title: A Sliding Window Approach to Optimize the Time-varying Parameters of a Spatially-explicit and Stochastic Model of COVID-19

abstract: The implementation of non-pharmaceutical public health interventions can have simultaneous impacts on pathogen transmission rates as well as host mobility rates. For instance, with SARS-CoV-2, masking can influence host-to-host transmission, while stay-at-home orders can influence mobility. Importantly, transmission rates and mobility patterns can influence pathogen-induced hospitalization rates. This poses a significant challenge for the use of mathematical models of disease dynamics in forecasting the spread of a pathogen; to create accurate forecasts in spatial models of disease spread, we must simultaneously account for time-varying rates of transmission and host movement. In this study, we develop a statistical model-fitting algorithm to estimate dynamic rates of SARS-CoV-2 transmission and host movement from geo-referenced hospitalization data. Using simulated data sets, we then test whether our method can accurately estimate these time-varying rates simultaneously, and how this accuracy is influenced by the spatial population structure. Our model-fitting method relies on a highly parallelized process of grid search and a sliding window technique that allows us to estimate time-varying transmission rates with high accuracy and precision, as well as movement rates with somewhat lower precision. Estimated parameters also had lower precision in more rural data sets, due to lower hospitalization rates (i.e., these areas are less data-rich). This model-fitting routine could easily be generalized to any stochastic, spatially-explicit modeling framework, offering a flexible and efficient method to estimate time-varying parameters from geo-referenced data sets.

category: public and global health


title: Administration approaches of nursing assistants in hospitals: a scoping review

abstract:
ObjectivesAdministration of nursing assistants is closely associated with patient outcomes, but the current circumstances are tough and need improvement. There was limited research evaluating the intrahospital administration of nursing assistants, and there is a lack of available systematic reviews of the area. The aim of this article was to identify and synthesize the literature on intrahospital nursing assistants administration approaches.

DesignScoping review.

Search strategyWe searched PubMed, Embase, APA PsycInfo, Wanfang Med, SinoMed, CINAHL, Ovid Emcare, Scopus, ProQuest, CNKI, NICE, AHRQ, CADTH, JBI EBP and Cochrane DSR for English and Chinese language articles published between January 2011 and March 2022. Publications on administration approaches, models and appraisal tools of nursing assistants in hospitals, including qualitative, quantitative, mix-methods studies and evidence syntheses, were considered eligible.

Results36 eligible studies were included for the review with an acceptable quality. We identified one administration model, nine administration methods, fifteen educational programmes and seven appraisal tools from the included studies. The frequency effect size analysis yielded 15 topics of main focus at four levels, whilst suggesting that the previous articles were mostly (33%) focused on the competency of nursing assistants, and the lectures were the most (80%) used strategy in quality improvement projects. The evidence-based quality of the original studies was considerably low, indicating the huge gaps between the evidence-based research and the management practice.

ConclusionsA series of practical intrahospital administration approaches was revealed, and fifteen mostly focused topics were identified. We need probe more thoroughly in this area, based more on effective management theories and frameworks, and employing methods of higher quality. This scoping review will help managers find more effective methods to improve the quality of care. Researchers may focus more on evidence-based nursing skills and methods in nursing assistant administration using the 15 topics as breakthrough points.

Strengths and limitationsO_LIFirst scoping review of practical administration approaches for nursing assistants in hospitals.
C_LIO_LIPresenting the main topics and focus of related articles.
C_LIO_LIDevelopment of the nursing assistant administration was widely varied among countries.
C_LIO_LIMost of the included studies were of moderate-to-low methodological quality, and huge gap exists between the evidence-based research and the management practice.
C_LI

category: nursing


title: Where the truth really lies: Listening to voices from African American communities in the Southern States about COVID-19 vaccine information and communication

abstract:
BackgroundHigh uptake of COVID-19 vaccine is one of the most promising measures to control the pandemic. However, some African American (AA) communities exhibit vaccination hesitancy due to mis-or dis-information. It is important to understand the challenges in accessing reliable COVID-19 vaccine information and to develop feasible health communication interventions based on voices from AA communities.

MethodsWe conducted two focus group discussions (FGDs) among 18 community leaders recruited from three counties in South Carolina on October 8 and October 29, 2021. The FGDs were conducted online via Zoom meetings. The FGD data were managed and thematically analyzed using QSR NVivo 12 software.

ResultsParticipants (73% female and 61% between the ages of 18 and 30) worked primarily in colleges (55.5%), churches (39%), and health agencies (5.5%). We found that challenges of accessing reliable COVID-19 vaccine information in AA communities primarily included structural barriers, information barriers, and lack of trust. Community leaders recommended recruiting trusted messengers, using homecoming events, football games, and other social events to reach target populations and conducting health communication campaigns through open dialogue among stakeholders.

ConclusionHealth communication interventions on COVID-19 vaccine uptake should be grounded in ongoing community engagement, trust-building activities, and transparent communication about vaccine development. Tailoring health communication interventions to different groups may help reduce misinformation spread and thus promote vaccination in AA communities in the Southern States.

category: infectious diseases


title: Vaccine effectiveness of two and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong

abstract:
BackgroundHong Kong maintained extremely low circulation of SARS-CoV-2 until a major community epidemic of Omicron BA.2 starting in January 2022. Both mRNA BNT162b2 (BioNTech/Fosun Pharma) and inactivated CoronaVac (Sinovac) vaccines are widely available, however coverage has remained low in older adults. Vaccine effectiveness in this predominantly infection-naive population is unknown.

MethodsWe used individual-level case data on mild/moderate, severe/fatal and fatal hospitalized COVID-19 from December 31, 2021 to March 8, 2022, along with census information and coverage data of BNT162b2 and CoronaVac. We used a negative binomial model, adjusting for age and calendar day to estimate vaccine effectiveness of one, two and three dose schedules of both vaccines, and relative effectiveness by number of doses and vaccine type.

FindingsA total of 12.7 million vaccine doses were administered in Hong Kongs 7.3 million population, and we analyzed data from confirmed cases with mild/moderate (N=5,474), severe/fatal (N=5,294) and fatal (N=4,093) COVID-19. Two doses of either vaccine protected against severe disease and death, with higher effectiveness among adults [≥]60 years with BNT162b2 (VE: 88.2%, 95% confidence interval, CI: 84.4%, 91.1%) compared to CoronaVac (VE: 74.1%, 95% CI: 67.8%, 79.2%). Three doses of either vaccine offered very high levels of protection against severe outcomes (VE: 98.1%, 95% CI: 97.1%, 98.8%).

InterpretationThird doses of either BNT162b2 or CoronaVac provide substantial additional protection against severe COVID-19 and should be prioritized, particularly in older adults who received CoronaVac primary schedules. Longer follow-up is needed to assess persistence of different vaccine platforms and schedules.

FundingCOVID-19 Vaccines Evaluation Program, Chinese Center for Disease Control and Prevention


title: Socioeconomic status and immune aging in older US Adults in the Health and Retirement Study

abstract:
BackgroundLife course socioeconomic and demographic factors including educational attainment, race and ethnicity, and childhood (SES) are very powerful predictors of large inequalities in aging, morbidity, and mortality. Immune aging, including accumulation of late-differentiated, senescent-like lymphocytes and lower level of naive lymphocytes, may play a role in the development of the age-related health inequalities. However, there has been little research investigating association between socioeconomic status and immune aging, particularly age-related changes in lymphocyte percentages.

MethodsThis study used nationally representative data from more than 9000 US adults from the Health and Retirement Study to investigate associations between educational attainment, race and ethnicity, and childhood SES and lymphocyte percentages.

ResultsRespondents with lower educational attainment, Hispanic adults, and those who had a parent with less than high school education had lymphocyte percentages consistent with more highly accelerated immune aging compared to those with greater educational attainment, non-Hispanic White adults, and respondents who had parents with a high school education, respectively. Associations between education, Hispanic ethnicity, and parents education and late differentiated senescent-like T lymphocytes (TemRA) and B cells were largely driven by cytomegalovirus (CMV) seropositivity.

ConclusionsResults suggest that CMV is a major driver of observed SES inequalities in immunosenescence and may therefore be an important target for interventions. Naive T lymphocytes may be particularly affected by socioeconomic position and may therefore be of particular interest to research interested in inequalities in health and aging.

category: epidemiology


title: Effect of prior infection, vaccination, and hybrid immunity against symptomatic BA.1 and BA.2 Omicron infections and severe COVID-19 in Qatar

abstract:
BACKGROUNDProtection offered by five different forms of immunity, combining natural and vaccine immunity, was investigated against SARS-CoV-2 Omicron symptomatic BA.1 infection, symptomatic BA.2 infection, BA.1 hospitalization and death, and BA.2 hospitalization and death, in Qatar, between December 23, 2021 and February 21, 2022.

METHODSSix national, matched, test-negative case-control studies were conducted to estimate effectiveness of BNT162b2 (Pfizer-BioNTech) vaccine, mRNA-1273 (Moderna) vaccine, natural immunity due to prior infection with pre-Omicron variants, and hybrid immunity from prior infection and vaccination.

RESULTSEffectiveness of only prior infection against symptomatic BA.2 infection was 46.1% (95% CI: 39.5-51.9%). Effectiveness of only two-dose BNT162b2 vaccination was negligible at -1.1% (95% CI: -7.1-4.6), but nearly all individuals had received their second dose several months earlier. Effectiveness of only three-dose BNT162b2 vaccination was 52.2% (95% CI: 48.1-55.9%). Effectiveness of hybrid immunity of prior infection and two-dose BNT162b2 vaccination was 55.1% (95% CI: 50.9-58.9%). Effectiveness of hybrid immunity of prior infection and three-dose BNT162b2 vaccination was 77.3% (95% CI: 72.4-81.4%). Meanwhile, prior infection, BNT162b2 vaccination, and hybrid immunity all showed strong effectiveness >70% against any severe, critical, or fatal COVID-19 due to BA.2 infection. Similar levels and patterns of effectiveness were observed for BA.1 and for the mRNA-1273 vaccine.

CONCLUSIONSThere are no discernable differences in the effects of prior infection, vaccination, and hybrid immunity against BA.1 versus BA.2. Hybrid immunity resulting from prior infection and recent booster vaccination confers the strongest protection against either subvariant. Vaccination enhances protection of those with a prior infection.


title: Synthesizing evidence from the earliest studies to support decision-making: to what extent could the evidence be reliable?

abstract: In evidence-based practice, new topics generally only have a few studies available for synthesis. As a result, the evidence of such meta-analyses raised large concerns. We investigated the robustness of the evidence of meta-analyses from these earliest studies. Real-world data from the Cochrane Database of Systematic Reviews (CDSR) were collected. We emulated meta-analyses with the earliest 1 to 10 studies through cumulative meta-analysis from eligible meta-analyses. The magnitude and the direction of meta-analyses with the earliest few studies were compared to the full meta-analyses. From the CDSR, we identified 20,227 meta-analyses of binary outcomes and 7,683 meta-analyses of continuous outcomes. Under the tolerable difference of 20% on the magnitude of the effects, the convergence proportion ranged from 24.24% (earliest 1 study) to 77.45% (earliest 10 studies) for meta-analyses of few earliest studies with binary outcomes. For meta-analyses of continuous outcomes, the convergence proportion ranged from 13.86% to 56.52%. In terms of the direction on the effects, even when only 3 studies were available at the earliest stage, the majority had the same direction to full meta-analyses; Only 19% for binary outcomes and 12% for continuous outcomes changed the direction as further evidence accumulated. Synthesizing evidence from the earliest studies is feasible to support urgent decision-making, and in most cases, the decisions would be reasonable. Considering the potential uncertainties, it is essential to evaluate the confidence of the evidence of these meta-analyses and update the evidence when necessary.


title: Assessment of a vancomycin dosing guideline and identification of predictive factors associated with dose and drug trough levels

abstract:
BackgroundGuidelines and therapeutic drug monitoring are widely used to optimise vancomycin dosing, but their impact remains unclear.

ObjectivesTo assess and optimise vancomycin dosing guidelines in a UK teaching hospital group.

MethodsWe conducted a retrospective study to evaluate guideline compliance and drug levels following the introduction of a new vancomycin guideline. We used multivariable regression models to investigate factors associated with dosing compliance, drug levels and acute kidney injury (AKI).

Results3,767 patients received intravenous vancomycin for [≥]24h between 01-January-2016 and 01-June-2021. Compliance with recommended loading and initial maintenance doses increased reached 84% and 70% respectively; 72% of subsequent maintenance doses were correctly adjusted. Only 26% first and 32% subsequent levels reached the target range. Drug levels were independently higher in older patients (1.14mg/L per 10 years older with twice-daily dosing [95%CI 1.03,1.25]), with lower eGFR (0.46 mg/L per 10 mL/min/1.73m2lower [0.40,0.52]) and higher Elixhauser scores (0.72mg/L per unit higher [0.57,0.88]). For patients with ongoing vancomycin treatment, the conditional probability of achieving target levels at 5 days was >50% and close to 90% at 10 days. Incidence of AKI was low (5.7%), with no evidence that AKI risk increased after guideline implementation (OR=1.09 per year [0.97,1.22], p=0.14). Model estimates were used to propose updated age, weight and eGFR specific guidelines.

ConclusionDespite good compliance with guidelines for vancomycin dosing, the proportion of drug levels achieving the target range remained suboptimal. Adjusting existing guidelines is required to ensure appropriate dosing and better attainment of therapeutic drug levels.

category: pharmacology and therapeutics


title: What works for whom with telemental health? A rapid realist review

abstract:
BackgroundTelemental health (delivering mental health care via video calls, telephone calls or text messages) is increasingly widespread. Telemental health appears to be useful and effective in providing care to some service users in some settings, especially during an emergency restricting face-to-face contact such as the COVID-19 pandemic. However, important limitations have been reported, and telemental health implementation risks reinforcing pre-existing inequalities in service provision. If it is to be widely incorporated in routine care, a clear understanding is needed of when and for whom it is an acceptable and effective approach, and when face-to-face care is needed.

ObjectiveThe aim of this rapid realist review was to develop theory about which telemental health approaches work, or do not work, for whom, in which contexts and through what mechanisms.

MethodsRapid realist reviewing involves synthesising relevant evidence and stakeholder expertise to allow timely development of context-mechanism-outcome (CMO) configurations in areas where evidence is urgently needed to inform policy and practice. The CMOs encapsulate theories about what works for whom, and by what mechanisms. Sources included eligible papers from (a) two previous systematic reviews conducted by our team on telemental health, (b) an updated search using the strategy from these reviews, (c) a call for relevant evidence, including "grey literature", to the public and key experts, and (d) website searches of relevant voluntary and statutory organisations. CMOs formulated from these sources were iteratively refined, including through (a) discussion with an expert reference group including researchers with relevant lived experience and front-line clinicians and (b) consultation with experts focused on three priority groups: 1) children and young people, 2) users of inpatient and crisis care services, and 3) digitally excluded groups.

ResultsA total of 108 scientific and grey literature sources were included. From our initial CMOs, we derived 30 overarching CMOs within four domains: 1) connecting effectively; 2) flexibility and personalisation; 3) safety, privacy and confidentiality; and 4) therapeutic quality and relationship. Reports and stakeholder input emphasised the importance of personal choice, privacy and safety, and therapeutic relationships in telemental health care. The review also identified particular service users likely to be disadvantaged by telemental health implementation, and a need to ensure that face-to-face care of equivalent timeliness remains available. Mechanisms underlying successful and unsuccessful application of telemental health are discussed.

ConclusionsService user choice, privacy and safety, the ability to connect effectively and fostering strong therapeutic relationships, need to be prioritised in delivering telemental health care. Guidelines and strategies co-produced with service users and frontline staff are needed to optimise telemental health implementation in real-world settings.

category: psychiatry and clinical psychology


title: Development and clinimetric testing of the Unified Drug-Induced Movement Disorders Scale (UDIMS)

abstract:
ObjectiveSeveral movement disorders develop secondary to the use of psychotropic drugs, for which multiple symptom rating scales are in common use. We planned to develop the Unified Drug-Induced Movement Scale (UDIMS) to assess the severity and impact of drug-induced dyskinesia, tremor, drug-induced parkinsonism, akathisia, dystonia and myoclonus with a single instrument.

MethodsBased on a literature review, consultation and pilot work, a 12-item instrument was developed, with each item rated on a 0-4 scale. The clinimetric properties of UDIMS were examined in 53 psychiatric patients on psychotropic medications, using established ratings scales for validation. The factor structure of the scale was examined, and the movement disorder correlates of distress and disability were determined.

ResultsThe instrument has good inter-rater reliability. Its correspondence with three other scales - Abnormal Involuntary Movements Scale, Simpson-Angus Scale and Prince Henry Hospital Akathisia Scale - for the relevant items was high. A principal components analysis yielded four factors, considered to represent tremor, parkinsonism, akathisia and dyskinesia. Overall movement-disorder related disability was related to parkinsonism and dyskinesia, while distress to all four components.

ConclusionsUDIMS is a reliable and valid scale to quantify a range of drug-induced movement disorders (DIMDs), that obviates the need for the use of multiple rating scales. Its widespread use by both clinicians and researchers, and further refinement based on this, will help promote the detection and treatment of drug-induced movement disorders, thereby reducing both distress and disability.


title: Association between tobacco exposure, blood pressure, and arterial stiffness in South African adults and children

abstract:
IntroductionSociodemographic factors, health status and health behaviour have all been associated with arterial stiffness. We examined the association between tobacco use or exposure and pulse wave velocity (PWV, a marker of arterial stiffness) in black South African adults and children against a background of other known risk factors.

MethodsTwo datasets were used: African-PREDICT (A-P; n=587 apparently healthy black adult men and women, 20-30 years) and Birth-to-Twenty-Plus (Bt20; n=95 black adult women, 28-68 years and n=47 black children, 4-10 years). A cotinine value >10 ng/ml in urine (Bt20) or serum (A-P) was considered as tobacco exposed and carotid-femoral PWV was measured using the SphygmoCor XCEL device. Regression analysis included cotinine and other known risk factors.

ResultsOne third of adults (32%) and almost half of all children (45%) were tobacco exposed with the prevalence of elevated blood pressure (BP) approximately twice as high as their non-exposed counterparts (adults, p=0.014; children, p=0.017). Cotinine was the only variable that significantly associated positively with PWV in both adults and children in univariate analysis (p<0.05), but only MAP remained significant for adults in multivariate analysis (p=0.001).

ConclusionsIn this sample, tobacco exposure was adversely associated with vascular health in adults and children. BP was higher in the tobacco exposed adults and children compared to their non-exposed counterparts. These findings suggest tobacco cessation programs for adults should include screening for blood pressure and consider the impact of tobacco exposure on childrens vascular health.


title: The dramatic surge of excess mortality in the United States between 2017 and 2021

abstract:
ImportancePrevious studies have shown the pre-pandemic emergence of a gap in mortality between the United States and other high-income nations. This gap was estimated to account for nearly one in seven US deaths in 2017.

ObjectiveThe number and proportion of US deaths that can be attributed to this gap is expected to have grown during the pandemic. This study aims at quantifying this growth at the end of 2021.

DesignThis cross-sectional study uses publicly available 2017 to 2021 data on deaths from all causes and 2020-2021 Covid-19 death counts in the United States and five European countries. Number of deaths are combined with publicly available estimates of population size by sex and age group in these European countries to produce sex- and age-specific mortality rates. These rates are averaged and applied to the US population by sex and age-group to compare the resulting and actual US death counts.

SettingThe United States and the five most populous countries in Western Europe.

ParticipantsAll deceased individuals in these countries are included in the death counts. This study does not use individual records.

InterventionNone.

Main Outcome and MeasureTotal number of US deaths and their counterfactuals when substituting average sex- and age-specific mortality rates for the European countries to those that prevailed in the United States.

ResultsThe counterfactuals reveal 711,109 to 747,783 excess deaths in the United States in 2021, amounting to 20.8% to 21.7% of all US deaths that year (3,426,249). Excess deaths increased by 320,436 to 331,477 between 2017 and 2021, 80.0% to 82.7% more than the 2017 estimate. A decomposition of the lower figure showed that population change contributed little to the 2017-2021 increase in excess deaths (33,545 additional deaths). Covid-19 mortality alone continue contributed 230,672 excess deaths in 2021, more than 2020, whereas other causes of deaths contributed 56,219 more excess deaths in 2021 than in 2017.

DiscussionThe proportion of US deaths that would be avoided if the United States could achieve the mortality of its West European counterparts surged to more than one in five during the pandemic. The large and still growing contribution of Covid-19 to excess mortality in the United States is consistent with vaccination rates plateauing at lower levels than in European countries. The overall increase in mortality from other causes during the pandemic increasingly separates the United States from West European countries as well.

Key PointsO_ST_ABSQuestionC_ST_ABSHow many fewer deaths would the United States experience with the same mortality rates as comparable European countries?

FindingsUsing death counts from the United States and five large European countries, this cross-sectional study estimates 711,109 to 744,783 fewer US deaths in 2021 if the United States could achieve the average sex- and age-specific mortality rates of these five countries. This is an 80.0% to 82.7% increase relative to the same figure for 2017.

MeaningThe dramatic surge in excess mortality in the United States during the pandemic demonstrates chronic societal vulnerabilities rooted in the fundamental determinants of mortality.


title: Acceptance of COVID-19 vaccine among healthcare workers in Katsina state, Northwest Nigeria

abstract:
High acceptance of COVID-19 vaccines is crucial to ending the COVID-19 pandemic. Healthcare workers (HCWs) are frontline responders in the fight against COVID-19, they were prioritized to receive the COVID-19 vaccine in Nigeria. This study assessed the acceptance of the COVID-19 vaccine among HCWs in Katsina State using an online structured questionnaire and predicted variables that could increase the acceptance of the vaccine among HCWs using logistic regression analysis.

A total of 793 HCWs were included in this study. Of these, 65.4% (n=519) of them were male and 36.2% (n=287) were aged between 30-39 years. Eighty percent (80%, n=638) of the HCWs have been tested for the SARS-CoV-2 out of which 10.8% (n=65) of them tested positive. The majority of the HCWs (97.3%, n=765) believed that the COVID-19 vaccine was safe and 90% (n=714) of the HCWs have received the first dose of the COVID-19 vaccine. Our findings showed that the age of the HCW, their COVID-19 testing status, and the type of health facility they work (either public or private) were the main predictors for the acceptance of the COVID-19 vaccine among HCWs in Katsina State. HCWs between the age of 30-39 years were more likely (OR:7.06; 95% CI: 2.36, 21.07; p < 0.001) to accept the vaccine than others. In the same vein, HCWs that have been tested for COVID-19 were more likely (OR:7.64; 95% CI: 3.62, 16.16; p < 0.001) to accept the vaccine than those that have not been tested. In addition, HCWs in public health facilities were more likely (OR: 2.91; 95% CI: 1.17, 6.11; p = 0.094) to accept the COVID-19 vaccine than their counterparts in private HFs.

There was a high acceptance of the COVID-19 vaccines among HCWs in Katsina State. More emphasis should be paid on adherence to non-pharmaceutical interventions and availability of vaccines for HCWs in private hospitals.


title: Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anaemic elective surgery patients: a systematic review

abstract:
BackgroundIron supplementation and erythropoiesis-stimulating agent (ESA) administration represent the hallmark therapies in preoperative anaemia treatment, as reflected in a set of evidence-based treatment recommendations made during the 2018 International Consensus Conference on Patient Blood Management. However, little is known about the safety of these therapies. This systematic review investigated the occurrence of adverse events (AEs) during or after treatment with iron and/or ESAs.

MethodsFive databases (The Cochrane Library, MEDLINE, Embase, Transfusion Evidence Library, Web of Science) and two trial registries (ClinicalTrials.gov, WHO ICTRP) were searched until November 6 2020. Randomized controlled trials (RCTs), cohort and case-control studies investigating any AE during or after iron and/or ESAs administration in adult elective surgery patients with preoperative anaemia were eligible for inclusion, and judged using the Cochrane Risk of Bias tools. The GRADE approach was used to assess the overall certainty of evidence.

Results26 RCTs and 16 cohort studies involving a total of 6062 patients were included, providing data on 6 comparisons: (1) Intravenous (IV) versus oral iron, (2) IV iron versus usual care/no iron, (3) IV ferric carboxymaltose versus IV iron sucrose, (4) ESA+iron versus control (placebo and/or iron, no treatment), (5) ESA+IV iron versus ESA+oral iron, and (6) ESA+IV iron versus ESA+IV iron (different ESA dosing regimens). Most AE data concerned mortality/survival (n=24 studies), thromboembolic (n=22), infectious (n=20), cardiovascular (n=19) and gastrointestinal (n=14) AEs. Very low-certainty of evidence was assigned to all but one outcome category. This uncertainty results from both low quantity and quality of AE data due to high risk of bias caused by limitations in study design, data collection and reporting.

ConclusionsIt remains unclear if ESA and/or iron therapy is associated with AEs in preoperatively anaemic elective surgery patients. Future trial investigators should pay more attention to the systematic collection, measurement, documenting and reporting of AE data.

category: surgery


title: A Standardised Protocol for Neuro-endoscopic Lavage for Post-haemorrhagic Ventricular Dilatation: A Delphi Consensus Approach

abstract:
PurposeNeuro-endoscopic lavage (NEL) has shown promise as an emerging procedure for intraventricular haemorrhage (IVH) and post-haemorrhagic ventricular dilatation (PHVD). However, there is considerable variation with regards to the indications, objectives, and surgical technique in NEL. There is currently no randomised trial evidence that supports the use of NEL in the context of PHVD. This study aims to form a consensus on technical variations in the indications and procedural steps of NEL.

MethodsA mixed methods modified Delphi consensus process was conducted between consultant paediatric neurosurgeons across the United Kingdom. Stages involved literature review, survey, focused online consultation and iterative revisions until > 80% consensus was achieved.

ResultsTwelve consultant paediatric neurosurgeons from 10 centres participated. A standardised protocol including indications, a 3-phase operative workflow (pre-ventricular, intraventricular, post-ventricular) and post-operative care was agreed upon by 100% of participants. Case- and surgeon-specific variation was considered and included through delineation of mandatory, optional, and not recommended steps.

ConclusionExpert consensus on a standardised protocol for NEL was achieved, delineating the surgical workflow into three phases: pre-ventricular, intraventricular, and post-ventricular, each consisting of mandatory, optional, and not recommended steps. The work provides a platform for future trials, training, and implementation of NEL.


title: Presumptive Multidrug-Resistant Escherichia coli Isolated in Drinking Water and Soil Sources from Kadamaian, Sabah

abstract: Multi-drug-resistant Escherichia coli poses a great threat to human health. E. coli is often used as fecal indicator bacteria to study the sources and fate of fecal contamination in the environment. This study focused on water and soil samples in tourist parks around Kadamaian, Kota Belud from three different villages of Kampung Napungguk, Kampung Pinalabuh and Kampung Tinata. From 23 of tested presumptive E. coli isolates, the percentage of antimicrobial-resistant against a series of antibiotic concentrations ranging from 25, 50, 100 to 500 g/ml showed resistance towards Chloramphenicol (91.3%), Penicillin (82.6%), Tetracycline (73.9%) and Kanamycin (30.43%). This finding suggested the presence of multi-drug resistance (MDR) of presumptive E. coli from soil samples of Kampung Napungguk and Kampung Tinata. This study alarms the presence of MDR which need further research on identifying the bacterial strains using molecular methods. The findings can then be used to create awareness of potential disease outbreaks in the tourist areas.

category: occupational and environmental health


title: Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program

abstract:
The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL.

The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1,161 proteins in a nested-case control study within 2 prospective cohorts (n=252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n=479 cases and 479 controls). Eligible participants had any history of smoking and cases were diagnosed within 3 years of blood draw. The Nodule Malignancy project measured 1,077 proteins among participants with a heavy smoking history within 4 LDCT screening studies (n=425 cases within 5 years of blood draw, 398 benign-nodule controls, and 430 nodule-free controls).

The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its lung cancer discriminative performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n=1,696 cases and 2,926 subcohort representatives), and in the Nodule Malignancy project within 5 LDCT screening studies (n=675 cases, 648 benign-nodule controls, and 680 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.

category: oncology


title: Exploring patient experiences and concerns in the online Cochlear Implant community: a natural language processing approach

abstract:
ImportanceThere is a paucity of research examining patient experiences of cochlear implants, with existing studies limited by small sample sizes and closed question-answer style formats.

ObjectiveTo use natural language processing methods to explore patient experiences and concerns in the online cochlear implant (CI) community when in conversation with each other.

DesignCross-sectional study of the online Reddit r/CochlearImplants forum. No date restrictions were imposed; data were retrieved on 11 November 2021 and analysed between November 2021 and March 2022. The following details were extracted for each post: 1) original post content, 2) post comments, and 3) metadata for the original post and user.

SettingOnline Reddit forum r/CochlearImplants.

ParticipantsConsecutive sample of all users posting on the r/CochlearImplants forum from 1 March 2015 to 11 November 2021.

Main Outcomes and MeasuresNatural language processing using the BERTopic automated topic modelling technique was employed to cluster posts into semantically similar topics. Topic categorisation was manually validated by two independent reviewers and Cohens Kappa calculated to determine inter-rater reliability between machine vs human and human vs human categorisation.

ResultsWe retrieved 987 posts from 588 unique Reddit users on the r/CochlearImplants forum. Posts were initially categorised by BERTopic into 16 different Topics, which were increased to 22 Topics following manual inspection. The most popular topics related to CI connectivity (n = 112), adults considering getting a CI (n=107), surgery-related posts (n = 89) and day-to-day living with a CI (n = 85). Topics with the most comments included Choosing cochlear implant brand (mean = 12.9 comments) and Adults considering getting a CI (mean = 12.2 comments). Cohens kappa among all posts was 0.62 (machine vs human) and 0.72 (human vs human), and among categorised posts was 0.85 (machine vs human) and 0.84 (human vs human).

Conclusions and RelevanceThis cross-sectional study of social media discussions amongst the online cochlear implant community identified common attitudes, experiences and concerns of patients living with, or seeking, a cochlear implant. Our validation of natural language processing methods to categorise topics shows that automated analysis of similar Otolaryngology-related content is a viable and accurate alternative to manual qualitative approaches.

Key pointsO_ST_ABSQuestionC_ST_ABSWhat are the main patient experiences and concerns reported by the online cochlear implant (CI) community?

FindingsIn this cross-sectional study of 987 posts from the Reddit forum r/CochlearImplants, we employed and validated a natural language processing approach to identify a variety of common themes discussed by current and prospective CI users. These ranged from CI connectivity and day-to-day living with a CI to queries about choosing a CI brand and post-op expectations.

MeaningAnalysis of social media using automated topic modelling techniques is a viable and insightful method to explore CI user experiences.

category: otolaryngology


title: Seasonality of Common Human Coronaviruses in the United States, 2014-2021

abstract:
The four common human coronaviruses (HCoVs), including two alpha (HCoV-NL63 and HCoV-229E) and two beta (HCoV-HKU1 and HCoV-OC43) types, generally cause mild, upper respiratory illness. HCoVs are known to have seasonal patterns and variation in predominant types each year, but defined measures of seasonality are needed. We defined seasonality of HCoVs during July 2014 to November 2021 in the United States using a retrospective method applied to National Respiratory and Enteric Virus Surveillance System (NREVSS) data. In the six HCoV seasons prior to 2020-2021, onsets ranged from October to November, peaks from January to February, and offsets from April to June; most (>93%) HCoV detections occurred within the defined seasonal onsets and offsets. The 2020-2021 HCoV season onset was delayed by 11 weeks compared to prior seasons, likely due to COVID-19 mitigation efforts. Better defining HCoV seasonality can inform clinical preparedness and the expected patterns of emerging HCoVs.

Article Summary LineThe typical common HCoV season in the United States starts between October and November, peaks towards the end of January, and ends between April and June, but the 2020-2021 season was markedly delayed compared to prior seasons.


title: Predictors of poor outcome in patients diagnosed with drug-resistant tuberculosis in the Torres Strait / Papua New Guinea border region

abstract:
Drug-resistant tuberculosis (DR-TB) is an ongoing challenge in the Torres Strait / Papua New Guinea border region. Treatment success rates have historically been poor for patients diagnosed with DR-TB, leading to increased transmission and resistance multiplication risk. This study aimed to identify predictors of poor outcome in patients diagnosed with DR-TB to inform programmatic improvements.

A retrospective study of all DR-TB cases who presented to Australian health facilities in the Torres Strait between 1 March 2000 and 31 March 2020 was performed. This time period covers four distinct TB programmatic approaches. Univariate and multivariate predictors of poor outcome were analysed. Poor outcome was defined as treatment default, treatment failure and death (versus cure or completion).

In total, 133 patients with resistance to at least one TB drug was identified. The vast majority (123/133; 92%) of DR-TB patients had pulmonary involvement; and of these, 41% (50/123) had both pulmonary and extrapulmonary TB. Poor outcomes were observed in 29% (39/133) of patients. Patients living with human immunodeficiency virus, renal disease or diabetes (4/133; 4/133; 3/133) had an increased frequency of poor outcome (p <0.05), but numbers were very small. Among all 133 DR-TB patients, 41% had a low lymphocyte count, which was significantly associated with poor outcome (p <0.05). Overall, outcome improved in recent years with a 50% increase in the chance of a good outcome per year group over the study period; on binary logistic regression analysis. Being a close contact of a known TB case was associated with improved outcome.

While DR-TB treatment outcomes have improved over time, it remains important to prevent DR-TB spread and resistance multiplication resulting from suboptimal treatment. Enhanced surveillance for DR-TB, better cross border collaboration and consistent diagnosis and management of comorbidities and other risk factors should further improve patient care and outcomes.


title: Immunogenic superiority and safety of Biological E CORBEVAX vaccine compared to COVISHIELD (ChAdOx1 nCoV-19) vaccine studied in a phase III, single blind, multicenter, randomized clinical trial

abstract:
BackgroundOptimum formulation of Biological Es CORBEVAX vaccine that contains protein sub unit of Receptor Binding Domain (RBD) from the spike protein of SARS-COV-2 formulated with aluminum hydroxide (Al3+) and CpG1018 as adjuvants was selected in phase-1 and 2 studies and proven to be safe, well tolerated and immunogenic in healthy adult population. In the current study, additional data was generated to determine immunogenic superiority of CORBEVAX vaccine over COVISHIELD vaccine and safety in larger and older population.

MethodsThis is a phase III prospective, single blinded, randomized, active controlled study (CTRI/2021/08/036074) conducted at 20 sites across India in healthy adults aged between 18-80 years. This study has two arms; immunogenicity arm and safety arm. Participants in immunogenicity arm were randomized equally to either CORBEVAX or COVISHIELD vaccination groups to determine the immunogenic superiority. Healthy adults without a history of Covid-19 vaccination or SARS-CoV-2 infection, were enrolled.

FindingsThe safety profile of CORBEVAX vaccine was comparable to the comparator vaccine COVISHIELD in terms of overall AE rates, related AE rates and medically attended AEs. Majority of reported AEs were mild in nature, and overall CORBEVAX appeared to cause fewer local and systemic adverse reactions/events. Overall, two grade-3 serious AEs (Dengue fever and femur fracture) were reported and they are unrelated to study vaccine. Neutralizing Antibody titers, against both Ancestral and Delta strain, induced post two-dose vaccination regimen were higher in the CORBEVAX arm as compared to COVISHIELD and the analysis of GMT ratios demonstrated immunogenic superiority of CORBEVAX in comparison with COVISHIELD. Both CORBEVAX and COVISHIELD vaccines showed comparable seroconversion post vaccination when assessed against anti-RBD IgG response. The subjects in CORBEVAX cohort also exhibited higher Interferon-gamma secreting PBMCs post stimulation with SARS-COV-2 RBD peptides than the subjects in COVISHIELD cohort.

InterpretationsNeutralizing antibody titers induced by CORBEVAX vaccine against Delta and Ancestral strains were protective, indicative of vaccine effectiveness of >90% for prevention of symptomatic infections based on the Correlates of Protection assessment performed during Moderna and Astra-Zeneca vaccine Phase III studies. Safety findings revealed that CORBEVAX vaccine has excellent safety profile when tested in larger and older population.

FundingBIRAC-division of Department of Biotechnology, Government of India, and the Coalition for Epidemic Preparedness Innovations funded the study.


title: Determinants of passive antibody effectiveness in SARS-CoV-2 infection

abstract: Neutralising antibodies are an important correlate of protection from SARS-CoV-2 infection. Multiple studies have investigated the effectiveness of passively administered antibodies (either monoclonal antibodies, convalescent plasma or hyperimmune immunoglobulin) in preventing acquisition of or improving the outcome of infection. Comparing the results between studies is challenging due to different study characteristics including disease stage, trial enrolment and outcome criteria, and different product factors, including administration of polyclonal or monoclonal antibody, and antibody targets and doses. Here we integrate data from 37 randomised controlled trials to investigate how the timing and dose of passive antibodies predicts protection from SARS-CoV-2 infection. We find that both prophylactic and early therapeutic administration (to symptomatic ambulant subjects) have significant efficacy in preventing infection or progression to hospitalisation respectively. However, we find that effectiveness of passive antibody therapy in preventing clinical progression is significantly reduced with administration at later clinical stages (p<0.0001). To compare the dose-response relationship between different treatments, we normalise the administered antibody dose to the predicted neutralisation titre (after dilution) compared to the mean titre observed in early convalescent subjects. We use a logistic model to analyse the dose-response curve of passive antibody administration in preventing progression from symptomatic infection to hospitalisation. We estimate a maximal protection from progression to hospitalisation of 70.2% (95% CI: 62.1 - 78.3%). The dose required to achieve 50% of the maximal effect (EC-50) for prevention of progression to hospitalisation was 0.19-fold (95% CI: 0.087 - 0.395) of the mean early convalescent titre. This suggests that for current monoclonal antibody regimes, doses between 7- and >1000-fold lower than currently used could still achieve around 90% of the current effectiveness (depending on the variant) and allow much more widespread use at lower cost. For convalescent plasma, most current doses are lower than required for high levels of protection. This work provides a framework for the rational design of future passive antibody prophylaxis and treatment strategies for COVID-19.


title: Prevalence of neutralizing antibody to human coronavirus 229E in Taiwan

abstract:
BackgroundFour members in the Coronaviruses family including 229E circulating in the community were known to cause mild respiratory tract infections in humans. The epidemiologic information of the seasonal human coronavirus (HCoV) may help gain insight into the development of the ongoing pandemic of coronavirus disease since 2019 (COVID-19).

MethodsPlasma collection containing 1558 samples was obtained in 2010 for an estimate of the prevalence and severity of 2009 pandemic influenza A H1N1 in Taiwan. Of 1558 samples, 200 were randomly selected from those aged < 1 year to > 60 years. The neutralizing antibody titers to HCoV-229E were determined in the serums using live virus ATCC(R) VR-740 cultivating in the Huh-7 cell line.

ResultsSeroconversion of HCoV-229E (titer [≥] 1:2) was identified as early as less than 5 years of age. Among 140 subjects aged younger than or equal to 40 years, all of them had uniformly low titers (< 1:10) and the geometric mean titers (GMTs) were not significantly different for those aged 0-5, 6-12, 13-18 and 19-40 years (P > 0.1). For 60 subjects greater than 40 years old, a majority (39, 65%) of them had high titers [≥] 1:10 and the GMTs were significantly increased with advanced age (P < 0.0001). Age was the most significant factor predicting seropositivity in the multivariate analysis, with an adjusted odds ratio of 1.107 and a 95% adjusted confidence interval of 1.061-1.155 (P < 0.0001).

ConclusionHCoV-229E infection occurred as early as younger than 5 years old in Taiwanese and the magnitudes of neutralizing titers against HCoV-229E increased with advanced age beyond 40 years.


title: Assessment of cardiovascular & pulmonary pathobiology in vivo during acute COVID-19

abstract:
ImportanceAcute COVID-19-related myocardial, pulmonary and vascular pathology, and how these relate to each other, remains unclear. No studies have used complementary imaging techniques, including molecular imaging, to elucidate this.

ObjectiveWe used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID-19.

Design, Setting and ParticipantsConsecutive patients presenting with acute COVID-19 were recruited during hospital admission in a prospective cross-sectional study. Imaging involved computed-tomography coronary-angiography (CTCA - identified coronary disease), cardiac 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron-emission tomography/computed-tomography (18F-FDG-PET/CT - identified vascular, cardiac and pulmonary inflammatory cell infiltration) and cardiac magnetic-resonance (CMR - identified myocardial disease), alongside biomarker sampling.

ResultsOf 33 patients (median age 51 years, 94% male), 24 (73%) had respiratory symptoms, with the remainder having non-specific viral symptoms. Nine patients (35%, n=9/25) had CMR defined myocarditis. 53% (n=5/8) of these patients had myocardial inflammatory cell infiltration. Two patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with myocarditis (8.4ng/L [IQR 4.0-55.3] vs 3.5ng/L [2.5-5.5], p=0.07) or myocardial cell infiltration (4.4ng/L [3.4-8.3] vs 3.5ng/L [2.8-7.2], p=0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR 5-31%) and 11% (7-18%) respectively. Neither were associated with presence of myocarditis.

Conclusions and relevanceMyocarditis was present in a third patients with acute COVID-19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is non-ischaemic, and not due to a vasculitic process.

Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the pathobiology of the cardiac, pulmonary and vascular systems during acute COVID-19 infection ?

FindingsOver a third of patients with acute COVID-19 had myocarditis by cardiac MRI criteria. Myocardial inflammatory cell infiltration was present in about two thirds of patients with myocarditis. No associations were observed between the degree of pulmonary involvement and presence of myocarditis. There was no evidence of obstructive coronary artery disease or evidence of large vessel vasculitis.

MeaningMyocarditis is common in acute COVID-19 infection, and may be present in the absence of significant pulmonary involvement. The cause of myocarditis is inflammatory cell infiltration in the majority of cases, but in about a third of cases this is not present. The mechanism of cardiac pathology in acute COVID-19 is non-ischaemic, and vascular thrombosis in acute COVID-19 is not due to significant coronary artery disease or a vasculitic process.

category: cardiovascular medicine


title: Child protection contact among children of culturally and linguistically diverse backgrounds: a South Australian linked data study

abstract:
AimTo determine the cumulative incidence of child protection (CP) system contact, maltreatment type, source of reports up to age 7, and sociodemographic characteristics for Culturally and Linguistically Diverse (CALD) Australian children.

MethodsA South Australian (SA) whole-of-population linked administrative data study of children followed from birth up to age 7, using child protection, education, health, and birth registrations data. Participants: SA born children enrolled in their first year of school from 2009-2015 (N = 76 563). CALD defined as non-Aboriginal or Torres Strait Islander, spoken language other than English, Indigenous or Sign, or had at least one parent born in a non-English speaking country. Outcomes measures: For CALD and non-CALD children the cumulative incidence of CP reports up to age 7, relative risk and risk differences for all CP contact (reporting through to out-of-home care (OOHC)) and age, primary maltreatment type, reporter type, and socioeconomic characteristics were estimated. Sensitivity analyses explored population selection and different CALD definitions.

ResultsBy age 7, 11.2% of CALD children were screened in compared to 18.8% of non-CALD (RD 7.6 percentage points (95% CI: 6.9-8.3)), and 0.6% of CALD children experienced OOHC compared to 2.2% of non-CALD (RD 1.6 percentage points (95% CI: 1.3-1.8)). Among both groups, most common abuse type was emotional and the most common reporter types were police and education sector. Socioeconomic characteristics were broadly similar. Sensitivity analyses results were consistent with primary analyses.

ConclusionBy age 7, contact with any level of child protection was lower for CALD compared to non-CALD children. Estimates based on primary and sensitivity analyses suggested CALD children were 5 to 9 percentage points less likely have a report screened-in, and from 1.0 to 1.7 percentage points less likely to have experienced OOHC.

What is already known on this topicIn Australia, Aboriginal and/or Torres Strait Islander children are over represented in the child protection system.

In England and United States child protection contact vary between ethnicities with over-representation of Black and African American, and under-representation of Asian children.

Disparities in child protection contact between ethnicities are largely driven by socioeconomic disadvantage.

What this paper addsCALD children were less likely to have contact across all levels of child protection from reporting to OOHC. By age 7, 11.2% of CALD children were screened-in compared to 18.8% of non-CALD.

Sensitivity analysis suggested CALD children were 5 to 9 percentage points less likely to have a report screened-in, and from 1.0 to 1.7 percentage points less likely to have experienced OOHC.

CALD and non-CALD groups did not markedly differ by the type of maltreatment, source of report, or on background socioeconomic factors.


title: Venous Thromboembolism in Ambulatory Covid-19 patients: Clinical and Genetic Determinants

abstract:
BackgroundSubstantial evidence suggests that severe Covid-19 leads to an increased risk of Venous Thromboembolism (VTE). We aimed to quantify the risk of VTE associated with ambulatory Covid-19, study the potential protective role of vaccination, and establish key clinical and genetic determinants of post-Covid VTE.

MethodsWe analyzed a cohort of ambulatory Covid-19 patients from UK Biobank, and compared their 30-day VTE risk with propensity-score-matched non-infected participants. We fitted multivariable models to study the associations between age, sex, ethnicity, socio-economic status, obesity, vaccination status and inherited thrombophilia with post-Covid VTE.

ResultsOverall, VTE risk was nearly 20-fold higher in Covid-19 vs matched non-infected participants (hazard ratio [HR] 19.49, 95% confidence interval [CI] 11.50 to 33.05). However, the risk was substantially attenuated amongst the vaccinated (HR: 2.79, 95% CI 0.82 to 9.54). Older age, male sex, and obesity were independently associated with higher risk, with adjusted HRs of 2.00 (1.61 to 2.47) per 10 years, 1.66 (1.28 to 2.15), and 1.85 (1.29 to 2.64), respectively. Further, inherited thrombophilia led to an HR 2.05, 95% CI 1.15 to 3.66.

ConclusionsAmbulatory Covid-19 was associated with a striking 20-fold increase in incident VTE, but no elevated risk after breakthrough infection in the fully vaccinated. Older age, male sex, and obesity were clinical determinants of Covid-19-related VTE. Additionally, inherited thrombophilia doubled risk further, comparable to the effect of 10-year ageing. These findings reinforce the need for vaccination, and call for targeted strategies to prevent VTE during outpatient care of Covid-19.


title: Biofabrication of multiplexed electrochemical immunosensors for simultaneous detection of clinical biomarkers in complex fluids

abstract: Simultaneous detection of multiple disease biomarkers in unprocessed whole blood is considered the gold standard for accurate clinical diagnosis. Here, we report the development of a 4-plex electrochemical (EC) immunosensor with on-chip negative control capable of detecting a range of biomarkers in small volumes (15 {micro}L) of complex biological fluids, including serum, plasma, and whole blood. A framework for fabricating and optimizing multiplexed sandwich immunoassays is presented that is enabled by use of EC sensor chips coated with an ultra-selective, antifouling, nanocomposite coating. Cyclic voltammetry evaluation of sensor performance was carried out by monitoring the local precipitation of an electroactive product generated by horseradish peroxidase linked to a secondary antibody. EC immunosensors demonstrated high sensitivity and specificity without background signal with a limit of detection in single-digit pg/mL in multiple complex biological fluids. These multiplexed immunosensors enabled simultaneous detect of four different biomarkers in plasma and whole blood with excellent sensitivity and selectivity. This rapid and cost-effective biosensor platform can be further adapted for use with different high affinity probes for any biomarker, and thereby create for a new class of highly sensitive and specific multiplexed diagnostics.

category: neurology


title: Oral injury in Kendo players: a cross-sectional survey

abstract: This study evaluated the risk of oral injury in Kendo. We hypothesized that Kendo players in Japan may experience oral injury due to the use of face protector for kendo (men) with inaccurate measurements or wearing it incorrectly. The survey included 400 kendo players (male, 276; female, 174) and covered four areas: the relationship between the characteristics, percentage of oral injury, temporomandibular disorder (TMD), and use of men. Based on the who experience of oral injury, participants were classified into  trauma and  non-trauma groups. Those who suffered oral injury were 179 (44.8 %; males, n=118; females, n=61). In the past month, 32 (8.2%) Kendo players reported that their matches/training were affected by dental/oral problems. For TMD, 50 participants had a total score >8.5 from four screening questions. For 289 (72.3%) participants, the men they are currently wearing fit well. Of those that reported that their men do not fit properly, 48 (12.0%) felt that their men were too large, and 14 (3.5%) felt that their men were too small. Years of experience and clenching of ones jaws during an offensive Kendo movement significantly contributed to oral injury. Clenching ones jaws during a defensive Kendo move, current men fit, sleep bruxism, and morning symptoms from sleep bruxism significantly contributed to TMD. Men with an accurate sizing allows proper field of vision, eliminating head shifting inside men during strikes and movements. This suggests that vision can be secured by adjusting the ties on men, chin movement, and the way one looks through the men. Since Kendo equipment is originally a Japanese craft, it has high artistry. Thus, properly worn Kendo equipment brings higher functionality and esthetic appeal.

category: sports medicine


title: Prognostic accuracy of qSOFA score, SIRS criteria, and EWSs for in-hospital mortality among adult patients presenting with suspected infection to the emergency department (PASSEM): protocol for an international multicentre prospective external validation cohort study

abstract:
IntroductionEarly identification of a patient with infection who may develop sepsis is of utmost importance. Unfortunately, this remains elusive because no single clinical measure or test can reflect complex pathophysiological changes in patients with sepsis. However, multiple clinical and laboratory parameters indicate impending sepsis and organ dysfunction. Screening tools using these parameters can help identify the condition, such as SIRS, quick SOFA (qSOFA), National Early Warning Score (NEWS), or Modified Early Warning Score (MEWS). We aim to externally validate qSOFA, SIRS, and NEWS/NEWS2/MEWS for in-hospital mortality among adult patients with suspected infection who presenting to the emergency department.

Methods and analysisPASSEM study is an international prospective external validation cohort study. For 9 months, each participating centre will recruit consecutive adult patients who visited the emergency departments with suspected infection and are planned for hospitalisation. We will collect patients demographics, vital signs measured in the triage, initial white blood cell count, and variables required to calculate Charlson Comorbidities Index; and follow patients for 90 days since their inclusion in the study. The primary outcome will be 30-days in-hospital mortality. The secondary outcome will be intensive care unit (ICU) admission, prolonged stay in the ICU (i.e., >72 hours), and 30-as well as 90-days all-cause mortality. The study started in December 2021 and planned to enrol 2851 patients to reach 200 in-hospital death. The sample size is adaptive and will be adjusted based on prespecified consecutive interim analyses.

Ethics and disseminationThe Aseer Regional Committee for Research Ethics in the General Directorate of Health Affairs-Aseer Region has approved this study. Informed consent is not required for this study due to its complete observational nature and absence of interventions or invasive procedures. We will publish studys results in peer-reviewed journals and may present them at scientific conferences.

Study registration numberClinicalTrials.gov identifier: NCT05172479

category: emergency medicine


title: Support needs of people living with obesity during transition from tertiary obesity treatment to community care

abstract:
BackgroundAs the number of people living with obesity increases, the maintenance of treatment outcomes is especially pertinent. Treatment at tertiary obesity services have proven to be successful, but patients need to be transitioned out of these services to community-based care to accommodate the influx of new patients. Little is known about the support needs of patients after transition from acute tertiary obesity services. It is important to establish the supports needed by these patients, especially in the context of maintaining treatment outcomes and ensuring continuity of care.

MethodsA qualitative study was conducted to identify the support needs of people with obesity as they transition to community care. Patients and clinicians recruited from a tertiary obesity clinic participated in semi-structured interviews and focus groups to explore factors influencing transition and supports needed in the community. Data was collected through audio recordings, transcribed verbatim and analysed thematically.

ResultsA total of 16 patients and 7 clinicians involved in the care of these patients participated between July 2020 and July 2021. Themes identified included the influence of clinic and individual factors on transition, the benefits of phased transition, patient-centred communication, and the role of social support. It was found that dependency and lack of self-efficacy, as well as low social support, hindered transition efforts. It was also identified that patients required substantial integrated professional and social support structures in the community to adequately address their care needs both during and following transition.

ConclusionInterventions are needed to provide social community services following transition to ensure adequate community care that can support the maintenance of treatment outcomes. Such services should be integrated and address the social needs of people living with obesity.

category: endocrinology


title: Prevalence and determinants of peripheral arterial disease in children with nephrotic syndrome

abstract: Peripheral arterial disease (PAD) is the least studied complication of nephrotic syndrome (NS). Risk factors which predispose children with NS to developing PAD include hyperlipidaemia, hypertension and prolonged use of steroids. The development of PAD significantly increases the morbidity and mortality associated with NS as such children are prone to sudden cardiac death. The ankle brachial index (ABI) is a tool that has been proven to have high specificity and sensitivity in detecting PAD even in asymptomatic individuals. We aimed to determine the prevalence of PAD in children with NS and to identify risk factors that can independently predict its development. A comparative cross-sectional study was conducted involving 200 subjects (100 with NS and 100 apparently healthy comparative subjects that were matched for age, sex and socioeconomic class). Systolic blood pressures were measured in all limbs using the pocket Doppler machine (Norton Doppler scan machine). ABI was calculated as a ratio of ankle to arm systolic blood pressure. PAD was defined as ABI less than 0.9. The prevalence of PAD was significantly higher in children with NS than matched comparison group (44.0% vs 6.0%, p < 0.001). Average values of waist and hip circumference were significantly higher in subjects with PAD than those without PAD (61.68{+/-} 9.1cm and 67.6{+/-} 11.2 cm vs 57.03 {+/-} 8.3cm and 65.60{+/-} 12.5cm respectively, p< 0.005). Serum lipids (triglyceride, very low density lipoprotein, total cholesterol and low density lipoprotein) were also significantly higher in subjects with PAD than those without PAD [106.65mg/dl (67.8-136.7) vs 45.72mg/dl (37.7-61.3), 21.33mg/dl (13.6-27.3) vs 9.14mg/dl (7.5-12.3), 164.43mg/dl (136.1-259.6) vs 120.72mg/dl (111.1-142.1) and 93.29mg/dl (63.5-157.3) vs 61.84mg/dl (32.6-83.1), respectively p< 0.05]. Increasing duration since diagnosis of NS, having a steroid resistant NS and increasing cumulative steroid dose were independent predictors of PAD in children with NS; p< 0.05 respectively).

category: pediatrics


title: Translation and validation of the Cultural Competence Self-assessment Checklist of Central Vancouver Island Multicultural Society for Health Professionals

abstract:
IntroductionThe World Health Organisation emphasizes the importance of training future healthcare practitioners to practice respectful and person-centred health care. The importance of this can be demonstrated in the example of cultural competence, which has been observed to be associated with improved patient satisfaction and concordance with recommended treatment. The aim of this study was to translate and validate in the Greek language the Cultural Competence Self-assessment Checklist of the Central Vancouver Island Multicultural Society and test it in the population of health scientists in Cyprus.

MethodsA cross-sectional analysis took place between October 2021 and January 2022 in 300 health scientists in Cyprus using convenient sampling. The sample consisted of doctors, nurses, psychologists, social workers and physiotherapists. In order to test the questionnaires internal consistency reliability we used the Cronbachs coefficient alpha.

ResultsAfter the translation of the Cultural Competence Self-assessment Checklist there was a Cronbachs alpha indication of 0.7 in all three thematic units of the checklist. 300 participants filled in the research tool, 241 women (80.3%) and 59 men (19.6). Only 2% of the sample had attended a cultural competence training before or had an expertise.

ConclusionsThe Greek version of the Cultural Competence Self-assessment Checklist of the Central Vancouver Island Multicultural Society is a valid instrument that can be used in the Greek language referring to health scientists both in Cyprus and Greece.


title: Post- intravitreal injection endophthalmitis pattern during the COVID-19 pandemic with implementation of patient masking

abstract:
PurposeTo evaluate the role of patient facial mask on the occurrence of post- intravitreal injection (IVI) endophthalmitis in a real word setting.

DesignRetrospective cohort.

ParticipantsPatients receiving IVIs between 20 February 2019 and 20 February 2021; a 12-month period before the official beginning of COVID-19 epidemic in Iran and a 12-month period after that.

InterventionIn the pre-COVID era patients underwent IVI without a facial mask while in the COVID era patients were treated with an untapped facial mask. Physicians and staff had facial mask in both periods. IVIs were administered in a dedicated operating room and no strict talk policy was followed.

Main outcome measureThe rate of post-IVI endophthalmitis.

ResultsA total number of 53927 injections was performed during the study period: 34277 in pre-COVID and 19650 in COVID periods; with a 42.7 % decrease in the number of injections. The endophthalmitis occurred in 7 eyes (0.02%) in pre-COVID and 7 eyes (0.03%) in COVID era (p=0.40). In multivariate analysis, after adjustment for intercorrelations between eyes and multiple injections in one patient, there was no statistically significant association between wearing facial masks by the patients and risk of endophthalmitis (relative risk= 1.47, 95% confidence interval of 0.97-2.22; p=0.071).

ConclusionPatients facial masking is probably not associated with increased risk of post-injection endophthalmitis.

category: ophthalmology


title: Vegetable intake and metabolic risk factors: A Mendelian randomization study

abstract:
BackgroundThe associations between vegetable intake and metabolic risk factors remain inconsistent. This study was aimed to investigate the association between cooked and raw vegetable intake with serum lipids, body mass index (BMI), blood pressure and glycemic traits.

MethodsThis was a two-sample Mendelian randomization study. Nine and 19 genetic variants were identified from genome-wide association studies (GWAS) as instrumental variables for cooked and raw vegetable intake. Summary-level statistics were used from GWAS of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, systolic blood pressure, diastolic blood pressure, BMI, fasting glucose, fasting insulin, glycated haemoglobin and 2-hour glucose after oral glucose tolerance test. Multivariable MR with inverse-variance weighted method was performed as primary analysis, while median-based method and MR-Egger method were performed as sensitivity analyses.

ResultsVegetable intake was not associated with total cholesterol (-0.06 [-0.30, 0.18] and -0.02 [-0.20, 0.16] for each serving increase of cooked and raw vegetable intake) and triglyceride (-0.12 [-0.36, 0.13] and 0.03 [-0.15, 0.22]). Null evidence was observed for associations between vegetable intake and lipoproteins, blood pressure, BMI, insulin and glycemic measures. Sensitivity analyses generated similar null associations.

ConclusionsWe found null association between vegetable intake and metabolic risk factors. This is consistent with previous MR findings of null associations between diet-derived antioxidants and metabolic risk factors.


title: Vegetable intake and cardiovascular risk: genetic evidence from Mendelian randomization

abstract:
BackgroundObservational studies have demonstrated inverse associations between vegetable intake and cardiovascular diseases. However, the results are prone to residual confounding. The separate effects of cooked and raw vegetable intake remain unclear. This study aims to investigate the association between cooked and raw vegetable intake with cardiovascular outcomes using Mendelian randomization (MR).

MethodsWe identified 15 and 28 genetic variants associated statistically and biologically with cooked and raw vegetable intake, which were used as instrumental variables to estimate the associations with coronary heart disease (CHD), stroke, heart failure (HF) and atrial fibrillation (AF). In one-sample analysis using individual participant data from UK Biobank, we adopted two stage least square approach. In two-sample analysis, we used summary level statistics from genome-wide association analyses. The independent effects of cooked and raw vegetable intake were examined with multivariable MR analysis. The one-sample and two-sample estimates were combined via meta-analysis. Bonferroni correction was applied for multiple comparison.

ResultsIn the meta-analysis of 1.2 million participants on average, we found null evidence for associations between cooked and raw vegetable intake with CHD, HF, or AF. Raw vegetable intake was nominally associated with stroke (odds ratio [95% confidence interval] 0.82 [0.69 - 0.98] per 1 serving increase daily, p = 0.03), but this association did not pass corrected significance level.

ConclusionsCooked and raw vegetable intake was not associated with CHD, AF or HF. Raw vegetable intake is likely to reduce risk of stroke, but warrants more research. Solely increasing vegetable intake may have limited protection, if any, on cardiovascular health. This calls for more rigorous assessment on health burden associated with low vegetable consumption.


title: Viral load dynamics of SARS-CoV-2 Delta and Omicron variants following multiple vaccine doses and previous infection

abstract: An important, and often neglected, aspect of vaccine effectiveness is its impact on pathogen transmissibility, harboring major implications for public health policies. As viral load is a prominent factor affecting infectivity, its laboratory surrogate, qRT-PCR cycle threshold (Ct), can be used to investigate the infectivity-related component of vaccine effectiveness. While vaccine waning has previously been observed for viral load, during the Delta wave, it is yet unknown how Omicron viral load is affected by vaccination status, and whether vaccine-derived and natural infection protection are sustainable. By analyzing results of more than 460,000 individuals we show that while recent vaccination reduces Omicron viral load, its effect wanes rapidly. In contrast, a significantly slower waning rate is demonstrated for recovered COVID-19 individuals. Thus, while the vaccine is effective in decreasing morbidity and mortality, their relative minute effect on transmissibility and rapid waning call for reassessment of the scientific justification for "vaccine certificate", as it may promote false reassurance and promiscuous behavior.


title: Burden of PCR-Confirmed SARS-CoV-2 Reinfection in the U.S. Veterans Administration, March 2020 - January 2022

abstract:
An essential precondition for successful "herd immunity" strategies for the control of SARS-CoV-2 is that reinfection with the virus be relatively rare. Some infection control, prioritization, and testing strategies for SARS-CoV-2 were designed on the premise of rare re-infection. The U.S. Veterans Health Administration (VHA) includes 171 medical centers and 1,112 outpatient sites of care, with widespread SARS-CoV-2 test availability. We used the VHAs unified, longitudinal electronic health record to measure the frequency of re-infection with SARS-CoV-2 at least 90 days after initial diagnosis

We identified 308,051 initial cases of SARS-CoV-2 infection diagnosed in VHA between March 2020 and January 2022; 58,456 (19.0%) were associated with VHA hospitalizations. A second PCR-positive test occurred in 9,203 patients in VA at least 90-days after their first positive test in VHA; 1,562 (17.0%) were associated with VHA hospitalizations. An additional 189 cases were identified as PCR-positive a third time at least 90-days after their second PCR-positive infection in VHA; 49 (25.9%) were associated with VHA hospitalizations.

The absolute number of re-infections increased from less than 500 per month through November 2021, to over 4,000 per month in January 2022.

category: public and global health


title: Impact of Transition from Conventional Open Radical Cystectomy to Laparoscopic Radical Cystectomy for Neobladder: A Retrospective Study

abstract:
BackgroundEarly operative recovery and good Quality of life are important goals of radical cystectomy. We compare the pre, peri and post operative data between Open radical cystectomy (ORC) and Laparoscopic radical cystectomy (LRC) surgery of neobladder.

Patients and MethodsRetrospective analysis of 13 male consecutive patients who underwent radical cystectomy by a single surgeon was done. Diagnosis of all patients was of invasive bladder cancer. Abdominal and preoperative staging was done using computed tomography. None of them received neoadjuvant chemotherapy. All the patients received same standard template bilateral pelvic lympadenenectomy. The urinary diversion included orthotopic neobladder. All patients were consented prior to study participation.

ResultsOf the 13 male patients, six had ORC with neobladder while 7 underwent LRC surgery. Baseline characteristics (age, BMI, comorbidities, tumour grade, lymph node status) were similar in both groups. Incision length was significantly smaller in LRC as compared to ORC group (p <0.0001). Although the operative time was longer in LRC group as compared to ORC it was sufficed by reduced time for analgesics, shorter hospital stay (p<0.05), besides earlier time to liquid intake with immediate removal of nasogastric tube (p<0.001). No major complications were observed in the LRC unlike ORC group where one patient died at 30 days.

ConclusionsBased on the observations of our small study sample peri and postoperative outcomes are promising for LRC compared to ORC for patients undergoing neobladder in terms of the smaller incision length associated with less pain and complications, with speedy recovery without jeopardizing oncological outcomes. Transition of surgeon from ORC to LRC was advantageous to patients.

category: urology


title: Development and Validation of the Michigan Chronic Disease Simulation Model (MICROSIM)

abstract:
Strategies to prevent or delay Alzheimers disease and Alzheimers disease-related dementias (AD/ADRD) are urgently needed. Blood pressure (BP) management is a promising strategy for AD/ADRD prevention and the key element in the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet the effects of different population level BP control strategies across the life course on AD/ADRD are not known.

Large-scale randomized controlled trials are the least biased approach to identifying the effect of BP control on AD/ADRD, yet trials may be infeasible due to the need for prolonged follow-up and very large sample sizes. Thus, simulation analyses leveraging the best available observational data may be the best and most practical approach to answering these questions.

In this manuscript, we describe the design principles, implementation details, and population-level validation of a novel population health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP COG) study of the effect of BP levels over the life course on cognitive decline and dementia.

MICROSIM was designed by applying computer programming best practices to create a novel simulation model. The initial purpose of this extensible, open-source framework is to explore a series of questions related to the impact of different blood pressure management strategies on late-life cognition and all-cause dementia, as well as the effects on race differences in all-cause dementia incidence. Ultimately, though, the framework is designed to be extensible such that a variety of different clinical conditions could be added to the framework.

category: health informatics


title: Home Care Follow up determine the point of inversion of IL-6 levels in relation to C-Reactive Protein as the cytokine storm marker in COVID-19

abstract: The IL-6 has been used for the characterization of the cytokine storm induced by SARS-CoV-2, but so far, no one has found out when and in whom the cytokine storm develops. Our study demonstrates how early and longitudinal clinical-based monitoring and dosing of five markers (C-reactive protein, IL-6, fibrinogen, ferritin and D-dimer) helped to identify whod developed the cytokine storm. The peak of IL-6 in pg/mL proportionally higher than the peak of CRP in mg/L was sufficient to define the timing of the evolution of cytokine storm syndrome. The administration of antibiotic therapy, anticoagulant therapy and pulse therapy resolved the infection and prevented the progressive deterioration of the lung function of the patients with potential for development of severe COVID-19.

category: infectious diseases


title: Mass drug administration campaigns: Comparing two approaches for schistosomiasis and soil-transmitted helminths prevention and control in selected southern Malawi districts

abstract:
Preventive chemotherapy using mass drug administration (MDA) is one of the key interventions recommended by WHO, to control neglected tropical diseases. In Malawi, health workers distribute anti-helminthic drugs annually with most support from donors. The mean community coverage of MDA from 2018 to 2020 were high at 87% for praziquantel and 82% for albendazole, however posing a sustainability challenge once donor support diminishes. This study was conducted to compare use of the community-directed intervention (CDI) approach with the use of health workers in delivery of MDA. It was carried out in three districts, where cross-sectional, mixed-methods approach to data collection during baseline and follow-up assessments was used.

Knowledge levels were high for what schistosomiasis is (65% - 88%) and what STH are (32% - 83%); and low for what causes schistosomiasis (32% - 58%), causes of STH (7% - 37%), intermediate organisms for schistosomiasis (13% - 33%) and types of schistosomiasis (2% - 26%). At follow-up, increases in praziquantel coverage were registered in control (86% to 89%) and intervention communities (83% to 89%); decreases were recorded for control (86% to 53%) and intervention schools (79% to 59%). Assessment of the costs for implementation of the study indicated that most resources were used at community (51%), health centre (29%) and district levels (19%). The intervention arm used more resources at health centre (27%) and community levels (44%) than the control arm at 2% and 4% respectively. Health workers and community members perceived the use of the CDI approach as a good initiative and more favorable over the standard practice of delivering MDA.

The use of the CDI in delivery of MDA campaigns against schistosomiasis and STH is feasible, increases coverage and is acceptable in intervention communities. This could be a way forward addressing the sustainability concern when donor support wanes.

Trial RegistrationPACTR202102477794401

Author summaryWorld Health Organization recommends mass drug administration (MDA) as a key control measure against neglected tropical diseases. In Malawi, community-based health workers distribute drugs for schistosomiasis and soil-transmitted helminths (STH) annually, using mostly donor support which raises concern on the programme sustainability without such support. This study compared the use of the local community people as volunteers in delivery of effective MDA against schistosomiasis and STH, defined as community-directed intervention (CDI) approach, with current standard practice of using community-based health workers. The MDA coverage in both groups was noted to be high, with community-based health workers, volunteers, community leaders and people welcoming the CDI approach as good, convenient, acceptable and satisfactory initiative. Therefore, this CDI approach is a positive and sustainable move towards successful delivery of MDA against schistosomiasis and STH in endemic and limited resource settings, using local community volunteers.


title: Clinical validation and the evaluation of a colorimetric SARS-CoV-2 RT-LAMP assay identify its robustness against RT-PCR

abstract: The novel coronavirus has infected millions of people all around the world and has posed a great risk to global health. Rapid and accurate tests are needed to take early precautions and control the disease. The most routinely used method is real time polymerase chain reaction (RT-PCR) which stands as the gold standard in the detection of SARS-COV-2 viral RNA. However, robust assays as accurate as RT-PCR have been developed for rapid diagnosis and efficient control of the spread of the disease. Reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) is one of the time-saving, accurate and cost-effective alternative methods to RT-PCR. In this study, we study the improved RT-LAMP colorimetric assay (N-Fact) to detect SARS-COV-2 viral RNA within 30 minutes using a primer sets special to N gene. Moreover, RT-LAMP colorimetric assay is subjected to authorized clinical studies to test its ability to detect COVID-19 in its early phases. The results reveal RT-LAMP colorimetric assay is an efficient, robust, and rapid assay to be used as in vitro diagnostic tool display competitiveness compared to RT-PCR.


title: Dynamics of anti-SARS-CoV-2 seroconversion in individual patients and at the population level

abstract:
The immune response and specific antibody production in COVID-19 are among the key factors that determine both prognostics for individual patients and the global perspective for controlling the pandemics. So called "dark figure", that is, a part of population that has been infected but not registered by the health care system, make it difficult to estimate herd immunity and to predict pandemic trajectories.

Here we present a follow up study of population screening for hidden herd immunity to SARS-CoV-2 in individuals who had never been positively diagnosed against SARS-CoV-2; the first screening was in May 2021, and the follow up in December 2021. We found that specific antibodies targeting SARS-CoV-2 detected in May as the "dark figure" cannot be considered important 7 months later due to their significant drop. On the other hand, among participants who at the first screening were negative for anti-SARS-CoV-2 IgG, and who have never been diagnosed for SARS-CoV-2 infection nor vaccinated, 26% were found positive for anti-SARS-CoV-2 IgG. This can be attributed to of the "dark figure" of the recent, fourth wave of the pandemic that occurred in Poland shortly before the study in December. Participants who were vaccinated between May and December demonstrated however higher levels of antibodies, than those who undergone mild or asymptomatic (thus unregistered) infection. Only 7% of these vaccinated participants demonstrated antibodies that resulted from infection (anti-NCP). The highest levels of protection were observed in the group that had been infected with SARS-CoV-2 before May 2021 and also fully vaccinated between May and December.

These observations demonstrate that the hidden fraction of herd immunity is considerable, however its potential to suppress the pandemics is limited, highlighting the key role of vaccinations.


title: Mitochondrial DAMPs as mechanistic biomarkers of mucosal inflammation in Crohn's disease and Ulcerative Colitis

abstract: The MUSIC study is a multi-centre, longitudinal study set in the real world IBD clinical setting to investigate and develop a new biomarker approach utilising mitochondrial DAMP and circulating DNA in assessing mucosal healing in Crohns disease. We present the study protocol (approved by East of Scotland Research Ethics Service, Scotland, United Kingdom - Reference No. 19/ES/0087) on 17th September 2019 and registered in ClinicalTrials.gov as NCT04760964 for this on-going project based in Scotland, UK.

category: gastroenterology


title: Undiagnosed COVID-19 in households with a child with mitochondrial disease

abstract:
BackgroundThe impact of the COVID-19 pandemic on medically fragile populations, who are at higher risk of severe illness and sequelae, has not been well characterized. Viral infection is a major cause of morbidity in children with mitochondrial disease (MtD), and the COVID-19 pandemic represents an opportunity to study this vulnerable population.

MethodsA convenience sampling cross-sectional serology study was conducted (October 2020 to June 2021) in households (N = 20) containing a child with MtD (N = 22). Samples (N = 83) were collected in the home using a microsampling apparatus and shipped to investigators. Antibodies against SARS-CoV-2 nucleocapsid (IgG), spike protein (IgG, IgM, IgA), and receptor binding domain (IgG, IgM, IgA) were determined by enzyme linked immunosorbent assay.

ResultsWhile only 4.8% of participants were clinically diagnosed for SARS-CoV-2 infection, 75.9% of study participants were seropositive for SARS-CoV-2 antibodies. Most samples were IgM positive for spike or RBD (70%), indicating that infection was recent. This translated to all 20 families showing evidence of infection in at least one household member. For the children with MtD, 91% had antibodies against SARS-CoV-2 and had not experienced any adverse outcomes at the time of assessment. For children with recent infections (IgM+ only), serologic data suggest household members as a source.

ConclusionsCOVID-19 was highly prevalent and undiagnosed in households with a child with MtD through the 2020-2021 winter wave of the pandemic. In this first major wave, children with MtD tolerated SARS-CoV-2 infection well, potentially due to household adherence to CDC recommendations for risk mitigation.

FundingThis study was funded by the Intramural Research Program of the National Institutes of Health (HG200381-03).

Clinical trial numberNCT04419870


title: Altered microRNA expression in severe COVID-19: potential prognostic and pathophysiological role

abstract:
BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is ongoing. The pathophysiology of SARS-CoV-2 infection is beginning to be elucidated but the role of microRNAs (miRNAs), small non-coding RNAs that regulate gene expression, remains incompletely understood. They play a role in the pathophysiology of viral infections with potential use as biomarkers. The objective of this study was to identify miRNAs as biomarkers of severe COVID-19 and to analyze their role in the pathophysiology of SARS-CoV-2 infection.

MethodsmiRNA expression was measured in nasopharyngeal swabs from 20 patients with severe COVID-19, 21 patients with non-severe COVID-19 and 20 controls. Promising miRNAs to differentiate non-severe from severe COVID-19 patients were identified by differential expression analysis and sparse Partial Least Squares-Discriminant Analysis (sPLS-DA). ROC analysis, target prediction, GO enrichment and pathway analysis were used to analyze the role and the pertinence of these miRNAs in severe COVID-19.

ResultsThe number of expressed miRNAs was lower in severe COVID-19 patients compared to non-severe COVID-19 patients and controls. Among the differentially expressed miRNAs between severe COVID-19 and controls, 5 miRNAs were also differentially expressed between severe and non-severe COVID-19. sPLS-DA analysis highlighted 8 miRNAs, that allowed to discriminate the severe and non-severe COVID-19 cases. Target and functional analysis revealed enrichment for genes involved in viral infections and the cellular response to infection as well as one miRNA, hsa-miR-15b-5p, that targeted the SARS-CoV-2 RNA.

The comparison of results of differential expression analysis and discriminant analysis revealed three miRNAs, namely hsa-miR-125a-5p, hsa-miR-491-5p and hsa-miR-200b-3p. These discriminated severe from non-severe cases with areas under the curve ranging from 0.76 to 0.80.

ConclusionsOur analysis of miRNA expression in nasopharyngeal swabs revealed several miRNAs of interest to discriminate severe and non-severe COVID-19. These miRNAs represent promising biomarkers and possibly targets for antiviral or anti-inflammatory treatment strategies.


title: Sequential appearance and isolation of a SARS-CoV-2 recombinant between two major SARS-CoV-2 variants in a chronically infected immunocompromised patient

abstract: Genetic recombination is a major evolutionary mechanism among RNA viruses, and it is common in coronaviruses, including those infecting humans. A few SARS-CoV-2 recombinants have been reported to date whose genome harbored combinations of mutations from different mutants or variants, but a single patients sample was analyzed, and the virus was not isolated. Here, we re-port the gradual creation of a hybrid genome of B.1.160 and Alpha variants in a lymphoma patient chronically infected for 14 months, and we isolated the recombinant virus. The hybrid genome was obtained by next-generation sequencing, and recombination sites were confirmed by PCR. This consisted of a parental B.1.160 backbone interspersed with two fragments, including the spike gene, from an Alpha variant. Analysis of seven sequential samples from the patient decoded the recombination steps, including the initial infection with a B.1.160 variant, then a concurrent infec-tion with this variant and an Alpha variant, the generation of hybrid genomes, and eventually the emergence of a predominant recombinant virus isolated at the end of the patients follow-up. This case exemplifies the recombination process of SARS-CoV-2 in real life, and it calls for intensifying genomic surveillance in patients coinfected with different SARS-CoV-2 variants, and more gener-ally with several RNA viruses, as this may lead to the creation of new viruses.


title: Protocol for an automated, pragmatic, embedded, adaptive randomised controlled trial: behavioural economics-informed mobile phone-based reminder messages to improve clinic attendance in a Botswanan schools-based vision screening programme

abstract:
BackgroundClinic non-attendance rates are high across the African continent. Emerging evidence suggests that phone-based reminder messages could make a small but important contributing to reducing non-attendance. We used behavioral economics principles to develop an SMS and voice reminder message to improve attendance rates in a school-based eye screening programme in Botswana.

MethodsWe will test a new theory-informed SMS and voice reminder message in a national school-based eye screening programme in Botswana. The control will be the standard SMS message used to remind parents/guardians to bring their child for ophthalmic assessment. All messages will be sent three times. The primary outcome is attendance for ophthalmic assessment. We will use an automated adaptive approach, starting with a 1:1:1:1 allocation ratio. Patients will not be blinded,

DiscussionAs far as we are aware, only one other study has used behavioral economics to inform the development of reminder messages to be deployed in an African healthcare setting. Our study will will use an adaptive trial design, embedded in a national screening programme. Our approach can be used to trial other forms of reminder message in the future.

Trial registrationISRCTN:96528723. Registered 5th January 2022, https://doi.org/10.1186/ISRCTN96528723

Administrative informationNote: the numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers. The order of the items has been modified to group similar items (see http://www.equator-network.org/reporting-guidelines/spirit-2013-statement-defining-standard-protocol-items-for-clinical-trials/).

O_TBL View this table:
org.highwire.dtl.DTLVardef@1f7f1ecorg.highwire.dtl.DTLVardef@12bca45org.highwire.dtl.DTLVardef@1ecabe7org.highwire.dtl.DTLVardef@109da0aorg.highwire.dtl.DTLVardef@1c9d56a_HPS_FORMAT_FIGEXP  M_TBL C_TBL


title: Psychometric properties of upper limb kinematics during functional tasks in children and adolescents with dyskinetic cerebral palsy

abstract:
AimDyskinetic cerebral palsy (DCP) is characterised by involuntary movements, and the movement patterns of children with DCP have not been extensively studied during upper limb tasks. The aim of this study is to evaluate psychometric properties of upper limb kinematics in participants with DCP and typically developing (TD) participants.

MethodsTwenty TD participants and 20 participants with DCP performed three functional tasks: reaching forward, reach and grasp vertical and reach sideways during three-dimensional motion analysis. Joint angles at point of task achievement (PTA) and spatio-temporal parameters were evaluated within-and between sessions using intra-class correlation coefficients (ICC) and standard error of measurement (SEM). Independent t-tests/Mann-Whitney U tests were used to compare all parameters between groups.

ResultsWithin-session ICC values ranged from 0.55 to 0.99 for joint angles at PTA and spatio-temporal parameters for both groups during all tasks. Within-session SEM values ranged from 1.1{degrees} to 11.7{degrees} for TD participants and from 1.9{degrees} to 13.0{degrees} for participants with DCP. Eight within-session repetitions resulted in the smallest change in ICC and SEM values for both groups. Within-session variability was higher for participants with DCP in comparison with the TD group for the majority of the joint angles and spatio-temporal parameters. Intrinsic variability over time was small for all angles and spatio-temporal parameters, whereas extrinsic variability was higher for elbow pro/supination and scapula angles. Between-group differences revealed lower shoulder adduction and higher elbow flexion, pronation and wrist flexion, as well as higher trajectory deviation and a lower maximal velocity for participants with DCP.

ConclusionThis is the first study to assess the psychometric properties of upper limb kinematics in children and adolescents with DCP, showing that children with DCP show higher variability during task execution. However, their variable movement pattern can be reliably captured within- and between-sessions, if sufficient repetitions are taken into account within one session.