Covid-19 hospitalization among Finnish elderly and chronically ill. Vaccine effectiveness against hospitalization was moderate after 1 dose and increased to [≥]90% after 2 doses.


title: Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review

abstract:
BackgroundHow best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We systematically reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission and morbidity outcomes.

MethodsWe searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed.

FindingsThe search identified 1820 studies. 36 studies met the inclusion criteria and were narratively synthesised. 83% of studies described outcomes in high-income countries. We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably reductions in deaths could be increased, if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage.

InterpretationThe evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is however an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.


title: An extract of hops (Humulus lupulus L.) modulates gut peptide hormone secretion and reduces energy intake in healthy weight men: a randomised, cross-over clinical trial

abstract:
BackgroundGastrointestinal enteroendocrine cells express a range of chemosensory receptors involved in detecting the chemical composition of food during digestion. These receptors, including bitter taste receptors (T2Rs), may play an important role in regulating gut function and appetite.

ObjectiveTo establish the ability of Amarasate(R), a bitter supercritical CO2 extract of hops (Humulus lupulus L.) to modify acute energy intake, appetite and hormonal responses and establish a site of action.

DesignNineteen healthy-weight (BMI = 23.5 {+/-} 0.3 kg/m2) male volunteers completed a randomised three-treatment, double blind, cross-over study with a 1 week washout between treatments. Overnight-fasted participants were cannulated and provided with a standardised 2 MJ breakfast meal at 0900h. Treatments comprised a vehicle control (Placebo) or 500 mg of hops extract administered in either delayed release capsules (Duodenal) at 1100 h or quick release capsules (Gastric) at 1130 h. Ad libitum energy intake was recorded at an outcome meal (1200 h) and afternoon snack (1400 h), with blood samples taken and subjective ratings of appetite, gastrointestinal discomfort, vitality, meal palatability and mood assessed throughout the day.

ResultsCompared with placebo, both gastric and duodenal treatments significantly reduced (p < 0.05) total ad libitum energy intake by 911 {+/-} 308 kJ and 944 {+/-} 309 kJ, respectively. Both gastric and duodenal treatments significantly increased (p < 0.05) pre-meal ghrelin and post-prandial CCK, GLP-1 and PYY responses while reducing postprandial insulin, GIP and PP secretion with no significant impact on glycemia. In addition, gastric and duodenal treatments produced small but significant (p < 0.05) changes in vitality and gastrointestinal discomfort (e.g. nausea, bloating, abdominal discomfort) with mild-moderate adverse GI symptoms reported in the gastric treatment only. However, no significant treatment effects were observed for any subjective measures of appetite or meal palatability.

ConclusionBoth gastric and duodenal delivery of Amarasate(R) modulate the release of hormones involved in appetite and glycaemic regulation, providing a potential "bitter brake" on energy intake in healthy-weight men.

category: nutrition


title: THERAPEUTIC MAMMOPLASTY AUDIT FROM A SINGLE INSTITUTIONAL COHORT FROM INDIA

abstract:
IntroductionTherapeutic Mammoplasty (TM) is a Oncoplastic Breast Surgery (OBS) technique suitable for medium-to-large breasts with ptosis with large or multifocal/multicentric (MF/MC) tumors. Several studies have indicated that TM expands the scope, extent, and application of breast conservation surgery. This report describes in detail TM outcomes in Indian breast cancer (BC) patients.

MethodsFrom our single institutional cohort (n = 211), we present data related to surgical techniques, clinical management, oncological safety, cosmetic and patient reported outcomes (PROMs, based on Breast-Q questionnaire) from BC patients who underwent TM (categorized as simple, complex, extreme and split-reduction type)

ResultsMean age at diagnosis was 48.7 years. Majority of these patients had advanced stage (II/III) disease. 178 patients consented and 171 completed 1 year follow-up from 3 main groups (a) simple (n=87) (b) complex (n =39) and (c) extreme TM (n = 49). The post-operative complication rates were low (<10%) without any delay in adjuvant treatment. Cosmetic scores were good-to-excellent (n = 154). Post-1-year PROMs (n=149) revealed good-to-excellent score for satisfaction with breast, cosmetic outcome and psychosocial well-being for all TM types.

ConclusionOur study is a first detailed report describing a multi-factorial audit in TM single institutional cohort in Indian BC patients. We propose that our TM technique/s may be optimally suited for BC scenarios common in India namely (a) advanced stage BC patients with moderate-to-large breasts with mild/severe ptosis (b) multifocal, multicentric tumors (c) LABC at initial presentation.

category: oncology


title: Strong immunogenicity of heterologous prime-boost immunizations with the experimental vaccine GRAd-COV2 and BNT162b2 or ChAdOx1-nCOV19

abstract: Here we report on the humoral and cellular immune response in eight volunteers who autonomously chose to adhere to the Italian national COVID-19 vaccination campaign more than 3 months after receiving a single administration GRAd-COV2 vaccine candidate in the context of the phase 1 clinical trial. We observed a clear boost of both binding/neutralizing antibodies as well as T cell responses upon receipt of the heterologous BNT162b2 or ChAdOx1-nCOV19 vaccines. These results, despite the limitation of the small sample size, support the concept that a single-dose of an adenoviral vaccine may represent an ideal tool to effectively prime a balanced immune response, which can be boosted to high levels by a single dose of a different vaccine platform.


title: No effect of tDCS on fatigue and depression in chronic stroke patients: an exploratory randomized sham-controlled trial combining tDCS with computerized cognitive training

abstract: Fatigue and emotional distress rank high among self-reported unmet needs in stroke survivors. Currently, few treatment options exist for post stroke fatigue, a condition frequently associated with depression. Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have shown promise in alleviating fatigue and depression in other patient groups, but the acceptability and effects for chronic phase stroke survivors are not established. Here, we used a randomized sham-controlled design to evaluate the added effect of tDCS combined with computerized cognitive training to alleviate symptoms of fatigue and depression. 74 patients were enrolled at baseline (mean time since stroke = 26 months) and 54 patients completed the intervention. Self-report measures of fatigue and depression were collected at five consecutive timepoints, spanning a period of two months. While fatigue and depression severity were reduced during the course of the intervention, Bayesian analyses provided evidence for no added effect of tDCS. Less severe symptoms of fatigue and depression were associated with higher improvement rate in select tasks, and study withdrawal was higher in patients with more severe fatigue and younger age. Time-resolved analyses of individual symptoms by a network-approach suggested overall higher centrality of fatigue symptoms (except item 1 and 2) than depression symptoms. In conclusion, the results support the notion of fatigue as a significant stroke sequela with possible implications for treatment adherence and response, but reveal no effect of tDCS on fatigue or depression.

category: rehabilitation medicine and physical therapy


title: Complexity and Variability Analyses of Motor Activity Distinguish Mood States in Bipolar Disorder

abstract:
AimsChanges in motor activity are core symptoms of mood episodes in bipolar disorder. The manic state is characterized by increased variance, augmented complexity and irregular circadian rhythmicity when compared to healthy controls. The aim was to characterize differences in motor activity when comparing manic patients to their euthymic selves.

MethodsMotor activity was collected from 14 bipolar inpatients in mania and remission. 24-h recordings and 2-h time series in the morning and evening were analyzed for mean activity, variability and complexity. Lastly, the recordings were analyzed with the similarity graph algorithm and graph theory concepts such as edges, bridges, connected components and cliques.

ResultsWhen compared to euthymia, over the duration of approximately one circadian cycle, the manic state presented reduced variability, displayed by decreased standard deviation (p = 0.013) and augmented complexity shown by increased sample entropy (p = 0.025). During mania there were also fewer edges (p = 0.039) and more bridges (p = 0.026). Similar changes in variability and complexity were observed in the 2-h morning and evening sequences, mainly in the estimates of the similarity graph algorithm. A comparison of morning and evening sequences within states revealed no significant change in estimates for mania. Contrarily, the euthymic state showed significant evening differences in variance and complexity, displayed by fewer edges (p = 0.010) and an increased number of connected components (p = 0.009).

ConclusionThe motor activity of mania is characterized by altered complexity, variability, and circadian rhythms when compared within-subject to euthymia.

category: psychiatry and clinical psychology


title: C Reactive Protein based early intervention for home quarantined COVID-19 patients to avoid complications and hospitalization.

abstract:
BackgroundAs India was reeling under the relentless onslaught of the second wave of COVID -19, the hospitals were over-crowded and resources were inaccessible. Many COVID -19 positive patients had to stay at home and reach out to their family physicians for guidance. This gave us an opportunity to observe a group of patients in home quarantine. The challenge was daunting. We could not afford to allow these patients to deteriorate as hospital beds and oxygen support were not readily available. Therefore, we developed an innovative approach to monitor these patients and to intervene at the optimal time to avoid hospitalization.

Based on objective biochemical tests like elevated CRP and clinical signs like persistent high-grade fever, we initiated early low dose steroids and antibiotics prior to the onset of hypoxia. None of the home quarantined patients deteriorated because of the timely medical intervention. These patients neither required oxygen support nor hospitalization. We therefore present our new treatment model for home quarantined COVID-19 patients along with our suggestions for implementing the model at the community level.

Methods25 patients under home quarantine who contacted online for medical guidance underwent clinical and biochemical evaluation. CT radiological examination was done whenever indicated. Treatments were initiated under medical guidance based on the CRP values and clinical presentation.

ResultsAmong the 25 patients, 40% of the patients (10/25) had mild symptoms with normal CRP. 24% of the patients (6/25) had mild symptoms with elevated CRP. 36% of patients (9/25) had elevated CRP with persistent high fever. All the 25 patients recovered over the next four weeks.

ConclusionWe propose an early objective assessment of inflammatory markers like CRP prior to the onset of hypoxia during home quarantine and early, need-based intervention under medical guidance to avoid complications and hospitalization.

category: respiratory medicine


title: High-Risk Endometrial Cancer Assessed by Immediate Intraoperative Frozen Sections of Sentinel Lymph Nodes - A Retrospective Study.

abstract:
While sentinel lymph node (SLN) sampling has been established for low-risk endometrial cancer, few data exists on high-risk histologies. This study aims to measure the accuracy of immediate intraoperative SLN biopsy with frozen section in high-risk endometrial cancer. Patients diagnosed with endometrial cancer of high-grade histology (grade 3 endometrioid, clear cell, serous, carcinosarcoma, de- or undifferentiated histology) between 2014 and 2019 at a single institution who underwent SLN mapping, followed by pelvic lymphadenectomy with or without para-aortic lymphadenectomy were included. SLNs were assessed intraoperatively using multiple frozen sections and H&E staining. Lymph node metastases detected by SLN biopsy were compared with complete lymphadenectomy specimens.

35 patients with high-grade endometrial cancer histology underwent SLN mapping followed by lymphadenectomy. In 34 of 35 (97%) of these patients mapping with at least one SLN was successful. Positive SLNs were identified in 7/34 patients (20.6%). There were no patients who had positive lymph nodes on complete lymphadenectomy without a positive SLN, resulting in 100% sensitivity, and 0% false-negative rate.

SLN mapping using intraoperative frozen sections in high-risk endometrial cancer demonstrated 100% sensitivity and 0% false-negative rate, provides immediate feedback on successful SLN mapping and valuable intraoperative information on the disease status guiding the intraoperative decision for completion lymphadenectomy.

HighlightsO_LIIntraoperative SLN assessment in high-grade endometrial cancer by frozen section.
C_LIO_LI100% sensitivity and 0% false-negative rate compared to complete lymphadenectomy.
C_LIO_LIProtocol provides immediate intraoperative feedback on successful SLN mapping.
C_LIO_LIProtocol helps inform surgeons decision to proceed with complete lymphadenectomy.
C_LI

category: obstetrics and gynecology