title: Responsive caregiving, opportunities for early learning, and children's safety and security during COVID-19: A rapid review

abstract:
IntroductionDuring the COVID-19 pandemic, there have been drastic changes in family life and programs and services that promote and protect early childhood development. Global stakeholders have raised concerns that the pandemic is putting enormous strain on parents and other caregivers, compromising capabilities and enabling environments for nurturing care of young children and therefore likely impacting childrens development.

MethodologyThis rapid review takes stock of emerging research on nurturing care for young children during the COVID-19 crisis. Two databases were searched in addition to an extensive search for grey literature, drawing on 112 scholarly and scientific studies from more than 30 countries that have examined components of nurturing care during the pandemic, namely: responsive caregiving, early learning and play, and childrens safety and security.

ResultsThere are some reports of unexpected positive benefits of the pandemic on families, including increased father involvement in caregiving. But more commonly, the studies findings reveal numerous issues of concern, including parental and caregiver mental health difficulties and less responsive parent-child relationships, increased screen time among children, limited opportunities for outdoor play, and fractured systems for responding to potential child neglect and maltreatment. Evidence suggests limited access and challenges in the provision of remote learning for the youngest learners, such as those in early childhood education.

ConclusionThe findings can inform global stakeholders, who have advocated for increased support and funding to ensure young children and other caregivers are supported and protected during the COVID-19 pandemic. There is an urgent need for action-oriented implementation studies - those that go beyond identifying trends and begin to pinpoint "what works" to effectively promote and protect nurturing care during emergencies such as the COVID-19 pandemic.

Key questionsO_ST_ABSWhat is already known?C_ST_ABSThe most fundamental promotive experiences in the early years of life to reach optimal development come from nurturing care and protection received from parents, family, and community, which have lifelong benefits including improved health and wellbeing. Health and other emergencies are detrimental to the provision of nurturing care.

What are the new findings?Findings from this rapid review reveal numerous areas of concern, including families reporting mental health difficulties and less responsive parent-child relationships, increased screen time among children, limited opportunities for outdoor play, and fractured systems for responding to potential child neglect and maltreatment. As with other features of this pandemic, not all families are affected equally: financially vulnerable families are much more likely to experience negative ramifications. The pandemic is also disproportionately affecting parents and other caregivers with young children, particularly mothers, those with pre-existing mental health difficulties, and those caring for children with disabilities.

What do the new findings imply?Findings highlight the need for action by governments, civil society, international and community-based organizations to improve support for families so that the pandemic does not break the provision of nurturing care and wipe out decades of progress, especially for vulnerable families and children.


title: How reacted USA with the first case of Bubonic Plague on 21 August?

abstract: The present work studies the reactions of citizens from United States of America (USA) during the first cases of Bubonic Plague in the territory on August 2020, during pandemic generated by Covid-19. The interest of the study is analyze the posts of users from all the states of USA following a Text Mining approach. The collection of data is performed through Twitter Application Program Interface (API) of Twitter, considering keywords: bubonic plague and black death. The results show the states with highest number of coronavirus has more publication than others and the interest about treatments, political issues and public health.

category: public and global health


title: An alternative approach for bioanalytical assay development for wastewater-based epidemiology of SARS-CoV-2

abstract:
Wastewater-based epidemiology could be applied to track down SARS-CoV-2 outbreaks at high spatio-temporal resolution and could potentially be used as an early-warning for emergence of SARS-CoV-2 circulation in the general population. Epidemiological surveillance of SARS-CoV-2 could play a role in monitoring the spread of the virus in the population and controlling possible outbreaks. However, sensitive sample preparation and detection methods are necessary to detect trace levels of SARS-CoV-2 RNA in influent wastewater (IWW).

Unlike predecessors, method development of a SARS-CoV-2 RNA concentration and detection procedure was performed with IWW samples with high viral SARS-CoV-2 loads (in combination with seeding IWW with a surrogate coronavirus). This is of importance since the SARS-CoV-2 genome in IWW might have already been subject to in-sewer degradation into smaller genome fragments or might be present in a different form (e.g. cell debris,...). Centricon Plus-70 (100 kDa) centrifugal filter devices resulted in the lowest and most reproducible Ct-values for SARS-CoV-2 RNA. Lowering pore sizes did not improve our limit of detection and quantification. Real-time polymerase chain reaction (qPCR) was employed for the amplification of the N1, N2, N3 and E_Sarbeco-gene.

This is one of the first studies to apply digital polymerase chain reaction (dPCR) for the detection of SARS-CoV-2 RNA in IWW. Interestingly, qPCR results were comparable with dPCR results suggesting that qPCR is a valid method. In this study, dPCR was also used as a proxy to assess the precision of qPCR. In this light, dPCR showed high variability at low concentration levels (100 copies/{micro}L), indicating that variability in bioanalytical assays for SARS-CoV-2 RNA might be substantial.

On average, the N2-gene showed high in-sample stability in IWW for 10 days of storage at 4 {degrees}C. Between-sample variability was substantial due to the low native concentrations in IWW. Additionally, the E-gene proved to be less stable compared to the N2-gene and showed higher variability. Freezing the IWW samples resulted in a 10-fold decay of loads of the N2- and E-gene in IWW.

Although WBE can already aid in filling some knowledge gaps in the epidemiological surveillance of SARS-CoV-2, future WBE studies should aim to further validate and standardize bioanalytical assays, especially with regards to methodological limitations.

HighlightsO_LIDevelopment of an analytical procedure for detection of SARS-CoV-2 RNA in wastewater
C_LIO_LIExtraction recovery was evaluated in influent wastewater
C_LIO_LIPrecision measured with dPCR used as a proxy for qPCR
C_LIO_LIqPCR of the N2 gene fragment showed high in-sample stability of SARS-CoV-2 on average
C_LI


title: Early introductions and community transmission of SARS-CoV-2 variant B.1.1.7 in the United States

abstract: The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2500 COVID-19 cases associated with this variant have been detected in the US since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight the primary ports of entry for B.1.1.7 in the US and locations of possible underreporting of B.1.1.7 cases. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.


title: Association of demographic and occupational factors with SARS-CoV-2 vaccine uptake in a multi-ethnic UK healthcare workforce: a rapid real-world analysis

abstract:
BackgroundHealthcare workers (HCWs) and ethnic minority groups are at increased risk of COVID-19 infection and adverse outcome. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination is now available for frontline UK HCWs; however, demographic/occupational associations with vaccine uptake in this cohort are unknown. We sought to establish these associations in a large UK hospital workforce.

MethodsWe conducted cross-sectional surveillance examining vaccine uptake amongst all staff at University Hospitals of Leicester NHS Trust. We examined proportions of vaccinated staff stratified by demographic factors, occupation and previous COVID-19 test results (serology/PCR) and used logistic regression to identify predictors of vaccination status after adjustment for confounders.

FindingsWe included 19,044 HCWs; 12,278 (64.5%) had received SARS-CoV-2 vaccination. Compared to White HCWs (70.9% vaccinated), a significantly smaller proportion of ethnic minority HCWs were vaccinated (South Asian 58.5%, Black 36.8% p<0.001 for both). After adjustment, factors found to be negatively associated with vaccine uptake were; younger age, female sex, increasing deprivation and belonging to any non-White ethnic group (Black: aOR0.30, 95%CI 0.26-0.34, South Asian:0.67, 0.62-0.72). Those that had previously had confirmed COVID-19 (by PCR) were less likely to be vaccinated than those who had tested negative.

InterpretationEthnic minority HCWs and those from more deprived areas as well as younger, female staff are less likely to take up SARS-CoV-2 vaccination. These findings have major implications for the delivery of SARS-CoV-2 vaccination programmes in HCWs and the wider population and should inform the national vaccination programme to prevent the disparities of the pandemic from widening.

FundingNIHR, UKRI/MRC


title: Is multimorbidity associated with risk of elder abuse? Findings from the AHSETS study

abstract:
IntroductionCommensurate with demographic and lifestyle transition, increasing magnitude of multimorbidity is common among older adults in low- and middle-income countries (LMIC). At the same time the rising prevalence of elder abuse is concurrently observed in these populations. However, little is known about the elder abuse in the context of multimorbidity with no reports on their interplay from LMIC settings. This study examined the association of multimorbidity with the risk of elder abuse and its correlates in a rural elderly population of Odisha, India.

MethodsThe data was collected as a part of our ASHETS study encompassing 725 older adults residing in rural Odisha, India. Multimorbidity was assessed by previously validated MAQ PC tool. Hwalek-Sengstock elder abuse screening test (HS-EAST) was used to assess the risk of elder abuse. Care dependence was measured by Katz index questionnaire. We performed ordinal logistic regression models to identify the correlates of elder abuse.

ResultsAround 48.8% (95% CI:45.13-52.53%) older adults had multimorbidity while 33.8% (95% CI:30.35-37.35%) had some form of care dependence. Out of 725, 56.6% (CI 52.85 - 60.19%) were found to be at low-risk elder abuse and 15.9% (CI 13.27 - 18.72%) being at high-risk. The risk of elder abuse was significantly associated with multimorbidity (AOR=1.88; 95%CI: 1.54-2.21), economic dependence (AOR=1.62; 95%CI: 1.25-1.99) and functional dependence (AOR=1.86; 95%CI: 1.42-2.29). Staying alone (AOR= 1.75; 95%CI: 1.13-2.38) and lower socio-economic status (AOR=2.96; 95%CI: 2.09-3.84) were two other significant correlates.

ConclusionsOlder adults with multimorbidity are at 1.88 times higher risk of elder abuse compared to their non-multimorbid counterparts. Both economic and functional dependence are associated with an increase in elder abuse. This suggests the mediating role of care dependence in the pathway to elder abuse in multimorbidity. Future geriatric multimorbidity assessment studies should consider screening for care dependence as well as elder abuse while designing integrated care models.


title: Population Age-Ineligible for COVID-19 Vaccine in the United States: Implications for State, County, and Race/Ethnicity Vaccination Targets

abstract:
BackgroundWe examined the geographic and racial/ethnic distribution of the SARS-CoV-2 vaccine age-ineligible population (0-15 years old) in the U.S., and calculated the proportion of the age-eligible population that will need to be vaccinated in a given geo-demographic group in order to achieve either 60% or 75% vaccine coverage for that population as a whole.

MethodsUS Census Bureau population estimates for 2019 were used to calculate the percent vaccine ineligible and related measures for counties, states, and the nation as a whole. Vaccination targets for the 30 largest counties by population were calculated. Study measures were calculated for racial/ethnic populations at the national (n=7) and state (n=6) levels.

ResultsPercent of population ineligible for vaccine varied widely both geographically and by race/ethnicity. State values ranged from 15.8% in Vermont to 25.7% in Utah, while percent ineligible of the major racial/ethnic groups was 16.4% of non-Hispanic whites, 21.6% of non-Hispanic Blacks, and 27.5% of Hispanics. Achievement of total population vaccine coverage of at least 75% will require vaccinating more than 90% of the population aged 16 years and older in 29 out of 30 of the largest counties in the U.S.

ConclusionsThe vaccine-ineligibility of most children for the next 1-2 years, coupled with reported pervasive vaccine hesitancy among adults, especially women and most minorities, means that achievement of adequate levels of vaccine coverage will be very difficult for many vulnerable geographic areas and for several racial/ethnic minority groups, particularly Hispanics, Blacks, and American Indians.


title: A Bayesian hierarchical model with integrated covariate selection and misclassification matrices to estimate neonatal and child causes of death

abstract: Reducing neonatal and child mortality is a global priority. In countries without comprehensive vital registration data to inform policy and planning, statistical modelling is used to estimate the distribution of key causes of death. This modelling presents challenges given that the input data are few, noisy, often not nationally representative of the country from which they are derived, and often do not report separately on all of the key causes. As more nationally representative data come to be available, it becomes possible to produce country estimates that go beyond fixed-effects models with national-level covariates by incorporating country-specific random effects. However, the existing frequentist multinomial model is limited by convergence problems when adding random effects, and had not incorporated a covariate selection procedure simultaneously over all causes. We report here on the translation of a fixed effects, frequentist model into a Bayesian framework to address these problems, incorporating a misclassification matrix with the potential to correct for mis-reported as well as unreported causes. We apply the new method and compare the model parameters and predicted distributions of eight key causes of death with those based on the previous, frequentist model.


title: Performing arts as a health resource? An umbrella review of the health impacts of music and dance participation

abstract: An increasing body of evidence notes the health benefits of arts engagement and participation. However, specific health effects and optimal modes and  doses of arts participation remain unclear, limiting evidence-based recommendations and prescriptions. The performing arts are the most popular form of arts participation, presenting substantial scope for established interest to be leveraged into positive health outcomes. Results of a three-component umbrella review (PROSPERO ID #: CRD42020191991) of relevant systematic reviews (33), epidemiologic studies (9) and descriptive studies (87) demonstrate that performing arts participation is broadly health promoting activity. Beneficial effects of performing arts participation were reported in healthy (non-clinical) children, adolescents, adults, and older adults across 17 health domains (9 supported by moderate-high quality evidence (GRADE criteria)). Positive health effects were associated with as little as 30 (acute effects) to 60 minutes (sustained weekly participation) of performing arts participation, with drumming and both expressive (ballroom, social) and exercise-based (aerobic dance, Zumba) modes of dance linked to the broadest health benefits. Links between specific health effects and performing arts modes/doses remain unclear and specific conclusions are limited by a still young and disparate evidence base. Further research is necessary, with this umbrella review providing a critical knowledge foundation.


title: Impacts of school closures on physical and mental health of children and young people: a systematic review

abstract:
BackgroundThe well-documented links between education and health mean that school closures during the COVID-19 pandemic are likely to be associated with significant health harms to children and young people (CYP). A systematic review of the evidence is needed to inform policy decisions around school closures and re-openings during the pandemic.

MethodsWe undertook a high-quality systematic review of observational quantitative studies (published or preprint) of the impacts of school closures (for any reason) on the health, wellbeing and educational outcomes of CYP, excluding impacts of closure on transmission of infection (PROSPERO CRD42020181658). We used a machine learning approach for screening articles, with decisions on inclusion and data extraction performed independently by 2 researchers. Quality was assessed for study type. A narrative synthesis of results was undertaken as data did not allow meta-analysis.

Results16,817 records were screened, of which 151 were reviewed in full-text and 72 studies were included from 20 countries. 33% were cohort studies using historical control periods; 19% pre-post studies; and 46% cross-sectional studies which assessed change by comparison with population reference data. 63% were high-quality, 25% medium-quality and 13% low-quality. Cause of closure in all studies was the first COVID-19 pandemic wave with the exception of 5 influenza studies and 1 teacher strike.

27 studies concerning mental health identified considerable impacts across emotional, behavioural and restlessness/inattention problems; 18-60% of CYP scored above risk thresholds for distress, particularly anxiety and depressive symptoms. Two studies reported non-significant rises in suicide rates. Self-harm and psychiatric attendances were markedly reduced, indicating a rise in unmet mental health need. Child protection referrals fell 27-39%, with a halving of the expected number of referrals originating in schools.

19 studies concerning health service use showed marked reductions in emergency department (ED) presentations and hospital admissions, with evidence of delayed presentations and potential widening of inequalities in vaccination coverage. Data suggested marked rises in screen-time and social media use and reductions in physical activity however data on sleep and diet were inconclusive. Available data suggested likely higher harms in CYP from more deprived populations.

ConclusionsSchool closures as part of broader social distancing measures are associated with considerable harms to CYP health and wellbeing. Available data are short-term and longer-term harms are likely to be magnified by further school closures. Data are urgently needed on longer-term impacts using strong research designs, particularly amongst vulnerable groups. These findings are important for policy-makers seeking to balance the risks of transmission through school-aged children with the harms of closing schools.


title: The Missing Science: Epidemiological data gaps for COVID-19 policy in the United States

abstract: We report on a scoping study of COVID-19 epidemiological data available for COVID-19 policy and management decisions for U.S. settings. We synthesize current US Centers for Disease and Control and Prevention (CDC) estimates for parameter of infectious transmission, infection severity, and disease burden, and summarize epidemiologic contributions to these parameters published by CDC-affiliated investigators through Oct 30, 2020. Authoritative estimates of most infectious transmission and infection severity parameters exist but rely primarily on data from studies conducted in non-U.S. populations. Estimates of secondary infection risks for household, workplace, school, or other community settings are lacking and estimates of the clinical fraction remain uncertain. The CDC reports multiple disease incidence and prevalence measures at national and state geographies, including some measures disaggregated by age group, race/ethnicity and sex; however, nationally uniform disease burden measures are not available at the sub-state level or for sub-populations defined by exposure setting, limiting opportunities for targeted interventions. CDC-affiliated investigators authored 133 quantitative studies on COVID-19 through Oct 30, 2020; however only 34 employed analytic methods. The remainder were descriptive. Of the 34 analytic studies, eleven reported on risk factors for infection, seven reported on risk factors for severe disease, three on symptomatic infections, three reported secondary infection risks, and four reported on indirect pandemic effects. Gaps remain in the epidemiological data required for an efficient and equitable public health policy response to COVID-19. The existence of these gaps one year after the onset of the COVID-19 pandemic underscores the need for standardizing data collection and research priorities and protocols in the context of a rapidly emerging infectious disease epidemics.


title: 'Leading from the front implementation strategies increase the success of influenza vaccination drives among healthcare workers: A reanalysis of Systematic Review evidence using Intervention Component Analysis (ICA) and Qualitative Comparative Analysis (QCA)

abstract:
BackgroundSeasonal influenza vaccination of healthcare workers (HCW) is widely recommended to protect staff and patients. A previous systematic review examined interventions to encourage uptake finding that hard mandates, such as loss of employment for non-vaccination, were more effective than soft mandates, such as signing a declination form, or other interventions such as incentives. Despite these overarching patterns the authors of the review concluded that  substantial heterogeneity remained requiring further analysis. This paper reanalyses the evidence using Intervention Component Analysis (ICA) and Qualitative Comparative Analysis (QCA) to examine whether the strategies used to implement interventions explain the residual heterogeneity.

MethodsWe used ICA to extract implementation features and trialists reflections on what underpinned the success of the intervention they evaluated. The ICA findings then informed and structured two QCA analyses to systematically analyse associations between implementation features and intervention outcomes. Analysis 1 examined hard mandate studies. Analysis 2 examined soft mandates and other interventions.

ResultsIn Analysis 1 ICA revealed the significance of  leading from the front rather than  top-down implementation of hard mandates. Four key features underpinned this: providing education prior to implementation; two-way engagement so HCW can voice concerns prior to implementation; previous use of other strategies so that institutions  dont-go-in-cold with hard-mandates; and support from institutional leadership. QCA revealed that either of two configurations were associated with greater success of hard mandates. The first involves two-way engagement, leadership support and a  dont-go-in-cold approach. The second involves leadership support, education and a  dont-go-in-cold approach. Reapplying the  leading from the front theory in Analysis 2 revealed similar patterns.

ConclusionsRegardless of intervention type a  leading from the front approach to implementation will likely enhance intervention success. While the results pertain to flu vaccination among HCWs, the components identified here may be relevant to public health campaigns regarding COVID-19 vaccination.


title: Evaluating COVID-19 reporting data in the context of testing strategies across 31 LMICs

abstract:
0.1 BackgroundCOVID-19 case counts are the predominant measure used to track epidemiological dynamics and inform policy decision-making. Case counts, however, are influenced by testing rates and strategies, which have varied over time and space. A method to consistently interpret COVID-19 case counts in the context of other surveillance data is needed, especially for data-limited settings in low- and middle-income countries (LMICs).

0.2 MethodsWe leverage statistical analyses to detect changes in COVID-19 surveillance data. We apply the pruned exact linear time change detection method for COVID-19 case counts, number of tests, and test positivity rate over time. With this information, we categorize change points as likely driven by epidemiological dynamics or non-epidemiological influences such as noise.

0.3 FindingsHigher rates of epidemiological change detection are more associated with open testing policies than with higher testing rates. We quantify alignment of non-pharmaceutical interventions with epidemiological changes. LMICs have the testing capacity to measure prevalence with precision if they use randomized testing. Rwanda stands out as a country with an efficient COVID-19 surveillance system. Sub-national data reveal heterogeneity in epidemiological dynamics and surveillance.

0.4 InterpretationRelying solely on case counts to interpret pandemic dynamics has important limitations. Normalizing counts by testing rate mitigates some of these limitations, and open testing policy is key to efficient surveillance. Our findings can be leveraged by public health officials to strengthen COVID-19 surveillance and support programmatic decision-making.

0.5 FundingThis publication is based on models and data analysis performed by the Institute for Disease Modeling at the Bill & Melinda Gates Foundation.

Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched for articles on the current practices, challenges, and proposals for COVID-19 surveillance in LMICs. We used Google Scholar with search terms including "COVID surveillance." Existing studies were found to be qualitative, anecdotal, or highly location-specific.

Added value of this studyWe developed a quantitative method that makes use of limited information available from LMICs. Our approach improves interpretation of epidemiological data and enables evaluation of COVID-19 surveillance dynamics across countries.

Implications of all the available evidenceOur results demonstrate the importance of open testing for strong surveillance systems, bolstering existing anecdotal evidence. We show strong alignment across LMICs between non-pharmaceutical interventions and epidemiological changes. We demonstrate the importance of considering sub-national heterogeneity of epidemiological dynamics and surveillance.


title: Identification of high-risk COVID-19 patients using machine learning

abstract: The current COVID-19 public health crisis, caused by SARSCoV-2 (severe acute respiratory syndrome coronavirus 2), has produced a devastating toll both in terms of human life loss and economic disruption. In this paper we present a machine-learning algorithm capable of identifying whether a given patient (actually infected or suspected to be infected) is more likely to survive than to die, or vice-versa. We train this algorithm with historical data, including medical history, demographic data, as well as COVID-19-related information. This is extracted from a database of confirmed and suspected COVID-19 infections in Mexico, constituting the official COVID-19 data compiled and made publicly available by the Mexican Federal Government. We demonstrate that the proposed method can detect high-risk patients with high accuracy, in each of four identified treatment stages, thus improving hospital capacity planning and timely treatment. Furthermore, we show that our method can be extended to provide optimal estimators for hypothesis-testing techniques commonly-used in biological and medical statistics. We believe that our work could be of use in the context of the current pandemic in assisting medical professionals with real-time assessments so as to determine health care priorities.


title: The global distribution of COVID-19 vaccine: The role of macro-socioeconomics measures

abstract: Since coronavirus disease 2019 (covid-19) has continued to spread globally, many countries have progressed clinical trials and started vaccinations at the end of December 2020. This report aims to analyze the association of COVID-19 vaccine distribution and two macro-socioeconomics measures, including human development index (HDI) and Gross domestic product (GDP), among 25 countries till the first week of February 2021. Our results indicate that a higher GDP per Capita is positively associated with higher COVID-19 vaccine distribution. However, UAE and Israel have more successful vaccine distribution outcomes regardless of their GDP. In addition, the result shows HDI does not have a significant relationship with vaccine distribution. Although these macro-socioeconomic measures may be counted as a vital indicator for vaccine distribution, other factors may play roles in vaccine distribution, including well-developed health infrastructure, a centralized political system, and population size.


title: Persistence of SARS-CoV-2 antibodies and symptoms in an Irish Healthcare Worker (HCW) setting: Results of the COVID Antibody Staff Testing (CAST) Study

abstract:
ObjectivesThis study examined the natural history, including incidence and prevalence, of SARS-CoV-2 antibodies serially up to 6 months post infection in Irish Healthcare Workers (HCWs) at an academic tertiary maternity hospital, during the first pandemic peak from March to September 2020.

DesignThis single centre observational study profiled SARS-CoV-2 incidence and infection using viral RNA detected using oro/nasopharyngeal swabs accompanied by serological assessment of study participants for the presence of S SARS-CoV-2 antibodies. Participant demographics were also collected alongside information on clinical symptoms and time to recovery. Real time polymerase-chain-reaction (RT-PCR) for viral RNA SARS-CoV-2 detection was performed using the Allplex SARS-CoV-2 three gene target 2019-nCoV assay (SeeGene Inc., Rep. of Korea) or the Xpert Xpress SARS-CoV-2 assay on the GeneXpert platform (Cepheid, USA). Blood samples were obtained at the time of initial swab and at up to 4 time points thereafter, for the serological assessment of antibodies against both the spike and nucleocapsid protein antigens of SARS-CoV-2. Serological response was measured using the Captia Anti-SARS-CoV-2 (IgG) ELISA (Trinity Biotech) as part of a clinical performance evaluation. Two other testing methods were also used; the Anti-SARS-CoV-2 ELISA (IgG) assay (EuroImmun) and the Abbott Anti-SARS-CoV-2 IgG 75 kit on the Architect i2000SR instrument (Abbott Laboratories).

SettingAcademic Tertiary Maternity Hospital in Dublin, Ireland.

ParticipantsWe invited symptomatic and asymptomatic healthcare workers employed at the Rotunda Maternity Hospital to participate in the CAST study.

Main Outcome MeasuresThe CAST study aimed to examine incidence and clinical symptoms of SARS-CoV-2 in HCWs and to determine the presence and longevity of antibodies in this group. We also sought to examine the clinical utility of the Captia Anti-SARS-CoV-2 (IgG) ELISA (Trinity Biotech) and to compare it to the current "accepted" gold standard platform in Ireland.

ResultsBy July 2020, 398 molecular tests had been completed on symptomatic staff with clinical suspicion of SARS-CoV-2 infection. In this cohort, 14% (n=54/398) had SARS-CoV-2 RNA detected by RT-PCR. The CAST study enrolled 137 HCWs with 86 participants symptomatic at time of swab collection and a further 51 asymptomatic control participants. SARS-CoV-2 RNA was detected in 52% (n=45/86) symptomatic study participants and serological positivity was confirmed in 98% (n=44/45) of those participants. Asymptomatic SARS-CoV-2 RNA infection was detected in 4% (n=2/51) of control participants with a seropositivity rate in this group of 8% (n=4/51). We demonstrated that 95% of SARS-CoV-2 PCR positive participants have detectable levels of antibodies at 100 days post infection, which persisted in 91% of participants at day 160+. Ongoing symptoms up to six months post infection were present in 50% of study participants with positive PCR and serology results. These data will be important to consider for long-term workforce planning in a healthcare setting, as the ongoing pandemic continues.

FundingThe CAST study was supported by the Rotunda Hospital and Trinity Biotech.


title: Risk Perceptions, Knowledge and Behaviors of General and High-Risk Adult Populations towards COVID-19: A Systematic Scoping Review

abstract:
BackgroundThe COVID-19 pandemic represents a major crisis for governments and populations around the globe. A large number of studies have been conducted worldwide to understand peoples awareness and behavioral response towards the disease. The publics risk perceptions, knowledge, and behaviors are key factors that play a vital role in the transmission of infectious diseases. Our scoping review aims to map the early evidence on risk perceptions, knowledge, and behaviors of general and high-risk adult populations towards COVID-19.

MethodsA systematic scoping review was conducted of peer-reviewed articles in five databases (MEDLINE-Ovid, EMBASE-Ovid, PsycINFO-Ovid, Web of Science, and CINAHL-EBSCO) on studies conducted during the early stage of COVID-19 (January to June, 2020). The gray literature was also searched through Open Grey, Scopus, Wonder, Social Science Research Network, MedRxiv, and websites of major public health organizations. Twenty studies meeting the inclusion criteria were included, appraised and analyzed.

ResultsDuring the early stage of the pandemic, levels of risk perceptions, knowledge, and behaviors towards COVID-19 were moderate to high in both general and high-risk adult populations. The perceived severity of the disease was slightly higher than the perceived susceptibility of getting COVID-19 during the first wave of COVID-19. Adults were knowledgeable about preventive behaviors, including hand-washing, mask-wearing, social distancing, and avoidance behaviors. Nevertheless, an important knowledge gap regarding the asymptomatic transmission of COVID-19 was reported in many studies. Our review identified hand-washing and avoiding crowded places as dominant preventive behaviors at the early stage of the pandemic. Staying at home, reducing social contacts, and avoiding public transport were less widespread in general populations than in high-risk adult groups. Being a female, older, and more educated was associated with better knowledge of COVID-19 and appropriate preventive behaviors.

ConclusionThis scoping review offers a first understanding of general and high-risk adults risk perceptions, knowledge, and behaviors towards COVID-19 during the early stage of the COVID-19 pandemic. Further research should be undertaken to assess psychological and behavioral responses over time. Research gaps have been identified in the relationship between ethnicity and risk perceptions, knowledge, and behaviors towards COVID-19.

Contribution to the field statementSince the beginning of the pandemic, a large number of primary studies have been conducted worldwide to understand peoples awareness and behavioral response towards COVID-19. Nevertheless, no review has mapped the early evidence on the perceptions, knowledge, and preventive behaviors of adult populations towards the transmission of this new disease. To the best of our knowledge, this is the first scoping review that offers an understanding of the general and high-risk adults risk perceptions, knowledge, and behaviors (RPKB) towards COVID-19 during the early stage of the COVID-19 pandemic. This review also identified sociodemographic factors associated with adults RPKB regarding COVID-19. As the virus does not affect individuals equally, knowing these factors can help to mitigate the negative effects of COVID-19 in certain population groups by developing targeted communication strategies that will facilitate their engagement in preventive measures. Finally, research gaps have been identified in the relationship between ethnicity and RPKB towards COVID-19. The existence of a disproportionate number of COVID-19 fatalities within Black populations should signal the possible gaps in RPKB towards COVID-19 in these communities. Additional studies on ethnic health disparities can help public health authorities to introduce targeted actions towards these communities during the COVID-19 pandemic.


title: Deep learning models for COVID-19 chest x-ray classification: Preventing shortcut learning using feature disentanglement

abstract: In response to the COVID-19 global pandemic, recent research has proposed creating deep learning based models that use chest radiographs (CXRs) in a variety of clinical tasks to help manage the crisis. However, the size of existing datasets of CXRs from COVID-19+ patients are relatively small, and researchers often pool CXR data from multiple sources, for example, using different x-ray machines in various patient populations under different clinical scenarios. Deep learning models trained on such datasets have been shown to overfit to erroneous features instead of learning pulmonary characteristics - a phenomenon known as shortcut learning. We propose adding feature disentanglement to the training process, forcing the models to identify pulmonary features from the images while penalizing them for learning features that can discriminate between the original datasets that the images come from. We find that models trained in this way indeed have better generalization performance on unseen data; in the best case we found that it improved AUC by 0.13 on held out data. We further find that this outperforms masking out non-lung parts of the CXRs and performing histogram equalization, both of which are recently proposed methods for removing biases in CXR datasets.

category: radiology and imaging


title: Summary of the Effects of Exercise Therapy in Non-Communicable Diseases: Clinically Relevant Evidence from Meta-Analyses of Randomized Controlled Trials

abstract:
There is strong evidence that exercise therapy leads to better measured and self-reported physical fitness and function in patients with chronic diseases, along with improvements in body composition. The evidence for other health benefits has not been summarized as systematically across different chronic diseases. Given the volume of research that has appeared in the past decade, this review of meta-analyses of randomized controlled trials (RCTs) in patients with specific chronic diseases summarizes the evidence regarding exercise therapy for various outcomes to help practitioners in prescribing exercise therapy for their patients. Meta-analyses published before Jan 1, 2021, based on at least four RCTs, and investigating the effect of exercise therapy on the same outcome among patients with a specific chronic disease were screened. These meta-analyses show that, in addition to improvements in fitness and function, various cardio-metabolic risk factor levels are improved in most of the common cardio-metabolic diseases, pain is reduced in musculoskeletal diseases, mood (depression and anxiety) and health-related quality of life are improved in various disease categories, and disease-specific indicators of disease progression are improved for conditions such as type 2 diabetes, hypertension, coronary heart disease, heart failure, claudication, chronic obstructive pulmonary disease, rheumatoid arthritis, fibromyalgia, depression, anxiety, and schizophrenia. Physicians should consider prescribing exercise to their patients with chronic disease conditions to improve their physical fitness, mood, and health-related quality of life and to slow down the progression of disease. This improves a patients possibility to enjoy an active and independent life.

Key pointsO_LIThis study summarizes the data from meta-analyses of randomized controlled trials (RCTs) on the effects of exercise therapy in patients and discusses the clinical relevance of the findings.
C_LIO_LIThe findings include the following: various cardio-metabolic risk factor levels are improved in most of the common cardio-metabolic diseases, pain is reduced in musculoskeletal diseases, mood (depression and anxiety) and health-related quality of life are improved in various disease categories, and disease-specific indicators of disease progression are improved in conditions such as type 2 diabetes, hypertension, coronary heart disease, heart failure, claudication, chronic obstructive pulmonary disease, fibromyalgia, depression, anxiety, and schizophrenia.
C_LIO_LIRCTs usually test the same exercise program for all trial participants. To tailor the exercise therapy intervention in real life, individually based factors, such as disease status, fitness level, personal exercising interests and possibilities, and the infrastructure making different exercise therapy modalities possible in the patients everyday environment should all be considered.
C_LI

category: rehabilitation medicine and physical therapy


title: Effects of THAM Nasal Alkalinization on Airway Microbial Communities: A Pilot Study

abstract:
ObjectivesIn cystic fibrosis (CF), loss of CFTR-mediated bicarbonate secretion reduces the airway surface liquid (ASL) pH causing airway host defense defects. Aerosolized sodium bicarbonate can reverse these defects, but its effects are short-lived. Aerosolized tromethamine (THAM) also raises the ASL pH but its effects are much longer lasting. In this pilot study, we tested the hypothesis that nasally administered THAM would alter the nasal bacterial composition in adults with and without CF.

MethodsSubjects (n=32 total) received intranasally administered normal saline or THAM followed by a wash out period prior to receiving the other treatment. Nasal bacterial cultures were obtained prior to and after each treatment period.

ResultsAt baseline, nasal swab bacterial counts were similar between non-CF and CF subjects, but CF subjects had reduced microbial diversity. Both nasal saline and THAM were well-tolerated. In non-CF subjects, nasal airway alkalinization decreased both the total bacterial density and the gram-positive bacterial species recovered. In both non-CF and CF subjects, THAM decreased the amount of C. accolens detected, but increased the amount of C. pseudodiphtheriticum recovered on nasal swabs. A reduction in S. aureus nasal colonization was also found in subjects who grew C. pseudodiphtheriticum.

ConclusionsThis study shows that aerosolized THAM is safe and well-tolerated and that nasal airway alkalinization alters the composition of mucosal bacterial communities.

category: respiratory medicine


title: Development of a new Aerosol Barrier Mask for mitigation of spread of SARS-CoV-2 and other infectious pathogens

abstract: The COVID-19 pandemic has caused huge impact on public health and significantly changed our lifestyle. This is due to the fast airborne oro-nasal transmission of SARS-CoV-2 from the infected individuals. The generation of liquid aerosolized particles occurs when the COVID-19 patients speak, sing, cough, sneeze, or simply breathe. We have developed a novel aerosol barrier mask (ABM) to mitigate the spread of SARS-CoV-2 and other infectious pathogens. This Aerosol Barrier Mask is designed for preventing SARS-CoV-2 transmission while transporting patients within hospital facilities. This mask can constrain aerosol and droplet particles and trap them in a biofilter, while the patient is normally breathing and administrated with medical oxygen. The system can be characterized as an oxygen delivery and mitigation mask which has no unfiltered exhaled air dispersion. The mask helps to prevent the spread of SARS-CoV-2, and potentially other infectious respiratory pathogens and protects everyone in general, especially healthcare professionals.


title: CLINICAL PERFORMANCE OF THE CALL SCORE FOR THE PREDICTION OF ADMISSION TO ICU AND DEATH IN HOSPITALIZED PATIENTS WITH COVID-19 PNEUMONIA IN A REFERENCE HOSPITAL IN PERU

abstract:
ObjectiveDetermine the CALL SCOREs diagnostic accuracy for the prediction of ICU admission and death in patients hospitalized for COVID-19 pneumonia in a reference hospital in Peru.

MethodsWe performed an analytical cross-sectional observational study. We included patients with COVID-19 pneumonia treated at the "Dos de Mayo" National Hospital. Patients over 18 years old with a diagnosis confirmed by rapid or molecular testing were included. Those with an incomplete, illegible, or missing medical history and/or bacterial or fungal pneumonia were excluded. Data were extracted from medical records. The primary outcomes were mortality and admission to the ICU. The Call Score was calculated for each patient (4 to 13 points) and classified into three risk groups. Summary measures were presented for qualitative and quantitative variables. The area under the model curve and the operational characteristics (sensitivity, specificity) were calculated for the best cut-off point.

ResultsThe Call Score reported an area under the curve of 0.59 (IC95%: 0.3 to 0.07), p = 0.43 for predicting death. However, for a cut-off point of 5.5, a sensitivity of 87%and a specificity of 65%were obtained. The area under the curve for ICU admission was 0.67 (95%CI: 0.3 to 0.07), p = 0.43; the 5.5 cut-off point showed a sensitivity of 82%and a specificity of 51%.

ConclusionsThe Call Score shows a low performance for predicting mortality and admission to the ICU in Peruvian patients.


title: Anti-nuclear matrix protein 2 antibody-positive idiopathic inflammatory myopathies represent extensive myositis without dermatomyositis-specific rash

abstract:
ObjectiveMyositis-specific autoantibodies (MSAs) define distinct clinical subsets of idiopathic inflammatory myopathies (IIMs). The anti-nuclear matrix protein 2 (NXP2) antibody, a MSA detected in juvenile/adult IIMs, has been reported to be associated with a high risk of subcutaneous calcinosis, subcutaneous edema, and internal malignancies. The study aimed to clarify the clinical features of anti-NXP2 antibody-positive IIMs in detail.

MethodsThis multi-center retrospective observational study on 76 anti-NXP2 antibody-positive patients. The antibody was detected via a serological assay using immunoprecipitation and western blotting. The patients were selected from 162 consecutive Japanese patients with IIMs.

ResultsThe cohort of anti-NXP2 antibody-positive IIMs included 29 juvenile patients and 47 adult patients. Twenty-seven (35.5%) patients presented with polymyositis phenotype without dermatomyositis-specific skin manifestations (heliotrope rash and Gottron sign/papules); this was more common in the adults than children (48.9% vs. 15.8%, P < 0.01). Nine (11.8%) patients had subcutaneous calcinosis, and 20 (26.3%) patients had subcutaneous edema. In addition, the proportion of patients with muscle weakness extending to the distal limbs was high (36 patients [47.4%]) in this cohort. Adult patients had a higher prevalence of malignancy than the general population (age-standardized incidence ratio of malignancies: 22.4).

ConclusionAnti-NXP2 antibody-positive IIMs, which include dermatomyositis sine dermatitis, are characterized by atypical skin manifestations and extensive muscular involvement.

category: rheumatology


title: Knowledge and practices related to menstruation among Lucknow college students in North India: results from cross-sectional survey

abstract:
BackgroundGirls in many low and middle-income countries enter puberty with knowledge gaps and misconceptions about menstruation may lead to unsafe hygienic practices that increase health risk. Despite such importance, educated girls knowledge and hygienic practice towards menstruation are not well addressed in India. Consequently, the present study attempted to assess menstrual hygiene knowledge and practice among college students in Lucknow city in north India.

MethodAn online college-based cross-sectional study design was employed in Lucknow, the capital of Uttar Pradesh in India. Data collection was carried out from September 11 to September 25, 2020, using a google form among undergraduate and Postgraduate students. All variables that were significant at bivariate level (at P-value < 0.05) were entered into multivariate analysis using a logistic regression model to control for confounding factors. In the final model, P-value of less than 0.05 was used as a base to identify factors having a statistically significant association with poor knowledge and hygiene practice at corresponding 95% confidence interval.

ResultsMore than half of students ages of menarche were between 12-15 years, and duration of menses flow was between 3-5 days. The most common premenstrual symptom was abdominal pain (67%) and back pain (50.5%). Majority of the students had first time discussed menstrual problems with their mothers (69.2%). Around 94% of students were currently using a sanitary pad as an absorbent. Regarding cleanliness, about (90.9%) girls clean their genitals after urinating during mensuration. Around 18.9% used medication during menstruation. Multivariate analyses reveal that students of Science and Technology (vs Commerce and Management Students) and monthly family income 50-100 thousand (vs < 25 thousands) were associated with good knowledge about menstruation. In contrast, students fathers were graduates (vs school educated); the occupation was  Other(vs Farmer); living in a nuclear family(vs Joint family) and residing in urban areas(vs Rural) were less likely to have good menstruation knowledge. Besides, good hygiene practices are less likely to have with  Other Religion(vs Hindu), working mother(vs Housewife), monthly family income between 25 to 50 thousand(vs <25 thousands), and Nuclear family(vs Joint family) (p<0.05).

ConclusionsMost college students had poor knowledge but followed hygienic practices correctly. It demonstrates a need to design acceptable awareness creation and advocacy programs to improve college students knowledge during menstruation. Of all the sociodemographic factors, monthly income and types of family influenced students knowledge and practices related to menstruation.

category: sexual and reproductive health


title: Polygenic score for physical activity provides odds for multiple common diseases

abstract:
PurposeIt has been suggested that genetic pleiotropy, in which the same genes affect two or more traits, may partially explain the frequently observed associations between high physical activity (PA) and later reduced morbidity or mortality. However, the evidence about pleiotropy from human studies is limited. This study investigated associations between PA polygenic risk scores (PRSs) and cardiometabolic diseases among the Finnish population.

MethodsPRSs for device-measured overall PA were adapted to a FinnGen study cohort of 218,792 individuals with genome-wide genotyping and extensive digital longitudinal health register data. Associations between PA PRS and body mass index (BMI), diseases, and mortality were analysed with linear and logistic regression models. The number of different disease endpoints varied between 894 and 111,108 in FinnGen cohort.

ResultsA high PA PRS predicted a lower BMI ({beta} -0.025 kg/m2 per one standard deviation (SD) change in PA PRS, SE 0.013, p=1.87x10-80). The PA PRS also predicted a lower risk for diseases that typically develop later in life or not at all among highly active individuals. A lower disease risk was systematically observed for cardiovascular diseases [odds ratio, OR per 1 SD change in PA PRS 0.95, p=9.5*10-19) and, for example, hypertension [OR 0.93, p=2.7*10-44), type 2 diabetes (OR 0.91, p=4.1*10-42), and coronary heart disease (OR 0.95 p=1.2*10-9). Participants with high PA PRS had also lower mortality risk (OR 0.97, p=0.0003). We did not observe statistically significant associations with hypothetical control conditions, such as osteoarthritis and osteoporosis.

ConclusionsGenetically less active persons are at a higher risk of developing cardiometabolic diseases, which may partly explain the previously observed associations between low PA and higher disease and mortality risk. The same inherited physical fitness and metabolism related mechanisms may be associated both with PA levels and with cardiometabolic disease risk.

category: sports medicine


title: Place of preperitoneal pelvic packing in severe pelvic traumatisms: About 20 cases performed in a French military level one trauma center

abstract:
BackgroundThe overall mortality of hemodynamically unstable pelvic fractures is high. Hemorrhage triggers off the Moore lethal triad. Hemostatic management during the golden hour is essential. Combined with pelvic stabilisation, preperitoneal pelvic packing (PPP) is proposed to control venous and bony bleeding, while arterioembolisation can stop arterial bleeding. No international consensus has yet prioritized these procedures. The aim of this study was to analyse a serie of PPP in a military level one trauma center and propose an algorithm for hemodynamically unstable pelvic traumas regardless of the military facility.

MethodFrom January 2010 to December 2020, every patient from our military institution with a hemodynamically unstable pelvic fracture underwent PPP combined with pelvic stabilisation. Before 2012 data were retrospectively collected from database (PMSI), after 2012 data were prospectively recorded in our polytrauma database and retrospectively analysed. The care algorithm applied focused on hemodynamic status of polytraumatised patients on admission. Primary criteria were early hemorrhage-induced mortality (<24h) and overall mortality (<30d). Secondary criteria were systolic blood pressure (SBP) and red blood cells (RBC) units administered.

Results20 patients with a pelvic fracture had a PPP. Mean age was 49,65 +/-23,97 years and median ISS was 49 (31; 67). The decrease of blood transfusion and increase of SBP between pre- and postoperative values were statistically significant. Eight patients (40%) had postoperative arterial pelvic blush and 7 patients were embolised. The early mortality by refractory hemorrhagic shock was 25% (5/20). Overall mortality at 30 days was 50% (10/20).

ConclusionPPP is a quick, easy, efficient and safe procedure. It can control venous, bony and sometimes arterial bleeding. PPP is part of damage control surgery and we propose it in first line. Angio-embolization remains complementary. Besides, PPP is the only means available in precarious conditions of practice, notably in military forward units.

category: surgery


title: Exposure to per- and polyfluoroalkyl substances associates with altered lipid profile of breast milk

abstract:
BackgroundChemical composition of human breast milk is highly variable inter- and intra-individually. Environmental factors are suspected to partly explain the compositional variation, however, their impact on breast milk composition is currently poorly understood.

ObjectivesWe sought (1) to define the impact of maternal exposure to per- and polyfluoroalkyl substances (PFAS) on lipid composition of human breast milk, and (2) to study the combined impact of maternal PFAS exposure and breast milk lipid composition on the growth of the infants.

MethodsIn a mother-infant study (n=44) we measured the levels of PFAS and lipids in maternal serum and conducted lipidomics analysis of breast milk at birth and at 3 months of infant age, by using ultra high performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry. Maternal diet was studied by a validated food frequency questionnaire.

ResultsPFAS levels were inversely associated with total lipid levels in the breast milk collected at birth. In the high exposure group, the ratio of acylated saturated and polyunsaturated fatty acids in triacylglycerols was increased. Moreover, high exposure to PFAS associated with the altered phospholipid composition, which was indicative of unfavorable increase in the size of milk fat globules. These changes in the milk lipid composition were further associated with slower infant growth and with elevated intestinal inflammatory markers.

DiscussionOur data suggest that the maternal exposure to PFAS impacts the nutritional quality of the breast milk, which, in turn, may have detrimental impact on the health and growth of the children later in life.

category: toxicology


title: Evaluation of the Knowledge of University Students in the Health Area About Sexually Transmitted Infections: A Cross-Sectional Study

abstract:
IntroductionSexually transmitted infections (STI) have consequences that negatively affect the populations quality of life and health. Young adults are susceptible to low access to preventive measures and a greater risk behavior risk. The objective was to evaluate and compare STI Knowledge in university students from health courses, a public institution, and a private institution of higher education in Brazil.

Methodsa cross-sectional study conducted in 2019 in Brazil at the FEMA School of Medicine in Assis-SP and the University of the State of Sao Paulo (UNESP) in Marilia in the courses of Physiotherapy, Speech Therapy, and Occupational Therapy, in undergraduate students, over 18 years of age, through a self-applied questionnaire translated and adapted to the Brazilian Portuguese from the STD-KQ - Transmitted Disease Knowledge Questionnaire.

Results462/700 students participated (66.66%) 18-46 years of age (mean 21.46 years, +/- 3.61), 99 men and 363 women. In the private institution, 262/340 (77.06%), and in the public institution, 200/360 (55.55%). The mean age was 22.21 (+/- 4.21) years among men and 21.25 (+/- 3.41) years among women. The mean percentage of the 28 test questions correct answers was 52.07%. The average number of correct responses per student was 17.49 out of 28 possible, 62% (+/- 4.97). The distribution between the groups was normal. In the multiple linear regression model for the percentage of correct answers, adjusted for the confounding variables, the intercept was 55.2. The students of the private institution answered 19,655 questions more than the public one (P<.001), and for each semester of graduation, the students answered 1,628 more questions (P<.001). There were no relevant differences regarding the gender and age of the students.

Conclusionthere are gaps in STI knowledge among university students in the health area. The students of the first semesters of the courses, and, in particular, students from a public educational institution, had a significantly lower performance of the right in the questionnaire applied. Thus, actions to promote STI knowledge and preventive attitudes are necessary among university students.

category: medical education


title: Outcomes of COVID-19 among Patients with End Stage Renal Disease on Remdesivir

abstract:
BACKGROUNDSince the beginning of the COVID-19 pandemic, there has been widespread use of remdesivir in adults and children. There is little known information about its outcomes in patients with severe renal dysfunction or end-stage renal disease who are on hemodialysis.

METHODSA retrospective, multicenter study was conducted on patients with end-stage renal disease on hemodialysis that were discharged after treatment for COVID-19 between April 1st and December 31st, 2020. Primary endpoints were the length of stay, mortality, maximum oxygen requirements along with the escalation of care needing mechanical ventilation. Secondary endpoints included change in C reactive protein, d dimer levels, and disposition.

RESULTSA total of 52 charts were reviewed, of which 28 met the inclusion criteria. 14 patients received remdesivir, and 14 patients did not receive remdesivir. The majority of patients were caucasian, female, with diabetes mellitus and hypertension. The mean age was 65.33 +14.14 years. All the patients in the remdesivir group received dexamethasone as compared to only 30% of patients in the non-remdesivir group. There was no significant difference in C reactive protein, d dimer levels, and disposition between the two groups. Approximately 35% of the patients died, 18% required intensive ventilation, and the mean length of stay was 12.21 days.

DISCUSSIONThe study demonstrated no clinically significant difference in length of stay, maximum oxygen requirements, or mortality in COVID-19 patients with end-stage renal disease in the remdesivir group as compared to the non-remdesivir group. Further studies are needed to study the effects of remdesivir on the renal function and disease course in patients with chronic kidney disease stage 4 or 5 that are not on dialysis.

category: nephrology


title: Classification of Brain Injury Pathophysiology With GFAP and UCH-L1

abstract:
BackgroundBrain injury is pathophysiologically diverse, with many cases presenting with mixed pathologies. Utilizing objective measures to investigate the pathophysiology of injury would aid in understanding prognosis and targeting therapeutics.

ObjectiveThe goal of this study is to develop a traumatic brain injury classification scheme based on open source deep learning computer tomography (CT) analysis and the two serum biomarkers, glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal L1 (UCH-L1).

MethodsMachine learning was utilized to develop a novel algorithm capable of classifying the type of brain injury based on a CT scan analysis algorithm and GFAP and UCH-L1 concentrations. Injury was stratified into one of four groups: spontaneous hemorrhage, oxygen deprivation, trauma resulting in vascular injury or high-velocity trauma with negative CT scan.

Outcomes100 research subjects were enrolled. Using a combination of CT analysis and serum markers, the subjects with CT positive trauma were distinguishable from those with spontaneous hemorrhage, ischemic injury, CT negative trauma and controls with AUCs of 0.96, 0.99., 0.98 and 1.00 respectively. Ischemic injury was distinguishable from CT positive trauma with an AUC of 0.98. All forms of brain injury could be distinguished from controls with AUC = 1.00.

DiscussionAn open source algorithmic CT scan analysis algorithm and serum biomarkers accurately classified the nature of brain injury across major etiologies. Further implementation of such algorithms and addition of other objective measures will enable better prognostication of injury and improved development of therapeutics.

category: neurology


title: Machine Learning with Objective Serum Markers and Algorithmic Deep Learning Computed Tomography Scan Analysis for Classification of Brain Injury


title: Cerebrospinal fluid hemoglobin drives subarachnoid hemorrhage-related secondary brain injury

abstract: Secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH-SBI) is a significant contributor to poor outcomes in patients after rupture of an intracranial aneurysm. The lack of diagnostic biomarkers and novel drug targets represent an unmet need. Prior experimental evidence has suggested cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) as a pathophysiological driver of SAH-SBI. The aim of this study was to investigate the clinical and pathophysiological association between CSF-Hb and SAH-SBI. We prospectively enrolled 47 consecutive patients and collected daily CSF samples within 14 days after aneurysm rupture. There was very strong evidence for a positive association between CSF-Hb and SAH-SBI. The diagnostic accuracy of CSF-Hb for SAH-SBI markedly exceeded that of established methods (area under the curve: 0.89 [0.85-0.92]). Temporal LC-MS/MS CSF proteomics demonstrated that erythrolysis accompanied by an adaptive macrophage response are the two dominant biological processes occurring in the CSF space after aneurysm rupture. To further investigate the pathophysiology between CSF-Hb and SAH-SBI, we explored the vasoconstrictive and lipid peroxidation activities of Hb ex-vivo. These experiments revealed critical inflection points overlapping CSF-Hb concentration thresholds in patients with SAH-SBI. Selective Hb depletion and in-solution neutralization by the Hb-scavenger haptoglobin or the heme-scavenger hemopexin efficiently attenuated the vasoconstrictive and lipid peroxidation activities of CSF-Hb in patient CSF. Collectively, the clinical association between high CSF-Hb levels and SAH-SBI, the underlying pathophysiological rationale, and the favorable effects of haptoglobin and hemopexin in ex-vivo experiments position CSF-Hb as a highly attractive biomarker and potential drug target.


title: Relating resting EEG power spectra to age-related differences in cognitive performance: An observational pilot study.

abstract:
BackgroundPrevious research has shown the slope of the EEG power spectrum differentiates between older and younger adults in various experimental cognitive tasks. Here, we extend that work, assessing the relation between the EEG power spectrum and performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a widely-used neuropsychological instrument that assesses a broad range of cognitive domains.

MethodsForty-four participants (21 younger adults, 23 older adults) completed the RBANS with EEG data collected at-rest. Using spectral parameterization, we tested the mediating effect of the spectral slope on age-related differences in subsequent cognitive task performance.

ResultsOlder adults performed reliably worse on the RBANS overall, and on the Attention and Delayed Memory domains. However, evidence of mediation was only found for the Coding subtest, a measure of information processing speed.

ConclusionsWe found some evidence that the slope of the resting EEG power spectrum mediated age-related differences in cognition. These effects were evident only in tasks requiring speeded processing, whereas this effect was not statistically significant for delayed memory, even though age-related differences were present.


title: Resting EEG spectral slopes are associated with age-related differences in information processing speed


title: Scoping Review of Existing Stroke Guidelines; Argument for a Value-Added Change

abstract:
Background and PurposeStroke represents one of the most important causes of morbidity ( eighty million patients with disabling of ongoing effects of stroke at a given time, globally) and mortality (the second leading cause of death) worldwide. Innovative systems biology-based approach is likely to increase the understanding of the underpinning of acute stroke promise to enhance stroke prevention, acute treatment, and neurorehabilitation. Recent growing body of evidence with shared pathobiology with COVID-19 and the critically important role of inflammation in the context of stroke points to far-reaching consequences of acute stroke, just as in the case of COVID-19 ( post-acute event issues as well as long term issues).

So far, stroke typically defined by late-appearing disease manifestation by the range of stroke subtypes as defined by the WHO or American Stroke Association. This definition neglects the underlying pathobiological mechanisms such as low-grade chronic inflammation and already compromised vascular system. Diseases such as stroke is hardly a simple result of a single problem, but rather a complex cascade of pathobiological processes and interactions in a complex biochemical environment. The evidence of changes in innate immunity and adaptive immunity during the index event of acute stroke and recovery over next 3-12 months can be easily elicited with simple bedside blood tests such as neutrophil-lymphocyte ratio (NLR) with well over 300 published papers including several systematic reviews and meta-analyses confirming this. Global standard operating procedures (SOP) of stroke care dictated by the national and international stroke guidelines at present. It is imperative to explore the evidence of systems biology approach in current stroke guidelines. This is likely to be a key turning point in managing stroke across the continuum (prevention, management of acute event and rehabilitation).

MethodsWe systematically searched for guideline recommendation on the day-to-day use of peripheral inflammatory markers such as NLR published in the English language between January 1, 2005, and December 2020. Any other evidence of systems biology-based approach or recommendation was explored within the selected guidelines for this scoping review. Only the latest guideline per writing group was selected. Each guideline was analyzed independently by 2 to 4 authors to determine clinical scenarios explained/given, scientific evidence used, and recommendations presented in the context of systems biology.

ResultsThe scoping review found 3,830 (3830) titles with 119 guidelines from 46 countries included for this review ( Figure 1; PRISMA diagram). Stroke-related organizations wrote Sixty-five per cent of the guidelines while national ministries wrote a fewer number of guidelines. We were primarily interested in recommendations for acute management in AIS published in the English language. Fifteen eligible guidelines were identified from 15 different countries/regions. None of the guidelines recommended the routine use of peripheral markers of inflammation, such as NLR, among their acute assessment and management recommendations. None of the existing guidelines explored the systems biology approach to one of the most complex diseases affecting the human brain, stroke.

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/21251660v1_fig1.gif" ALT="Figure 1">
View larger version (23K):
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O_FIG O_LINKSMALLFIG WIDTH=194 HEIGHT=200 SRC="FIGDIR/small/21251660v1_fig2.gif" ALT="Figure 2">
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org.highwire.dtl.DTLVardef@53a03aorg.highwire.dtl.DTLVardef@3c62e1org.highwire.dtl.DTLVardef@7fc9e7org.highwire.dtl.DTLVardef@1a08d29_HPS_FORMAT_FIGEXP  M_FIG O_FLOATNOFigure 2:C_FLOATNO PRISMA Diagram

C_FIG ConclusionsThis systematic review has identified a significant evidence-practice gap in all existing national stroke guidelines published in English medium as of October 2020. These guidelines included the only current "living stroke guidelines, Stroke Guidelines from Australia with a real opportunity to modernize the living stroke guidelines with systems biology approach and provide 2020 vision towards better stroke care globally.

Investigation of complex disease such as stroke is best served through a systems biology approach. One of the easiest places to start is simple blood tests such as total white cell count and NLR. Systems biology approach point us towards simple tools such immune-inflammatory index (SII), Sunshine Prognostic Score (SPS) which should pave the way for the stroke physician community address the challenges in systems biology approach in stroke care. These challenges include translating bench research to the bedside, managing big data ( continuous pulse, blood pressure, sleep, Oxygen saturation, progressive changes in NLR, SII, SPS, etc.). Working with an interdisciplinary team is also provide a distinct advantage.


title: Timely referral for advanced therapy in Parkinsons disease. Development of a screening tool

abstract:
ObjectivesTo develop a screening tool for timely referral for advanced therapy (AT) in patients with Parkinsons disease (PD), and to compare the newly-developed tool with the published 5-2-1 criteria.

DesignCross-sectional, diagnostic, observational study and multivariable logistic regression analysis for item selection.

Setting8 hospitals in the Northern part of the Netherlands situated in the catchment area of a specialized movement disorder centre.

Participants259 consecutive PD patients not yet on AT visiting the outpatient clinic of participating hospitals from February 2017 to July 2018.

Predictors24 patient and disease characteristics as assessed by the treating neurologists, and scores on the NMS questionnaire.

OutcomeApparent eligibility for referral for AT based on consensus by a panel of 5 experts in the field of AT.

Results17 patients were deemed eligible for referral for AT (point prevalence: 6.6%). Presence of response fluctuations and troublesome dyskinesias were the strongest independent predictors of being eligible for referral. Both variables were included in the final model, as well as levodopa equivalent daily dose. Decision curve analysis showed that the new model outperformed the 5-2-1 criteria. A simple chart was constructed to provide guidance for referral. Discrimination of this simplified scoring system was good (AUC after bootstrapping: 0.97).

ConclusionThe screening tool may improve efficiency of referral and subsequent treatment with AT in patients with PD. External validation is required prior to application in daily practice.

Anyone who wishes to share, reuse, remix, or adapt this material must obtain permission from the corresponding author.


title: Returning to nursing during the COVID-19 pandemic: experiences and needs of re-entering nurses

abstract:
AimAssessing the needs and experiences of re-entering nurses during the COVID-19 pandemic.

BackgroundDuring the COVID-19 outbreak in the Netherlands, thousands of former nurses have returned to nursing to support healthcare staff. After a period of absence and with little time to prepare, these former nurses re-entered during a challenging, uncertain and rapidly evolving pandemic. Little is known about the experiences and needs of these re-entering nurses.

DesignQualitative study

MethodsWe conducted semi-structured interviews with 20 purposively selected nurses who had re-entered nursing during the first wave of the COVID-19 pandemic in the Netherlands. Interviews were transcribed verbatim and analysed via thematic content analysis. This study followed the COREQ guidelines.

ResultsParticipants mentioned that a lack of a clear job description led to unclarity about the kind of tasks that re-entering nurses were expected and allowed to perform. This unclarity was especially notable in the newly established COVID-19 departments. Re-entering nurses mentioned to wish for an easily accessible mentorship structure and an individualised and practical training program. Re-entering nurses felt supported by a positive team dynamic, which was shaped by the sense of urgency and relevance of their work and helped them deal with stressful experiences.

ConclusionThe results indicate that a rapid and safe return to nursing during a pandemic could be facilitated by: a clear description of roles and responsibilities; an individualised assessment determining the competences and knowledge disparities of re-entering nurses; practical training focussing on competencies needed during a pandemic; and a collaborative mentorship structure to guide re-entering nurses.

Relevance to clinical practiceThe rapid recruitment of former nurses to mitigate an acute shortage of qualified nurses could play a vital role during a pandemic. To deploy these nurses effectively, safely and sustainably, it is important to address the needs of these re-entering nurses.

What does this paper contribute towards the wider global clinical community?O_LIThis research showed the need to prepare a flexible individualised training programme which could support re-entering nurses during crisis situations, such as a pandemic.
C_LIO_LIA responsive mentorship structure helps to provide support to re-entering nurses in a dynamic, uncertain and rapidly evolving situation.
C_LIO_LIIn a rapidly evolving situation, it is essential to continue to create clarity about the roles and responsibilities of re-entering nurses.
C_LI

category: nursing


title: Association of Germline BRCA Pathogenic Variants with Diminished Ovarian Reserve: A Meta-Analysis of Individual Patient-Level Data.

abstract:
PurposeTo determine whether germline BRCA pathogenic variants (gBRCA) are associated with decreased ovarian reserve.

Materials and MethodsAn individual patient-data meta-analysis was performed using 5 datasets on 828 evaluable women who were tested for gBRCA. Of those, 250 carried gBRCA while 578 had tested negative and served as controls. Of the women with gBRCA, four centers studied those affected with breast cancer (n=161) and one studied unaffected individuals (n=89). The data were adjusted for the center, age, body mass index, smoking and oral contraceptive pill use before the final analysis. Anti-mullerian hormone (AMH) levels in affected women were drawn before pre-systemic therapy.

ResultsMean ages of women with vs. without gBRCA1/2 (34.1{+/-} 4.9 vs. 34.3{+/-} 4.8 years; p=0.48), and with gBRCA1 vs gBRCA2 (33.7{+/-} 4.9 vs. 34.6{+/-} 4.8 years; p=0.16) were similar. After the adjustments, women with gBRCA1/2 had significantly lower AMH levels compared to controls (23% lower; 95% CI: 4-38%, p=0.02). When the adjusted analysis was limited to affected women (157 with gBRCA vs. 524 without, after exclusions), the difference persisted (25% lower; CI: 9-38%, p=0.003). The serum AMH levels were lower in women with gBRCA1 (33% lower; CI: 12-49%, p=0.004) but not gBRCA2 compared to controls (7% lower; CI: 31% lower to 26% higher, p=0.64).

ConclusionsYoung women with gBRCA pathogenic variants, particularly of those affected and with gBRCA1, have lower serum AMH levels compared to controls. They may need to be preferentially counselled about the possibility of shortened reproductive lifespan due to diminished ovarian reserve.

ContextO_ST_ABSKey objectiveC_ST_ABSDNA repair deficiency is emerging as a joint mechanism for breast cancer and reproductive aging. Recent studies showed that ovarian reserve maybe lower in women with BRCA pathogenic variants (gBRCA) due to DNA repair deficiency. However, clinical studies using the most sensitive serum ovarian reserve marker Anti-Mullerian-Hormone (AMH) provided mixed results. Given the heterogeneity of the data from clinical studies, we performed an individual patient data (IPD) meta-analysis to determine if gBRCA are associated with lower ovarian reserve.

Knowledge generatedgBRCA are associated with diminished ovarian reserve, as determined by serum AMH and this association is restricted to gBRCA1. This finding is firmer for affected women as this IPD meta-analysis predominantly studied those with breast cancer.

RelevanceWomen with gBRCA may have shortened reproductive life span due to diminished ovarian reserve and should be proactively counseled for fertility preservation especially if faced with chemotherapy or delaying childbearing.

category: obstetrics and gynecology


title: Efficacy of Wang Nam Yen herbal tea on human milk production: A randomized controlled trial

abstract:
BackgroundInsufficient milk production is a common problem affecting breastfeeding women, in particular following Cesarean delivery. Wang Nam Yen herbal tea is a promising traditional Thai medicine used by postpartum women to stimulate milk production, as an alternative to pharmaceutical galactagogues. We aimed to compare the efficacy of Wang Nam Yen herbal tea, domperidone, and placebo, in increasing milk production in mothers who underwent Cesarean delivery.

MethodsWomen who underwent uncomplicated cesarean delivery at Sunpasitthiprasong Hospital were randomized into three groups. The participants received the treatments daily for three consecutive days. The primary outcome was breast milk volume at 72 hours after delivery. Secondary outcomes were pregnancy and neonatal outcomes, adverse events, and participant satisfaction.

ResultsOf the 1,450 pregnant women that underwent cesarean delivery, 120 women were enrolled. Their mean age and gestational ages were 28.7 years and 38.4 weeks, respectively. Breast milk volume at 72 hours postpartum was significantly different among the three groups (p = 0.030). The posthoc Bonferroni correction indicated a significant difference in breast milk volume between Wang Nam Yen herbal tea group and placebo control group (p = 0.007) while there was no difference between Wang Nam Yen herbal tea group and domperidone group (p = 0.806) and between domperidone group and placebo control group (p = 0.018). There was no difference in pregnancy and neonatal outcomes, adverse events, and participant satisfaction among the three groups.

ConclusionWang Nam Yen herbal tea was effective in augmenting breast milk production at 72 hours postpartum in mothers following cesarean delivery, and there was no evidence that herbal tea and domperidone differed in terms of augmenting breast milk production.

Trial registrationThe study was approved by the institutional review board of Sunpasithiprasong Hospital (No.061/2559) and was registered TCTR20170811003 with the Thai Clinical Trial Registry.


title: Distinct gut and vaginal microbiota profile in women with Recurrent Implantation Failure and Unexplained Infertility

abstract:
BackgroundImplantation failure limits the success rate of natural and in vitro fertilization (IVF)-assisted conceptions. Evidence suggests dysbiosis in the female reproductive tract impacts implantation failure. However, whether gut dysbiosis influences implantation failure and whether it accompanies reproductive tract dysbiosis remains unexplored.

MethodWe recruited 11fertile women as the controls, and a cohort of 20 women diagnosed with implantation-failure associated infertility, which included 10 women diagnosed with recurrent implantation failure (RIF), and 10 women diagnosed with unexplained infertility (UE). Using next-generation amplicon sequencing, we compared the diversity, structure, and composition of fecal and vaginal bacteria of the controls with that of the infertile cohort. While we sequenced fecal samples of all the participants (n=31), we could only sequence 8 vaginal samples in each group (n=24).

ResultsCompared with the controls, -diversity of the gut bacteria, analysed by Chao 1 and Shannon indices, among the infertile groups declined (p{square}<{square}0.05). {beta}-diversity between the controls and infertile cohort, measured by both Bray-Curtis and Jaccard distances, differed significantly (p{square}<{square}0.05). Taxa analysis of the gut bacteria revealed enrichment of Gram-positive bacteria, mainly of the phylum Firmicutes, in the RIF group. In contrast, Gram-negative bacteria were relatively more abundant in the UE group. Additionally, mucus-producing bacteria genera such as Prevotella and Sutterella declined in the infertile cohort (p{square}<{square}0.05). Intriguingly, significant enrichment (p{square}<{square}0.05) of the genus Hungatella, associated with trimethylamine N-oxide (TMAO) production, occurred in the infertile cohort. Vaginal microbiota was dominated by L. iners across the groups, with the UE group showing the highest levels. Of the three groups, the RIF group had the least diverse vaginal microbiota. Taxa analysis showed higher levels of anaerobic bacteria such as Leptotrichia, Snethia, and Prevotella in the controls.

ConclusionWe posit that in the setting of the compromised gut mucosal barrier, the phyla Firmicutes generates TNF--driven systemic inflammation, leading to RIF, whereas an overload of Gram-negative bacteria induces IL-6-driven systemic inflammation, leading to UE. Additionally, Hungatella-induced elevation of TMAO levels causes platelet hypercoagulability, synergistically contributing to implantation failure. Finally, vaginal dysbiosis does not appear to co-occur with gut dysbiosis.


title: Workplace measures against COVID-19 during the winter third wave in Japan: company size-based differences

abstract:
ObjectivesLittle is known about workplace measures against coronavirus disease 2019 (COVID-19) in Japan after the first state of emergency period, especially in micro-, small-, and medium-sized enterprises (MSMEs). This study aimed to provide an overview of the current situation of anti-COVID-19 measures in Japanese enterprises, considering company size.

MethodsThis study was an Internet-based nationwide cross-sectional study. Data were collected using an online self-administered questionnaire in December 2020 during the third wave of COVID-19. The chi-squared test for trend was performed to calculate the p-value for trend for each workplace measure across company sizes.

ResultsFor the 27,036 participants, across company sizes, the most prevalent workplace measure was encouraging mask wearing at work, followed by requesting that employees refrain from going to work when ill and restricting work-related social gatherings and entertainment. These measures were implemented by approximately 90% of large-scale enterprises and by more than 40% of micro- and small-scale enterprises. In contrast, encouraging remote working and restricting eating and drinking at personal workspaces were implemented by less than half of large-scale enterprises and by around 15% of micro- and small-scale enterprises. There were statistically significant differences in all workplace measures by company size (all p-values < .001).

ConclusionsWe found that various responses to COVID-19 had been taken in workplaces. However, some measures, including remote working, were still not well implemented, especially in smaller enterprises. The findings suggest that occupational health support for MSMEs is urgently needed to mitigate the current wave of COVID-19.

category: occupational and environmental health


title: Evaluation of Facial Protection Against Close-Contact Droplet Transmission

abstract:
BackgroundFace shields are used as an alternative to facemasks, but their effectiveness in mitigating the spread of SARS-CoV-2 is unclear. The goal of this study is to compare the performance of face shields, surgical facemasks, and cloth facemasks for mitigation of droplet transmission during close contact conditions.

MethodsA novel test system was developed to simulate droplet transmission during close contact conditions using two breathing headforms (transmitter and receiver) placed 4 feet apart with one producing droplets containing a DNA marker. Sampling coupons were placed throughout the test setup and subsequently analyzed for presence of DNA marker using quantitative PCR.

ResultsAll PPE donned on the transmitter headform provided a significant reduction in transmission of DNA marker to the receiver headform: cloth facemask (78.5%), surgical facemask (89.4%), and face shield (96.1%). All PPE resulted in increased contamination of the eye region of the transmitter headform (9,525.4% average for facemasks and 765.8% for the face shield). Only the face shield increased contamination of the neck region (207.4%), with the cloth facemask and surgical facemask resulting in reductions of 85.9% and 90.2%, respectively.

ConclusionsThis study demonstrates face shields can provide similar levels of protection against direct droplet exposure compared to surgical and cloth masks. However, all PPE tested resulted in release of particles that contaminated surfaces. Contamination caused by deflection of the users exhalation prompts concerns for contact transmission via surfaces in exhalation flow path (e.g., face, eyeglasses, etc.).


title: Prostate cancer screening in hospitalized patients: Results from the Nationwide Inpatient Sample

abstract:
BackgroundProstate cancer (PCa) is the most common non-skin cancer in American men. The aim of the study was to determine the nationwide prevalence, trends, and predictors of inpatient PCa screening encounters in patients with average risk of PCa using the National Inpatient Sample (NIS) database.

MethodsThe NIS database from 2006 to 2014 was used to evaluate PCa screening among hospitalized patients in the United States (US). All hospitalized male patients between the ages of 45 and 69 at average risk for PCa were included. The outcome was whether a patient had an encounter for prostate cancer as noted on their discharge record. Variables analyzed included demographic factors, hospital characteristics, and other concomitant diagnoses for prostate or male urinary problems.

ResultsThe prevalence of inpatient PCa screening was 2.57 per 100,000 hospital discharges. In a multivariate setting, the following were significant factors associated with greater odds of inpatient PCa screening: Medicare (AOR: 3.07; P = 0.0016), Self-Pay or Uninsured patients (AOR: 1.74; P = 0.0371), rural (AOR: 11.9; P = < 0.0001) or urban nonteaching hospitals (AOR: 5.26; P = < 0.0001), receiving care in the Midwest (AOR: 4.90; P = < 0.0001), a diagnosis for urinary tract infections (P = 0.0367), genitourinary symptoms (P < 0.0001), hyperplasia of prostate (P = 0.0006), or other male genital disorder (P < 0.0001).

ConclusionAccording to current cancer screening guidelines, PSA screening should include shared decision making between physicians and patients. In light of unequal access to quality healthcare, there exist disparities in uninsured and rural patients for cancer screening. Screening tools such as prostate specific antigen (PSA) are minimally invasive modalities in the inpatient setting that can help screen individuals at increased risk for the development of prostate cancer, allowing for early detection, prevention, improved rates of cure and ultimately, decreased rates of mortality.

category: oncology


title: Patient and physician shared decision making behaviors in oncology: Evidence on adequate measurement properties of the iSHARE questionnaires

abstract:
ObjectivesWe have developed two questionnaires to assess the shared decision making (SDM) process in oncology; the iSHAREpatient and iSHAREphysician. In this study, we aimed to determine: scores, construct validity, test-retest agreement (iSHAREpatient), and inter-rater (iSHAREpatient-iSHAREphysician) agreement.

MethodsPhysicians from seven Dutch hospitals recruited cancer patients, and completed the iSHAREphysician and SDM-Questionnaire-physician version. Their patients completed the: iSHAREpatient, 9-item SDM-Questionnaire, Decisional Conflict Scale, Combined Outcome Measure for Risk communication And treatment Decision making Effectiveness, and Perceived Efficacy in Patient-Physician Interactions. We formulated, respectively, one (iSHAREphysician) and 10 (iSHAREpatient) a priori hypotheses regarding correlations between the iSHARE questionnaires and questionnaires assessing related constructs. To assess test-retest agreement patients completed the iSHAREpatient again 1-2 weeks later.

ResultsIn total, 151 treatment decision making processes with unique patients were rated. Dimension and total iSHARE scores were high both in patients and physicians. The hypothesis on the iSHAREphysician and 9/10 hypotheses on the iSHAREpatient were confirmed. Test-retest and inter-rater agreement were >.60 for most items.

ConclusionsThe iSHARE questionnaires show high scores, have good construct validity, substantial test-retest agreement, and moderate inter-rater agreement.

Practice implicationsResults from the iSHARE questionnaires can inform both physician- and patient-directed efforts to improve SDM in clinical practice.


title: RNA expression classifiers from a model of breast epithelial cell organization to predict pathological complete response in triple negative breast cancer

abstract:
Pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is correlated with better outcomes for breast cancer, especially for triple negative breast cancer (TNBC). We developed RNA expression classifiers from a model of breast epithelial cell organization to predict which patients will achieve pCR to NAC, and which will have residual disease (RD). An exclusive collection of retrospective formalin-fixed, paraffin-embedded (FFPE) pretreatment biopsies from 222 multi-institutional breast cancer patients treated with NAC, including 90 TNBC patients, were processed using standard procedures. A novel strategy using machine learning algorithms and statistical cross-validation were used to develop predictive classifiers based on AmpliSeq differential gene expression analysis of patient samples. Two RNA expression classifiers of 18 genes and 15 genes applied sequentially to the total cohort, classified patients into three distinct classes which accurately identified 83.75% of pCR and 86.62% of RD patients in the total population, and 92.10% of pCR and 80.77% of RD patients in the TNBC subset. This new approach identified a subset of TNBC patients predicted to have RD showing significantly higher levels of Ki-67 expression and having significantly poorer survival rates than the other TNBC patients. Stratification of patients may allow identification of TNBC patients with the worst prognosis prior to NAC, allowing for personalized treatments with the potential to improve patient outcomes.

Statement of SignificanceStratification of TNBC patients by prognosis prior to NAC, may allow for more personalized treatment approaches with the potential to improve patient outcomes and reduce toxicity.


title: Risk of Corona virus disease 2019 (COVID-19) among spectacles wearing population of Northern India

abstract:
IntroductionSevere Acute Respiratory Syndrome Corona virus-2 (SARS-CoV-2) spread mainly through respiratory droplets and contact routes. Long term use of spectacles may prevent repeated touching and rubbing of the eyes. Aim of the study is to find out the protective effectiveness of the spectacles against COVID-19, if present.

ObjectivesTo know the association between infection with SARSCoV-2 and wearing of spectacles.

Materials and methodsIn this study, 304 patients of Corona virus disease 2019 (COVID-19) were selected. Their spectacles wearing behaviour were assessed through a questionnaire. Spectacles wearing behaviour of general population were obtained from older studies (for comparison). Data was put in the tabulate form and Chi- Square test was used for statistical analysis.

ResultsIn this study, among the 304 total patients, 58 patients showed the behavior of using spectacles continuously during day time and always on outdoor activities. While the spectacles wearing behaviour is about 40% among general Indian population. The protective effectiveness of the spectacles was found statistically significant (p-value. 00113).

ConclusionThe present study showed that the occurrence of Covid-19 was less in spectacles wearing population than the population not wearing those. The nasolacrimal duct may be a route of virus transmission from conjunctival sac to the nasopharynx.

category: ophthalmology


title: Potential Association of Mitochondrial Haplogroups and A8860G Mutation with Breast Cancer Risk

abstract: The last decade has witnessed great progresses regarding the molecular basis of breast cancer with discovery of different nuclear susceptibility genes; in addition investigations and researches regarding mitochondrial DNA (mtDNA) mutations in breast cancer have been started. Mitochondrial haplogroup determinants (single nucleotide polymorphism SNP) and somatic mitochondrial mutations have recently been studied as possible risk factors for carcinogenic processes in different tissues, hence in order to identify breast cancer related SNPs and haplogroups among the population of Sulaimaniyah city/Iraq, the entire mitochondrial genome of 20-breast cancer samples and comparable controls were sequenced. Haplogrep 2.0 was used for haplogroup identification; Chi-square and Fishers exact test were applied to assess relational significance. HV haplogroup in the cancer samples appeared to be a risk factor for breast cancer compared to the most common H haplogroup in control samples with a p-values of 0.002 and 0.006 respectively and an Odd Ratio (OR) = 28.00. Besides, SNP (A8860G) was also identified as a risk factor for breast cancer as compared to other randomly selected SNPs (A750G, A1438G and C7028T) with p values {square}0.05 and OR >1.

category: genetic and genomic medicine


title: Towards a gene-level map of resilience to genetic variants associated with autism

abstract: While over a hundred genes are significantly associated with autism, little is known about the prevalence of variants affecting them in the general population. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Using data from more than 13,000 autistic individuals and 210,000 undiagnosed individuals, we provide a gene-level map of the odds ratio for autism associated to rare loss-of-function (LoF) variants in 185 genes robustly associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the phenotype of undiagnosed individuals heterozygous for such variants and show that they exhibit a decrease in fluid intelligence, qualification level and income, and an increase in material deprivation. These effects were larger for LoFs in autism-associated genes than in other LoF-intolerant genes and appeared largely independent of sex and polygenic scores for autism. Using brain imaging data from 21,049 UK-Biobank individuals, we provide evidence for smaller cortical surface area and volume among carriers of LoFs in genes with high odds ratios for autism. Our gene-level map is a key resource to distinguish genes with high and low odds ratio for autism, and highlights the importance of including quantitative data on both diagnosed and undiagnosed individuals to better delineate the effect of genetic variants beyond the categorical diagnosis. Data are available at https://genetrek.pasteur.fr/.


title: Sub-diagnostic effects of genetic variants associated with autism