abstract:
Procedures carried out in acute care settings, such as emergency departments (EDs), are among the most common sources of acute pain experienced by children. Such procedures may include intravenous insertions (IVs), venipuncture, and wound irrigation and repair. Inadequately managed procedural pain can cause negative short-term and long-term implications for children, ranging from anxiety to aversion to healthcare. Parents have repeatedly expressed that they do not have the necessary tools to comfort or distract their child during uncomfortable medical procedures. As such, the purpose of this study was to work with parents to develop and evaluate two digital tools for pediatric procedural pain.

A whiteboard animation video and interactive infographic were developed following a systematic review and interview with parents. Prototypes were tested in five ED waiting rooms in two Canadian provinces. Sites included those in urban, rural, and remote settings. Overall, parents rated the tools highly, suggesting that engaging with parents to develop arts-based digital tools is a highly effective method in ensuring that parents can understand and utilize complex health information.

Author ContributionsThis study was conducted under the supervision of Drs. Shannon D. Scott (SDS) and Lisa Hartling (LH), PIs for translation Evidence in Child Health to enhance Outcomes (ECHO) Research and the Alberta Research Centre for Health Evidence (ARCHE), respectively. Both PIs designed the research study and obtained research funding through Translating Emergency Knowledge for Kids (TREKK) Networks of Centres of Excellence of Canada (NCE).

SDS designed and supervised all aspects of tool development and evaluation.

LH co-designed and supervised the qualitative study involving interviews with parents and systematic review of parent experiences and information needs.

Tony An developed the infographic.

Kassi Shave conducted and analyzed qualitative interviews with parents.

Anne Le (AL) conducted usability testing.

AL analyzed usability data.

All authors contributed to the writing of this technical report and provided substantial feedback.

This work was funded by:

Networks of Centres of ExcellenceO_LIKlassen, T., Hartling, L., Jabbour, M., Johnson, D., & Scott, S.D. (2015). Translating emergency knowledge for kids (TREKK). Networks of Centres of Excellence of Canada Knowledge Mobilization Renewal ($1,200,000). January 2016 - December 2019.
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Women and Childrens Health Research Institute (WCHRI)O_LIScott, S.D & Hartling L. (2016). Translating Emergency Knowledge for Kids renewal. Women and Childrens Health Research Institute (matched dollars, $150,000). April 2016 - December 2019.
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This report should be cited asLe, A., Hartling, L., Scott, S.D. (2021). The development and usability testing of two arts-based knowledge translation tools for pediatric procedural pain. Technical Report. ECHO Research, University of Alberta.

Available at: http://www.echokt.ca/research/technical-reports/

category: pediatrics


title: Did social factors buffer against the effect of adversities on self-harm during the COVID-19 pandemic? A longitudinal analysis of 49,227 UK adults

abstract:
BackgroundLittle is known about which factors exacerbate and buffer the impact of COVID-19 -related adversities on changes in thinking about and engaging in self-harm over time.

AimsTo examine how changes in four social factors contribute to changes in self-harm thoughts and behaviours over time and how these factors in turn interact with adversities and worries about adversities to increase risk for these outcomes.

MethodData from 49,227 UK adults in the UCL COVID-19 Social Study were analysed across the first 59 weeks of the pandemic. Fixed effects logistic regressions examined time-varying associations between social support quality, loneliness, number of days of face-to-face contact for [≥]15 minutes, and number of days phoning/video calling for [≥]15 minutes with self-harm thoughts and behaviours. We then examined how these four factors in turn interacted with the total number of adversities and worries about adversity on outcomes.

ResultsIncreases in the quality of social support decreased the likelihood of both outcomes, whilst greater loneliness increased their likelihood. Associations were inconsistent for telephone/video contact and face-to-face contact with outcomes. Social support buffered and loneliness exacerbated the impact of adversity experiences with self-harm behaviours. Other interactions were inconsistent, and some were in the unexpected direction.

ConclusionsThese findings suggest the importance of the quality of ones social support network, rather than the mere presence of contact, is important for reducing the likelihood of self-harm behaviours in the context of COVID-19 pandemic-related adversity and worry.

category: psychiatry and clinical psychology


title: An Extended Susceptible-Exposed-Infected-Recovered (SEIR) Model with Vaccination for Forecasting the COVID-19 Pandemic in Sri Lanka

abstract: The role of modelling in predicting the spread of an epidemic is important for health planning and policies. This study aimed to apply a compartmental model for predicting the variations of epidemiological parameters in Sri Lanka. We used a dynamic Susceptible-Exposed-Infected-Recovered-Vaccinated (SEIRV) model and simulated potential vaccine strategies under a range of epidemic conditions. The predictions were based on different vaccination coverages (5% to 90%), vaccination-rates (1%, 2%, 5%) and vaccine-efficacies (40%, 60%, 80%) under different R0 (2,4,6). We estimated the duration, exposed, and infected populations. When the R0 was increased, the days of reduction of susceptibility and the days to reach the peak of the infection were reduced gradually. At least 45% vaccine coverage is required for reducing the infected population to mitigate a disastrous situation in Sri Lanka. The results revealed that when R0 is increased in the SEIRV model along with the increase of vaccination efficacy and vaccination rate, the population to be vaccinated is reducing. Thus, the vaccination offers greater benefits to the local population by reducing the time to reach the peak, exposed and infected population through flattening the curves.

category: public and global health


title: An Extended Susceptible-Exposed-Infected-Recovered (SEIR) Model with Vaccination for Predicting the COVID-19 Pandemic in Sri Lanka


title: Association between overcrowded households, multigenerational households, and COVID-19: a cohort study

abstract:
IntroductionThe role of overcrowded and multigenerational households as a risk factor for COVID-19 remains unmeasured. The objective of this study is to examine and quantify the association between overcrowded and multigenerational households, and COVID-19 in New York City (NYC).

MethodsWe conducted a Bayesian ecological time series analysis at the ZIP Code Tabulation Area (ZCTA) level in NYC to assess whether ZCTAs with higher proportions of overcrowded (defined as proportion of estimated number of housing units with more than one occupant per room) and multigenerational households (defined as the estimated percentage of residences occupied by a grandparent and a grandchild less than 18 years of age) were independently associated with higher suspected COVID-19 case rates (from NYC Department of Health Syndromic Surveillance data for March 1 to 30, 2020). Our main measure was adjusted incidence rate ratio (IRR) of suspected COVID-19 cases per 10,000 population. Our final model controlled for ZCTA-level sociodemographic factors (median income, poverty status, White race, essential workers), prevalence of clinical conditions related to COVID-19 severity (obesity, hypertension, coronary heart disease, diabetes, asthma, smoking status, and chronic obstructive pulmonary disease), and spatial clustering.

Results39,923 suspected COVID-19 cases presented to emergency departments across 173 ZCTAs in NYC. Adjusted COVID-19 case rates increased by 67% (IRR 1.67, 95% CI = 1.12, 2.52) in ZCTAs in quartile four (versus one) for percent overcrowdedness and increased by 77% (IRR 1.77, 95% CI = 1.11, 2.79) in quartile four (versus one) for percent living in multigenerational housing. Interaction between both exposures was not significant ({beta}interaction = 0.99, 95% CI: 0.99-1.00).

ConclusionsOver-crowdedness and multigenerational housing are independent risk factors for suspected COVID-19. In the early phase of surge in COVID cases, social distancing measures that increase house-bound populations may inadvertently but temporarily increase SARS-CoV-2 transmission risk and COVID-19 disease in these populations.


title: Estimating Vaccination Effects on COVID-19 outbreak course in Japan

abstract:
BackgroundAs of the end of 2021 year, the rate of completion for second-dose administration was almost 80% in Japan.

ObjectWe evaluated waning of vaccine effectiveness for COVID-19 in Japan, controlling for mutated strains, the Olympic Games, and countermeasures.

MethodThe effective reproduction number R(t) was regressed on current vaccine coverage and data of a certain number of days prior, as well as shares of mutated strains, and an Olympic Games dummy variable along with data of temperature, humidity, mobility, and countermeasures. The study period was February, 2020 through December 7, as of December 28, 2021.

ResultsEstimation results indicate that the past vaccine coverage of older than 60 days prior raises R(t) significantly and cancelled vaccine effectiveness completely.

Discussion and ConclusionResults indicate significant waning of vaccine effectiveness from 60 days after the second dose.


title: Estimating Vaccination Effects and Variant Strains on COVID-19 outbreak course in Japan, as of June, 2021.


title: Estimating Vaccination Effects and Variant Strains on COVID-19 outbreak course in Japan, as of August, 2021


title: Vaccine Effectiveness for the COVID-19 in Japan


title: Waning of Vaccine Effectiveness for the COVID-19 vaccine in Japan


title: Continuous Positive Airway Pressure (CPAP) for Moderate to Severe Covid19 Acute Respiratory Distress Syndrome (CARDS) in a Resource limited setting

abstract:
IntroductionCovid19 Acute Respiratory Distress Syndrome (CARDS) poses a challenge in management particularly due to limited capacity of ventilated intensive care beds and staffing, and this is exacerbated in resource poor settings with poor patient outcomes. Within this context CPAP has been trialled for CARDS although mainly in resource rich settings.

MethodsThis study retrospectively analyses the survival outcomes and characteristics of a cohort of patients with moderate to severe CARDS were treated exclusively with CPAP in a rural secondary level hospital in Pakistan with limited previous critical care expertise.

Results32 out of the 41 patients (78%) who were treated with CPAP survived overall (30/37 (81%) who were treated according to protocol).

DiscussionResults suggest non inferiority to CARDS outcomes of critical care units employing Intubation and Mechanical Ventilation (IMV) in resource rich settings. CPAP should be promoted as an efficacious and cost-effective method for treating CARDS within the context of the pandemic surge of Covid19 in resource poor settings.

Key MessagesO_ST_ABSWhat is the key question?C_ST_ABSIs Continuous Positive Airway Pressure (CPAP) an effective treatment for Covid19 Acute Respiratory Distress Syndrome (CARDS) in a resource poor setting in a pandemic surge context?

What is the bottom line?Survival rate for CARDS on CPAP in our single centre retrospective cohort study is 78% which is similar to outcomes from critical care centres in resource rich settings employing Intubation and Mechanical Ventilation (IMV) and better than outcomes in many critical care centres in resource poor settings. This suggests CPAP should be promoted as an efficacious and cost-effective method for managing the pandemic surge of CARDS in resource poor settings.

Why read on?The current surge of Covid19 CARDS in resource poor settings poses a significant challenge in terms of effective management given cost and resource restraints, reflected by poor outcomes in overwhelmed critical care centres employing IMV. This is the largest study so far documenting the survival outcomes and characteristics of patients with CARDS treated exclusively with CPAP within a resource poor setting.

category: respiratory medicine


title: Prevalence of different sleep problems in patients with respiratory diseases presented to a respiratory outdoor clinic: A Descriptive analysis

abstract:
IntroductionA patient with compromised respiratory system due to some diseases, may have disturbed sleep to a great extent. It has been proved in various community based epidemiologic studies. Though most of such studies available had concentrated on single respiratory disease like COPD or Asthma in the community. But such studies are hardly available for patients attending a respiratory clinic, where all respiratory ailments were evaluated with concurrent sleep problems. The present study is one such.

MethodsTotal 163 patients were screened and among them 100 were selected as the study group. The patients were enquired with a standard questionnaire provided to them. In addition, they were given seperate questionnaire as STOP BANG, Insomnia Severity Index Score, RLS questionnaire. Those persons with STOP BANG > 5, were also advised for a Polysomnography (PSG), if not already done. Descriptive statistical analysis has been carried out in the present study.

ResultsThe present study is a cross-sectional depiction of relationships between various respiratory diseases and sleep problems. As per this study, most patients were asthmatic and commonest sleep problem was OSA. A subgroup analysis was done to determine the significance of difference of various parameters between the three groups of asthmatic patients, patients having COPD and the  Other group.

DiscussionSubjective sleep problems were significantly more in Asthma group than COPD group (p<0.0362). The mean STOP BANG was more in COPD group than the Asthma group (p<0.0301). Though OSA was the commonest sleep problem between the three groups, but the prevalence was not statistically significant between them. More patients in the COPD group had insomnia, but it was not statistically significantly more than in Asthma group. Sleeping pill use was significantly more in COPD group than the Asthma group (p<0.0039).

ConclusionSleep problems are common in patients with respiratory diseases and OSA is the most common problem according to the present study. Asthma patients had more subjective sleep problems. Sleeping pill use is more common in COPD patients instead of having less subjective sleep complaints than asthma patients.


title: Nusinersen in adult patients with 5q spinal muscular atrophy: a multicenter observational cohorts study

abstract:
ObjectiveTo assess safety and efficacy of nusinersen in adult 5q spinal muscular atrophy (SMA) patients.

MethodsPatients older than 15 years and followed at least for 6 months with one motor scale (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb module, RULM) in five referral centers were included. Clinical and patients global impression of change (CGI-C and PGI-C) were recorded in treated patients at the last visit. Functional scales (Egen Klassification, EK2; Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R) and the percent-predicted forced vital capacity were collected when available.

ResultsSeventy-nine SMA patients (39 treated with nusinersen) were included. Compared with untreated patients, treated patients showed a significant improvement of 2 points ({+/-}0.46) in RULM (p<0.001) after six months. After a mean follow-up of 16 months, nusinersen treatment was associated with a significant improvement in HFMSE (OR=1.15, p=0.006), 6MWT (OR=1.07, p<0.001), and EK2 (OR=0.81, p=0.001).

Compared with untreated patients, more treated patients experienced clinically meaningful improvements in all scales, but these differences were statistically significant only for RULM (p=0.033), ALSFRS-R (p=0.005), and EK2 (p<0.001). According to the CGI-C and PGI-C, 64.1% and 61.5% of treated patients improved with treatment. Being non-sitter was associated with less response to treatment, while longer time of treatment was associated with better response. Most treated patients (77%) presented at least one adverse event, mostly mild.

ConclusionsNusinersen treatment associates to some improvements in adult SMA patients. Most severely affected patients with complex spines are probably those with the most unfavorable risk-benefit ratio.

category: neurology


title: Human and machine learning of prognostic prediction for prelabor rupture of membranes and the time of delivery: a nationwide development, validation, and deployment using medical history

abstract:
ImportancePrognostic predictions of prelabor rupture of membranes lack proper sample sizes and external validation.

ObjectiveTo develop, validate, and deploy statistical and/or machine learning prediction models using medical histories for prelabor rupture of membranes and the time of delivery.

DesignA retrospective cohort design within 2-year period (2015 to 2016) of a single-payer, government-owned health insurance database covering 75.8% individuals in a country

SettingNationwide healthcare providers (n=22,024) at primary, secondary, and tertiary levels

Participants12-to-55-year-old women that visit healthcare providers using the insurance from [~]1% random sample of insurance holders stratified by healthcare provider and category of family: (1) never visit; (2) visit only primary care; and (3) visit all levels of care

PredictorsMedical histories of diagnosis and procedure (International Classification of Disease version 10) before the latest visit of outcome within the database period

Main Outcomes and MeasuresPrelabor rupture of membranes prognostication (area under curve, with sensitivity, specificity, and likelihood ratio), the time of delivery estimation (root mean square error), and inference time (minutes), with 95% confidence interval

ResultsWe selected 219,272 women aged 33 {+/-} 12 years. The best prognostication achieved area under curve 0.73 (0.72 to 0.75), sensitivity 0.494 (0.489 to 0.500), specificity 0.816 (0.814 to 0.818), and likelihood ratio being positive 2.68 (2.63 to 2.75) and negative 0.62 (0.61 to 0.63). This outperformed models from previous studies according to area under curve of an external validation set, including one using a biomarker (area under curve 0.641; sensitivity 0.419; sensitivity 0.863; positive likelihood ratio 3.06; negative likelihood ratio 0.67; n=1177). Meanwhile, the best estimation achieved {+/-} 2.2 and 2.6 weeks respectively for predicted events and non-events. Our web application only took 5.14 minutes (5.11 to 5.18) per prediction.

Conclusions and RelevancePrelabor rupture of membranes and the time of delivery were predicted by medical histories; but, an impact study is required before clinical application.

Key PointsO_ST_ABSQuestionC_ST_ABSCan we use medical histories of diagnosis and procedure in electronic health records to predict prelabor rupture of membranes and the time of delivery before the day in nationwide insured women?

FindingsIn this prognostic study applying retrospective cohort paradigm, a significant predictive performance was achieved and validated. The area under receiver operating characteristics curve was 0.73 with the estimation errors of {+/-} 2.2 and 2.6 weeks for the time of delivery.

MeaningPreliminary prediction can be conducted in a wide population of insured women to predict prelabor rupture of membranes and estimate the time of delivery.

category: obstetrics and gynecology


title: Prognostication for prelabor rupture of membranes and the time of delivery in nationwide insured women: development, validation, and deployment


title: Genetic overlap between multivariate measures of human functional brain connectivity and psychiatric disorders

abstract: Psychiatric disorders are complex, heritable, and highly polygenic. Supported by findings of abnormalities in functional magnetic resonance imaging (fMRI) based measures of brain connectivity, current theoretical and empirical accounts have conceptualized them as disorders of brain connectivity and dysfunctional integration of brain signaling, however, the extent to which these findings reflect common genetic factors remains unclear. Here, we performed a multivariate genome-wide association analysis of fMRI-based functional brain connectivity in a sample of 30,701 individuals from the UK Biobank and investigated the shared genetic determinants with seven major psychiatric disorders. The analysis revealed significant genetic overlap between functional brain connectivity and schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, autism spectrum disorder, anxiety, and major depression, adding further genetic support for the dysconnectivity hypothesis of psychiatric disorders and identifying potential genetic and functional targets for future studies.

category: genetic and genomic medicine


title: A polygenic risk score predicts mosaic loss of chromosome Y in circulating blood cells

abstract: Mosaic loss of Y chromosome (LOY) in leukocytes is associated with risk for death and disease in men. We investigated a polygenic risk score (PRS) for LOY comprising 156 previously associated germline variants, in 5131 men aged [≥]70 years. Levels of LOY were estimated using microarrays and validated by whole genome sequencing. After adjusting for covariates, the PRS was a significant predictor of LOY (odds ratio 1.74). Men in the highest quintile of the PRS distribution had >5-fold higher risk of LOY than the lowest. A PRS for LOY could become a useful tool for risk prediction and targeted intervention.


title: Histone H3 lysine 27 acetylation profile undergoes two global shifts in undernourished children and suggests one-carbon metabolite insufficiency

abstract:
BackgroundStunting is a condition in which a child does not reach their full growth potential due to chronic undernutrition. It arises during the first two years of a childs life and is associated with developmental deficiencies and life-long health problems. Current interventions provide some benefit, but new approaches to prevention and treatment grounded in a molecular understanding of stunting are needed. Epigenetic analyses are critical as they can provide insight into how signals from a poor environment lead to changes in cell function.

ResultsHere we profiled histone H3 acetylation on lysine 27 (H3K27ac) in peripheral blood mononuclear cells (PBMCs) of 18-week-old and one-year-old children living in an urban slum in Dhaka, Bangladesh. We show that 18-week-old children destined to become stunted have elevated levels of H3K27ac overall, functional analysis of which indicates activation of the immune system and stress response pathways as a primary response to a poor environment with high pathogen load. Conversely, overt stunting at 1-year-of age is associated with globally reduced H3K27ac that is indicative of metabolic rewiring and downregulation of the immune system and DNA repair pathways that are likely secondary responses to chronic exposure to a poor environment with limited nutrients. The results from one-year-old children also point toward deficiency in one-carbon metabolism, which is further supported by integrative analysis with results from histone H3 trimethylation on lysine 4 (H3K4me3).

ConclusionsThe epigenomes of stunted children undergo two global changes in H3K27ac within their first year of life, which are associated with probable initial hyperactive immune responses followed by reduced metabolic capacity. Limitation of one-carbon metabolites may play a key role in the development of stunting. Trial registration: ClinicalTrials.gov NCT01375647. Registered 17 June 2011, retrospectively registered.


title: The valuation of outcomes for the temporary and chronic health states associated with Chlamydia trachomatis infection

abstract:
BackgroundEliciting health-state utility values (HSUVs) for some diseases is complicated by the mix of associated temporary (THSs) and chronic health states (CHSs). This study uses one such disease, chlamydia infection, to explore the challenges. The objectives were to:

O_LIDefine a set of health-state descriptions related to chlamydia and
C_LIO_LIDerive HSUVs for these health states (both temporary and chronic).
C_LI

MethodsHSUVs were elicited for seven health states (five THSs and two CHSs) depicting the symptoms of chlamydia, developed using evidence from the literature and clinical experts. The chained time trade-off (TTO) and visual analogue scale (VAS) were applied to THSs while conventional TTO was applied to the CHSs. Ectopic pregnancy was used as the anchor for the chained TTO approach. The study sampled from three different population groups and the survey was administered face-to-face.

ResultsOne hundred participants were assessed with an interview completion rate of 100%. Mean TTO utilities were consistently higher than VAS scores. The aggregated mean chained TTO results for the THS ranged from 0.46 (SD, 0.24) for ectopic pregnancy, to 0.77 (SD 0.21) for cervicitis.

ConclusionsChained TTO was shown to be feasible in this population and the resulting HSUVs could have implications for economic evaluations for chlamydia prevention and control. Methodological challenges included the development of health-state descriptions, the selection, and the duration of appropriate anchor state.

category: health economics


title: Using deep learning to analyze the compositeness of musculoskeletal aging reveals that spine, hip and knee age at different rates, and are associated with different genetic and non-genetic factors

abstract: With age, the musculoskeletal system undergoes significant changes, leading to diseases such as arthritis and osteoporosis. Due to the aging of the world population, the prevalence of such diseases is therefore expected to starkly increase in the coming decades. While numerous biological age predictors have been developed to assess musculoskeletal aging, it remains unclear whether these different approaches and data capture a single aging process, or if the diverse joints and bones in the body age at different rates. In the following, we leverage 42,000 full body, spine, hip and knee X-ray images and musculoskeletal biomarkers from the UK Biobank and use artificial intelligence to build the most accurate musculoskeletal aging predictor to date (RMSE=2.65{+/-}0.01 years; R-Squared=87.6{+/-}0.1%). Our predictor is composite and can be used to assess spine age, hip age and knee age, in addition to general musculoskeletal aging. We find that accelerated musculoskeletal aging is moderately correlated between these different musculoskeletal dimensions (e.g hip vs. knee: Pearson correlation=.351{+/-}.004). Musculoskeletal aging is heritable at more than 35%, and the genetic factors are partially shared between joints (e.g hip vs. knee: genetic correlation=.52{+/-}.04). We identified single nucleotide polymorphisms associated with accelerated musculoskeletal aging in approximately ten genes for each musculoskeletal dimension. General musculoskeletal aging is for example associated with a TBX15 variant linked to Cousin syndrome and acromegaloid facial appearance syndrome. Finally, we identified biomarkers, clinical phenotypes, diseases, environmental and socioeconomic variables associated with accelerated musculoskeletal aging in each dimension. We conclude that, while the aging of the different components of the musculoskeletal system is connected, each bone and joint can age at significantly different rates.

category: health informatics


title: Sepsis Subphenotyping Based on Organ Dysfunction Trajectory

abstract:
PurposeAlthough organ dysfunction is a defining element of sepsis, its trajectory is not well studied. We sought to identify whether there are distinct Sequential Organ Failure Assessment (SOFA) score trajectory-based subphenotypes in sepsis.

MethodsWe created 72-hour SOFA score trajectories in patients with sepsis from two diverse intensive care unit (ICU) cohorts. We then used Dynamic Time Warping (DTW) to compute patient similarities to capture evolving heterogeneous sequences and establish similarities between groups with distinct trajectories. Hierarchical agglomerative clustering (HAC) was utilized to identify subphenotypes based on SOFA trajectory similarities. Patient characteristics were compared between subphenotypes and a random forest model was developed to predict subphenotype membership, within 6 hours of ICU arrival. The model was then tested on the validation cohort.

ResultsA total of 4,678 and 3,665 unique sepsis patients were included in development and validation cohorts. In the development cohort, four subphenotypes of organ dysfunction were identified: Rapidly Worsening (n=612, 13.08%), Delayed Worsening (n=960, 20.52%), Rapidly Improving (n=1,932, 41.3%) and Delayed Improving (n=1174, 25.1%). In-hospital mortality for patients within different subphenotypes demonstrated distinct patterns over time. Similar subphenotypes and their associated outcome patterns were replicated in the multicenter validation cohort.

ConclusionFour novel, clinically-defined, trajectory-based sepsis subphenotypes were identified and validated. Trajectory based subphenotyping is useful for describing the natural history of sepsis in the ICU. Understanding the pathophysiology of these differential trajectories may reveal unanticipated therapeutic targets for patients with sepsis and identify more precise populations and endpoints for the predictive enrichment of clinical trials.


title: COVID-19 Vaccine Coverage Index: Identifying barriers to COVID-19 vaccine uptake across U.S. counties

abstract:
ImportanceThe United States is in a race against time to vaccinate its population to contain the COVID-19 pandemic. With limited resources, a proactive, targeted effort is needed to reach widespread community immunity.

ObjectiveIdentify county-level barriers to achieving rapid COVID-19 vaccine coverage and validate the index against vaccine rollout data.

DesignEcological study

SettingPopulation-based

ParticipantsLongitudinal COVID-19 vaccination coverage data for 50 states and the District of Columbia and 3118 counties from January 12 through May 25, 2021.

Exposure(s)The COVID-19 Vaccine Coverage index (CVAC) ranks states and counties on barriers to coverage through 28 indicators across 5 themes: historic undervaccination, sociodemographic barriers, resource-constrained health system, healthcare accessibility barriers, and irregular care-seeking behaviors. A score of 0 indicates the lowest level of concern, whereas a score of 1 indicates the highest level of concern.

Main Outcome(s) and Measure(s)State-level vaccine administrations from January 12 through May 25, 2021, provided by the Centers for Disease Control and Prevention (CDC) and Our World In Data. County-level vaccine coverage as of May 25, 2021, provided by the CDC.

ResultsAs of May 25, 2021, the CVAC strongly correlated with the percentage of population fully vaccinated against COVID-19 by county (r = -0.39, p=2.2x10-16) and state (r=-0.77, p=4.9x10-11). Low-concern states and counties have fully vaccinated 26.5% [t=6.8, p=1.7x10-7] and 26% (t=22.0, p=2.2x10-16) more people, respectively, compared to their high-concern counterparts. This vaccination gap is at its highest point since the start of vaccination and continues to grow. Higher concern on each of the five themes predicts a lower rate of vaccination at the county level (all p<.001). We identify five types of counties with distinct barrier profiles.

Conclusions and RelevanceThe CVAC measures underlying barriers to vaccination and is strongly associated with the speed of rollout. As the coverage gap between high- and low-concern regions continues to grow, the CVAC can inform a precision public health response targeted to underlying barriers.

Key PointsO_ST_ABSQuestionC_ST_ABSWhich U.S. counties face barriers to COVID-19 vaccine rollout, and are these communities vaccinating fewer individuals?

FindingsThe COVID-19 Vaccine Coverage Index (CVAC) comprises five themes reflecting county-level concern for low coverage. We report rural, regional, and racial divides in exposure to these vaccination barriers. The top third of states and counties of highest concern have vaccinated 19% and 20% fewer people, respectively, compared to regions of least concern.

MeaningThe CVAC can help contextualize progress to widespread COVID-19 vaccine coverage, identifying underlying community-level factors that could be driving suboptimal rollout to inform precision solutions.

category: health policy


title: Data Driven Monitoring in Community Based Management of SAM children using Psychometric Techniques: An Operational Framework

abstract:
BackgroundThe success of the Community Based Management of Severe Malnutrition (CSAM)programme, largely depends on the knowledge and skills of Front-Line Workers (FLWs).A robust supportive supervision system in CSAM should be tailored to individualistic learning needs by distinguishing the FLWs as per their ability and simultaneously identifying the task domains to be emphasized more in supervisory visits.This paper details the ability assessment strategy developed and employed in the selected geographical locations in state of Madhya Pradesh (Central India) among the 197 Anganwadi workers (FLWs involved in CSAM implementation)

MethodologyA 25 items tool was developed based on an analytical construct for ability estimation through Rasch Analysis (RA). RA models the probability of right/wrong answer as a function of person(participants) and item (questions) parameters and calculates the item difficulty in relation with person ability on same unidimensional linear scale. The fitting of the data to Rasch model (Rasch diagnostic) was tested by both numeric (Anderson LR and Wald test) and graphical method. Suitable visualization like Item Characteristic Curve (ICC) and Person Item Map (PIM) were plotted in RA.

Further a quadratic allocation of all AWWs into 4 quadrants were done as per the ability estimation (Rasch score) and adjusted numbers of SAM/MAM children in her center.

ResultsThe item easiness parameter ({beta}) value related to Diarrhoeal assessment was lowest (-2.32, -2.91 to -1.73) and related to peer assessment consequential action (2.009, 1.669-2.348)) was highest (most difficult). Anderson LR test (LR=31.32, df=24, p=0.079) showed the absence of global outliers. Quadrant analysis using the permutations of ability score and adjusted burden of malnutrition further mapped 41/197 (20.8%) FLWs to low ability -high burden quadrant and 44/197(25%) as low ability low burden quadrant.

ConclusionRASCH assessment may address the innate challenges to maintain homogeneity, discrimination capacity and linearity in a raw score-based measurement construct. The monitoring strategy developed on this thus may offer a judicious, pragmatic and thematic approach to supportive supervision in CSAM program.


title: Evaluation of Domain Generalization and Adaptation on Improving Model Robustness to Temporal Dataset Shift in Clinical Medicine

abstract:
ImportanceTemporal dataset shift associated with changes in healthcare over time is a barrier to deploying machine learning-based clinical decision support systems. Algorithms that learn robust models by estimating invariant properties across time periods for domain generalization (DG) and unsupervised domain adaptation (UDA) might be suitable to proactively mitigate dataset shift.

ObjectiveTo characterize the impact of temporal dataset shift on clinical prediction models and benchmark DG and UDA algorithms on improving model robustness.

Design, Setting, and ParticipantsIn this cohort study, intensive care unit patients from the MIMIC-IV database were categorized by year groups (2008-2010, 2011-2013, 2014-2016 and 2017-2019). Tasks were predicting mortality, long length of stay, sepsis and invasive ventilation. Feedforward neural networks were used as prediction models. The baseline experiment trained models using empirical risk minimization (ERM) on 2008-2010 (ERM[08-10]) and evaluated them on subsequent year groups. DG experiment trained models using algorithms that estimated invariant properties using 2008-2016 and evaluated them on 2017- 2019. UDA experiment leveraged unlabelled samples from 2017-2019 for unsupervised distribution matching. DG and UDA models were compared to ERM[08-16] models trained using 2008-2016.

Main Outcome(s) and Measure(s)Main performance measures were area-under-the-receiver-operating-characteristic curve (AUROC), area-under-the-precision-recall curve and absolute calibration error. Threshold-based metrics including false-positives and false-negatives were used to assess the clinical impact of temporal dataset shift and its mitigation strategies.

ResultsIn the baseline experiments, dataset shift was most evident for sepsis prediction (maximum AUROC drop, 0.090; 95% confidence interval (CI), 0.080-0.101). Considering a scenario of 100 consecutively admitted patients showed that ERM[08-10] applied to 2017-2019 was associated with one additional false-negative among 11 patients with sepsis, when compared to the model applied to 2008-2010. When compared with ERM[08-16], DG and UDA experiments failed to produce more robust models (range of AUROC difference, -0.003-0.050).

Conclusions and RelevanceDG and UDA failed to produce more robust models compared to ERM in the setting of temporal dataset shift. Alternate approaches are required to preserve model performance over time in clinical medicine.

KEY POINTSO_ST_ABSQuestionC_ST_ABSCan algorithms that estimate invariant properties across environments for domain generalization and unsupervised domain adaptation improve the robustness of machine learning-derived clinical prediction models to temporal dataset shift?

FindingsIn this cohort study using 4 clinical outcomes, domain generalization and unsupervised domain adaptation algorithms did not meaningfully outperform the standard model training algorithm - empirical risk minimization - in learning robust models that generalize over time in the presence of temporal dataset shift.

MeaningThese findings highlight the difficulty of improving robustness to dataset shift with purely data-driven techniques that do not leverage prior knowledge of the nature of the shift and the requirement of alternate approaches to preserve model performance over time in clinical medicine.

category: health systems and quality improvement


title: Clinical Significance of a combination of Biochemical Indexes and Immunity Indexes for hepatitis B disease Prediction

abstract:
ObjectivesTo explore the clinical significance of the detection of biochemical indexes and immune indexes in the prediction of hepatitis B (HBV) disease.

Methods150 patients with HBV disease who were treated in our hospital from 2018 to 2020 were selected and divided into acute HBV group (group A), chronic HBV group (group B) and Cirrhosis group (C group), every group included 50 cases, and 50 healthy people were selected as the control group. Peripheral venous blood was collected from subjects from 4 groups, and immune indexes (plasma immunoglobulin G (IgG), plasma immunoglobulin A (IgA), plasma immunoglobulin M (IgM)) of HBV were measured by immune nephelometry, and biochemical indexes (alanine aminotransferase (ALT) and amino acid transaminase (AST)) of HBV were measured by fasting rate method.

ResultsCompared with the control group, the immune nephelometry results and fasting rate method showed that the expression of immune indexes (IgG, IgA and IgM) and the expression of biochemical indexes (ALT and AST)in group A, B and C patients were increased significantly (P <0.05), and both of the expression of immune indexes and the biochemical indexes in HBV patients showed an increasing trend accompanied with the aggravation of HBV patients (A<B <C) (P<0.05).

ConclusionThe detection of immune indexes and biochemical indexes has important clinical significance in prediction of HBV patients condition, and detect a combination of biochemical indexes and immune indexes can be used to make a comprehensive judgment to provide a reliable laboratory basis for diagnosis of HBV patients condition.

category: infectious diseases


title: Impact of vaccination in reducing Hospital expenses, Mortality and Average length of stay among COVID 19 patients. A retrospective cohort study from India

abstract:
Background & AimWHO listed vaccine hesitancy among the top 10 global threats to health and there are very few reports highlighting vaccine benefits against COVID-19. The aim of this study was to study the impact of vaccination on reducing the average length of stay (ALOS), intensive care unit (ICU) requirement, mortality and cost of the treatment among COVID-19 patients.

MethodsIn this retrospective cohort study all the patients above 45 years who underwent treatment for COVID-19 were included. The data of patients treated pan India during the period March & April 2021 with the diagnosis of COVID-19, under health insurance cover, were extracted to study parameters like the ALOS, mortality, ICU requirement, total hospital expenses incurred and the vaccination status.

ResultsAmong 3820 patients with COVID-19, 3301 (86.4%) were unvaccinated while 519 (13.6%) were vaccinated. Among the unvaccinated the mean (s.d) ALOS was 7 days. Fourteen days after second dose of vaccination this was significantly less (p=0.01) at 4.9. The mean total hospital expense among the unvaccinated was Rs. 277850. Fourteen days after second dose of vaccination this was further less (p=0.001) at Rs. 217850. Among the unvaccinated population 291/3301 (8.8%) required ICU and this was significantly less (p=0.03) at 31/519 (6%) among the vaccinated. Among those who received two doses of vaccination it was further less at 1/33 (3%). The mortality among unvaccinated patients was 16/3301 (0.5%) while there was no mortality among the vaccinated. Among those who received two doses of vaccination there was a 66% relative risk reduction in ICU stay and 81% relative risk reduction in mortality.

ConclusionsThere was a significant reduction in ALOS, ICU requirement, mortality & treatment cost in patients who had completed two doses of vaccination. These findings may be used in motivating public and promoting vaccination drive.


title: ADESSO detects SARS-CoV-2 and its variants: extensive clinical validation of an optimised CRISPR-Cas13-based COVID-19 test

abstract: SARS-CoV-2 is the causative agent for a pandemic that has had immense consequences for the health and economic sectors worldwide. While PCR testing and later antigen tests have proven critical for helping to stem the spread of the virus, these methods suffer from general applicability and sensitivity, respectively. Moreover, the emergence of variant strains creates the need for flexibility to correctly and efficiently diagnose the presence of substrains in the population. To address these needs we have developed the diagnostic test ADESSO (Accurate Detection of Evolving SARS-CoV-2 through SHERLOCK Optimization) which employs the Cas13 system to diagnose patients in as little as 1 hour without sophisticated equipment. Using an extensive panel of clinical samples, we demonstrate that ADESSO correctly identifies COVID-19 positive samples at a sensitivity and specificity comparable to RT-qPCR on extracted RNA and higher than antigen tests for unextracted samples. Taken together, ADESSO is a fast, sensitive and cheap method that can be applied in a point of care (POC) setting to diagnose COVID-19 and can be quickly adjusted to detect new variants.


title: ADESSO: a rapid, adaptable and sensitive Cas13-based COVID-19 diagnostic platform


title: COVID in Post Vaccinated individuals- Beacon of Light

abstract:
IntroductionCOVISHIELD and COVAXIN have been introduced post rapid approval as COVID vaccines in India, which has the second most COVID cases across countries. These vaccines are being administered in a two-dose schedule from 16 Jan 2021. This study deals with the clinical profile of individuals who developed COVID infection post-COVID vaccination.

This is the first study of similar nature in India.

MethodologyThe study population comprised of individuals who were detected to be COVID positive 04 weeks post-vaccination and were compared with individuals detected positive within the first 04 weeks of vaccination. Data was collected in a digital questionnaire format and analyzed with SPSS v-23 software. Clinical features were profiled in detail. Chi-square analysis was done to find out the association of various demographic features with the severity of the disease.

ResultsIn the study population, fever was the commonest symptom (75.1%) followed by anosmia (72.1%), and shortness of breath (16.3%). There was a lower incidence of fever, cough, dyspnea, and requirement of hospitalization in the study population as compared to the control group and previous epidemiological data. The time required for complete recovery and disease severity was favorable in our study population. There was a significant correlation in the rate of hospitalization among the study group and the comparative group (p=0.0001) and between the number of dosage of COVID vaccine with the lowest SpO2 recorded (p=0.001).

ConclusionThis study will boost the ongoing initiative of having a maximal vaccinated population countrywide and emphasize the need for two doses of vaccination.


title: Data-Driven Patterns in Protective Effects of Ibuprofen and Ketorolac on Hospitalized Covid-19 Patients

abstract: The impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on patients with Covid-19 has been unclear. A major reason for this uncertainty is the confounding between treatments, patient comorbidities, and illness severity. Here, we perform an observational analysis of over 3000 patients hospitalized for Covid-19 in a New York hospital system to identify the relationship between in-patient treatment with Ibuprofen or Ketorolac and mortality. Our analysis finds evidence consitent with a protective effect for Ibuprofen and Ketorolac, with evidence stronger for a protective effect of Ketorolac than for a protective effect of Ibuprofen.


title: Mucosal-Associated Invariant T (MAIT) Cells are Highly Activated in Duodenal Tissue of Humans with Vibrio cholerae O1 Infection

abstract: Mucosal-associated invariant T (MAIT) cells are unconventional T lymphocytes with a semi-conserved TCR, activated by the presentation of vitamin B metabolites by the MHC-I related protein, MR1, and with diverse innate and adaptive effector functions. The role of MAIT cells in acute intestinal infections, especially at the mucosal level, is not well known. Here, we analyzed the presence and phenotype of MAIT cells in duodenal biopsies and paired peripheral blood samples, in patients during and after culture-confirmed Vibrio cholerae O1 infection. Immunohistochemical staining of duodenal biopsies from cholera patients identified MAIT cells in the lamina propria, but not in the lining of villous and crypt epithelia. We observed significantly higher frequencies of duodenal MAIT cells at the acute stage (day 2) of V. cholerae infection as compared to late convalescence (day 30, p = 0.0049). By flow cytometry, we showed that duodenal MAIT cells are more activated than peripheral MAIT cells (p < 0.01 across time points), although there were no significant differences between duodenal MAITs at day 2 and day 30. We found fecal markers of intestinal permeability and inflammation to be correlated with the loss of duodenal (but not peripheral) MAIT cells, and single-cell sequencing revealed differing T cell receptor usage between the duodenal and peripheral blood MAIT cells. In summary, we show that MAIT cells are present and highly activated in the lamina propria of the duodenum during V. cholerae infection. Future work into the trafficking and tissue-resident function of MAIT cells is warranted.


title: Dysphagic disorder in a cohort of COVID-19 patients: evaluation and evolution

abstract:
BackgroundCOVID-19 is a multisystem disease complicated by respiratory failure requiring sustanined mechanical ventilation (MV). Prolongued oro-tracheal intubation is associated to an increased risk of dysphagia and bronchial aspiration. Purpose of this study was to investigate swallowing disorders in critically ill COVID-19 patients.

MethodsThis was a retrospective study analysing a consecutive cohort of COVID-19 patients admitted to the Intensive Care Unit (ICU) of our Hospital. Data concerning dysphagia were collected according to the Gugging Swallowing Screen (GUSS) and related to demographic characteristics, clinical data, ICU Length-Of-Stay (LOS) and MV parameters.

ResultsFrom March 2 to April 30 2020, 31 consecutive critically ill COVID-19 patients admitted to ICU were evaluated by speech and language therapists (SLT). Twenty-five of them were on MV (61% through endotracheal tube and 19% through tracheostomy); median MV lenght was 11 days. Seventeen (54.8%) patients presented dysphagia; a correlation was found between first GUSS severity stratification and MV days (p < 0.001), ICU LOS (p < 0.001), age (p = 0.03) and tracheostomy (p = 0.042). No other correlations were found. At 16 days, 90% of patients had fully recovered; a significant improvement was registered especially during the first week (p < 0.001).

ConclusionCompared to non-COVID-19 patiens, a higher rate of dysphagia was reported in COVID-19 patients, with a more rapid and complete recovery. A systematic early SLT evaluation of COVID-19 patients on MV may thus be useful to prevent dysphagia-related complications.

category: intensive care and critical care medicine


title: Nasogastric tube in critical care setting: combining ETCO2 and pH measuring to confirm correct placement

abstract:
Introductionnasogastric tube (NGT) placement is a common procedure performed in critical care setting. Chest X-Ray is the diagnostic gold-standard to confirm correct placement, with the downsides of both the need for critical care patients mobilization and intrinsic actinic risk. Other potential methods to confirm NGT placement have shown lower accuracy compared to chest X-ray; ETCO2 and pH analysis have singularly yet investigated as an alternative to the gold standard. Aim of this study was to determine thresholds in combine measurements of ETCO2 and pH values, at which correct NGT positioning can be confirmed with the highest accuracy.

Material & Methodsa prospective, multicenter, observational trial; a continuous cohort of eligible patients was allocated to two arms, to identify clear cut-off threshold able to detect correct NGT tip positioning with the maximal accuracy. Patients underwent general anesthesia and orotracheal intubation; in the first group difference between tracheal and esophageal ETCO2 values were assessed. In the second group difference between esophageal and gastric pH values were determined.

Resultsfrom November 2020 to March 2021, 85 consecutive patients were enrolled: 40 in the ETCO2 group and 45 in the pH group. The ETCO2 ROC analysis for predicting NGT tracheal misplacement demonstrate an optimal ETCO2 cutoff value of 25.5 mmHg, where both sensitivity than specificity reach 1.0 (AUC 1.0, p < 0.001). The pH ROC analysis for predicting NGT correct gastric placement demonstrated the optimal pH cutoff value at 4.25, with a mild diagnostic accuracy (AUC 0.79, p < 0.001).

DiscussionA device capable of combining the presence of a negative marker with a positive marker could be accurate enough in identifying the correct NGTs positioning. Further studies are required to validate the reproducibility of these results by a specific device, whose accuracy also ought to be compared with standard chest X-ray.

Trial number: NCT03934515 (www.clinicaltrials.gov)


title: Integration of molecular inflammatory interactome analyses reveals dynamics of circulating cytokines and extracellular vesicle long non-coding RNAs and mRNAs in heroin addicts during acute and protracted withdrawal

abstract: Heroin addiction and withdrawal influence multiple physiological functions, including immune responses, but the mechanism remains largely elusive. The objective of this study was to investigate the molecular inflammatory interactome, particularly the cytokines and transcriptome regulatory network in heroin addicts undergoing withdrawal, compared to healthy controls (HCs). Twenty-seven cytokines were simultaneously assessed in 41 heroin addicts, including 20 at the acute withdrawal (AW) stage and 21 at the protracted withdrawal (PW) stage, and 38 age- and gender-matched HCs. Disturbed T-helper(Th)1/Th2, Th1/Th17, and Th2/Th17 balances, characterized by reduced interleukin (IL)-2, elevated IL-4, IL-10, and IL-17A, but normal TNF-, were present in the AW subjects. These imbalances were mostly restored to the baseline at the PW stage. However, the cytokines TNF-, IL-2, IL-7, IL-10, and IL-17A remained dysregulated. This study also profiled exosomal long non-coding RNA (lncRNA) and mRNA in the plasma of heroin addicts, constructed co-expression gene regulation networks, and identified lncRNA- mRNA-pathway pairs specifically associated with alterations in cytokine profiles and Th1/Th2/Th17 imbalances. Altogether, a large amount of cytokine and exosomal lncRNA/mRNA expression profiling data relating to heroin withdrawal was obtained, providing a useful experimental and theoretical basis for further understanding of the pathogenic mechanisms of withdrawal symptoms in heroin addicts.

category: addiction medicine


title: Fluid administration guided by inferior vena cava ultrasound before spinal anaesthesia may reduce post procedural hypotension rate

abstract:
PURPOSEThis study was conducted to estimate the incidence of hypotension after spinal anaesthesia after inferior vena cava ultrasound (IVCUS) guided volaemic optimization compared with a control group in patients undergoing elective surgery. According to ESICM guidelines, hypotension was defined as two systolic arterial pressure (SAP) measurements < 80 mmHg and / or a mean arterial pressure (MAP) < 60 mmHg, or a drop in SAP of more than 50 mmHg or more than 25% from baseline, or a decrease in MAP by more than 30% from baseline and / or clinical signs/symptoms of inadequate perfusion.

MATERIALS AND METHODSFrom May 2014 to February 2019, a prospective, controlled, randomised, three-arm, parallel-group trial was performed in our tertiary hospital. In the IVCUS group (I, 132 patients) and passive leg raising test group (L, 148 patients), a pre-anaesthesia volume optimization was achieved following a fluid response protocol. In control group (C, 149 patients), no specific intervention was performed.

RESULTS474 patients were collected. In group I, hypotension rate was 35%. In group L hypotension rate was 44%. In group C hypotension rate was 46%. An 11% reduction rate in hypotension (95% CI -1 to -24%, P=0.047) was observed between the group I and the group C. A 2% reduction rate in hypotension (95% CI -3 to -5%, P=0.428) was observed between group L and the group C. Total fluid amount administered was greater in the I group I than in the group C (593 ml versus 453 ml, P=0.015) and greater in the group L than the group C (511 ml versus 453 ml, P=0.11).

CONCLUSIONIVCUS guided fluid optimisation decrease the incidence of arterial hypotension after spinal anaesthesia.

category: anesthesia


title: A Qualitative System Dynamics Model for Effects of Workplace Violence and Clinician Burnout on Agitation Management in the Emergency Department

abstract:
BackgroundOver 1.7 million episodes of agitation occur annually across the United States in emergency departments (EDs), some of which lead to workplace assaults on clinicians and require invasive methods like physical restraints to maintain staff and patient safety. Recent studies demonstrated that experiences of workplace violence lead to symptoms of burnout, which may impact future decisions regarding use of physical restraints on agitated patients. To capture the dynamic interactions between clinicians and agitated patients under their care, we applied qualitative system dynamics methods to develop a model that describes causal feedback mechanisms of clinician burnout and the use of physical restraints to manage agitation.

MethodsWe convened an interprofessional panel of clinician stakeholders and agitation experts for a series of model building sessions to develop the current model. The panel derived the final version of our model over ten sessions of iterative refinement and modification, each lasting approximately three to four hours. We incorporated findings from prior studies on agitation and burnout as a result of workplace violence, identifying interpersonal and psychological factors likely to influence our outcomes of interest to form the basis of our model.

ResultsThe final model resulted in five main sets of feedback loops that describe key narratives regarding the relationship between clinician burnout and agitated patients becoming physically restrained: (1) use of restraints decreases agitation and risk of assault, leading to increased perceptions of safety and decreasing use of restraints in a balancing feedback loop which stabilizes the system; (2) clinician stress leads to a perception of decreased safety and lower threshold to restrain, causing more stress in a negatively reinforcing loop; (3) clinician burnout leads to a decreased perception of colleague support which leads to more burnout in a negatively reinforcing loop; (4) clinician burnout leads to negative perceptions of patient intent during agitation, thus lowering threshold to restrain and leading to higher task load, more likelihood of workplace assaults, and higher burnout in a negatively reinforcing loop; and (5) mutual trust between clinicians causes increased perceptions of safety and improved team control, leading to decreased clinician stress and further increased mutual trust in a positively reinforcing loop.

ConclusionsOur system dynamics approach led to the development of a robust qualitative model that illustrates a number of important feedback cycles that underly the relationships between clinician experiences of workplace violence, stress and burnout, and impact on decisions to physically restrain agitated patients. This work identifies potential opportunities at multiple targets to break negatively reinforcing cycles and support positive influences on safety for both clinicians and patients in the face of physical danger.

category: emergency medicine


title: Coverage and effectiveness of mRNA SARS-CoV-2 vaccines among United States Veterans

abstract:
ImportanceThe effectiveness of mRNA vaccination in a large and diverse American population, with older age and higher co-morbidity has not been assessed.

ObjectiveTo describe the scope of the mRNA vaccination rollout among the diverse U.S. Veterans population, and to study the mRNA COVID-19 vaccine effectiveness (VE) against infection, symptomatic disease, hospitalization, and death.

MethodsVaccination histories were obtained from medical records to determine if patients tested for SARS-CoV-2 were unvaccinated, partially vaccinated (first dose of mRNA COVID-19 vaccine), or fully vaccinated (two doses) at time of testing. First, coverage with any COVID-19 vaccination was described for all Veterans enrolled in Veterans Health Administration (VHA). Second, to evaluate VE, a matched test-negative case-control evaluation was conducted utilizing SARS-CoV-2 positive (cases [n=16,690]) and SARS-CoV-2 negative (controls [n=61,610]) tests from Veterans aged [≥]18 years old who routinely sought care at a VHA facility and were tested from December 14, 2020, through March 14, 2021. VE was calculated from odds ratios (ORs) with 95% confidence intervals (CI).

ResultsBy March 7, 2021, among 6,170,750 Veterans, 1,547,045 (23%) received at least one COVID-19 vaccination. mRNA COVID-19 VE against infection, regardless of symptoms, was 94% (95% CI 92-95) and 58% (95%CI 54-62) for full and partial vaccination (vs. no vaccination), respectively. VE against infection was similar across subpopulations, and it was not significantly different from VE against symptomatic disease. VE against COVID-19-related hospitalization and death for full vs. no vaccination was 89% (95%CI 81-93) and 99% (95%CI 87-100), respectively.

Conclusions and RelevanceThe VHAs efficient and equitable distribution of effective vaccines decreased COVID-19 infections, hospitalization, and mortality similarly for all Veterans, including Veterans with low income, homeless Veterans, immunocompromised, the elderly, minorities, and rural Veterans thus reducing health inequalities.

category: epidemiology


title: Coverage and Effectiveness of mRNA COVID-19 Vaccines among Veterans


title: Dysregulation of the Kennedy Pathway and Tricarboxylic Acid Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

abstract:
BackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease that is characterized by unexplained physical fatigue unrelieved by rest. Symptoms also include cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. A syndrome clinically similar to ME/CFS has been reported following well-documented infections with the coronaviruses SARS-CoV and MERS-CoV. At least 10% of COVID-19 survivors develop post acute sequelae of SARS-CoV-2 infection (PASC). Although many individuals with PASC have evidence of structural organ damage, a subset have symptoms consistent with ME/CFS including fatigue, post exertional malaise, cognitive dysfunction, gastrointestinal disturbances, and postural orthostatic intolerance. These common features in ME/CFS and PASC suggest that insights into the pathogenesis of either may enrich our understanding of both syndromes, and could expedite the development of strategies for identifying those at risk and interventions that prevent or mitigate disease.

MethodsUsing regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of 888 metabolic analytes in plasma samples of 106 ME/CFS cases and 91 frequency-matched healthy controls.

ResultsIn ME/CFS cases, regression, Bayesian and enrichment analyses revealed evidence of peroxisomal dysfunction with decreased levels of plasmalogens. Other findings included decreased levels of several membrane lipids, including phosphatidylcholines and sphingomyelins, that may indicate dysregulation of the cytidine-5-diphosphocholine pathway. Enrichment analyses revealed decreased levels of choline, ceramides and carnitines, and increased levels of long chain triglycerides (TG) and hydroxy-eicosapentaenoic acid. Elevated levels of dicarboxylic acids were consistent with abnormalities in the tricarboxylic acid cycle. Using machine learning algorithms with selected metabolites as predictors, we were able to differentiate female ME/CFS cases from female controls (highest AUC=0.794) and ME/CFS cases without self-reported irritable bowel syndrome (sr-IBS) from controls without sr-IBS (highest AUC=0.873).

ConclusionOur findings are consistent with earlier ME/CFS work indicating compromised energy metabolism and redox imbalance, and highlight new abnormalities that may provide insights into the pathogenesis of ME/CFS.

One Sentence SummaryPlasma levels of plasmalogens are decreased in patients with myalgic encephalomyelitis/chronic fatigue syndrome suggesting peroxisome dysfunction.


title: Evidence for Peroxisomal Dysfunction and Dysregulation of the CDP-Choline Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome


title: Mild Adverse Events of Sputnik V Vaccine Extracted from Russian Language Telegram Posts via BERT Deep Learning Model

abstract:
BackgroundThere is a limited amount of data on the COVID-19 vector vaccine Gam-COVID-Vac (Sputnik V) safety profile. Previous infodemiology studies showed that social media discourse could be analyzed to assess the most concerning adverse events (AE) caused by drugs.

ObjectiveWe aimed to investigate mild AEs of Sputnik V based on a participatory trial conducted on Telegram in the Russian language. We compared AEs extracted from Telegram with other limited databases on Sputnik V and other COVID-19 vaccines. We explored symptom co-occurrence patterns and determined how counts of administered doses, age, gender, and sequence of shots could confound the reporting of AEs.

Materials and MethodsWe collected a unique dataset consisting of 11,515 self-reported Sputnik V vaccine AEs posted on the Telegram group, and we utilized natural language processing methods to extract AEs. Specifically, we performed multi-label classifications using the deep neural language model BERT "DeepPavlov", which we pre-trained on a Russian language corpus and applied to the Telegram messages. The resulting AUC score was 0.991. We chose symptom classes that represented the following AEs: fever, pain, chills, fatigue, nausea/vomiting, headache, insomnia, lymph node enlargement, erythema, pruritus, swelling, and diarrhea.

ResultsThe results of the retrospective analysis showed that females reported more AEs than males (1.2-fold, P<.001). In addition, there were more AEs from the first dose than from the second dose (1.13-fold, P<.001), and the number of AEs decreased with age ({beta} = .05 per year, P<.001). The results also showed that Sputnik V AEs were more similar to other vector vaccines (132 units) compared with mRNA ones (241 units) according to the average Euclidean distance between the vectors of AE frequencies. Elderly Telegram users reported significantly more (5.6-fold on average) systemic AEs than their peers, according to the results of the phase III clinical trials published in The Lancet. However, the AEs reported in Telegram posts were consistent (Pearson correlation r=.94, P=.02) with those reported in the Argentinian post-marketing AE registry.

ConclusionAfter receiving the Sputnik V vaccination, Telegram users complained about pain (47%), fever (47%), fatigue (34%), and headache (25%). The results showed that the AE profile of Sputnik V was comparable with other COVID-19 vaccines. Examining the sentinel properties of participatory trials (which is subject to self-reporting biases) could still provide meaningful information about pharmaceutics, especially if only a limited amount of information on AEs is provided by producers.


title: Modelling, Simulations and Analysis of the First COVID-19 Epidemic in Shanghai

abstract: To date, over 178 million people on infected with COVID-19. It causes more 3.8 millions deaths. Based on a previous symptomatic-asymptomatic-recoverer-dead differential equation model (SARDDE) and the clinic data of the first COVID-19 epidemic in Shanghai, this paper determines the parameters of SARDDE. Numerical simulations of SARDDE describe well the outcomes of current symptomatic individuals, recovered symptomatic individuals, and died individuals, respectively. The numerical simulations suggest that both symptomatic and asymptomatic individuals cause lesser asymptomatic spread than symptomatic spread; blocking rate of about 95.5% cannot prevent the spread of the COVID19 epidemic in Shanghai. The strict prevention and control strategies implemented by Shanghai government is not only very effective but also completely necessary. The numerical simulations suggest also that using the data from the beginning to the day after about 19 days at the turning point can estimate well the following outcomes of the COVID-19 academic. It is expected that the research can provide better understanding, explaining, and dominating for epidemic spreads, prevention and control measures.


title: A physically plausible incidence rate for compartmental epidemiological models

abstract: Motivated by the recent trajectory of SARS-Cov-2 new infection incidences in Germany and other European countries, this note reconsiders the need to use a non-linear incidence rate function in deterministic compartmental models for current SARS-Cov-2 epidemic modelling. Employing a homogenous contact model, it derives such function systematically using stochastic arguments. The presented result, which is relevant to modelling of proliferation of arbitrary infectious diseases, integrates well with previous analyses, in particular closes an analytical "gap" mentioned in London and Yorke (1973) and complements the stability related work on incidence rate functions of the form {beta}IpSq seen for example in Liu, Hethcote and Levin (1987).


title: Inequalities in initiation of COVID19 vaccination by age and population group in Israel- December 2020-April 2021

abstract:
BackgroundIn Israel, COVID19 vaccination coverage varies widely by population group and age. Despite the vaccine being locally and freely available in the entire country. Comparing crude coverage between localities and population groups is misleading because of differing age structures in different population groups. In order to describe inequalities in COVID19 vaccine initiation we determined differences in age-specific dose 1 vaccine coverage between the main population groups in Israel, and characterised the influence of age on vaccine coverage within each of these groups.

MethodsWe obtained daily doses administered by municipality and age from the Ministry of Health, and demographic data from the Central Bureau of Statistics. We determined whether the relative proportion of people vaccinated in each age group (15-19, 20-29, 30-39, 40-49, 50-59, 60+) changed by population group (General Jewish, Ultra-Orthodox and Arab) using ANOVA and quantified association between age, population group and vaccine coverage using binomial regression.

Results8,507,723 individuals in 268 localities were included. Compared with the General Jewish population, vaccine coverage was lower among the Arab and Ultra-Orthodox populations and lowest in the Ultra-Orthodox population in all age groups. Gaps between population groups differed according to age group (p<0.001). In all populations, coverage decreased with decreasing age (p<0.001). The Ultra-orthodox population was the least vaccinated in all age groups relatively to those aged 60 and over

ConclusionsIn all age groups, the Ultra-Orthodox population had the lowest vaccine coverage. The younger the age group, the more Ultra-Orthodox Jews are diverging from their age peers in terms of initiating COVID19 vaccination. These findings suggest generational differences in terms of vaccination behaviour in this group. Qualitative studies understanding the causes behind this divergence can inform tailored vaccination strategies.


title: Statistical tests for heterogeneity of clusters and composite endpoints

abstract: Clinical trials and epidemiological cohort studies often group similar diseases together into a composite endpoint, to increase statistical power. A common example is to use a 3-digit code from the International Classification of Diseases (ICD), to represent a collection of several 4-digit coded diseases. More recently, data-driven studies are using associations with risk factors to cluster diseases, leading this article to reconsider the assumptions needed to study a composite endpoint of several potentially distinct diseases. An important assumption is that the (possibly multivariate) associations are the same for all diseases in a composite endpoint (not heterogeneous). Therefore, multivariate measures of heterogeneity from meta-analysis are considered, including multi-variate versions of the I2 and Q statistics. Whereas meta-analysis offers tools to test heterogeneity of clustering studies, clustering models suggest an alternative heterogeneity test, of whether the data are better described by one, or more, clusters of elements with the same mean. The assumptions needed to model composite endpoints with a proportional hazards model are also considered. It is found that the model can fail if one or more diseases in the composite endpoint have different associations. Tests of the proportional hazards assumption can help identify when this occurs. It is emphasised that in multi-stage diseases such as cancer, some germline genetic variants can strongly modify the baseline hazard function and cannot be adjusted for, but must instead be used to stratify the data.


title: Breastfeeding mother-child clinical outcomes after COVID-19 vaccination

abstract:
This is a prospective cohort study of 88 lactating women in Singapore who received two doses of BNT162b2 vaccination (Pfizer/BioNTech), whereby outcomes of mother-child dyads within 28 days after the second vaccine dose were determined through a structured questionnaire. Minimal effects related to breastfeeding were reported in this cohort; 3 of 88 (3.4%) women had mastitis with 1 of 88 (1.1%) women experiencing breast engorgement. We report an incidence of lymphadenopathy in our cohort at 5 of 88 (5.7%). Reassuringly, there was no change in reported breastmilk supply after vaccination. The most common side effect was pain/redness/swelling at the injection site, which was experienced by 57 of 88 (64.8%) women. There were no serious adverse events of anaphylaxis and hospital admissions. No adverse symptoms were reported in 67 of 88 (76.1%) breastfed children.

Whats known on this subjectTwo studies reported no serious adverse effects in both mother-child dyads after mRNA COVID-19 vaccination in mothers. Up to 61.9-67% lactating women experienced minor side effects.

What this study addsWe report an incidence of lymphadenopathy in our cohort at 5.7% as opposed to 0.3% from the Pfizer-BioNTech COVID-19 trial. Reassuringly, there was no change in reported milk supply after vaccination. Minimal effects related to breastfeeding were reported in this cohort; 3 (3.4%) women had mastitis with 1 person experiencing breast engorgement. The most common side effect was pain/redness/swelling at the injection site at 64.8%, which was experienced by 57 of 88 (65%) women. No adverse symptoms were reported in the breastfed children.

category: pediatrics


title: REPAIR OF ABDOMINAL WALL DEFECTS WITH ACELLULAR BOVINE PERICARDIUM MATRIX - A MULTICENTER PROSPECTIVE STUDY

abstract:
BackgroundThe association of prosthetic meshes in the abdominal wall repair, reducing the recurrence rates in an impactful way, has become an almost mandatory routine for the success of these surgeries. After decades using non-biological synthetic implants, from the 90s onwards biological membranes of animal or human origin were introduced - the so called acellular biological matrices - beginning a new era in abdominal wall defects correction.

MethodsThirty patients underwent repair for different abdominal wall deformities, with acellular matrices of bovine pericardium, in a total of 40 anatomically individualized implants. The median follow-up was 22 months, with patients evaluated clinically and radiologically. In three cases, biopsies of the implanted areas were performed, allowing histological analysis of the material.

ResultsThere was no recurrence of hernias in any of the cases, both clinically and radiologically. There was also no record of hematomas, infections or any phenomenon of a local or systemic reaction nature. Radiologically, it was not possible to visualize the matrices at the implantation site in any of the analysed postoperative periods. Biopsies showed important tissue neoformation replacing the implanted membranes, with important deposition of collagen, normal-looking cellularized tissue, and absence of foreign body reactions.

ConclusionsThe analysed matrices showed similarity to other biological membranes described in the international literature. Representing an important update and conceptual evolution, biological matrices must be incorporated into the therapeutic arsenal in abdominal wall repairs.

category: surgery


title: Predicting thermal injury patient outcomes in a Tertiary-Care Burn Centre, Pakistan

abstract:
ObjectivesTo explore candidate parameters for their ability to predict survival and length of hospital stay (LOS) in thermal burns patients, to prepare multivariate predictive models for these two outcomes, and to compare performance of native models to other models.

MethodsA retrospective cohort study was undertaken based on record review. Data was extracted from files of patients admitted to a tertiary-care burn centre in Lahore, Pakistan from January 1, 2020 to October 31, 2020. Univariate preselection was used to prepare multivariate logistic regression models for each outcome of interest (survival and LOS). Multivariate models were tested and compared to other models.

ResultsIncreasing TBSA of burn was positively associated with reduced survival and prolonged length of stay. Advancing age and full-thickness burns independently predicted decreased survival. Burn etiology showed prognostic value: petrol-flame burns predicted decreased survival and prolonged LOS; scald was associated with improved survival-odds and shorter LOS. The Survival-model consisted of (1) Baux score, (2) TBSA>40% and (3) serum albumin <3.5g/dl (AUC=0.968, Nagelkerke R2=0.797). The LOS-model consisted of (1) TBSA2 and (2) serum albumin concentration (AUC= 0.832, Nagelkerke R2 =0.408). In tests of discrimination and calibration, native models prepared for survival and LOS outcomes outperformed other models applicable to our dataset.

ConclusionData from a South Asian burn center has been used to explore factors influencing prognosis for their utility in predictive models for survival and the duration of hospital stay. The significant prognostic roles of TBSA, age, inhalational injury, burn-depth, etiology of burn, anatomic site of burn, hypoalbuminemia and other biochemical parameters were observed. These tools hold significance in guiding healthcare policy and in communications with patients and their families.


title: Association of the inflammation-related proteome with dementia development at older age: results from a large, prospective, population-based cohort study

abstract:
ImportanceChronic inflammation is increasingly recognized as a central feature of several forms of dementia.

ObjectiveTo determine which biomarkers of the inflammation-related proteome are associated with all-cause dementia, Alzheimers disease (AD), or vascular dementia (VD).

DesignAnalyses were performed in a case-cohort study design based on an ongoing German population-based cohort study.

SettingSerum samples of study participants were collected at baseline (2000-20002), and participants were followed up for 17 years. Information about a dementia diagnosis was collected during follow-up via collection of medical records from general practitioners.

ParticipantsAscertainment of potential dementia development during follow-ups was conducted for 6,284 study participants aged 50-75 years at baseline. Biomarker measurements were performed in a randomly collected sample of 1,435 participants and all incident dementia cases of the rest of the cohort (n=393).

Main Outcomes and MeasuresAll-cause dementia, AD and VD were the primary outcomes of this analysis.

ResultsBiomarkers were analyzed in 504 all-cause dementia cases (mean age, 67.0 [SD, 5.1] years; 262 female [52.0%], and 242 male [48.0%]) and 1,278 controls (mean age, 61.9 [standard deviation (SD): 6.5] years; 703 female [55.0%], and 575 male [45.0%]). Among the dementia cases, 163 participants developed AD and 195 VD. After correction for multiple testing, 58 biomarkers were statistically significantly associated with all-cause dementia, 22 with AD, and 33 with VD incidence. All analyses were adjusted for potential confounders. Besides single biomarker associations, we identified four biomarker clusters based on the strongest and independently associated biomarkers CX3CL1, EN-RAGE, LAP TGF-beta-1 and VEGF-A. CX3CL1 (Odds ratio [95%-confidence interval] per 1 standard deviation increase: 1.41 [1.24-1.60]) and EN-RAGE (1.41 [1.25-1.60]) were associated with all-cause dementia incidence, EN-RAGE (1.51 [1.25-1.83]) and LAP TGF-beta-1 (1.46 [1.21-1.76]) with AD incidence, and VEGF-A (1.43 [1.20-1.70]) with VD incidence. All named associations were stronger among APOE {varepsilon}4 negative subjects.

Conclusion and RelevanceThis study shows for the first time that the majority of inflammation-related proteins measured in serum samples (58 of 72 tested (80.6%)) are associated with all-cause dementia incidence. Future studies should not only concentrate on single biomarkers but also the complex relationships in biomarker clusters.

Key PointsO_ST_ABSQuestionC_ST_ABSWhich biomarkers of the inflammatory proteome are risk factors for dementia?

FindingsAfter correction for multiple testing, in this large prospective cohort study (n=1,782), 58 of 72 tested (80.6%) inflammation-related proteins were associated with all-cause dementia.

Furthermore, 22 and 33 were significantly associated with Alzheimers disease and vascular dementia. Due to high inter-correlation, only four biomarkers (CX3CL1, EN-RAGE, LAP TGF-beta-1, VEGF-A) were independently associated with dementia outcomes.

MeaningThe underlying pathophysiology of dementia development might involve complex inflammatory protein clusters, and the identified biomarkers might be promising new drug targets, early diagnostic markers, or parts of prediction models.


title: The Refractive Error and Vision Impairment Estimation With Spectacle data (REVIEWS) study

abstract:
ObjectiveTo investigate whether spectacle lens sales data can be used to estimate the population distribution of refractive error amongst ametropes and hence estimate the current and future risk of vision impairment.

DesignCross Sectional Study

SubjectsA total 141,547,436 spectacle lens sales records from an international European lens manufacturer between the years 1998 and 2016.

MethodsAnonymized patient spectacle lens sales data including refractive error information was provided by a major European spectacle lens manufacturer. Data from the Gutenberg Health Survey was digitized to allow comparison of a representative, population-based sample to the spectacle lens sales data. A bootstrap analysis was completed to assess the comparability of both datasets. The expected level of vision impairment due to myopia at age 75 was calculated for both datasets using a previously published risk estimation equation combined with a saturation function.

Main Outcome MeasuresComparability of spectacle lens sales data on refractive error to typical population surveys of refractive error and its potential utility to predict vision impairment due to refractive error.

ResultsEquivalent estimates of the population distribution of spherical equivalent refraction can be provided from spectacle lens data within limits. For myopia, the population distribution was equivalent to the Gutenberg Health Survey ([≤] 5% deviation) for levels [≤]-2.0 dioptres, while for hyperopia the distribution was equivalent ([≤] 5% deviation) for levels [≥] +3.0 diopters. The estimated rates of vision impairment due to myopia were not statistically significantly different ({chi}2 = 182, DoF = 169, p = 0.234) between the spectacle lens data and Gutenberg Health Survey data.

ConclusionsThe distribution of refractive error and hence the risk of vision impairment due to refractive error within a population can be determined using spectacle lens sales data. Pooling this type of data from multiple industry sources could provide a cost effective, timely and globally representative mechanism for monitoring the evolving epidemiology of refractive error and associated vision impairment.

category: ophthalmology


title: The Knowledge and Attitude of Physicians Regarding Vaccinations in Yerevan, Armenia: Challenges for COVID-19

abstract:
BackgroundThis primary-data analysis investigates the current level of awareness and medical knowledge of physicians in 20 health facilities in Yerevan, Armenia regarding vaccination - specifically with regard to HPV infection and the recently-introduced Gardasil vaccine used against HPV infection - that may have implications for successful roll-outs of national programmes for new vaccines, including those for COVID-19.

MethodsA questionnaire-based cross-sectional study was completed by 348 physicians who met the study inclusion criteria, from 20 out of 36 randomly selected healthcare facilities in Yerevan, Armenia, between Dec 2017 to Sep 2018. The aim of the questionnaire was to identify physicians awareness of and attitudes to HPV-related cervical cancer and the Gardasil vaccine. Responses were analysed using SPSS software (Version 16).

ResultsThe responding physicians displayed a respectable level of knowledge and awareness regarding vaccination with regard to some characteristics (e.g. more than 81% knew that HPV infection was commonly asymptomatic, 87% were knew that HPV infection was implicated in most cervical cancers and 87% knew that cervical cancer is the most prevalent cancer amongst women) but low knowledge in others and poor understanding of key issues such as the age at which women were most likely to develop cervical cancer (only 15% answered correctly); whether or not the vaccine should be administered to people who had already been affected (27% answered correctly) and whether sexually active young people should be treated for infection before vaccination (26%). Lack of confidence within the surveyed groups regarding the value of vaccination and, in particular concerns over the reasons for administering it to certain age cohorts, was driven by misconceptions.

ConclusionsArmenian physicians awareness of vaccine characteristics, the reasons for their inclusion in the national vaccination programme and the characteristics of the diseases they treat can be poor. The study further suggests that drivers of vaccine hesitancy are complex, may not be consistent from vaccine to vaccine, and may vary from generation to generation. The Armenian healthcare sector may need to provide additional training, awareness-raising and educational activities to improve understanding of and trust in vaccination programmes. Further studies are warranted to better understand knowledge, attitudes and practices (KAP) regarding immunization and vaccination programmes amongst Armenian healthcare workers.


title: Hybrid-Quantum approach for the optimal lockdown to stop the SARS-CoV-2 community spread subject to maximizing nation economy globally

abstract: Owing to the SARS-CoV-2 epidemic (severe acute respiratory coronavirus 2 syndromes), the global situation has changed drastically. Several countries, including India, Europe, U.S.A., introduced a full state/nation lockdown to minimize the disease transmission through human interaction after the virus entered the population and to minimize the loss of human life. Millions of people have gone unemployed due to lockdown implementation, resulting in business and industry closure and leading to a national economic slowdown. Therefore, preventing the spread of the COVID-19 virus in the world while also preserving the global economy is an essential problem requiring an effective and immediate solution. Using the compartmental epidemiology S, E, I, R or D (Susceptible, Exposed, Infectious, Recovery or Death) model extended to multiple population regions we predict the evolution of the SARS-CoV-2 disease and construct an optimally scheduled lockdown calendar to execute lockdown over phases, using the well-known Knapsack problem. A comparative analysis of both classical and quantum models shows that our model decreases SARS-CoV-2 active cases while retaining the average global economic factor, GDP, in contrast to the scenario with no lockdown.


title: Genetic analyses of common infections in the Avon Longitudinal Study of Parents and Children cohort

abstract: The burden of infections on an individual and public health is profound. Many observational studies have shown a link between infections and the pathogenesis of disease; however a greater understanding of the role of host genetics is essential. Children from the longitudinal birth cohort, the Avon Longitudinal Study of Parents and Children, had 14 antibodies measured in plasma at age 7: Alpha-casein protein, beta-casein protein, cytomegalovirus, Epstein-Barr virus, feline herpes virus, Helicobacter pylori, herpes simplex virus 1, influenza virus subtype H1N1, influenza virus subtype H3N2, measles virus, Saccharomyces cerevisiae, Theilers virus, Toxoplasma gondii, and SAG1 protein domain, a surface antigen of Toxoplasma gondii measured for greater precision. We performed genome-wide association analyses of antibody levels against 14 infections (N = 357 - 5010) and identified three genome-wide signals (P < 5x10-8), two associated with measles virus antibodies and one with Toxoplasma gondii antibodies. In an association analysis focused on the human leukocyte antigen (HLA) region of the genome, we further detected 15 HLA alleles at a two-digit resolution and 23 HLA alleles at a four-digit resolution associated with five antibodies, with eight HLA alleles associated with Epstein-Barr virus antibodies showing strong evidence of replication in UK Biobank. Our findings provide a useful resource for any future studies using the ALSPAC infection data and contributes to the understanding of the architecture of host genetics related to infections.


title: Defining hypoxemia from pulse oximeter measurements of oxygen saturation in well children at low altitude in Bangladesh: an observational study

abstract:
BackgroundThe World Health Organization defines hypoxemia, a low peripheral oxyhemoglobin saturation (SpO2), as <90%. Although hypoxemia is an important risk factor for mortality of children with respiratory infections, the optimal SpO2 threshold for defining hypoxemia is uncertain in low-income and middle-income countries (LMICs). We derived a SpO2 threshold for hypoxemia from well children in Bangladesh residing at low altitude.

MethodsWe prospectively enrolled well, 3-35 month old children participating in a pneumococcal vaccine evaluation in Sylhet district, Bangladesh between June and August 2017. Trained health workers conducting community surveillance measured the SpO2 of children using a Masimo Rad-5(R) pulse oximeter with a wrap sensor. We used standard summary statistics to evaluate the SpO2 distribution, including whether the distribution differed by age or sex. We considered the 2.5th, 5th, and 10th percentiles of SpO2 as possible lower thresholds for hypoxemia.

ResultsOur primary analytical sample included 1,470 children (mean age 18.6 +/- 9.5 months). Median SpO2 was 98% (interquartile range, 96-99%), and the 2.5th, 5th, and 10th percentile SpO2 was 91%, 92%, and 94%. No child had a SpO2 <90%. Children 3- 11 months old had a lower median SpO2 (97%) than 12-23 month olds (98%) and 24- 35 month olds (98%) (p=0.039). The SpO2 distribution did not differ by sex (p=0.959).

ConclusionA SpO2 threshold for hypoxemia derived from the 2.5th, 5th, or 10th percentile of well children is higher than <90%. If a higher threshold than <90% is adopted into LMIC care algorithms then decision-making using SpO2 must also consider the childs clinical status to minimize misclassification of well children as hypoxemic. Younger children in lower altitude LMICs may require a different threshold for hypoxemia than older children. Evaluating the mortality risk of sick children using higher SpO2 thresholds for hypoxemia is a key next step.

Key MessagesO_LIWhat is the key question? The ideal peripheral oxyhemoglobin saturation (SpO2) threshold for defining hypoxemia among children in low-income and middle-income countries is unknown.
C_LIO_LIWhat is the bottom line? A SpO2 threshold for hypoxemia set at any of the 2.5th, 5th, or 10th percentiles of SpO2 measurements from well children in a lower altitude setting is higher than the <90% threshold currently recommended by the World Health Organization.
C_LIO_LIWhy read on? This study is a possible model for other research seeking to establish SpO2 thresholds for hypoxemia in children and provides evidence for health policy makers to consider before implementing higher SpO2 thresholds than currently in practice in lower altitude settings of low-income and middle-income countries.
C_LI


title: EVALUATION OF HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH DIABETES IN DIFFERENT CARE SETTINGS A CROSS SECTIONAL STUDY IN ALAIN, UAE

abstract:
PurposeThis study aims to assess health-related quality of life (HRQOL) in type 2 diabetic patients across four domains--physical, psychological, social, and environmental--and explore the possible determinants of these domains.

MethodsUsing a cross-sectional study design, 397 type 2 diabetic patients in Alain city were interviewed using validated questionnaires in three different care settings: primary, secondary and private health care facilities. The WHO Quality of Life instrument, generalized anxiety disorder score, and Patient Health Questionnaire (PHQ9) were employed.

ResultsThe participants comprised 270 females (68%) and 127 males (32%), with 68.9% in the 41-65 years age group; 49.6% were married. The most common comorbidities were dyslipidemia (69.3%), hypertension (61%), and osteoarthritis (24.7%). On a scale of 0 to 100, the highest QOL mean score was reported in the social relationship domain (78.3), followed by the environmental (77.7), psychological health (74.2), and physical health (70.7) domains.

The risk of depression was a strong determinant of poor physical health. Social factors have great impact on a patients health and well-being. We noticed no difference in HRQOL outcome between primary, secondary, and private health care facilities.

ConclusionThe social and mental health domains were the most influential in HRQOL among the participants. This finding supports targeting QOL assessments of patients with type 2 diabetes at the regular chronic diseases clinics and in the planning of population health management programs to ensure the best outcomes.

Plain English SummaryDiabetes mellitus is considered a major cause of morbidity and mortality worldwide. In our study we are aiming to explore difference in quality of life and quality of care in patients who access different health care facilities, primary health care clinics versus patients following in secondary care center and private center in Alain. By doing so, we will expand the knowledge regarding health related quality of life of people with diabetes in the UAE and opens the door for future international collaborative research in Diabetes.

category: primary care research


title: Reduction in left frontal alpha oscillations by transcranial alternating current stimulation in major depressive disorder is context-dependent in a randomized-clinical trial

abstract:
BackgroundLeft frontal alpha oscillations are associated with decreased approach motivation and have been proposed as a target for non-invasive brain stimulation for the treatment of depression and anhedonia. Indeed, transcranial alternating current stimulation (tACS) at the alpha frequency reduced left frontal alpha power and was associated with a higher response rate than placebo stimulation in patients with major depressive disorder (MDD) in a recent double-blind placebo controlled clinical trial.

MethodsIn this current study, we aimed to replicate such successful target engagement by delineating the effects of a single session of bifrontal tACS at the individualized alpha frequency (IAF-tACS) on alpha oscillations in patients with MDD. Electrical brain activity was recorded during rest and while viewing emotionally-salient images before and after stimulation to investigate if the modulation of alpha oscillation by tACS exhibited specificity with regards to valence.

ResultsIn agreement with the previous study of tACS in MDD, we found that a single session of bifrontal IAF-tACS reduced left frontal alpha power during the resting state when compared to placebo. Furthermore, the reduction of left frontal alpha oscillation by tACS was specific for stimuli with positive valence. In contrast, these effects on left frontal alpha power were not found in healthy control participants.

ConclusionTogether these results support an important role of tACS in reducing left frontal alpha oscillations as a future treatment for MDD.

National Clinical TrialNCT03449979, "Single Session of tACS in a Depressive Episode (SSDE)" https://www.clinicaltrials.gov/ct2/show/NCT03449979

category: psychiatry and clinical psychology