title: Childhood temperamental, emotional, and behavioral predictors of clinical mood and anxiety disorders in adolescence

abstract:
BackgroundMood and anxiety disorders, often emerging during adolescence, account for a large share of the global burden of disability. Prospectively assessed premorbid early signs and trajectories can provide useful insights for early detection and development of these disorders.

MethodsUsing the health registry linked Norwegian Mother, Father and Child Cohort Study (MoBa) of 110,367 children, we here examine cross-sectional and longitudinal association between temperamental traits, emotional and behavioral problems in childhood (0.5-8 years) and diagnosis of mood or anxiety (emotional) disorders in adolescence (10-18 years). We included birth year and sex, retrieved from the Medical Birth Registry of Norway, as covariates in all analyses.

ResultsLogistic regression analyses showed consistent and increasing associations between childhood negative emotionality, behavioral and emotional problems and adolescent diagnosis of emotional disorders, present from 6 months of age (negative emotionality) and with similar magnitude of association for the associated traits. Latent profile analysis incorporating latent growth models identified five developmental profiles of emotional and behavioral problems. A profile of early increasing behavioral and emotional problems with combined symptoms at 8 years (1.3% of sample) was the profile most strongly associated with emotional disorders in adolescence (OR vs. reference: 5.00, 95% CI: 3.73-6.30).

ConclusionsWe found a consistent and increasing association between negative emotionality, behavioral and emotional problems in early to middle childhood and mood and anxiety disorders in adolescence. A developmental profile coherent with early and increasing disruptive mood dysregulation across childhood was most predictive of adolescent emotional disorders. Our results highlight the importance of early emotional dysregulation and childhood as a formative period in the development of adolescent mood and anxiety disorders, supporting a potential for prevention and early intervention initiatives.

category: psychiatry and clinical psychology


title: Network-Based Methods for Psychometric Data of Eating Disorders: A Systematic Review

abstract: Network science represents a powerful and increasingly promising method for studying complex real-world problems. In the last decade, it has been applied to psychometric data in the attempt to explain psychopathologies as complex systems of causally interconnected symptoms. With this work, we aimed to review a large sample of network-based studies that exploit psychometric data related to eating disorders (ED) trying to highlight important aspects such as core symptoms, influences of external factors, comorbidities, and changes in network structure and connectivity across both time and subpopulations. A particular focus is here given to the potentialities and limitations of the available methodologies used in the field. At the same time, we also give a review of the statistical software packages currently used to carry out each phase of the network estimation and analysis workflow. Although many theoretical results, especially those concerning the ED core symptoms, have already been confirmed by multiple studies, their supporting function in clinical treatment still needs to be thoroughly assessed.


title: High Brain-Derived Neurotrophic Factor (BDNF) and Negative Psychological Flexibility associate with Early Fatigue Syndrome in healthy females

abstract:
BackgroundRecent studies showed that enhancing psychological flexibility could improve fatigue interference. Brain-Derived Neurotrophic Factor (BDNF), Heart Rate Variability (HRV), and Cortisol were proposed to involve biomarkers in psychological flexibility. Our study aims to explore the association of fatigue with psychological flexibility and related biomarkers.

MethodA cross-sectional study gathered data from a baseline characteristic mindful volunteer. Each participant was self-evaluated with the questionnaire of fatigue and psychological flexibility. The participants were evaluated potential biomarkers related to psychological flexibility including HRV, serum cortisol, and BDNF within one week after responding to the questionnaire.

ResultsThe 47 healthy females including 22 nurses and 25 occupational therapy students, mean age 29.70 {+/-} 12.55 years. The prevalence of fatigue is 38.30%. The multivariate analysis showed the independent factors associated with fatigue including negative psychological flexibility (OR 1.31, p=0.03) and high BDNF (OR 1.33, p=0.05).

ConclusionOur study found that psychological flexibility and high BDNF was independent factors associate with fatigue. This result provide insight that intervention that increase either psychological flexibility may prevent fatigue symptoms. The high BDNF may reflex the adaptive response of fatigue person and may be potential biomarkers for detecting early fatigue conditions.


title: Clinical and Demographic Characteristics of Treatment Requiring Retinopathy of Prematurity (ROP) in Big Premature Infants in Turkey - Report No: 1 (BIG-ROP STUDY)

abstract:
AimTo demonstrate the clinical and demographic features of infants with gestational age (GA) of 32-37 weeks (wk) and birth weight (BW) of >1500 g who developed treatment requiring retinopathy of prematurity (ROP).

MethodsRetrospective, observational, descriptive, multicentre study was conducted by the Turkish Ophthalmological Association ROP commission. Data on the infants with a GA of 32-37 wk and BW >1500 g who developed treatment-requiring ROP were collected from the 33 ROP centres in Turkey. GA, BW, type of hospital, neonatal intensive care units (NICU) level, length of stay in NICU, duration of oxygen therapy, comorbidities, type of ROP and time for treatment-requiring ROP (TR-ROP) development were analysed.

ResultsTotally 366 infants were included in the study. The mean GA and BW were 33{+/-}1 wk and 1896 {+/-} 316 g, respectively. Duration of hospitalization was 3-4 wk in 46.8% of them. The first ROP examination was performed at postnatal 4-5 wk in 80.3% of infants, which was significantly later in lower levels of NICU and non-university clinics. ROP was detected in 90.9% of infants at the first ROP examination, especially in clinics without an ophthalmologist. In 15.3% of the infants, treatment was required in postnatal fourth week, and the mean development of TR-ROP was 6.16 {+/-} 2.04 wk

ConclusionRoutine ROP screening thresholds need to be expanded in hospitals with suboptimal NICU conditions considering the development of TR-ROP in more mature and heavier preterm infants, and the first ROP examination should be no later than postnatal fourth week.

What is already known on this topicTreatment-requiring retinopathy of prematurity (TR-ROP) may develop in bigger and more mature infants with a gestational age >32 weeks and birth weight >1500g especially in low/middle-income countries where proper neonatal intensive care conditions could not be provided,

What this study addsThis is the first study analysing the regional differences and the effect of presence of the ophthalmologist and neonatologist in the same hospital as NICU on the development of TR-ROP in a nation-wide study in Turkey. This study emphasizes the high rate of ROP at the first examination in these bigger babies and progression to TR-ROP in a short time. The ROP in these infants may be more aggressive like A-ROP and may progress rapidly in a short time. The results of our study suggest the need for a timely (even earlier) screening for bigger infants and a revision to expand the limits of the ROP screening program to bigger infants in at least underdeveloped parts of Turkey. This may be generalized to all of the underdeveloped countries.

How this study might affect research, practice or policyScreening criteria for ROP need to be revised for the coverage of bigger infants in Turkey depending on the NICU conditions of the hospitals. Infants with a gestational age of >32 weeks and a birth weight of >1500 g may need to be screened for ROP earlier than postnatal four weeks. Increasing the number of well-educated neonatologists and ophthalmologists as well as other NICU conditions will improve neonatal care for ROP to the standards of developed countries.

category: ophthalmology


title: Estimating the burden of foodborne gastroenteritis due to nontyphoidal Salmonella enterica, Shigella and Vibrio parahaemolyticus in China

abstract: To estimate the incidence of foodborne gastroenteritis caused by nontyphoidal Salmonella enterica, Shigella, and Vibrio parahaemolyticus in China, population surveys and sentinel hospital surveillance were implemented in six provinces from July 2010 to July 2011, and a multiplier calculation model for the burden of disease was constructed. The multiplier for salmonellosis and V. parahaemolyticus gastroenteritis was estimated at 4,137 [95% confidence interval (CI) 2,320-5,663], and for shigellosis at 4,356 (95% CI 2,443-5,963). Annual incidence per 100,000 population was estimated as 245 (95% CI 138-336), 67 (95% CI 38-92), and 806 (95% CI 452-1,103) for foodborne salmonellosis, shigellosis, and V. parahaemolyticus gastroenteritis, respectively, indicating that foodborne infection caused by these three pathogens constitutes an important burden to the Chinese healthcare system. Continuous implementation of active surveillance of foodborne diseases, combined with multiplier models to estimate disease burden, makes it possible for us to better understand food safety status in China.

category: epidemiology


title: No evidence for environmental transmission risk of SARS-CoV-2 in the UK's largest urban river system: London as a case study

abstract: The presence of SARS-CoV-2 in untreated sewage has been confirmed in many countries but its incidence and infection risk in contaminated freshwaters is still poorly understood. The River Thames in the UK receives untreated sewage from 57 Combined Sewer Overflows (CSOs), with many discharging dozens of times per year. We investigated if such discharges provide a pathway for environmental transmission of SARS-CoV-2. Samples of wastewater, surface water, and sediment collected close to six CSOs on the River Thames were assayed over 8 months for SARS-CoV-2 RNA and infectious virus. Bivalves were sampled as sentinel species of viral bioaccumulation. Sediment and water samples from the Danube and Sava rivers in Serbia, where raw sewage is also discharged in high volumes, were assayed as a positive control. We found no evidence of SARS-CoV-2 RNA or infectious virus in UK samples, in contrast to RNA positive water and sediment samples from Serbia. Furthermore, we show that infectious SARS-CoV-2 inoculum is stable in Thames water and sediment for < 3 days, while RNA remained detectable for at least seven days. This indicates that dilution of wastewater likely limits environmental transmission, and that infectivity should be embedded in future risk assessments of pathogen spillover.


title: COVID-19 Vaccine Hesitancy among Marginalized Populations in the U.S. and Canada: Protocol for a Scoping Review

abstract:
IntroductionDespite the development of safe and highly efficacious COVID-19 vaccines, extensive barriers to vaccine deployment and uptake threaten the effectiveness of vaccines in controlling the pandemic. Notably, marginalization produces structural and social inequalities that render certain populations disproportionately vulnerable to COVID-19 incidence, morbidity, and mortality, and less likely to be vaccinated. The purpose of this scoping review is to provide a comprehensive overview of definitions/conceptualizations, elements, and determinants of COVID-19 vaccine hesitancy among marginalized populations in the U.S. and Canada.

Materials and MethodsThe proposed scoping review follows the framework outlined by Arksey and OMalley, and further developed by the Joanna Briggs Institute. It will comply with reporting guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The overall research question is: What are the definitions/conceptualizations and factors associated with vaccine hesitancy in the context of COVID-19 vaccines among adults from marginalized populations in the U.S. and Canada. Search strategies will be developed using controlled vocabulary and selected keywords, and customized for relevant databases, in collaboration with a research librarian. The results will be analyzed and synthesized quantitatively (i.e., frequencies) and qualitatively (i.e., thematic analysis) in relation to the research questions, guided by a revised WHO Vaccine Hesitancy Matrix.

DiscussionThis scoping review will contribute to honing and advancing the conceptualization of COVID-19 vaccine hesitancy and broader elements and determinants of underutilization of COVID-19 vaccination among marginalized populations, identify evidence gaps, and support recommendations for research and practice moving forward.

category: public and global health


title: Parapneumonic effusions related to Streptococcus pneumoniae: serotype and disease severity trends

abstract:
IntroductionStreptococcus pneumoniae epidemiology is changing in response to vaccination and some data suggest empyema incidence is increasing. However, differences exist between UK and USA studies. We describe trends in the clinical phenotype of adult pneumococcal pleural infection, including simple parapneumonic effusions (SPE) in the pneumococcal conjugate vaccination (PCV) era.

MethodsRetrospective cohort study, all adults [≥]16 years admitted to three large UK hospitals, 2006-2018 with pneumococcal disease. Medical records were reviewed for each clinical episode. Serotype data were obtained from the UKHSA national reference laboratory.

Results2477 invasive pneumococcal cases were identified: 459 SPE and 100 pleural infection cases. Incidence increased over time, including non-PCV-serotype disease. PCV7-serotype disease declined following paediatric PCV7 introduction, but the effect of PCV13 was less apparent as disease caused by the additional six serotypes plateaued with serotypes 1 and 3 causing such parapneumonic effusions from 2011 onwards.

Mortality was lower in pleural infection patients than SPE patients. Patients with frank pus had lower mortality then those without. 90-day mortality could be predicted by baseline increased RAPID score.

ConclusionPneumococcal infection continues to cause severe disease despite the introduction of PCVs. The predominance of serotype 1 and 3 in this adult UK cohort is in keeping with previous studies in paediatric and non-UK studies. Rising non-PCV serotype disease and limited impact of PCV13 on cases caused by serotypes 1 and 3 offset the reductions in adult pneumococcal parapneumonic effusion disease burden observed following introduction of the childhood PCV7 programme.

Take home messagePneumococcal parapneumonic effusions show increasing incidence despite PCV introduction, with serotype 1 and 3 persisting and increase in non-PCV13 disease. Pleural infection showed lower mortality than SPE, and baseline RAPID score predicted 90-day mortality.

category: respiratory medicine


title: Low Vision Rehabilitation Training and Referral Patterns Among Ophthalmologists

abstract:
ObjectiveVision impairment represents a growing burden to society and training protocols related to low vision rehabilitation (vision rehab) vary across ophthalmology residency programs. We surveyed practicing ophthalmologists regarding their vision rehab knowledge, confidence levels, and referral thresholds. We categorized subjects and compared response patterns between groups.

DesignProspective observational

Subjects185 practicing ophthalmologists

MethodsWe created an Ophthalmology Low Vision Questionnaire and administered it to all enrolled subjects via email. We categorized subjects based on duration of practice, subspecialty area, and exposure to vision rehab during residency training. We drew conclusions by comparing responses between various subject categories.

Main Outcome MeasuresThe primary outcome measure was comparison of confidence levels and thresholds for vision rehab referral across groups. We used statistical tests to look for associations between practice duration, subspecialty area, vision rehab exposure during residency, and referral patterns.

ResultsOphthalmologists practicing for 6 or less years were more likely to have had a formal vision rehab rotation during their residency training compared to ophthalmologists practicing for 7 or more years (P = 0.03). Ophthalmologists who completed a formal vision rehab rotation during residency reported greater confidence in their ability to appropriately identify patients who could benefit from vision rehab referral (P = 0.04) and referred patients at earlier visual acuity thresholds (P = 0.04). Clinical subspecialty did not have a significant effect on vision rehab referral confidence or thresholds.

ConclusionsVision rehab rotations during residency lead to improved referral confidence and earlier referral for these vital services. Standardization of vision rehab exposure across ophthalmology residency programs can help to improve outcomes for visually impaired patients.


title: Minimal SARS-CoV-2 classroom transmission at a large urban university experiencing repeated into campus introduction

abstract: SARS-CoV-2, the causative agent of COVID-19, has displayed person to person transmission in a variety of indoor situations. This potential for robust transmission has posed significant challenges to day-to-day activities of colleges and universities where indoor learning is a focus. Concerns about transmission in the classroom setting have been of concern for students, faculty and staff. With the simultaneous implementation of both non-pharmaceutical and pharmaceutical control measures meant to curb the spread of the disease, defining whether in-class instruction without any physical distancing is a risk for driving transmission is important. We examined the evidence for SARS-CoV-2 transmission on a large urban university campus that mandated vaccination and masking but was otherwise fully open without physical distancing during a time of ongoing transmission of SARS-CoV-2 both at the university and in the surrounding counties. Using weekly surveillance testing of all on-campus individuals and rapid contact tracing of individuals testing positive for the virus we found little evidence of in-class transmission. Of more than 140,000 in-person class events, only nine instances of potential in-class transmission were identified. When each of these events were further interrogated by whole-genome sequencing of all positive cases significant genetic distance was identified between all potential in-class transmission pairings, providing evidence that all individuals were infected outside of the classroom. These data suggest that under robust transmission abatement strategies, in-class instruction is not an appreciable source of disease transmission.

category: infectious diseases


title: Comorbidities Diminish the Likelihood of Seropositivity After SARS-CoV-2 Vaccination

abstract:
BackgroundThe impact of chronic health conditions (CHC) on serostatus post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is unknown.

MethodsWe assessed serostatus post-SARS-CoV-2 vaccination among fully vaccinated participants recruited between April 2021 through August 2021 in 18 years and older residents of Jefferson County, Kentucky, USA. Serostatus was determined by measuring SARS-CoV-2 Spike protein specific immunoglobulin (Ig) G (Spike IgG) antibodies via enzyme-linked immunoassay (ELISA) in peripheral blood samples.

ResultsOf the 5,178 fully vaccinated participants, 51 were seronegative and 5,127 were seropositive. Chronic kidney disease (CKD) (OR=13.49; 95% CI: 4.88-37.3; P<0.0001) and autoimmune disease (OR=11.34; 95% CI: 5.21-24.69; P<0.0001) showed highest association with negative serostatus in fully vaccinated participants. The absence of any CHC was strongly associated with positive serostatus (OR=0.37; 95% CI: 0.19-0.73; P=0.003). The risk of negative serostatus increased in the presence of two CHCs (OR=2.82; 95% CI: 1.14-7) to three or more CHCs (OR=4.52; 95% CI: 1.68-12.14). Similarly, use of 2 or more CHC related medications was significantly associated with seronegative status (OR=6.08; 95%: 2.01-18.35).

ConclusionsPresence of any CHC, especially CKD or autoimmune disease, increased the likelihood of seronegative status among individuals who were fully vaccinated to SAR-CoV-2. This risk increased with a concurrent increase in number of comorbidities, especially with multiple medications. Absence of any CHC was protective and increased the likelihood of a positive serological response post-vaccination. These results will help develop appropriate guidelines for booster doses and targeted vaccination programs.

category: allergy and immunology


title: The external validity of four risk scores predicting 30-day mortality after surgery

abstract:
BackgroundSurgical risk prediction tools can facilitate shared-decision-making and efficient allocation of perioperative resources. Such tools should be externally validated in target populations prior to implementation.

MethodsPredicted risk of 30-day mortality was retrospectively derived for surgical patients at Royal Perth Hospital from 2014 to 2021 using the Surgical Outcome Risk Tool (SORT) and the related NZRISK (n=44,031, 53,395 operations). In a sub-population (n=31,153), the Physiology and Operative Severity Score for the enumeration of Mortality (POSSUM) and the Portsmouth variant of this (P-POSSUM) were matched from the Copeland Risk Adjusted Barometer (C2-Ai, Cambridge, UK). The primary outcome was risk score discrimination of 30-day mortality as evaluated by area-under-receiver operator characteristic curve (AUROC) statistics. Calibration plots and outcomes according to risk decile and time were also explored.

ResultsAll four risk scores showed high discrimination (AUROC) for 30-day mortality (SORT=0.922, NZRISK=0.909, P-POSSUM=0.893; POSSUM=0.881) but consistently over-predicted risk. SORT exhibited the best discrimination and calibration. Thresholds to denote the highest and second-highest deciles of SORT risk (>3.92% and 1.52-3.92%) captured the majority of deaths (76% and 13% respectively) and hospital-acquired-complications. Year-on-year SORT calibration performance drifted towards over-prediction, reflecting a decrease in 30-day mortality over time despite an increase in the surgical population risk.

ConclusionsSORT was the best performing risk score in predicting 30-day mortality after surgery. Categorising patients based on SORT into low, medium (80-90th percentile) and high-risk (90-100th percentile) can guide future allocation of perioperative resources. No tools were sufficiently calibrated to support shared-decision-making based on absolute predictions of risk.

category: anesthesia


title: Longitudinal assessment of lung function in Swiss childhood cancer survivors

abstract:
RationaleChildhood cancer survivors (CCSs) are at increased risk for pulmonary morbidity due to exposure to lung-toxic treatments, including specific chemotherapies, radiotherapy, and surgery. Longitudinal data on lung function, with information on how outcomes change over time, in CCSs are scarce.

ObjectivesTo investigate lung function trajectories in childhood cancer survivors over time and investigate the association with lung-toxic treatment.

MethodsThis retrospective, multi-center cohort study included CCSs, who were diagnosed between 1990 and 2013 in Switzerland and had been exposed to lung-toxic chemotherapeutics or thoracic radiotherapy. Pulmonary function tests (PFTs) were obtained from hospital charts. We assessed quality of PFTs systematically and calculated z-scores and percentage predicted of forced expiratory volume in first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, total lung capacity (TLC) and diffusion capacity for carbon-monoxide (DLCO) based on recommended reference equations. We described lung function over time and determined risk factors for change in FEV1 and FVC using multivariable linear regression.

ResultsWe included 790 PFTs from 183 CCSs, with a median age of 12 years (IQR 7 - 14) at diagnosis. Common diagnoses were lymphoma (55%), leukemia (11%) and CNS tumors (12%). Median follow-up time was 5.5 years. Half (49%) of CCSs had at least one abnormal pulmonary function parameter, with restrictive impairment being common (22%). Trajectories of FEV1 and FVC started at z-scores of -1.5 at diagnosis and remained low throughout follow-up. CCSs treated with thoracic surgery started particularly low, with an FEV1 of -1.08 z-scores (-2.02 to -0.15) and an FVC of -1.42 z-scores (-2.27 to -0.57) compared to those without surgery. In CCS exposed to lung-toxic chemotherapeutics FEV1 z-scores increased slightly over time (0.12 per year; 95%CI 0.02 - 0.21).

ConclusionThe large proportion of CCSs with reduced lung function identified in this study underlines the need for more research and long-term surveillance of this vulnerable population.

category: pediatrics


title: Age-based differences in quantity and frequency of consumption when screening for harmful alcohol use

abstract:
AimsSurvey questions on usual quantity and frequency of alcohol consumption are regularly used in screening tools to identify drinkers requiring intervention. The aim of this study is to examine age-based differences in quantity and frequency of alcohol consumption on the Alcohol Use Disorders Identification Test (AUDIT) and how this relates to the prediction of harmful or dependent drinking

DesignCross sectional survey

SettingAustralia.

ParticipantsData was taken from 17,399 respondents who reported any alcohol consumption in the last year and were aged 18 and over from the 2016 National Drug Strategy Household Survey, a broadly representative cross-sectional survey on substance use.

MeasurementRespondents were asked about their frequency of consumption, usual quantity per occasion and the other items of the AUDIT.

FindingsIn older drinkers, quantity per occasion ({beta}=0.53 (0.43, 0.64 95%CI in 43-47 year olds as an example) is a stronger predictor of dependence than frequency per occasion ({beta}=0.24 (0.17, 0.31). In younger drinkers the reverse was true with frequency a stronger predictor ({beta}=0.54 (0.39, 0.69) in 23-27 year olds) than quantity ({beta}=0.26 (0.18, 0.34) in 23-27 year olds). Frequency of consumption was not a significant predictor of dependence in respondents aged 73 and over ({beta}=-0.03 (-0.08, 0.02)). Similar patterns were found when predicting harmful drinking. Despite this, since frequency of consumption increased steadily with age, the question on frequency was responsible for at least 65% of AUDIT scores in drinkers aged 53 and over.

ConclusionsThe items with a weaker association with dependent or harmful drinking in younger and older drinkers are the same items with the strongest influence on overall AUDIT scores. Further investigation into age-specific scoring of screening tools is recommended.


title: Impact of COVID-19 on Life Expectancy among Native Americans

abstract:
BackgroundThere has been little systematic research on the mortality impact of COVID-19 in the Native American population.

ObjectiveWe provide the first estimates of loss of life expectancy directly due to COVID-19 in 2020 and 2021 for the Native American population.

MethodsWe use several sources of data (the 2019 life table recently released by the National Center for Health Statistics for Native Americans, provisional COVID-19 deaths by age and race/ethnicity for 2020 and 2021, and population estimates from the US Census Bureau), along with multiple decrement techniques, to calculate life tables for Native Americans that include COVID-19 mortality.

ResultsNative Americans had much lower life expectancy than other groups before the pandemic, which set this population behind further: the estimated loss in life expectancy at birth due to COVID-19 for Native Americans is 2.5 years in 2020 and 2.8 years in 2021.

ConclusionsThese results underscore the disproportionate share of COVID-19 deaths experienced by Native Americans: a loss in 2020 due to COVID-19 that is almost three times as large as that for Whites and about a half-year greater than that for the Black population. Despite a successful vaccination campaign among Native Americans, the estimated loss in life expectancy at birth due to COVID-19 in 2021 unexpectedly exceeds that in 2020.

ContributionThe increased loss in life expectancy in 2021, despite higher vaccination rates than in other racial/ethnic groups, highlights the huge challenges faced by Native Americans in their efforts to control the deleterious consequences of the pandemic.


title: Demographic and clinical profile of black patients with chronic kidney disease attending Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa.

abstract:
BackgroundThe prevalence of chronic kidney disease (CKD) is increasing worldwide; black patients have an increased risk of developing CKD and end stage kidney disease (ESKD) at significantly higher rates than other races.

MethodsA cross sectional study was carried out on black patients with CKD attending the kidney outpatient clinic at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in South Africa, between September 2019 to March 2020. Demographic and clinical data were extracted from the ongoing kidney outpatient clinic records and interviews, and were filled in a questionnaire. Patients provided blood and urine for laboratory investigations as standard of care, data were descriptively and inferentially analysed using STATA version 17. Multivariable logistic regression analysis was used to identify demographic and clinical data associated with advanced CKD.

ResultsA total of 312 black patients with CKD were enrolled during the study period; 58% patients had advanced CKD, of whom 31.5 % had grossly increased proteinuria, 96.7 % had hypertension, 38.7 % had diabetes mellitus and 38.1 % had both hypertension and diabetes mellitus. For patients with advanced CKD, the median age was 61 (IQR 51-69) years, eGFR 33 (30 -39) mL/min/1.73 m2, serum bicarbonate 22 (IQR 20 - 24), hemoglobin 12.9 (IQR 11.5 - 14.0) g/dl, serum transferrin 2.44 (IQR 2.23 - 2.73) g/L, serum uric acid 0.43 (IQR 0.37 - 0.53) and serum potassium 4.4 (IQR 3.9 - 4.8) mmol/L. The prevalence of metabolic acidosis was 62.4 %, anemia 46.4 %, gout 30.9 %, low transferrin levels 16.6 % and hyperkalemia 8.8 % among those with advanced CKD, while the prevalence of metabolic acidosis and anemia was 46.6 % and 25.9 % respectively in those with early CKD. Variables with higher odds for advanced CKD after multivariable logistic regression analysis were hypertension (OR 3.3, 95 % CI 1.2 - 9.2, P = 0.020), diabetes mellitus (OR 1.8, 95 % CI 1.1 - 3.3, P = 0.024), severe proteinuria (OR 3.5, 95 % CI 1.9 - 6.5, P = 0.001), angina (OR 2.5, 95 % CI 1.2 - 5.1, P = 0.008), anaemia (OR 2.9, 95% CI 1.7 - 4.9, P= 0.001), hyperuricemia (OR 2.4, 95 % CI 1.4 - 4.1, P = 0.001), and metabolic acidosis (OR 2.0, 95% CI 1.2 - 3.1, P= 0.005). Other associations with advanced CKD were widow/widower (OR 3.2, 95 % CI 1.4 - 7.4, P = 0.006), low transferrin (OR 2.4, 95% CI 1.1 - 5.1, P= 0.028), hyperkalemia (OR 5.4, 95% CI 1.2 - 24.1, P= 0.029), allopurinol (OR 2.4, 95 % CI 1.4 - 4.3, P = 0.005) and doxazosin (OR 1.9, 95% CI 1.2 - 3.1, P = 0.006).

ConclusionHypertension and diabetes mellitus were strongly associated with advanced CKD, suggesting a need for primary and secondary population-based prevention measures. Metabolic acidosis, anaemia with low transferrin levels, hyperuricemia and hyperkalemia were highly prevalent in our patients, including those with early CKD, and they were strongly associated with advanced CKD, calling for the proactive role of clinicians and dietitians in supporting the needs of CKD patients in meeting their daily dietary requirements towards preventing and slowing the progression of CKD.

category: nephrology


title: Plasma MIA, CRP, and albumin predict cognitive decline in Parkinson's Disease

abstract:
ObjectiveUsing a multi-cohort, Discovery-Replication-Validation design, we sought new plasma biomarkers that predict which PD individuals will experience cognitive decline.

MethodsIn 108 Discovery Cohort PD individuals and 83 Replication Cohort PD individuals, we measured 940 plasma proteins on an aptamer-based platform. Using proteins associating with subsequent cognitive decline in both cohorts, we trained a logistic regression model to predict which PD patients showed fast (>=1 point drop/year on Montreal Cognitive Assessment (MoCA)) vs. slow (<1 point drop/year on MoCA) cognitive decline in the Discovery Cohort, testing it in the Replication Cohort. We developed alternate assays for the top three proteins and confirmed their ability to predict cognitive decline - defined by change in MoCA or development of incident Mild Cognitive Impairment (MCI) or dementia - in a Validation Cohort of 118 PD individuals. We investigated the top plasma biomarker for causal influence by Mendelian randomization.

ResultsA model with only three proteins (Melanoma Inhibitory Activity Protein (MIA), C-Reactive Protein (CRP), albumin) separated Fast vs. Slow cognitive decline subgroups with an AUC of 0.80 in the Validation Cohort. Validation Cohort PD individuals in the top quartile of risk for cognitive decline based on this model were 4.4 times more likely to develop incident MCI or dementia than those in the lowest quartile. Genotypes at MIA SNP rs2233154 associated with MIA levels and cognitive decline, providing evidence for MIAs causal influence.

ConclusionsAn easily-obtained plasma-based predictor identifies PD individuals at risk for cognitive decline. MIA may participate causally in development of cognitive decline.

category: neurology


title: Understanding social and environmental factors and their contribution mechanisms to HIV transmission among heterosexual men in Indonesia

abstract: The number of HIV infection among heterosexual men in Indonesia continues to increase. This paper describes social and environmental factors and the mechanisms through which these factors may have contributed to the transmission of HIV among men in Indonesia. A qualitative design using one-on-one and face-to-face in-depth interviews was employed to collect data from men living with HIV in Yogyakarta and Belu, from June to December 2019. Participants (n=40) were recruited using the snowball sampling technique. The logical model for socio-environmental determinants diagnosis was used to conceptualise the study and discuss the findings. The findings showed that social factors such as peer influence on sex, condom use and injecting drug use were contributing factors for HIV transmission among the participants. Other factors and drivers of HIV transmission included mobility, migration, and the environment the participants lived, worked and interacted, which facilitated their engagement in high-risk behaviours. The findings indicate the need for wide dissemination of information and education about HIV and condoms for men, within communities and migration areas in Indonesia and other similar settings globally in order to increase their understanding of the means of HIV transmission, and condom use for HIV prevention.

category: hiv aids


title: Transmission blocking activity of low dose tafenoquine in healthy volunteers experimentally infected with Plasmodium falciparum

abstract:
BackgroundBlocking the transmission of parasites from humans to mosquitoes is a key component of malaria control. Tafenoquine exhibits activity against all stages of the malaria parasite and may have utility as a transmission blocking agent. We aimed to characterize the transmission blocking activity of low dose tafenoquine.

MethodsHealthy adults were inoculated with P. falciparum 3D7-infected erythrocytes on day 0. Piperaquine was administered on days 9 and 11 to clear asexual parasitemia while allowing gametocyte development. A single 50 mg oral dose of tafenoquine was administered on day 25. Transmission was determined by enriched membrane feeding assays pre-dose and at 1, 4 and 7 days post-dose. Artemether-lumefantrine was administered following the final assay. Outcomes were the reduction in mosquito infection and gametocytemia post-tafenoquine, and safety parameters.

ResultsSix participants were enrolled, and all were infective to mosquitoes pre-tafenoquine, with a median 86% (range: 22-98) of mosquitoes positive for oocysts and 57% (range: 4-92) positive for sporozoites. By day 4 post-tafenoquine, the oocyst and sporozoite positivity rate had reduced by a median 35% (IQR: 16-46) and 52% (IQR: 40-62), respectively, and by day 7, 81% (IQR 36-92) and 77% (IQR 52-98), respectively. The decline in gametocyte density post-tafenoquine was not significant. No significant participant safety concerns were identified.

ConclusionLow dose tafenoquine reduces P. falciparum transmission to mosquitoes, with a delay in effect.

Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN12620000995976).

FundingQIMR Berghofer Medical Research Institute.


title: The retirement-health puzzle: Breathe a sigh of relief at retirement?

abstract:
ObjectivesWhile the health effects of retirement have been well studied, existing findings remain inconclusive, and the mechanisms underlying the linkage between retirement and health are unclear. Thus, this study aimed to evaluate the effects of retirement on health and its potential mediators.

MethodsUsing a national household survey conducted annually from 2004 to 2019 in Japan (the Japan Household Panel Survey), we evaluated the effects of retirement among Japanese men aged 50 or older on their health, in addition to other outcomes that could be attributed to health changes associated with retirement (i.e. health behaviours, psychological well-being, time use for unpaid activities, and leisure activities). As outcomes are not measured every year, we analysed 5,794-10,682 person-year observations by 975-1,469 unique individuals. To address the potential endogeneity of retirement, we adopted an instrumental variable fixed-effects approach based on policy changes in pension-eligible ages for employee pensions.

ResultsWe found that retirement improved psychological well-being, exercise habits, and time spent on unpaid work. The psychological benefits of retirement were no longer observed for longer durations after retirement, whereas healthy habits and unpaid activities continued. Moreover, health-related improvements after retirement occurred mostly in the higher-income group.

DiscussionEnhancement in personal quality of life owing to increased leisure time and stress reduction from work in addition to life style changes may be key to understanding the health benefits of retirement. Considering the mechanisms behind retirement-health relationships and potential heterogeneous effects is essential for healthy retirement lives when increasing the retirement age.

HighlightsO_LIIn line with theories, previous studies report mixed results on effects of retirement on health.
C_LIO_LIEmpirical evidence on mechanisms underlying the linkage between retirement and health is scarce.
C_LIO_LIRetirement effects on health and potential mediators are evaluated by a quasi-experimental approach.
C_LIO_LIRetirement improves psychological well-being, exercise habits, time spent on unpaid work, and satisfaction with leisure.
C_LIO_LIHealth-related improvements after retirement occur mostly in the higher-income group.
C_LI

category: health economics


title: "Now, I know my life is not over!": Introduction and Adaptation of the RESPECT HIV Intervention, OraQuick, and Trauma-Informed Care for Female Victims of Non-Partner Sexual Violence in Haiti

abstract:
IntroductionIn the Cite Soleil (CS) shantytown of Haiti, non-partner sexual violence (NPSV) is widespread, involves multiple assailants who do not use condoms and inflict intentional coital injuries. HIV prevalence in Haiti is 2.2%, CS HIV prevalence is 3.6% shame, guilt, self-blame and societal stigma impede access to HIV testing/treatment in a context of low confidentiality. In that context, NPSV victims often succumb to AIDS. Culturally adapted evidence-based HIV interventions (EBIs) can increase HIV awareness and reduce HIV risk.

MethodsFollowing the ADAPT-ITT model, we used purposive sampling to recruit and interview key stakeholders (age 18 and older) in four focus groups (Victims and health providers, as part of adaptation of an EBI HIV (RESPECT) with an orally administered RAPID HIV antibody test (OraQuick) to increase HIV awareness and testing and to reduce HIV risk for victims of NPSV (N=32, 8/focus group). We also introduced trauma-informed care (TIC) to address the post-assault trauma of NPSV victims. Stakeholders were introduced to RESPECT, participated in RESPECT role plays, interpreted OraQuick HIV screen results after viewing a demonstration of a sample collection, and provided feedback on TIC. ATLAS.ti facilitated thematic content analysis of focus group transcripts.

ResultsParticipants unanimously (100%) reported that RESPECT, OraQuick, and TIC were acceptable, feasible, and useful for increasing HIV awareness, reducing shame, guilt, and trauma, and empowering NPSV victims to reduce the risk of HIV acquisition/transmission in future consensual relationships.

ConclusionEstablishing the acceptability, feasibility and effectiveness of RESPECT, OraQuick, and TIC in CS is a crucial first step towards responding to the HIV prevention and trauma needs of NPSV victims.


title: COVID-19 Prediction using Genomic Footprint of SARS-CoV-2 in Air, Surface Swab and Wastewater

abstract:
ImportanceGenomic footprints of pathogens shed by infected individuals can be traced in environmental samples. Analysis of these samples can be employed for noninvasive surveillance of infectious diseases.

ObjectiveTo evaluate the efficacy of environmental surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for predicting COVID-19 cases in a college dormitory.

DesignUsing a prospective experimental design, air, surface swabs, and wastewater samples were collected from a college dormitory from March to May 2021. Students were randomly screened for COVID-19 during the study period. SARS-CoV-2 in environmental samples was concentrated with electronegative filtration and quantified using Volcano 2nd Generation-qPCR. Descriptive analyses were conducted to examine the associations between time-lagged SARS-CoV-2 in environmental samples and clinically diagnosed COVID-19 cases.

SettingThis study was conducted in a residential dormitory at the University of Miami, Coral Gables campus, FL, USA. The dormitory housed about 500 students.

ParticipantsStudents from the dormitory were randomly screened, for COVID-19 for 2-3 days / week while entering or exiting the dormitory.

Main OutcomeClinically diagnosed COVID-19 cases were of our main interest. We hypothesized that SARS-CoV-2 detection in environmental samples was an indicator of the presence of local COVID-19 cases in the dormitory, and SARS-CoV-2 can be detected in the environmental samples several days prior to the clinical diagnosis of COVID-19 cases.

ResultsSARS-CoV-2 genomic footprints were detected in air, surface swab and wastewater samples on 52 (63.4%), 40 (50.0%) and 57 (68.6%) days, respectively, during the study period. On 19 (24%) of 78 days SARS-CoV-2 was detected in all three sample types. Clinically diagnosed COVID-19 cases were reported on 11 days during the study period and SARS-CoV-2 was also detected two days before the case diagnosis on all 11 (100%), 9 (81.8%) and 8 (72.7%) days in air, surface swab and wastewater samples, respectively.

ConclusionProactive environmental surveillance of SARS-CoV-2 or other pathogens in a community/public setting has potential to guide targeted measures to contain and/or mitigate infectious disease outbreaks.

Key PointsO_ST_ABSQuestionC_ST_ABSHow effective is environmental surveillance of SARS-CoV-2 in public places for early detection of COVID-19 cases in a community?

FindingsAll clinically confirmed COVID-19 cases were predicted with the aid of 2 day lagged SARS-CoV-2 in environmental samples in a college dormitory. However, the prediction efficiency varied by sample type: best prediction by air samples, followed by wastewater and surface swab samples. SARS-CoV-2 was also detected in these samples even on days without any reported cases of COVID-19, suggesting underreporting of COVID-19 cases.

MeaningSARS-CoV-2 can be detected in environmental samples several days prior to clinical reporting of COVID-19 cases. Thus, proactive environmental surveillance of microbiome in public places can serve as a mean for early detection of location-time specific outbreaks of infectious diseases. It can also be used for underreporting of infectious diseases.


title: Determinants and causes of early neonatal mortality: Hospital based retrospective cohort study in Somali region of Ethiopia

abstract:
BackgroundEarly neonatal mortality occurs when a newborn dies within the first seven days of life. Despite interventions, newborn mortality in Ethiopia has grown over time (33 death per 1000 live births). Determinants varies on level of neonatal mortality. The studys goal was to determine magnitude of early newborn death, as well as its causes and drivers, in Newborn Intensive Care Unit of Referral hospital in Ethiopias Somali region.

MethodsHealth facility based retrospective study review was conducted between May 2019 to May 2021 in Shiek Hassan Yabare Referral Hospital of Jigjiga University of Ethiopia. All neonates between 0 to 7 days admitted at NICU and get registered using the new NICU registration book from May 2019 to May 2021 with complete data were included. Kobo toolkit was used for data collection and analyzed in SPSS 20. Logistic regression model was used to estimate determinants.

ResultThe magnitude of early neonatal mortality rate (defined as death between 0-7 days) of Ethiopias Somali region is estimated to be 130 per 1000 live births--That is say 130 newborn couldnt celebrate their seventh day in every 1000 live births. Hypothermia, prematurity, maternal death at birth and shorter length of stay in NICU were increasing the chance of neonatal mortality at early stage while neonatal resuscitation had shown protective effect against neonatal mortality. Similarly birth asphyxia, preterm, sepsis, and congenital abnormalities were major causes of admission and death in the NICU.

ConclusionThe magnitude of early neonatal mortality is considerable and causes are preventable. Enhancing quality of care including infection prevention and hypothermia through mentorship and encouraging the Kangaroo Mother Care practice is necessary at childbirth and NICU of the Hospital.

category: intensive care and critical care medicine


title: The Gut Microbiome and their Metabolites in Human Blood Pressure Variability

abstract: Blood pressure (BP) variability is an independent risk factor for cardiovascular events. Recent evidence supports a role for the gut microbiota in BP regulation. However, whether the gut microbiome is associated with BP variability is yet to be determined. Here, we aimed to investigate the interplay between the gut microbiome and their metabolites in relation to BP variability. Ambulatory BP monitoring was performed in 69 participants from Australia (55.1% women; mean{+/-}SD 59.8{+/-}7.26-years old, 25.2{+/-}2.83 kg/m2). This data was used to determine night-time dipping, morning BP surge (MBPS) and BP variability as standard deviation (SD). The gut microbiome was determined by 16S rRNA sequencing, and metabolite levels by gas chromatography. We identified specific taxa associated with systolic BP variability, night-time dipping and MBPS. Notably, Alistipesfinegoldii and Lactobacillus spp. were only present in participants within the normal ranges of BP variability, MBPS and dipping, while Prevotella spp. and various Clostridium spp. were found to be present in extreme dippers and the highest quartiles of BP SD and MBPS. There was a negative association between MBPS and microbial -diversity (r=-0.244, P=0.046). MBPS was also negatively associated with total levels of microbial metabolites called short-chain fatty acids (SCFAs) in the plasma (r=-0.305, P=0.020), particularly acetate (r=-0.311, P=0.017). In conclusion, gut microbiome diversity, levels of microbial metabolites, and the bacteria Alistipesfinegoldii and Lactobacillus were associated with lower BP variability, and Clostridium and Prevotella with higher BP variability. Thus, our findings suggest the gut microbiome and metabolites may be involved in the regulation of BP variability.

category: cardiovascular medicine


title: Conditions of Confinement in U.S. Carceral Facilities during COVID-19: Individuals Speak: Incarcerated during the COVID-19 Epidemic (INSIDE)

abstract:
ObjectivesWe aimed to describe conditions of confinement among people incarcerated in the United States during the coronavirus disease 2019 (COVID-19) pandemic and assess the feasibility of a community-science data collection approach.

MethodsWe developed a web-based survey with community partners to collect information on confinement conditions (COVID-19 safety, basic needs, support). Formerly incarcerated adults released after March 1, 2020, or non-incarcerated adults in communication with an incarcerated person (proxy) were recruited through social media from July 25, 2020, through March 27, 2021. Descriptive statistics were estimated in aggregate and separately by proxy or formerly incarcerated status. Additionally, we compared responses between proxy and formerly incarcerated respondents using chi-square or Fishers exact tests as appropriate based on alpha=0.05.

ResultsOf 378 responses, 94% were by proxy, and 76% reflected state prison conditions. Participants reported inability to physically distance ([≥]6ft at all times) (92%), inadequate access to soap (89%), water (46%), toilet paper (49%) and showers (68%). Among people who received mental healthcare before the pandemic, 75% reported reduced care. We found that responses were consistent between formerly incarcerated people and proxy-respondents.

ConclusionsOur findings suggest that a community-science approach to data collection is feasible. Based on these findings, COVID-19 safety and basic needs were not sufficiently addressed within some carceral settings. Thus, we recommend the lived experiences of incarcerated individuals should be included to make informed and equitable policy decisions.


title: Detecting Patient Position Using Bed-Reaction Forces and Monitoring Skin-Bed Interface Forces for Pressure Injury Prevention and Management

abstract:
Pressure injuries are largely preventable, yet they affect one in four Canadians across all healthcare settings. A key best practice to prevent and treat pressure injuries is to minimize prolonged tissue deformation by ensuring at-risk individuals are repositioned regularly (typically every 2 hours). However, adherence to repositioning is poor in clinical settings and expected to be even worse in homecare settings.

Our team has designed a position detection system for home use that uses machine learning approaches to predict a patients position in bed using data from load cells under the bed legs. The system predicts the patients position as one of three position categories: left-side lying, right-side lying, or supine. The objectives of this project were to: i) determine if measuring ground truth patient position with an inertial measurement unit can improve our system accuracy (predicting left-side lying, right-side lying, or supine) ii) to determine the range of transverse pelvis angles (TPA) that fully offloaded each of the great trochanters and sacrum and iii) evaluate the potential benefit of being able to predict the individuals position with higher precision (classifying position into more than three categories) by taking into account a potential drop in prediction accuracy as well as the range of TPA for which the greater trochanters and sacrum were fully offloaded.

Data from 18 participants was combined with previous data sets to train and evaluate classifiers to predict the participants TPA using four different position bin sizes ([~]70{degrees}, 45{degrees}, [~]30{degrees}, and 15{degrees}) and the effects of increasing precision on performance, where patients are left side-lying at -90{degrees}, right side-lying at 90{degrees} and supine at 0{degrees}). A leave-one-participant-out cross validation approach was used to select the best performing classifier, which was found to have an accuracy of 84.03% with an F1 score of 0.8399. Skin-bed interface forces were measured using force sensitive resistors placed on the greater trochanters and sacrum. Complete offloading for the sacrum was only achieved for the positions with TPA angles <-90{degrees} or >90{degrees}, indicating there was no benefit to predicting with greater precision than with three categories: left, right, and supine.

category: nursing


title: Detection of bacterial co-infections and prediction of fatal outcomes in COVID-19 patients presenting to the emergency department using a 29 mRNA host response classifier.

abstract:
ObjectiveClinicians in the emergency department (ED) face challenges in concurrently assessing patients with suspected COVID-19 infection, detecting bacterial co-infection, and determining illness severity since current practices require separate workflows. Here we explore the accuracy of the IMX-BVN-3/IMX-SEV-3 29 mRNA host response classifiers in simultaneously detecting SARS-CoV-2 infection, bacterial co-infections, and predicting clinical severity of COVID-19.

Methods161 patients with PCR-confirmed COVID-19 (52.2% female, median age 50.0 years, 51% hospitalized, 5.6% deaths) were enrolled at the Stanford Hospital ED. RNA was extracted (2.5 mL whole blood in PAXgene Blood RNA) and 29 host mRNAs in response to the infection were quantified using Nanostring nCounter.

ResultsThe IMX-BVN-3 classifier identified SARS-CoV-2 infection in 151 patients with a sensitivity of 93.8%. Six of 10 patients undetected by the classifier had positive COVID tests more than 9 days prior to enrolment and the remaining oscillated between positive and negative results in subsequent tests. The classifier also predicted that 6 (3.7%) patients had a bacterial co-infection. Clinical adjudication confirmed that 5/6 (83.3%) of the patients had bacterial infections, i.e. Clostridioides difficile colitis (n=1), urinary tract infection (n=1), and clinically diagnosed bacterial infections (n=3) for a specificity of 99.4%. 2/101 (2.8%) patients in the IMX-SEV-3 Low and 7/60 (11.7%) in the Moderate severity classifications died within thirty days of enrollment.

ConclusionsIMX-BVN-3/IMX-SEV-3 classifiers accurately identified patients with COVID-19, bacterial co-infections, and predicted patients risk of death. A point-of-care version of these classifiers, under development, could improve ED patient management including more accurate treatment decisions and optimized resource utilization.


title: Outdoor long-range transmission of COVID-19 and patient zero

abstract: Following the outdoor model of risk assessment developed in one of our previous studies, we demonstrate in the present work that long-range transport of infectious aerosols can initiate patient "zero" creation at distances downwind beyond one hundred kilometers. The very low probability of this outdoor transmission can be compensated by a high number and density of susceptibles such as it occurs in large cities.


title: Automation of plate inoculation and reading reduces process time in the clinical microbiology laboratory, compared to a manual workflow

abstract: We evaluated the benefits of automation for clinical microbiology laboratory workflow and compared the time required for culture inoculation and plate reading between manual processes and BD Kiestra (but Kiestra) automation. Kiestra automation consists of different modules, each of which facilitate different tasks and work together from specimen inoculation to results reporting. We tracked the steps and measured the associated times-to-completion for both manual and automated workflows, including number of plate touches, hands-on-time (HOT), total technologist time (TTT), and walk-away time (WAT). Manual and automated processes both included 90 samples, and a total of 180 agar plates. There were three media quantity protocols used to mimic common laboratory samples: 1) 30  urine specimens on one biplate; 2) 30  urine specimens divided across two plates; and 3) 30  blood or  wound specimens divided across three plates; all cultures incubated for a minimum of 18 hours prior to reading or imaging. Automation reduced HOT by 85% and overall plate touches by 88%. Automated inoculation (through implementation of the BD InoqulA module) resulted in a 100% reduction in plate touches and created 81.5-minutes of WAT. Automation of culture reading (through implementation of the BD ReadA incubation/plate imaging module and BD Synapsys Informatics) reduced HOT by 53%. Overall, laboratory automation resulted in shorter TTT and created WAT when compared to manual processes. Automation can facilitate increased processing capacity, more efficient use of the labor force, and reduced time to results in the clinical microbiology laboratory.


title: Human cell-camouflaged nanomagnetic scavengers restore immune homeostasis in a rodent model with bacteremia

abstract: Bloodstream infection caused by antimicrobial resistance pathogens is a global concern because it is difficult to treat with conventional therapy. Here we report scavenger magnetic nanoparticles enveloped by nanovesicles derived from blood cells (MNVs), which magnetically eradicate an extreme range of pathogens in an extracorporeal circuit. We quantitatively reveal that glycophorin A and complement receptor (CR) 1 on red blood cell (RBC)-MNVs predominantly capture human fecal bacteria, carbapenem-resistant (CR) E. coli, and extended-spectrum beta-lactamases-positive (ESBL-positive) E. coli, vancomycin-intermediate S. aureus (VISA), endotoxins, and proinflammatory cytokines in human blood. Additionally, CR3 and CR1 on white blood cell-MNVs mainly contribute to depleting the virus envelope proteins of Zika, SARS-CoV-2, and their variants in human blood. Supplementing opsonins into the blood significantly augments the pathogen removal efficiency due to its combinatorial interactions between pathogens and CR1 and CR3 on MNVs. The extracorporeal blood cleansing enables full recovery of lethally infected rodent animals within seven days by treating them twice in series. We also validate that parameters reflecting immune homeostasis, such as blood cell counts, cytokine levels, and transcriptomics changes, are restored in blood of the fatally infected rats after treatment.


title: Performance Evaluation of VIDAS Diagnostic Assays Detecting Dengue Virus NS1 Antigen, and Anti-Dengue Virus IgM and IgG Antibodies: a Multicenter, International Study

abstract: Dengue is a serious mosquito-transmitted disease caused by the dengue virus (DENV). Rapid and reliable diagnosis of DENV infection is urgently needed in dengue-endemic regions. We describe here the performance evaluation of the CE-marked VIDAS(R) dengue immunoassays developed for the automated detection of DENV NS1 antigen, and anti-DENV IgM and IgG antibodies. A multicenter concordance study was conducted in 1296 patients from dengueendemic regions in Asia, Latin America, and Africa. VIDAS(R) dengue results were compared to those of competitor enzyme-linked immunosorbent assays (ELISA). The VIDAS(R) dengue assays showed high precision (CV [≤] 10.7%) and limited cross-reactivity ([≤] 15.4%) with other infections. VIDAS(R) DENGUE NS1 Ag showed high positive and negative percent agreement (92.8% PPA, 91.7% NPA) in acute patients within 0-5 days of symptom onset. VIDAS(R) Anti-DENGUE IgM and IgG showed a moderate to high concordance with ELISA (74.8% to 90.6%) in post-acute and recovery patients. PPA was further improved in combined VIDAS(R) NS1/IgM (96.4% in 0-5 days acute patients) and IgM/IgG (91.9% in post-acute patients) tests. Altogether, the VIDAS(R) dengue NS1, IgM and IgG assays performed well, either alone or in combination, and should be suitable for the accurate diagnosis of DENV infection in dengue-endemic regions.


title: Should individuals be paid to participate in mass drug administration to control malaria?

abstract: Mass drug administration (MDA) is a malaria control strategy in which antimalarial drugs are offered to a whole community. Although MDA can potentially clear malaria from a community, it is not routinely used in eradication efforts because of ethical concerns and past failures to achieve lasting elimination. One potential means to improving the outcome of MDA is to incentivize individuals to participate, for example, through monetary payments. In this study our aim is to inform the decision to use MDA to eradicate malaria and explore whether individuals should be incentivized to participate. Through the lens of a mathematical model, we clarify how the costs and benefits of MDA are context-dependent. We highlight that in a community experiencing a good improvement in clinical case management - relative to the prevalence of malaria in the community - the addition of MDA can catalyze stable elimination. However, participation rates are critical and individuals who avoid every round of treatment can prevent elimination. We explore how, in this scenario, individual incentives could change the cost-benefit breakdown, measured at three levels - personal, local community and wider community.


title: Humoral and cellular immune responses to CoronaVac assessed up to one year after vaccination

abstract:
BackgroundThe Sinovac SARS-CoV-2 inactivated vaccine (CoronaVac) has been demonstrated to be safe, well tolerated, and efficacious in preventing mild and severe Covid-19. Although different studies have demonstrated its short-term immunogenicity, long-term cellular and humoral response evaluations are still lacking.

MethodsCellular and humoral responses were assessed after enrollment of volunteers in the PROFISCOV phase 3 double-blind, randomized, placebo-controlled clinical trial to evaluate CoronaVac. Assays were performed using flow cytometry to evaluate cellular immune response and an antigen binding electrochemiluminescence assay to detect antigen-specific antibodies to the virus.

ResultsFifty-three volunteers were selected for long term assessment of their SARS-CoV-2-specific immune responses. CD4+ T cell responses (including circulating follicular helper (cTfh, CD45RA- CXCR5+) expressing CD40L, as well as non-cTfh cells expressing CXCR3) were observed early upon the first vaccine dose, increased after the second dose, remaining stable for 6-months. Memory CD4+ T cells were detected in almost all vaccinees, the majority being central memory T cells. IgG levels against Wuhan/WH04/2020 N, S and receptor binding domain (RBD) antigens and the variants of concern (VOCs, including B.1.1.7/Alpha, B.1.351/Beta and P.1/Gamma) S and RBD antigens peaked 14 days after the second vaccine shot, and were mostly stable for a 1-year period.

ConclusionsCoronaVac two-doses regimen is able to induce a potent and durable SARS-CoV-2 specific cellular response. The cellular reaction is part of a coordinated immune response that includes high levels of specific IgG levels against parental and SARS-CoV-2 VOC strains, still detected after one year.

FundingFundacao Butantan, Instituto Butantan and Sao Paulo Research Foundation (FAPESP) (grants 2020/10127-1 and 2020/06409-1). This work has also been supported by NIH contract 75N93019C00065 (A.S, D.W). PATH facilitated reagent donations for this work with support by the Bill & Melinda Gates Foundation (INV-021239). Under the grant conditions of the foundation, a Creative Commons Attribution 4.0 generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission.


title: The transcriptional profile of keloidal Schwann cells

abstract:
Recently, a specific Schwann cell type with pro-fibrotic and tissue regenerative properties has been identified that contributes to keloid formation. In the present study, we have reanalysed published single cell RNA sequencing (scRNAseq) studies of keloids, healthy skin and normal scars to reliably determine the specific gene expression profile of the keloid-specific Schwann cell type in more detail.

We were able to confirm the presence of the repair-like, pro-fibrotic Schwann cell type in the datasets of all three studies and identified a specific gene set for these Schwann cells. In contrast to keloids, in normal scars the number of Schwann cells was neither increased nor was their gene expression profile distinctly different from Schwann cells of normal skin. In addition, our bioinformatics analysis provided evidence for a role of transcription factors of the kruppel-like factor family and members of the immediate early response genes, in the de-differentiation process of keloidal Schwann cells.

Together, our analysis strengthens the role of the pro-fibrotic Schwann cell type in the formation of keloids. Knowledge on the exact gene expression profile of these Schwann cells will facilitate their identification in other organs and diseases.

category: dermatology


title: Estimation of time-varying causal effects with multivariable Mendelian randomization: some cautionary notes

abstract:
IntroductionFor many exposures present across the lifecourse, the effect of the exposure may vary over time. Multivariable Mendelian randomization (MVMR) is an approach that can assess the effects of related risk factors using genetic variants as instrumental variables. Recently, multivariable Mendelian randomization has been used to estimate the effects of an exposure during distinct time periods.

MethodsWe investigated the behaviour of estimates from MVMR in a simulation study for different time-varying causal scenarios. We also performed an applied analysis to consider how MVMR estimates of body mass index on systolic blood pressure vary depending on the time periods considered.

ResultsEstimates from MVMR in the simulation study were close to the true values when the outcome model was correctly specified: that is, when the outcome was a discrete function of the exposure at the precise timepoints at which the exposure was measured. However, in more realistic cases, MVMR estimates were not only incorrect, but misleading. For example, in one scenario MVMR estimates for early life were clearly negative despite the true causal effect being constant and positive. In the applied example, estimates were highly variable depending on the time period in which genetic associations with the exposure were estimated.

ConclusionsThe poor performance of MVMR to study time-varying causal effects can be attributed to model misspecification and violation of the exclusion restriction assumption. We would urge caution about quantitative conclusions from such analyses and even qualitative interpretations about the direction, or presence or absence of a causal effect during a given time period.


title: Comparison of accelerometry-based measures of physical activity

abstract:
BackgroundGiven the evolution of processing and analyzing accelerometry data over the past decade, it is of utmost importance that we as a field understand how newer (e.g., MIMS) summary measures compare to long-established ones (e.g., ActiGraph activity counts).

ObjectiveOur study aims to compare and harmonize accelerometry-based measures of physical activity (PA) to increase the comparability, generalizability, and translation of findings across studies using objective measures of PA.

MethodsHigh resolution accelerometry data were collected from 655 participants in the Baltimore Longitudinal Study on Aging who wore an ActiGraph GT9X device at wrist continuously for a week. Data were summarized at the minute-level as activity counts (AC; measure obtained from ActiGraphs ActiLife software) and MIMS, ENMO, MAD, and AI (open-source measures implemented in R). The correlation between AC and other measures was quantified both marginally and conditionally on age, sex and BMI. Next, each pair of measures were harmonized using nonparametric regression of minute-level measurements.

ResultsThe study sample had the following characteristics: mean (sd) age of 69.8 (14.2), BMI of 27.3 (5.0) kg/m2, 54.5% females, and 67.9% white. The marginal participant-specific correlation between AC and MIMS, ENMO, MAD, and AI were 0.988, 0.867, 0.913 and 0.970, respectively. After harmonization, the mean absolute percentage error for predicting total AC from MIMS, ENMO, MAD, and AI was 2.5, 14.3, 11.3 and 6.3, respectively. The accuracy for predicting sedentary minutes based on AC (AC > 1853) using MIMS, ENMO, MAD and AI was 0.981, 0.928, 0.904, and 0.960, respectively. An R software with a unified interface for computation of the open-source measures from raw accelerometry data was developed and published as SummarizedActigraphy R package.

ConclusionsOur comparison of accelerometry-based measures of PA enables researchers to extend the knowledge from the thousands of manuscripts that have been published using ActiGraph AC to MIMS and other measures by demonstrating their high correlation and providing a harmonization mapping.


title: The decay of coronavirus in sewage pipes and the development of a predictive model for the estimation of SARS-CoV-2 infection cases based on wastewater surveillance

abstract: Wastewater surveillance serves as a promising approach to elucidate the silent transmission of SARS-CoV-2 in a given community by detecting the virus in wastewater treatment facilities. This study monitored the viral RNA abundance at one WWTP and three communities during the COVID-19 outbreak in the Yanta district of Xian city from December 2021 to January 2022. To further understand the decay of the coronavirus in sewage pipes, avian infectious bronchitis virus (IBV) was seeded in two recirculating water systems and operated for 90 days. Based on the viral abundance in the wastewater of Xian and the above data regarding the decay of coronavirus in sewage pipes, Monte Carol simulations were performed to estimate the infectious cases in Xian. The results suggested that the delta variant was first detected on Dec-10, five days earlier than the reported date of clinical samples. SARS-CoV-2 was detected on December 18 in the monitored community two days earlier than the first case and was consecutively detected in the following two sampling times. In pipelines without biofilms, the results showed that high temperature significantly reduced the viral RNA abundance by 2.18 log10 GC/L after experiencing 20 km travel distance, while only a 1.68 log10 GC/L reduction was observed in the pipeline with a low water temperature. After 90 days of operation, the biofilm matured in the pipeline in both systems. Reductions of viral RNA abundance of 2.14 and 4.79 log10 GC/L were observed in low- and high-temperature systems with mature biofilms, respectively. Based on the above results, we adjusted the input parameters for Monte Carol simulation and estimated 23.3, 50.1, 127.3 and 524.2 infected persons in December 14, 18, 22 and 26, respectively, which is largely consistent with the clinical reports. This work highlights the viability of wastewater surveillance for the early warning of COVID-19 at both the community and city levels, which represents a valuable complement to clinical approaches.


title: General Framework for Evaluating Outbreak Prediction, Detection, and Annotation Algorithms

abstract:
The COVID-19 pandemic has highlighted and accelerated the use of algorithmic-decision support for public health. The latters potential impact and risk of bias and harm urgently call for scrutiny and evaluation standards. One example is the early detection of local infectious disease outbreaks. Whereas many statistical models have been proposed and disparate systems are routinely used, each tai-lored to specific data streams and use, no systematic evaluation strategy of their performance in a real-world context exists.

One difficulty in evaluating outbreak prediction, detection, or annotation lies in the scales of different approaches: How to compare slow but fine-grained genetic clustering of individual samples with rapid but coarse anomaly detection based on aggregated syndromic reports? Or alarms generated for different, overlapping geographical regions or demographics?

We propose a general, data-driven, user-centric framework for evaluating hetero-geneous outbreak algorithms. Discrete outbreak labels and case counts are defined on a custom data grid, associated target probabilities are then computed and compared with algorithm output. The latter is defined as discrete "signals" are generated for a number of grid cells (the finest available in the benchmarking data set) with different weights and prior outbreak information from which then estimated outbreak label probabilities are derived. The prediction performance is quantified through a series of metrics, including confusion matrix, regression scores, and mutual information. The dimensions of the data grid can be weighted by the user to reflect epidemiological criteria.


title: Variant-specific burden of SARS-CoV-2 in Michigan: March 2020 through November 2021

abstract: Accurate estimates of total burden of SARS-CoV-2 are needed to inform policy, planning and response. We sought to quantify SARS-CoV-2 cases, hospitalizations, and deaths by age in Michigan. COVID-19 cases reported to the Michigan Disease Surveillance System were multiplied by age and time-specific adjustment factors to correct for under-detection. Adjustment factors were estimated in a model fit to incidence data and seroprevalence estimates. Age-specific incidence of SARS-CoV-2 hospitalization, death, and vaccination, and variant proportions were estimated from publicly available data. We estimated substantial under-detection of infection that varied by age and time. Accounting for under-detection, we estimate cumulative incidence of infection in Michigan reached 75% by mid-November 2021, and over 87% of Michigan residents were estimated to have had [≥]1 vaccination dose and/or previous infection. Comparing pandemic waves, the relative burden among children increased over time. Adults [≥]80 years were more likely to be hospitalized or die if infected in fall 2020 than if infected during later waves. Our results highlight the ongoing risk of periods of high SARS-CoV-2 incidence despite widespread prior infection and vaccination. This underscores the need for long-term planning for surveillance, vaccination, and other mitigation measures amidst continued response to the acute pandemic.


title: Serological Responses to the First Three Doses of SARS-CoV-2 Vaccination in Inflammatory Bowel Disease: A Prospective Cohort Study

abstract:
BackgroundIndividuals with inflammatory bowel disease (IBD) who are immunocompromised may have a reduced serological response to the SARS-CoV-2 vaccine. We investigated serological responses following 1st, 2nd, and 3rd doses of SARS-CoV-2 vaccination in those with IBD.

MethodsA prospective cohort study of persons with IBD (n = 496) assessed serological response 1-8 weeks after 1st dose vaccination, 1-8 weeks after 2nd dose, 8 or more weeks after 2nd dose, and at least 1 week after 3rd dose. Seroconversion and geometric mean titer (GMT) with 95% confidence intervals (CI) were assessed for antibodies to the SARS-CoV-2 spike protein. Multivariable linear regression models assessed the adjusted fold change (FC) in antibody levels.

ResultsSeroconversion and GMT increased from post-1st dose to 1-8 weeks post-2nd dose (81.6%, 1814 AU/mL vs. 98.7%, 9229 AU/mL, p<0.001), decreased after 8 weeks post-2nd dose (94.9%, 3002 AU/mL, p<0.001), and rebounded post-3rd dose (99.6%, 14639 AU/mL, p<0.001). Prednisone was the only IBD-related medication associated with diminished antibody response after 3rd-dose vaccination (FC: 0.07 [95% CI: 0.02, 0.20]). Antibody levels steadily decline following the 2nd (FC: 0.92 [95% CI: 0.90, 0.94] per week) and 3rd dose (FC: 0.88 [95% CI: 0.84, 0.92] per week) of the SARS-CoV-2 vaccine.

ConclusionA three-dose regimen of vaccination to SARS-CoV-2 yields a robust antibody response for those with IBD across all classes of IBD therapies except for prednisone. The decaying antibody levels following the 3rd dose of the vaccine should be monitored in future studies.

category: gastroenterology


title: Selective visuoconstructional impairment following mild COVID-19 with inflammatory and neuroimaging correlation findings.

abstract: People recovered from COVID-19 may still present complications including respiratory and neurological sequelae. In other viral infections, cognitive impairment occurs due to brain damage or dysfunction caused by vascular lesions and inflammatory processes. Persistent cognitive impairment compromises daily activities and psychosocial adaptation. Some level of neurological and psychiatric consequences were expected and described in severe cases of COVID-19. However, it is debatable whether neuropsychiatric complications are related to COVID-19 or to unfoldings from a severe infection. Nevertheless, the majority of cases recorded worldwide were mild to moderate self-limited illness in non-hospitalized people. Thus, it is important to understand what are the implications of mild COVID-19, which is the largest and understudied pool of COVID-19 cases. We aimed to investigate adults at least four months after recovering from mild COVID-19, which were assessed by neuropsychological, ocular and neurological tests, immune markers assay, and by structural MRI and 18FDG-PET neuroimaging to shed light on putative brain changes and clinical correlations. In approximately one-quarter of mild-COVID-19 individuals, we detected a specific visuoconstructive deficit, which was associated with changes in molecular and structural brain imaging, and correlated with upregulation of peripheral immune markers. Our findings provide evidence of neuroinflammatory burden causing cognitive deficit, in an already large and growing fraction of the world population. While living with a multitude of mild COVID-19 cases, action is required for a more comprehensive assessment and follow-up of the cognitive impairment, allowing to better understand symptom persistence and the necessity of rehabilitation of the affected individuals.

category: psychiatry and clinical psychology


title: Enabling Health Outcomes of Nature-based Interventions: A Systematic Scoping Review

abstract:
BackgroundThe burden of poor mental health and non-communicable disease is increasing, and some practitioners are turning to nature to provide the solution. Nature-based interventions could offer cost-effective solutions that benefit both human health and the environment by reconnecting individuals with nature. Importantly, the relative success of these interventions depends upon the accessibility of green and blue spaces, and the way in which people engage with them.

Aims and ObjectivesA scoping review was conducted to establish the evidence base for nature-based interventions as a treatment for poor mental and physical health, and to assess whether and how enablers influence engagement with natural outdoor environments.

MethodsThis scoping review followed the PRISMA-ScR and the associated Cochrane guidelines for scoping reviews. A literature search was performed across five databases and the grey literature, and articles were selected based on key inclusion and exclusion criteria. Exposure was the active engagement with natural environments. The primary outcome was mental health and the secondary outcome was physical health, both defined using established metrics. All data was extracted to a charting table and reported as a narrative synthesis.

ResultsThe final analysis included thirty-nine studies. Most of these focused on green spaces, with only five dedicated to blue spaces. Six nature-based health intervention types were identified: (i) educational interventions, (ii) physical activity in nature, (iii) wilderness therapy, (iv) leisure activities, (v) gardening and (vi) changes to the built environment. Of the 39 studies, 92.2% demonstrated consistent improvements across health outcomes when individuals engaged with natural outdoor environments (NOEs). Furthermore, of 153 enablers that were found to influence engagement, 78% facilitated engagement while 22% reduced engagement. Aspects such as the sense of wilderness, accessibility, opportunities for physical activity and the absence of noise/ air pollution all increased engagement.

ConclusionFurther research is still needed to establish the magnitude and relative effect of nature- based interventions, as well as to quantify the compounding effect of enablers on mental and physical health. This must be accompanied by a global improvement in study design. Nevertheless, this review has documented the increasing body of heterogeneous evidence in support of NBIs as effective tools to improve mental, physical, and cognitive health outcomes. Enablers that facilitate greater engagement with natural outdoor environments, such as improved biodiversity, sense of wilderness and accessibility, as well as opportunities for physical activity and an absence of pollution, will likely improve the impact of nature-based interventions and further reduce public health inequalities.


title: Did national holidays accelerate COVID-19 diffusion in Bangladesh? A case study

abstract:
Bangladesh registered 1573828 confirmed cases of COVID-19 and the death toll crossed the grim milestone of 27946 across the country as of 9th December, 2021. Despite the enforcement of stringent COVID-19 measures, including nationwide lockdowns, travel bans, tighter curbs on nonessential activities, and social distancing, the country witnessed an accelerated diffusion of coronavirus cases during the national events and festivals in 2020. The present study aims to examine the association between the national events / festivals and the transmission dynamics of COVID-19 by looking at the instantaneous reproduction number, Rt, of the 64 districts in Bangladesh. We further illustrate the COVID-19 diffusion explicitly in Dhaka Division at the first phase of the pandemic. The comprehensive analysis shows an escalation of Rt value in Dhaka and in all industrialized cities during the major events such as, Garments reopening and religious holidays in Bangladesh. Based on the analysis, a set of array measurements has been also suggested to evade the future pandemic risks while running the national festival activities.

HighlightsO_LIBangladesh confirmed 1573828 coronavirus cases and 27946 deaths due to the current COVID-19 outbreak.
C_LIO_LICountry observed significant COVID-19 diffusion in its business hubs during national holidays.
C_LIO_LIDhaka, the capital of Bangladesh, is the epicenter of the ongoing pandemic.
C_LIO_LICalculated Rt value illustrates its escalation in Dhaka and its neighboring cities at the time of national events.
C_LIO_LIBangladesh Government needs to consider interdisciplinary approaches and contextual policies to contain the future pandemic during any national events.
C_LI


title: Acceptance of COVID 19 vaccine among sub-Sahara African (SSA): a comparative study of residents and diaspora dwellers

abstract: The COVID-19 vaccines are being rolled out across all the Sub-Saharan Africa (SSA) countries, with countries setting targets for achieving full vaccination rates. The aim of this study was to compare the uptake of, resistance and hesitancy to the COVID-19 vaccine between SSA locally residents and in the diaspora. This was a cross-sectional study conducted using a web and paper-based questionnaire to obtain relevant information on COVID-19 vaccine acceptance. The survey items included questions on demography, uptake and planned acceptance or non-acceptance of the COVID-19 vaccines among SSAs. Multinomial logistic regression was used to determine probabilities of outcomes for factors associated with COVID-19 vaccination resistance and hesitancy among SSA respondents residing within and outside Africa. Uptake of COVID-19 vaccines varied among the local (14.2%) and diaspora (25.3%) residents. There was more resistance to COVID-19 vaccine among locals (68.1%) and across the sociodemographic variables of sex [ adjusted Relative Risk (ARR) =0.73, 95% CI; 0.58 - 0.93], primary/less [ARR =0.22, 95% CI; 0.12 - 0.40] and bachelors degree [ARR =0.58, 95% CI; 0.43 - 0.77] educational levels, occupation [ARR =0.32, 95% CI; 0.25 - 0.40] and working status [ARR =1.40, 95%CI; 1.06 - 1.84]. COVID-19 vaccine hesitancy was almost similar between locals and diasporas (17.7% and 17.8% respectively) significant only among healthcare workers [ARR =0.46, 95% CI; 0.16 - 1.35] in the diaspora after adjusting for the variables. Similarly, knowledge and perception of COVID-19 vaccine among locals were substantial, but only perception was remarkable to resistance [ARR =0.86, 95% CI; 0.82 - 0.90] and hesitancy [ARR =0.85, 95% CI; 0.80 - 0.90] of the vaccine. Differences exist in the factors that influence COVID-19 vaccine acceptance between local SSA residents and those in the diaspora. Knowledge about COVID-19 vaccines affects the uptake, resistance, and hesitancy to the COVID-19 vaccine. Information campaigns focusing on the efficacy and safety of vaccines could lead to improved acceptance of COVID-19 vaccines.


title: Socioeconomic, demographic and environmental factors inform intervention prioritization in urban Nigeria

abstract: Nigeria is one of three countries projected to have the largest absolute increase in the size of its urban population and this could intensify malaria transmission in cities. Accelerated urban population growth is out-pacing the availability of affordable housing and basic services and resulting in living conditions that foster vector breeding and heterogeneous malaria transmission. Understanding community determinants of malaria transmission in urban areas informs the targeting of interventions to populations at greatest risk. In this study, we analyzed cluster-level data from the Demographic and Health Surveys (DHS) and the Malaria Indicator Survey (MIS) as well as geospatial covariates to describe malaria burden and its determinants in areas administratively defined as urban in Nigeria. Overall, we found low malaria test positivity across urban areas. We observed declines in test positivity rate over time and identified the percentage of individuals with post-primary education, the percentage of individuals in the rich wealth quintiles, the percentage of individuals living in improved housing in 2015, all age population density, median age, the percentage of children under the age of five that sought medical treatment for fever, total precipitation and enhanced vegetation index as key community predictors of malaria transmission intensity. The unrepresentativeness of the DHS and MIS in urban settings at the state and geopolitical zonal level, regional differences in malaria seasonality across Nigeria, and information detection bias were among likely factors that limited our ability to compare malaria burden across geographic space and ultimately drove model uncertainty. Nevertheless, study findings provide a starting point for informing decisions on intervention prioritization within urban spaces and underscore the need for improved regionally-focused surveillance systems in Nigeria.


title: Examining Drivers of COVID-19 Vaccine Hesitancy in Ghana: The Roles of Political Allegiance, Misinformation Beliefs, and Sociodemographic Factors

abstract: The vast majority of people in the world who are unvaccinated against COVID-19 reside in LMIC countries in sub-Saharan Africa. This includes Ghana, where only 14.4% of the country is considered fully vaccinated as of March 2022. A key factor negatively impacting vaccination campaigns is vaccine hesitancy, defined as the delay in the acceptance, or blunt refusal, of vaccines. Three online cross-sectional surveys of Ghanaian citizens were conducted in August 2020 (N = 3048), March 2021 (N = 1558), and June 2021 (N = 1295) to observe temporal trends of vaccine hesitancy in Ghana, and to examine key groups and predictors associated with hesitancy. Quantitative measurements of hesitancy and participants subjective reasons for hesitancy were assessed, including predictors such as misinformation beliefs, political allegiance, and demographic and socioeconomic factors. Descriptive statistics were employed to analyse temporal trends in hesitancy between surveys, and logistic regression analyses were conducted to observe key predictors of hesitancy. Findings revealed that overall hesitancy decreased from 36.8% (95% CI: 35.1%-38.5%) in August 2020 to 17.2% (95% CI: 15.3%-19.1%) in March 2021. However, hesitancy increased to 23.8% (95% CI: 21.5%-26.1%) in June 2021. Key reasons for refusing the vaccine in June 2021 included not having enough vaccine-related information (50.6%) and concerns over vaccine safety (32.0%). Groups most likely to express hesitancy included Christians, urban residents, opposition political party voters, people with more years of education, females, people who received COVID-19 information from internet sources, and people who expressed uncertainty about their beliefs in common COVID-19 misinformation. Groups with increased willingness to vaccinate included elected political party voters and people who reported receiving information about COVID-19 from the Ghana Health Service. This study provides knowledge on Ghanaian population confidence and concerns about COVID-19 immunisations, and can support development of locally-tailored health promotion strategies.


title: Validation of a rapid potency assay for cord blood stem cells using phospho flow cytometry: the IL-3-pSTAT5 assay

abstract:
Public cord blood banks (CBBs) are required to measure cord blood units (CBUs) potency before their release, allowing for the identification of units that may be unsuitable for hematopoietic transplantation. We have developed a rapid flow cytometry assay based on the measurement of STAT-5 phosphorylation of CD34+ stem cells in response to IL-3 stimulation: the IL-3-pSTAT5 assay.

To adapt the assay from a research setting to its implementation within our CBB regulated operations, we proceeded with a full method validation and a correlation comparison of the IL-3-pSTAT5 assay results with the colony-forming unit assay (CFU) results. A total of 60 CBUs cryopreserved in vials were analyzed by flow cytometry to determine the sensitivity, specificity, intra-assay precision, robustness, reproducibility and inter-laboratory agreement of the assay. The CFU assay was also done on the same samples for comparison purposes.

The assay threshold was established at 50% CD34+CD45+pSTAT5+, which provides a 100% sensitivity and a 98.3% specificity. An average intra-assay CV of 7.3% was determined. All results met our qualitative results acceptance criteria regarding the inter-user and inter-laboratory agreements, IL-3 stimulation time, post-thaw incubation delay and staining time. The IL-3-pSTAT5 assay results correlated well with the total CFU determined using the CFU assay (r2 = 0.82, n = 56).

This study shows that our rapid flow cytometry assay can be successfully validated and that the potency data obtained display good sensitivity, specificity and robustness. These results demonstrate the feasibility of implementing this assay within CBB operations, as a validated CB potency assay.

category: transplantation


title: Pride and adversity among nurses and physicians during the pandemic in two US healthcare systems: a mixed methods analysis

abstract:
Our aims were to examine themes of the most difficult or distressing events reported by healthcare workers during the first wave of COVID-19 pandemic in two US health care systems in order to identify common themes and to relate them to both behavioral theory and measures of anxiety and depression.

We conducted a cross-sectional survey during the early phases of the COIVD-19 pandemic in the US. We measured symptoms of anxiety and depression separately, captured demographics, and asked two open-ended questions regarding events that were the most difficult or stressful, and reinforced pride. The open-end questions were independently coded into themes developed by the authors and mapped to factors related to fostering well-being according to the Self-Determination Theory.

We recruited 874 nurses and 248 physicians. About a half shared their most distressing experiences as well as those experiences they were most proud of related to their professions. Themes that emerged from these narratives were congruent with prediction of Self-Determination theory that autonomy-supportive experiences will foster pride, while autonomy-thwarting experiences will cause distress. Those who reported distressful events were more anxious and depressed compared to those who did not. Among those who reported incidences that reinforced pride in the profession, depression was rarer compared to those who did not. These trends were evident after allowing for medical history and other covariates in logistic regressions.

Causal claims from our analysis should be made with caution due to the research design, a cross-sectional study design. Understanding of perceptions of the pandemic by nurses and physicians may help identify sources of distress and means of reinforcing pride in the professions, thereby helping nurses and physicians cope with disasters, and shape workplace policies during disasters that foster well-being among first responders.

No Patient or Public Contribution: We studied physicians and nurses themselves.

category: occupational and environmental health


title: Health service research definition builder: An R Shiny application for exploring diagnosis codes associated with services reported in routinely collected health data

abstract: Many administrative health data-based studies define patient cohorts using procedure and diagnosis codes. The impact these criteria have on a studys final cohort is not always transparent to co-investigators or other audiences if access to the research data is restricted. We developed a SAS and R Shiny interactive research support tool which generates and displays the diagnosis code summaries associated with a selected medical service or procedure. This allows non-analyst users to interrogate claims data and groupings of reported diagnosis codes. The SAS program uses a tree classifier to find associated diagnosis codes with the service claims compared against a matched, random sample of claims without the service. Claims are grouped based on the overlap of these associated diagnosis codes. The Health Services Research (HSR) Definition Builder Shiny application uses this input to create interactive table and graphics, which updates estimated claim counts of the selected service as users select inclusion and exclusion criteria. This tool can help researchers develop preliminary and shareable definitions for cohorts for administrative health data research. It allows an additional validation step of examining frequency of all diagnosis codes associated with a service, reducing the risk of incorrect included or omitted codes from the final definition. In our results, we explore use of the application on three example services in 2016 US Medicare claims for patients aged over 65: knee arthroscopy, spinal fusion procedures and urinalysis. Readers can access the application at https://kelsey209.shinyapps.io/hsrdefbuilder/ and the code at https://github.com/kelsey209/hsrdefbuilder.

category: health informatics


title: Tongue Coating in COVID-19 Patients: A Case-Control Study

abstract: It has been suggested that COVID-19 patients have distinct tongue features, which may help to monitor the development of their condition. To determine if there was any specific tongue coating feature in COVID-19, this study investigated the difference in tongue coating between COVID-19 subjects and subjects with other acute inflammatory diseases characterized by fever. Tongue images taken with smartphones from three age-matched groups, namely, COVID group (n=92), non-COVID febrile group (n=92), and normal control group (n=92), were analyzed by two blinded raters according to a tongue coating scoring scheme, which assessed the levels of thick fur, slimy or greasy fur, discolored fur and composite index of tongue coating. Compared with control, significant increases in all coating indexes were found in the COVID group (P<0.001), as well as in the non-COVID febrile group (P<0.001). However, no difference was observed between COVID and non-COVID febrile groups for all coating indexes measured. In COVID-19 subjects, their scores of coating indexes had weak but significant correlations with certain inflammatory biomarkers, including WBC and neutrophil - lymphocyte ratio. It is concluded that COVID-19 subjects have pathological tongue coating patterns that are associated with inflammatory responses, and these coating patterns can help to indicate the direction of disease development.

category: infectious diseases