Interventions to improve executive functions in children aged 3 years and under: A systematic review.

BACKGROUND: Early executive functioning (EF) skills are foundational capabilities that predict school readiness, academic development and psychiatric risk. Early interventions enhancing these capabilities could have critical import in improving outcomes. However, to develop interventions, it is necessary to identify specific EF skills that will vary with child age. Thus, we aimed to examine the characteristics and efficacy of interventions targeting EF in infancy and early childhood up to age 3. METHODS: A comprehensive search of PubMed, Embase, CINAHL and APA PsycINFO databases was performed for studies published before December 2022. Randomized and non-randomized studies of interventions designed to improve at least one EF skill in children ≤3 years were included. EF skills included attentional control, inhibition/self-regulation, activity initiation, working memory, cognitive flexibility, planning ability, problem-solving and performance monitoring. We independently extracted data, used the revised Cochrane Risk-of-Bias tool to assess the quality of the evidence and conducted Synthesis Without Meta-analysis (SWiM). The overall quality of the evidence and the strength of recommendations was determined using elements of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Thirty-five studies met inclusion criteria (original n = 7467). Studies were highly variable in the EF skill targeted, target subject (i.e., child, parent and teacher), nature and dosage of the intervention, and timing of outcome assessment. Most interventions focused on improving impulse control and self-regulation. The overall quality of evidence was low to moderate with a high risk of bias, though six studies had low risk of bias but yielded mixed findings of efficacy. CONCLUSIONS: The relatively small number of early EF intervention studies uses such variable methods that there is currently no converging evidence of efficacy to recommend a specific intervention. Thus, findings support the need for a more systematic, targeted approach to the design and implementation of early EF interventions for target populations.

Evaluation of eight lateral flow tests for the detection of anti-SARS-CoV-2 antibodies in a vaccinated population.

BACKGROUND: Rapid determination of an individual's antibody status can be beneficial in understanding an individual's immune response to SARS-CoV-2 and for initiation of therapies that are only deemed effective in sero-negative individuals. Antibody lateral flow tests (LFTs) have potential to address this need as a rapid, point of care test. METHODS: Here we present a proof-of-concept evaluation of eight LFT brands using sera from 95 vaccinated individuals to determine sensitivity for detecting vaccination generated antibodies. Samples were analysed on eight different brands of antibody LFT and an automated chemiluminescent microparticle immunoassay (CMIA) that identifies anti-spike antibodies which was used as our reference standard. RESULTS: All 95 (100%) participants tested positive for anti-spike antibodies by the chemiluminescent microparticle immunoassay (CMIA) reference standard post-dose two of their SARS-CoV-2 vaccine: BNT162b2 (Pfizer/BioNTech, n = 60), AZD1222 (AstraZeneca, n = 31), mRNA-1273 (Moderna, n = 2) and Undeclared Vaccine Brand (n = 2). Sensitivity increased from dose one to dose two in six out of eight LFTs with three tests achieving 100% sensitivity at dose two in detecting anti-spike antibodies. CONCLUSIONS: These tests are demonstrated to be highly sensitive to detect raised antibody levels in vaccinated individuals. RDTs are low cost and rapid alternatives to ELISA based systems.

A novel, magnetic bead-based extraction method for the isolation of antimicrobial resistance genes with a case study in river water in Malawi.

AIMS: The environment is increasingly recognized as an important reservoir of antimicrobial resistance genes (ARGs), which can be identified using molecular platforms. Yet, environmental surveillance remains an underutilised tool as there is no agreement on the best strategy for sample processing. We aim to develop a low-cost extraction method independent to commercial kits or reagents. METHODS AND RESULTS: We present a novel, magnetic bead-based method for the isolation of ARGs from river water named MagnaExtract. We present this with analytic limit of detection as well as a case study in Southern Malawi. Here we compare the DNA yield from MagnaExtract with commercially available QIAGEN kits and the crude boil and spin method, using a high-resolution melt analysis PCR panel designed for the detection of third-generation cephalosporin and carbapenem-resistant genes from 98 water samples. CONCLUSION: The MagnaExtract method is comparable, and in some instance's superior to commercially available kits for the isolation of ARGs from river water samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The MagnaExtract approach offers a simple, affordable, high yielding extraction method that could be used for the detection of ARGs from river water samples in surveillance campaigns in East Africa.

HDL particle size is increased and HDL-cholesterol efflux is enhanced in type 1 diabetes: a cross-sectional study.

AIMS/HYPOTHESIS: The prevalence of atherosclerosis is increased in type 1 diabetes despite normal-to-high HDL-cholesterol levels. The cholesterol efflux capacity (CEC) of HDL is a better predictor of cardiovascular events than static HDL-cholesterol. This cross-sectional study addressed the hypothesis that impaired HDL function contributes to enhanced CVD risk within type 1 diabetes. METHODS: We compared HDL particle size and concentration (by NMR), total CEC, ATP-binding cassette subfamily A, member 1 (ABCA1)-dependent CEC and ABCA1-independent CEC (by determining [3H]cholesterol efflux from J774-macrophages to ApoB-depleted serum), and carotid intima-media thickness (CIMT) in 100 individuals with type 1 diabetes (37.6 ± 1.2 years; BMI 26.9 ± 0.5 kg/m2) and 100 non-diabetic participants (37.7 ± 1.1 years; 27.1 ± 0.5 kg/m2). RESULTS: Compared with non-diabetic participants, total HDL particle concentration was lower (mean ± SD 31.01 ± 8.66 vs 34.33 ± 8.04 µmol/l [mean difference (MD) -3.32 µmol/l]) in participants with type 1 diabetes. However, large HDL particle concentration was greater (9.36 ± 3.98 vs 6.99 ± 4.05 µmol/l [MD +2.37 µmol/l]), resulting in increased mean HDL particle size (9.82 ± 0.57 vs 9.44 ± 0.56 nm [MD +0.38 nm]) (p < 0.05 for all). Total CEC (14.57 ± 2.47%CEC/4 h vs 12.26 ± 3.81%CEC/4 h [MD +2.31%CEC/4 h]) was greater in participants with type 1 diabetes relative to non-diabetic participants. Increased HDL particle size was independently associated with increased total CEC; however, following adjustment for this in multivariable analysis, CEC remained greater in participants with type 1 diabetes. Both components of CEC, ABCA1-dependent (6.10 ± 2.41%CEC/4 h vs 5.22 ± 2.57%CEC/4 h [MD +0.88%CEC/4 h]) and ABCA1-independent (8.47 ± 1.79% CEC/4 h vs 7.05 ± 1.76% CEC/4 h [MD +1.42% CEC/4 h]) CEC, were greater in type 1 diabetes but the increase in ABCA1-dependent CEC was less marked and not statistically significant in multivariable analysis. CIMT was increased in participants with type 1 diabetes but in multivariable analysis it was only associated negatively with age and BMI. CONCLUSIONS/INTERPRETATION: HDL particle size but not HDL-cholesterol level is independently associated with enhanced total CEC. HDL particle size is greater in individuals with type 1 diabetes but even after adjusting for this, total and ABCA1-independent CEC are enhanced in type 1 diabetes. Further studies are needed to understand the mechanisms underlying these effects, and whether they help attenuate progression of atherosclerosis in this high-risk group. Graphical abstract.

IgG Seroconversion and Pathophysiology in Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

We investigated the dynamics of seroconversion in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During March 29-May 22, 2020, we collected serum samples and associated clinical data from 177 persons in London, UK, who had SARS-CoV-2 infection. We measured IgG against SARS-CoV-2 and compared antibody levels with patient outcomes, demographic information, and laboratory characteristics. We found that 2.0%-8.5% of persons did not seroconvert 3-6 weeks after infection. Persons who seroconverted were older, were more likely to have concurrent conditions, and had higher levels of inflammatory markers. Non-White persons had higher antibody concentrations than those who identified as White; these concentrations did not decline during follow-up. Serologic assay results correlated with disease outcome, race, and other risk factors for severe SARS-CoV-2 infection. Serologic assays can be used in surveillance to clarify the duration and protective nature of humoral responses to SARS-CoV-2 infection.

Glucose-6-phosphate dehydrogenase mutations in malaria endemic area of Thailand by multiplexed high-resolution melting curve analysis.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy in humans, is prevalent in tropical and subtropical areas where malaria is endemic. Anti-malarial drugs, such as primaquine and tafenoquine, can cause haemolysis in G6PD-deficient individuals. Hence, G6PD testing is recommended before radical treatment against vivax malaria. Phenotypic assays have been widely used for screening G6PD deficiency, but in heterozygous females, the random lyonization causes difficulty in interpreting the results. Over 200 G6PD variants have been identified, which form genotypes associated with differences in the degree of G6PD deficiency and vulnerability to haemolysis. This study aimed to assess the frequency of G6PD mutations using a newly developed molecular genotyping test. METHODS: A multiplexed high-resolution melting (HRM) assay was developed to detect eight G6PD mutations, in which four mutations can be tested simultaneously. Validation of the method was performed using 70 G6PD-deficient samples. The test was then applied to screen 725 blood samples from people living along the Thai-Myanmar border. The enzyme activity of these samples was also determined using water-soluble tetrazolium salts (WST-8) assay. Then, the correlation between genotype and enzyme activity was analysed. RESULTS: The sensitivity of the multiplexed HRM assay for detecting G6PD mutations was 100 % [95 % confidence interval (CI): 94.87-100 %] with specificity of 100 % (95 % CI: 87.66-100 %). The overall prevalence of G6PD deficiency in the studied population as revealed by phenotypic WST-8 assay was 20.55 % (149/725). In contrast, by the multiplexed HRM assay, 27.17 % (197/725) of subjects were shown to have G6PD mutations. The mutations detected in this study included four single variants, G6PD Mahidol (187/197), G6PD Canton (4/197), G6PD Viangchan (3/197) and G6PD Chinese-5 (1/197), and two double mutations, G6PD Mahidol + Canton (1/197) and G6PD Chinese-4 + Viangchan (1/197). A broad range of G6PD enzyme activities were observed in individuals carrying G6PD Mahidol, especially in females. CONCLUSIONS: The multiplexed HRM-based assay is sensitive and reliable for detecting G6PD mutations. This genotyping assay can facilitate the detection of heterozygotes, which could be useful as a supplementary approach for high-throughput screening of G6PD deficiency in malaria endemic areas before the administration of primaquine and tafenoquine.

Saliva Alternative to Upper Respiratory Swabs for SARS-CoV-2 Diagnosis.

PCR of upper respiratory specimens is the diagnostic standard for severe acute respiratory syndrome coronavirus 2 infection. However, saliva sampling is an easy alternative to nasal and throat swabbing. We found similar viral loads in saliva samples and in nasal and throat swab samples from 110 patients with coronavirus disease.

Contextualizing disability: a cross-sectional analysis of the association between the built environment and functioning among people living with spinal cord injury in the United States.

STUDY DESIGN: Secondary analysis of cross-sectional data from a multisite cohort study. OBJECTIVES: To analyze the association between the built environment and physical functioning reported by adults living with chronic spinal cord injury (SCI). SETTING: Four US Spinal Cord Injury Model Systems centers in New Jersey, Colorado, Illinois, and Michigan. METHODS: Participants were from the Spinal Cord Injury-Functional Index/Capacity (SCI-FI/C) development study. Survey data from N = 402 participants were geocoded for analysis. Geographic Information Systems (GIS) analysis was used to define five- and half-mile buffer areas around participants' residential addresses to represent the community and neighborhood environments, respectively, and to create measures of land use, residential density, destination density, and park space. The relationships between these built environment features and four domains of physical functioning-basic mobility, wheelchair mobility, self-care, and fine motor function-were modeled using ordinary least squares (OLS) regression. RESULTS: People with paraplegia living in neighborhoods with more destinations and a nearby park reported higher levels of self-care functioning. For people with tetraplegia, living in a community with more destinations was associated with better wheelchair mobility and fine motor functioning, and living in a neighborhood with high land use mix was associated with higher fine motor functioning scores. CONCLUSIONS: The association between the built environment and functioning after SCI is supported and in need of further investigation. Understanding the environmental context of disability may lead to community-based interventions and effective public policy that will attenuate the experience of limitations and promote accessibility on a larger scale.

Comparing parent and provider priorities in discussions of early detection and intervention for infants with and at risk of cerebral palsy.

BACKGROUND: Although literature suggests that parents need support when their child is diagnosed with cerebral palsy (CP), it is unclear to what extent providers implement these supports in practice and what parental perspectives surround provider early diagnosis and management of CP. Therefore, we aimed to characterize and compare experiences of providers and parents of children with CP with regards to early detection and intervention. METHOD: Seventeen parents participated in day-long world-café style workshops focused on categories extracted from the International Classification of Function framework and recent systematic reviews of early detection for CP. Thirty regional providers (generalists, specialists, and therapists) caring for infants with CP completed surveys with scaled score and open-ended questions. Quantitative and qualitative data were independently assessed by two reviewers to identify prominent themes. RESULTS: All parents (100%) stated early diagnosis or high risk for CP classification was beneficial compared with only 50% of providers who often gave early CP diagnoses before 12 months. Top parent priorities were honesty and positively phrased messages. Providers most often addressed cognition, primary care need, motor, and feeding issues (80%, 62%, 54%, 54% frequently/sometimes). Matching priorities for discussion were neuroimaging timing/risk/benefit, cognition, primary care, motor, and feeding/nutrition. Discordance occurred for participation, parent well-being, pain and vision, with parents wanting more education and resources. CONCLUSIONS: Receiving early diagnoses or high-risk for CP classification is a parent priority. Alignment between parents and providers exists for International Classification of Function domains of body functions/structures and activity, but less for those of environment, personal, and participation.

Patterns of Sacral Sparing Components on Neurologic Recovery in Newly Injured Persons With Traumatic Spinal Cord Injury.

OBJECTIVE: To assess the patterns of sacral sparing and recovery in newly injured persons with traumatic spinal cord injury (SCI). DESIGN: Retrospective analysis of data from the national Spinal Cord Injury Model Systems (SCIMS) database for patients enrolled from January 2011 to February 2015. SETTING: SCIMS centers. PARTICIPANTS: Individuals (N=1738; age ≥16y) with traumatic SCI admitted to rehabilitation within 30 days after injury with follow-up at discharge, at 1 year, or both. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: International Standards for Neurological Classification of Spinal Cord Injury examination results at admission and follow-up (discharge or 1y, or both). RESULTS: Conversion from an initial American Spinal Injury Association Impairment Scale (AIS) grade A to incomplete status was 20% at rehabilitation discharge and 27.8% at 1 year, and was greater in cervical and low paraplegia levels (T10 and below) than in high paraplegia level injuries (T1-9). Conversion from AIS B to motor incomplete was 33.9% at discharge and 53.6% at 1 year, and the initial sparing of all sacral sensory components was correlated with the greatest conversion to motor incomplete status at discharge and at 1 year. For patients with initial AIS C, the presence of voluntary anal contraction (VAC) in association with other sacral sparing was most frequently observed to improve to AIS D status at discharge. However, the presence of VAC alone as the initial sacral sparing component had the poorest prognosis for recovery to AIS D status. At follow-up, regaining sacral sparing components correlated with improvement in conversion for patients with initial AIS B and C. CONCLUSIONS: The components of initial and follow-up sacral sparing indicated differential patterns of neurologic outcome in persons with traumatic SCI. The more sacral components initially spared, the greater the potential for recovery; and the more sacral components gained, the greater the chance of motor recovery. Consideration of whether VAC should remain a diagnostic criterion sufficient for motor incomplete classification in the absence of other qualifying sublesional motor sparing is recommended.

Ambulance service recognition of health inequalities and activities for reduction: An evidence and gap map of the published literature.

Background: Emergency medical services (EMS) are often patients' first point of contact for urgent and emergency care needs. Patients are triaged over the phone and may receive an ambulance response, with potential conveyance to the hospital. A recent scoping review suggested disparities in EMS patient care in the United States. However, it is unknown how health inequalities impact EMS care in other developed countries and how inequalities are being addressed. Objectives: This rapid evidence map of published literature aims to map known health inequalities in EMS patients and describe interventions reducing health inequalities in EMS patient care. Methods: The search strategy consisted of EMS synonyms and health inequality synonyms. The MEDLINE/PubMed database was searched from 1 January 2010 to 26 July 2022. Studies were included if they described empirical research exploring health inequalities within ambulance service patient care. Studies were mapped on to the EMS care interventions framework and Core20PLUS5 framework. Studies evaluating interventions were synthesised using the United Kingdom Allied Health Professions Public Health Strategic Framework. Results: The search strategy yielded 771 articles, excluding duplicates, with two more studies added from hand searches. One hundred studies met the inclusion criteria after full-text review. Inequalities in EMS patient care were predominantly situated in assessment, treatment and conveyance, although triage and response performance were also represented. Studies mostly explored EMS health inequalities within ethnic minority populations, populations with protected characteristics and the core issue of social deprivation. Studies evaluating interventions reducing health inequalities (n = 5) were from outside the United Kingdom and focused on older patients, ethnic minorities and those with limited English proficiency. Interventions included community paramedics, awareness campaigns, dedicated language lines and changes to EMS protocols. Conclusions: Further UK-based research exploring health inequalities of EMS patients would support ambulance service policy and intervention development to reduce health inequality in urgent and emergency care delivery.

Factors associated with delayed diagnosis of leprosy in an endemic area in Northeastern Brazil: a cross-sectional study.

This study aimed to investigate the factors related to the individual and the health system that contribute to delayed diagnosis of leprosy in an endemic area in the Northeastern Brazil. This is a cross-sectional study of 120 individuals with leprosy. Demographic and clinical data and information on the factors related to the individual and the health system that contribute to delayed diagnosis of leprosy were obtained. Delayed diagnosis in months was estimated for each participant by interviews. A multivariate Poisson's regression analysis was performed between the outcome and the independent variables. The median delay in the diagnosis of leprosy was 10.5 (4.0-24.0) months. Approximately 12.6% of participants had grade 2 disability (G2D) at the time of diagnosis. In the multivariate Poisson regression analysis, males, older age, low schooling level, residing in urban areas, multibacellar or tuberculoid leprosy, not seeking healthcare immediately after symptom onset, suspected leprosy, excessive referrals, and the need for three or more consultations to confirm the diagnosis were associated with longer diagnostic delay. This study found a significant delay in the diagnosis of leprosy in Arapiraca, Northeastern Brazil, which may explain the continuously high rate of G2D among new cases. Factors related to the individual and the health system were associated with longer diagnostic delay. Interventions to raise awareness of the disease among the general population and strengthen primary health care are urgently needed.

Impact of blood pressure dysregulation on health-related quality of life in persons with spinal cord injury: development of a conceptual model.

OBJECTIVES: To identify medically relevant aspects of blood pressure dysregulation (BPD) related to quality of life in individuals with spinal cord injury (SCI), and to propose an integrated conceptual framework based on input from both individuals with SCI and their clinical providers. This framework will serve as a guide for the development of a patient-reported outcome (PRO) measure specifically related to BPD. DESIGN: Three focus groups with individuals with SCI and 3 groups with SCI providers were analyzed using grounded-theory based qualitative analysis to ascertain how blood pressure impacts health-related quality of life (HRQOL) in individuals with SCI. SETTING: Focus groups were conducted at 2 Veterans Affairs medical centers and a research center. PARTICIPANTS: Individuals with SCI (n=27) in 3 focus groups and clinical providers (n=25) in 3 focus groups. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Qualitative analysis indicated that all focus groups spent the highest percentage of time discussing symptoms of BPD (39%), followed by precipitators/causes of BPD (16%), preventative actions (15%), corrective actions (12%), and the impact that BPD has on social or emotional functioning (8%). While patient/consumer focus groups and provider focus groups raised similar issues, providers spent more time discussing precipitators/causes of BPD and preventative actions (38%) than patient/consumer groups (24%). CONCLUSIONS: These results suggest that BPD uniquely and adversely impacts HRQOL in persons with SCI. While both individuals with SCI and their providers highlighted the relevant symptoms of BPD, the SCI providers offered additional detailed information regarding the precipitators/causes and what can be done to prevent/treat BPD. Further, the results suggest that persons with SCI are aware of how BPD impacts their HRQOL and are able to distinguish between subtle signs and symptoms. These findings exemplify the need for a validated and sensitive clinical measurement tool that can assess the extent to which BPD impacts HRQOL in patients with SCI.

Implementation of Early Detection and Intervention for Cerebral Palsy in High-Risk Infant Follow-Up Programs: U.S. and Global Considerations.

Early detection and intervention for cerebral palsy is best practice for all high-risk infants according to international guidelines, consensus statements and research-supported evidence. It allows support for families and optimization of developmental trajectories into adulthood. All phases of implementation of CP early detection can be found across the world in high-risk infant follow-up programs, demonstrating feasibility and acceptability through standardized implementation science. The largest clinical network for CP early detection and intervention in the world has now sustained an average age at detection less than 12 months corrected age for more than 5 years. Targeted referrals and interventions for CP can now be offered to patients in optimal periods of neuroplasticity, and new therapies researched as the age of detection decreases. Implementation of guidelines and incorporation of rigorous CP research studies both allow high-risk infant follow-up programs to fulfill their mission of improving outcomes of those with the most vulnerable developmental trajectories from birth.

Efficacy, Safety, Patient Experience, and Tolerability of Risankizumab Administered by On-Body Injector for Moderate to Severe Crohn's Disease.

INTRODUCTION: In patients with moderate to severe Crohn's disease (CD), intravenous induction and subcutaneous maintenance dosing with risankizumab was efficacious and well tolerated. Long-term management of CD via self-administration of risankizumab using an on-body injector (OBI) may improve treatment adherence through convenience and ease of use. METHODS: Within the FORTIFY maintenance study, 46 patients from the United States (US) sites participated in an open-label extension Substudy and received 180 mg or 360 mg risankizumab delivered subcutaneously via OBI [360 mg (2.4 mL, 150 mg/mL) or 180 mg (1.2 mL, 150 mg/mL)]. At the Week 0 visit, patients were trained (pre-injection) by site staff, using Instructions for Use (IFU) and a training video, to self-administer risankizumab at Weeks 0 (on site), 8 (at home), and 16 (on site). Key objectives of the Substudy 4 were to assess OBI usability (observer rating of successful self-administration), hazard-free self-injection at Weeks 0 and 16, and patient rating of acceptability using the Self-Injection Assessment Questionnaire (SIAQ) at Weeks 0, 8, and 16. Additionally, the proportion of patients in clinical remission (CD Activity Index < 150) was collected at Weeks 0 and 16. RESULTS: All patients successfully self-administered risankizumab via OBI, including two patients who successfully self-administered with a second OBI (i.e., required two injection attempts). Acceptability of self-injection was high. Two patients (n = 2) experienced a use-related hazard. Stable clinical remission was observed with both risankizumab doses. Two patients experienced injection site reactions; neither was related to the OBI per investigator's assessment. Two device-related adverse events related to topical adhesive reactions were reported, both mild and resolved. No new safety risks were observed. CONCLUSION: The efficacy and safety of maintenance risankizumab delivered via OBI and OBI usability support the use of this device in patients with moderate to severe CD. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT03105102 (FORTIFY).

Multicenter Diagnostic Evaluation of OnSite COVID-19 Rapid Test (CTK Biotech) among Symptomatic Individuals in Brazil and the United Kingdom.

The COVID-19 pandemic has given rise to numerous commercially available antigen rapid diagnostic tests (Ag-RDTs). To generate and to share accurate and independent data with the global community requires multisite prospective diagnostic evaluations of Ag-RDTs. This report describes the clinical evaluation of the OnSite COVID-19 rapid test (CTK Biotech, CA, USA) in Brazil and the United Kingdom. A total of 496 paired nasopharyngeal (NP) swabs were collected from symptomatic health care workers at Hospital das Clínicas in São Paulo, Brazil, and 211 NP swabs were collected from symptomatic participants at a COVID-19 drive-through testing site in Liverpool, United Kingdom. Swabs were analyzed by Ag-RDT, and results were compared to quantitative reverse transcriptase PCR (RT-qPCR). The clinical sensitivity of the OnSite COVID-19 rapid test in Brazil was 90.3% (95% confidence interval [CI], 75.1 to 96.7%) and in the United Kingdom was 75.3% (95% CI, 64.6 to 83.6%). The clinical specificity in Brazil was 99.4% (95% CI, 98.1 to 99.8%) and in the United Kingdom was 95.5% (95% CI, 90.6 to 97.9%). Concurrently, analytical evaluation of the Ag-RDT was assessed using direct culture supernatant of SARS-CoV-2 strains from wild-type (WT), Alpha, Delta, Gamma, and Omicron lineages. This study provides comparative performance of an Ag-RDT across two different settings, geographical areas, and populations. Overall, the OnSite Ag-RDT demonstrated a lower clinical sensitivity than claimed by the manufacturer. The sensitivity and specificity from the Brazil study fulfilled the performance criteria determined by the World Health Organization, but the performance obtained from the UK study failed to do. Further evaluation of Ag-RDTs should include harmonized protocols between laboratories to facilitate comparison between settings. IMPORTANCE Evaluating rapid diagnostic tests in diverse populations is essential to improving diagnostic responses as it gives an indication of the accuracy in real-world scenarios. In the case of rapid diagnostic testing within this pandemic, lateral flow tests that meet the minimum requirements for sensitivity and specificity can play a key role in increasing testing capacity, allowing timely clinical management of those infected, and protecting health care systems. This is particularly valuable in settings where access to the test gold standard is often restricted.

Investigating One Health risks for human colonisation with extended spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Malawian households: a longitudinal cohort study.

BACKGROUND: Low-income countries have high morbidity and mortality from drug-resistant infections, especially from enteric bacteria such as Escherichia coli. In these settings, sanitation infrastructure is of variable and often inadequate quality, creating risks of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales transmission. We aimed to describe the prevalence, distribution, and risks of ESBL-producing Enterobacterales colonisation in sub-Saharan Africa using a One Health approach. METHODS: Between April 29, 2019, and Dec 3, 2020, we recruited 300 households in Malawi for this longitudinal cohort study: 100 each in urban, peri-urban, and rural settings. All households underwent a baseline visit and 195 were selected for longitudinal follow-up, comprising up to three additional visits over a 6 month period. Data on human health, antibiotic usage, health-seeking behaviours, structural and behavioural environmental health practices, and animal husbandry were captured alongside human, animal, and environmental samples. Microbiological processing determined the presence of ESBL-producing E coli and Klebsiella pneumoniae, and hierarchical logistic regression was performed to evaluate the risks of human ESBL-producing Enterobacterales colonisation. FINDINGS: A paucity of environmental health infrastructure and materials for safe sanitation was identified across all sites. A total of 11 975 samples were cultured, and ESBL-producing Enterobacterales were isolated from 1190 (41·8%) of 2845 samples of human stool, 290 (29·8%) of 973 samples of animal stool, 339 (66·2%) of 512 samples of river water, and 138 (46·0%) of 300 samples of drain water. Multivariable models illustrated that human ESBL-producing E coli colonisation was associated with the wet season (adjusted odds ratio 1·66, 95% credible interval 1·38-2·00), living in urban areas (2·01, 1·26-3·24), advanced age (1·14, 1·05-1·25), and living in households where animals were observed interacting with food (1·62, 1·17-2·28) or kept inside (1·58, 1·00-2·43). Human ESBL-producing K pneumoniae colonisation was associated with the wet season (2·12, 1·63-2·76). INTERPRETATION: There are extremely high levels of ESBL-producing Enterobacterales colonisation in humans and animals and extensive contamination of the wider environment in southern Malawi. Urbanisation and seasonality are key risks for ESBL-producing Enterobacterales colonisation, probably reflecting environmental drivers. Without adequate efforts to improve environmental health, ESBL-producing Enterobacterales transmission is likely to persist in this setting. FUNDING: Medical Research Council, National Institute for Health and Care Research, and Wellcome Trust. TRANSLATION: For the Chichewa translation of the abstract see Supplementary Materials section.

Detection of SARS-CoV-2 infection by saliva and nasopharyngeal sampling in frontline healthcare workers: An observational cohort study.

BACKGROUND: The SARS-CoV-2 pandemic has caused an unprecedented strain on healthcare systems worldwide, including the United Kingdom National Health Service (NHS). We conducted an observational cohort study of SARS-CoV-2 infection in frontline healthcare workers (HCW) working in an acute NHS Trust during the first wave of the pandemic, to answer emerging questions surrounding SARS-CoV-2 infection, diagnosis, transmission and control. METHODS: Using self-collected weekly saliva and twice weekly combined oropharyngeal/nasopharyngeal (OP/NP) samples, in addition to self-assessed symptom profiles and isolation behaviours, we retrospectively compared SARS-CoV-2 detection by RT-qPCR of saliva and OP/NP samples. We report the association with contemporaneous symptoms and isolation behaviour. RESULTS: Over a 12-week period from 30th March 2020, 40·0% (n = 34/85, 95% confidence interval 31·3-51·8%) HCW had evidence of SARS-CoV-2 infection by surveillance OP/NP swab and/or saliva sample. Symptoms were reported by 47·1% (n = 40) and self-isolation by 25·9% (n = 22) participants. Only 44.1% (n = 15/34) participants with SARS-CoV-2 infection reported any symptoms within 14 days of a positive result and only 29·4% (n = 10/34) reported self-isolation periods. Overall agreement between paired saliva and OP/NP swabs was 93·4% (n = 211/226 pairs) but rates of positive concordance were low. In paired samples with at least one positive result, 35·0% (n = 7/20) were positive exclusively by OP/NP swab, 40·0% (n = 8/20) exclusively by saliva and in only 25·0% (n = 5/20) were the OP/NP and saliva result both positive. CONCLUSIONS: HCW are a potential source of SARS-CoV-2 transmission in hospitals and symptom screening will identify the minority of infections. Without routine asymptomatic SARS-CoV-2 screening, it is likely that HCW with SARS-CoV-2 infection would continue to attend work. Saliva, in addition to OP/NP swab testing, facilitated ascertainment of symptomatic and asymptomatic SARS-CoV-2 infections. Combined saliva and OP/NP swab sampling would improve detection of SARS-CoV-2 for surveillance and is recommended for a high sensitivity strategy.