Asthma innovations from the second International Collaborative Asthma Network (ICAN) forum.

Asthma continues to cause morbidity and mortality despite advances in treatment that include biologics targeting Type 2 inflammation. The International Collaborative Asthma Network (ICAN) forum was developed with the primary goal of promoting innovative, collaborative research that focuses on mechanisms and treatment for asthma that does not respond or that responds poorly to currently available treatments. The mission of ICAN is innovation, collaboration, translation, and increasing high quality research. At the second ICAN meeting, presenters covered a broad scope and depth of asthma-related topics in the categories of complex data, novel therapeutics and diagnostics, breath analysis and microbiome, disease mechanisms, systemic effects, and circadian rhythm. Key actionable needs and research topics were identified during the group discussions. The presentations and discussions that occurred at the second ICAN had an immediate impact on asthma research in the form of new collaborations and implementation of new research ideas and techniques. The forum also served to connect early-stage investigators with investigators who are well established, thereby fostering innovation, translation, and collaboration well into the future. A third ICAN meeting is planned for 2025 to further the innovations and collaborations that will translate into novel therapies and diagnostics to improve the lives of patients with asthma.

Middle meningeal artery embolization following surgical evacuation of symptomatic chronic subdural hematoma improves outcomes, interim results of a prospective randomized trial.

BACKGROUND: Outcomes after surgical treatment of chronic subdural hematoma (cSDH) remain undesirable in a significant proportion of patients. We aimed to show the role of middle meningeal artery (MMA) embolization and to demonstrate its benefits. METHODS: Thirty-five patients with symptomatic cSDH were enrolled in a prospective randomized trial following evacuation surgery. Participants were randomized to embolization or control group (expectant management following surgical evacuation without embolization). Patients were followed throughout their hospitalization and outpatient follow-ups. The main goals of this planned interim analysis were to assess neurological outcome and resource utilization. RESULTS: The groups were comparable in terms of sex, age and follow-up retention rates. Side(s) of intervention(s) and hematoma size were similar. There was no statistical difference in neurological examination improvement at discharge, but at follow-up, we observed a decline in neurologic exam in the control group (p = 0.03). Control group participants required more re-interventions (p = 0.02) and were followed in clinic and during related readmissions for longer (p = 0.02). The number of imaging studies obtained in relation to the disease management was higher in the control group (p = 0.01). CONCLUSIONS: Our results suggest a beneficial role for the addition of MMA embolization to surgical intervention in the treatment of symptomatic chronic subdural hematoma. Neurological outcomes were significantly better in the embolization group. This contributed to less need for follow-up, re-interventions, and imaging studies.

Long-term impact of COVID-19 hospitalisation among individuals with pre-existing airway diseases in the UK: a multicentre, longitudinal cohort study - PHOSP-COVID.

Background: The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods: Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results: A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p<0.001), had higher burden of anxiety (29.1% versus 22.0%, p=0.002), depression (31.2% versus 24.7%, p=0.006), higher percentage of impaired mobility using short physical performance battery ≤10 (57.4% versus 45.2%, p<0.001) and 27% had a new disability (assessed by the Washington Group Short Set on Functioning) versus 16.6%, p=0.014. HRQoL assessed using EQ-5D-5L Utility Index was lower in the airways group (mean±SD 0.64±0.27 versus 0.73±0.25, p<0.001). Burden of breathlessness, fatigue and cough measured using a study-specific tool was higher in the airways group. Conclusion: Individuals with pre-existing airway diseases hospitalised due to COVID-19 were less likely to feel fully recovered, had lower physiological performance measurements, more burden of symptoms and reduced HRQoL up to 1 year post-hospital discharge.

Risk of cardiovascular events following COVID-19 in people with and without pre-existing chronic respiratory disease.

BACKGROUND: COVID-19 is associated with cardiovascular outcomes in the general population, but it is unknown whether people with chronic respiratory disease (CRD) have a higher risk of cardiovascular events post-COVID-19 compared with the general population and, if so, what respiratory-related factors may modify this risk in these people. METHODS: Primary and secondary care data from the National Health Service England were used to define a population of adults in England with COVID-19 (index date) between 1 January 2020 and 30 November 2021. Adjusted Cox proportional hazard regression was used to quantify the association between CRD, asthma-related factors, chronic obstructive pulmonary disease (COPD)-related factors, and risk of cardiovascular events. Asthma-specific factors included baseline asthma control, exacerbations, and inhaled corticosteroid (ICS) dose. COPD-specific risk factors included baseline ICS and exacerbations. Secondary objectives quantified the impact of COVID-19 hospitalisation and vaccine dose on cardiovascular outcomes. RESULTS: Of 3 670 455 people, those with CRD had a higher risk of cardiovascular events [adjusted hazard ratio (HRadj), 1.08; 95% confidence interval (CI) 1.06-1.11], heart failure (HRadj, 1.17; 95% CI, 1.12-1.22), angina (HRadj, 1.13; 95% CI, 1.06-1.20) and pulmonary emboli (HRadj, 1.24; 95% CI, 1.15-1.33) compared with people without CRD. In people with asthma or COPD, baseline exacerbations were associated with a higher risk of cardiovascular outcomes (HRadj, 1.36; 95% CI, 1.27-1.00 and HRadj, 1.35; 95% CI, 1.24-1.46, respectively). Regardless of CRD, the risk of cardiovascular events was lower with increasing COVID-19 vaccine dose. CONCLUSIONS: Higher risk of cardiovascular events post-COVID-19 might be explained by the underlying severity of the CRD, and COVID-19 vaccines were beneficial to both people with and those without CRD with regards to cardiovascualr events.

Newer treatment paradigm improves outcomes in the most common neurosurgical disease of the elderly: a literature review of middle meningeal artery embolization for chronic subdural hematoma.

Chronic subdural hematoma (cSDH) is one of the most prevalent neurosurgical diseases, especially in the elderly. Yet, its incidence is predicted to increase further, paralleling the growth of the geriatric population. While surgical evacuation is technically straightforward, it is associated with significant morbidity and mortality. In fact, 30% of patients are expected to have hematoma recurrence and to need repeat surgical evacuation, and 20% of patients are expected to lose independence and require long-term care. A pathophysiology more complex than originally presumed explains the disappointing results observed for decades. At its core, the formation of microcapillaries and anastomotic channels with the middle meningeal artery (MMA) perpetuates a constant cycle resulting in persistence of hematoma. The rationale behind MMA embolization is simple: to stop cSDH at its source. Over the last few years, this "newer" option has been heavily studied. It has shown tremendous potential in decreasing hematoma recurrence and improving neurological outcomes. Whether combined with surgical evacuation or performed as the only treatment, the scientific evidence to its benefits is unequivocal. Here, we aimed to review cSDH in the elderly and discuss its more recent treatment options with an emphasis on MMA embolization.

Novel WRN Helicase Inhibitors Selectively Target Microsatellite-Unstable Cancer Cells.

Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumors, and WRN inhibitors are in development. In this study, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target. Fragment-based screening led to the development of potent and highly selective WRN helicase covalent inhibitors. These compounds selectively suppressed MSI model growth in vitro and in vivo by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA repeats and DNA damage. Assessment of biomarkers in preclinical models linked TA-repeat expansions and mismatch repair alterations to compound activity. Efficacy was confirmed in immunotherapy-resistant organoids and patient-derived xenograft models. The discovery of potent, selective covalent WRN inhibitors provides proof of concept for synthetic lethal targeting of WRN in MSI cancer and tools to dissect WRN biology. Significance: We report the discovery and characterization of potent, selective WRN helicase inhibitors for MSI cancer treatment, with biomarker analysis and evaluation of efficacy in vivo and in immunotherapy-refractory preclinical models. These findings pave the way to translate WRN inhibition into MSI cancer therapies and provide tools to investigate WRN biology. See related commentary by Wainberg, p. 1369.

The Experience of Living With Polycystic Ovary Syndrome in the Military.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is the most prevalent reproductive endocrinopathy in women, ranging from 5% to 26% depending on diagnostic criteria applied. Common manifestations of PCOS include overweight and obesity, abnormal menstrual cycles, pelvic pain, increased facial and body hair, acne, and infertility. These abnormalities and associated complications have significant military operational and readiness implications. There is a large gap in research regarding active duty servicewomen (ADW) with PCOS. Therefore, the purpose of this study is to describe ADW's experience of living with PCOS and to describe the service-branch-specific differences among these women. MATERIALS AND METHODS: Moderator's guide, audiotapes, transcripts, and field notes. This was a qualitative descriptive study using focus groups and individual interviews. The David Grant Medical Center Institutional Review Board at Travis AFB, CA, USA, approved the study protocol. Women with PCOS were recruited from U.S. Air Force, Army, and Navy locations. Data were analyzed using constant comparative content analysis. RESULTS: Twenty-three servicewomen from 19 occupations across the Army, Navy, Air Force, and Marine Corps participated. Three overarching categories emerged: (1) challenges managing PCOS symptoms, (2) navigating the military health care system, and (3) navigating PCOS as a service member. CONCLUSIONS: Servicewomen may have significant career consequences related to PCOS sequelae, such as overweight, obesity, uncontrolled menstrual cycle, and pain. Managing the myriad of symptoms can distract women while deployed, in austere conditions, or at their home stations. As one of the most common cardiometabolic, reproductive endocrinologic conditions in women, PCOS has not received the attention, awareness, education, or research necessary to sufficiently support ADW with this condition. It is imperative that evidence-based strategies are developed to inform relevant and high-quality care for these warfighters. Future qualitative studies are needed to further describe specific stressors and needs of ADW with PCOS. Future intervention studies are also needed to evaluate effective management options for ADW with PCOS.

Missed Opportunities for Antifungal Stewardship during the COVID-19 Era.

Significant increases in antibacterial use were observed during the COVID-19 pandemic. However, subsequent analyses found this increase in antibiotic use to be excessive in comparison with the relatively low rates of bacterial coinfection. Although patients who are critically ill with COVID-19 may be at an increased risk for pulmonary aspergillosis, antifungal use in these populations remained underreported, particularly in later phases of the pandemic. This single-center, population-level cohort analysis compares the monthly use rates of mold-active antifungal drugs in the medical intensive care unit during April 2019-March 2020 (baseline) with those during April 2020-November 2022. The antifungal drugs included in the analysis were liposomal amphotericin B, anidulafungin, isavuconazonium, posaconazole, and voriconazole. We found that during 2020-2022, the usage of antifungal drugs was not significantly different from baseline for all included agents except isavuconazonium, which was used significantly more (p = 0.009). There were no changes in diagnostic modalities between the two time periods. The reported prevalence of and mortality from COVID-19-associated pulmonary aspergillosis (CAPA) may have resulted in higher rates of prescribing antifungal drugs for critically ill patients with COVID-19. Antimicrobial stewardship programs should develop and apply tools to facilitate more effective and appropriate antifungal use.

Blood transcriptomic signature in type-2 biomarker-low severe asthma and asthma control.

BACKGROUND: Patients with type-2 (T2) cytokine-low severe asthma often have persistent symptoms despite suppression of T2 inflammation with corticosteroids. OBJECTIVES: We sought to analyze whole blood transcriptome from 738 samples in T2-biomarker-high/-low patients with severe asthma to relate transcriptomic signatures to T2 biomarkers and asthma symptom scores. METHODS: Bulk RNA-seq data were generated for blood samples (baseline, week 24, week 48) from 301 participants recruited to a randomized clinical trial of corticosteroid optimization in severe asthma. Unsupervised clustering, differential gene expression analysis, and pathway analysis were performed. Patients were grouped by T2-biomarker status and symptoms. Associations between clinical characteristics and differentially expressed genes (DEGs) associated with biomarker and symptom levels were investigated. RESULTS: Unsupervised clustering identified 2 clusters; cluster 2 patients were blood eosinophil-low/symptom-high and more likely to be receiving oral corticosteroids (OCSs). Differential gene expression analysis of these clusters, with and without stratification for OCSs, identified 2960 and 4162 DEGs, respectively. Six hundred twenty-seven of 2960 genes remained after adjusting for OCSs by subtracting OCS signature genes. Pathway analysis identified dolichyl-diphosphooligosaccharide biosynthesis and assembly of RNA polymerase I complex as significantly enriched pathways. No stable DEGs were associated with high symptoms in T2-biomarker-low patients, but numerous associated with elevated T2 biomarkers, including 15 that were upregulated at all time points irrespective of symptom level. CONCLUSIONS: OCSs have a considerable effect on whole blood transcriptome. Differential gene expression analysis demonstrates a clear T2-biomarker transcriptomic signature, but no signature was found in association with T2-biomarker-low patients, including those with a high symptom burden.

Asthma innovations from the first International Collaborative Asthma Network forum.

Background: Many patients have uncontrolled asthma despite available treatments. Most of the new asthma therapies have focused on type 2 (T2) inflammation, leaving an unmet need for innovative research into mechanisms of asthma beyond T2 and immunity. An international group of investigators developed the International Collaborative Asthma Network (ICAN) with the goal of sharing innovative research on disease mechanisms, developing new technologies and therapies, organising pilot studies and engaging early-stage career investigators from across the world. This report describes the purpose, development and outcomes of the first ICAN forum. Methods: Abstracts were solicited from interdisciplinary early-stage career investigators with innovative ideas beyond T2 inflammation for asthma and were selected for presentation at the forum. Breakout sessions were conducted to discuss innovation, collaboration and research translation. Results: The abstracts were categorised into: 1) general omics and big data analysis; 2) lung-brain axis and airway neurology; 3) sex differences; 4) paediatric asthma; 5) new therapeutic targets inspired by airway epithelial biology; 6) new therapeutics targeting airway and circulating immune mediators; and 7) lung anatomy, physiology and imaging. Discussions revealed that research groups are looking for opportunities to further their findings using larger scale collaboration and the ability to translate their in vitro findings into clinical treatment. Conclusions: Through ICAN, teams that included interdisciplinary early-stage career investigators discussed innovation, collaboration and translation in asthma and severe asthma research. With a combination of fresh ideas and energetic, collaborative, global participation, ICAN has laid a firm foundation and model for future collaborative global asthma research.

Characteristics and risk factors for post-COVID-19 breathlessness after hospitalisation for COVID-19.

Background: Persistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation. Methods: PHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness. Results: We included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14-2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06-2.35), female sex (adjusted OR 1.56, 95% CI 1.21-2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00-1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35-0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14-0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63-0.69) and good calibration (calibration slope 1.00, 95% CI 0.80-1.21). Conclusions: Post-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.

Toxicity of Zinc to Aquatic Life in Tropical Freshwaters of Low Hardness.

Zinc (Zn) is a metal of potential concern for a uranium mine whose receiving waters are in the World-Heritage listed Kakadu National Park in northern Australia. The chronic toxicity of Zn was assessed using seven tropical species in extremely soft freshwater from a creek upstream of the mine. Sensitivity to Zn was as follows (most sensitive to least sensitive based on 10% effect concentrations [EC10s]): mussel Velesunio angasi > gastropod Amerianna cumingi > fish Mogurnda mogurnda > cladoceran Moinodaphnia macleayi > green hydra Hydra viridissima > green alga Chlorella sp. > duckweed Lemna aequinoctialis, with EC10s (<0.45 µm filtered fraction) ranging from 21 to 320 µg/L Zn and EC50s ranging from 52 to 1867 µg/L Zn. These data were used to inform the risk assessment for the rehabilitation of the mine-site and contribute to the global Zn dataset. Environ Toxicol Chem 2023;42:679-683. © 2023 Commonwealth of Australia. Environmental Toxicology and Chemistry © 2023 SETAC.

A Randomized Trial of a Composite T2-Biomarker Strategy Adjusting Corticosteroid Treatment in Severe Asthma: A Post Hoc Analysis by Sex.

BACKGROUND: Approximately 5% to 10% of patients with asthma have severe disease, with a consistent preponderance in females. Current asthma guidelines recommend stepwise treatment to achieve symptom control with no differential treatment considerations for either sex. OBJECTIVE: To examine whether patient sex affects outcomes when using a composite T2-biomarker score to adjust corticosteroid (CS) treatment in patients with severe asthma compared with standard care. METHODS: This is a post hoc analysis, stratifying patient outcomes by sex, of a 48-week, multicenter, randomized controlled clinical trial comparing a biomarker-defined treatment algorithm with standard care. The primary outcome was the proportion of patients with a reduction in CS treatment (inhaled and oral corticosteroids). Secondary outcomes included exacerbation rates, hospital admissions, and lung function. RESULTS: Of the 301 patients randomized, 194 (64.5%) were females and 107 (35.5%) were males. The biomarker algorithm led to a greater proportion of females being on a lower CS dose versus standard care, which was not seen in males (effect estimate: females, 3.57; 95% CI, 1.14-11.18 vs males, 0.54; 95% CI, 0.16-1.80). In T2-biomarker-low females, reducing CS dose was not associated with increased exacerbations. Females scored higher in all domains of the 7-item Asthma Control Questionnaire, apart from FEV1, but with no difference when adjusted for body mass index/anxiety and/or depression. Dissociation between symptoms and T2 biomarkers were noted in both sexes, with a higher proportion of females being symptom high/T2-biomarker low (22.8% vs 15.6%; P = .0002), whereas males were symptom low/T2-biomarker high (22.3% vs 11.4%; P < .0001). CONCLUSIONS: This exploratory post hoc analysis identified that females achieved a greater benefit from biomarker-directed CS optimization versus symptom-directed treatment.

Seasonal responses of macroinvertebrate assemblages to magnesium in a seasonally flowing stream.

Macroinvertebrates can be highly sensitive to elevated salinity in freshwater environments, and are known to respond to saline discharges. Magnesium (Mg) is a mine-related contaminant and is a potential environmental risk to a seasonally-flowing, receiving water stream in Kakadu National Park, located in the wet-dry tropics of Australia. The macroinvertebrate assemblage in the stream in the was characterised at four hydrographic phases, from early wet season flow to early dry season pools at flow cessation. On each of the four occasions representing the respective phases, individuals from the most abundant macroinvertebrate species present were collected and acutely exposed to a range (up to 19) of Mg concentrations under laboratory conditions. Sensitivity of taxa to Mg ranged between 39 mg/L Mg (Caenidae: Tasmanocoenis spp.) and 4400 mg/L Mg (Dytiscidae: Clypeodytes feryi), based on the 50% Lethal Concentration (LC50). Characterisation of the macroinvertebrate assemblage at each hydrographic phase indicated the seasons when Mg-sensitive species were present. Whilst no statistical differences in measures of seasonal sensitivity were found, the macroinvertebrate assemblages present during the early flow period had higher Mg-sensitivity than the assemblages present during other hydrographic phases. This could be attributed to the greater relative proportions of Mg-sensitive taxa (e.g. Ephemeroptera) present at early flow compared to greater relative proportions of more Mg-tolerant taxa (C. feryi and Hydacarina spp.) present during later hydrograph phases, especially periods of lower, or no, flow.

Prevalence, risk factors and treatments for post-COVID-19 breathlessness: a systematic review and meta-analysis.

Persistent breathlessness >28 days after acute COVID-19 infection has been identified as a highly debilitating post-COVID symptom. However, the prevalence, risk factors, mechanisms and treatments for post-COVID breathlessness remain poorly understood. We systematically searched PubMed and Embase for relevant studies published from 1 January 2020 to 1 November 2021 (PROSPERO registration number: CRD42021285733) and included 119 eligible papers. Random-effects meta-analysis of 42 872 patients with COVID-19 reported in 102 papers found an overall prevalence of post-COVID breathlessness of 26% (95% CI 23-29) when measuring the presence/absence of the symptom, and 41% (95% CI 34-48) when using Medical Research Council (MRC)/modified MRC dyspnoea scale. The pooled prevalence decreased significantly from 1-6 months to 7-12 months post-infection. Post-COVID breathlessness was more common in those with severe/critical acute infection, those who were hospitalised and females, and was less likely to be reported by patients in Asia than those in Europe or North America. Multiple pathophysiological mechanisms have been proposed (including deconditioning, restrictive/obstructive airflow limitation, systemic inflammation, impaired mental health), but the body of evidence remains inconclusive. Seven cohort studies and one randomised controlled trial suggested rehabilitation exercises may reduce post-COVID breathlessness. There is an urgent need for mechanistic research and development of interventions for the prevention and treatment of post-COVID breathlessness.

Development of a Site-Specific Guideline Value for Copper and Aquatic Life in Tropical Freshwaters of Low Hardness.

Copper (Cu) is a contaminant of potential concern for a uranium mine whose receiving waters are in the World Heritage-listed Kakadu National Park in northern Australia. The physicochemical characteristics of the freshwaters in this region enhance metal bioavailability and toxicity. Seven tropical species were used to assess the chronic toxicity of Cu in extremely soft freshwater from a creek upstream of the mine. Sensitivity to Cu was as follows: Moinodaphnia macleayi > Chlorella sp. > Velesunio sp. > Hydra viridissima > Amerianna cumingi > Lemna aequinoctialis > Mogurnda mogurnda. The 10% effect concentrations (EC10s) ranged from 1.0 µg/L Cu for the cladoceran Moinodaphnia macleayi to 9.6 µg/L for the fish M. mogurnda. The EC50s ranged from 6.6 µg/L Cu for the mussel Velesunio sp. to 22.5 µg/L Cu for M. mogurnda. Geochemical modeling predicted Cu to be strongly bound to fulvic acid (80%-99%) and of low bioavailability (0.02%-11.5%) under these conditions. Protective concentrations (PCs) were derived from a species sensitivity distribution for the local biota. The 99% PC (PC99), PC95, PC90, and PC80 values were 0.5, 0.8, 1.0, and 1.5 µg/L Cu, respectively. These threshold values suggest that the current Australian and New Zealand default national 99% protection guideline value for Cu (1.0 µg/L) would not provide adequate protection in freshwaters of low hardness, particularly for this area of high conservation value. The continuous criterion concentration predicted by the Cu biotic ligand model for conditions of low pH (6.1), low dissolved organic carbon (2.5 mg/L), low hardness (3.3 mg/L), and 27 °C was 0.48 µg/L Cu, comparable with the PC99. Consideration of the natural water quality conditions of a site is paramount for protective water quality guidelines. Environ Toxicol Chem 2022;41:2808-2821. © 2022 Commonwealth of Australia. Environmental Toxicology and Chemistry © 2022 SETAC.

Translational Research on Caregiver Reading and Playing Behaviors: Evidence from an In Vivo Community-based Intervention throughout the COVID-19 Pandemic.

This study provides a rigorous assessment of a community-based early child development (ECD) intervention to understand the drivers of caregivers' reading and playing practices in a low-resourced township in South Africa. Mentors visited 157 homes biweekly (2474 observations from 2019-21; children ages 0-5), completing surveys regarding caregiver behaviors and engagement. One hundred and fifty-seven caregivers (mostly Black, Zulu women) participated in the program during this time period and completed surveys biannually on their support system (modified version of the Multidimensional Scale of Perceived Support) and ECD beliefs (modified versions of the Parental Play Beliefs Scale and the Parent Opinion Survey). Longitudinal Hierarchical Linear Model revealed that several behaviors and beliefs significantly predicted positive parenting behaviors. Regression discontinuity plots suggest that positive parenting behaviors could continue and even improve following Covid-19 shutdowns, especially in homes with more intervention visits. This paper provides translational evidence on tangible ways interventions can engage caregivers in stimulating ECD behaviors.