Pilot Study of Heat-Stabilized Rice Bran Acceptability in Households of Rural Southwest Guatemala and Estimates of Fiber, Protein, and Micro-Nutrient Intakes among Mothers and Children.

Nutrient-dense, acceptable foods are needed in low-resource settings. Rice bran, a global staple byproduct of white rice processing, is rich in amino acids, fibers, and vitamins, when compared to other cereal brans. This pilot study examines the nutritional contribution of rice bran to the daily diets of mother-child pairs in rural southwest Guatemala. Thirty households were screened. Mothers (≥18 years) and children (6 to 24 months) completed 24 h dietary recalls at baseline and after 12 weeks (endline) for diet intake and diversity analyses. During biweekly visits for 12 weeks, households with <5 members received 14 packets containing 60 g of heat-stabilized rice bran, and those with ≥5 members received 28 packets. The macro- and micro-nutrient contributions of rice bran and whole, cooked black beans were included in dietary simulation models with average intakes established between the recalls and for comparison with dietary reference intakes (DRIs). A baseline child food frequency questionnaire was administered. The 27 mothers and 23 children with complete recalls were included in analyses. Daily maternal consumption of 10 g/d of rice bran plus 100 g/d of black beans resulted in all achieving at least 50% of the fiber, protein, magnesium, niacin, potassium, and thiamin DRIs. Daily child consumption of 3 g/d of rice bran plus 10 g/d of black beans resulted in all achieving at least 50% of the magnesium, niacin, phosphorous, and thiamine DRIs. For 15/17 food categories, male children had a higher intake frequency, notably for animal-source foods and coffee. Dietary rice bran coupled with black beans could improve nutritional adequacy, especially for fiber and key micro-nutrients, with broader implications for addressing maternal and child malnutrition in low-resource settings.

Access, interest and equity considerations for virtual global health activities during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: Global health activities (GHAs) reduce health disparities by promoting medical education, professional development, and resource sharing between high- and low- to middle-income countries (HICs and LMICs). Virtual global health activities facilitated continuity and bidirectionality in global health during the COVID-19 pandemic. While virtual engagement holds potential for promoting equity within partnerships, research on equitable access to and interest in virtual global health activities is limited. METHODS: We conducted a cross-sectional, online, mixed-methods survey from January to February 2022 examining access to virtual activities before and during the pandemic across resource settings. Eligible participants were participants or facilitators of global health activities. Closed- and open-ended questions elicited participants' access to and interest in virtual global health engagement. RESULTS: We analyzed 265 surveys from respondents in 45 countries (43.0% LMIC vs. HIC 57.0%). HIC respondents tended to report greater loss of in-person access due to the pandemic at their own institutions (16 of 17 queried GHAs), while LMIC respondents tended to report greater loss of in-person activities at another institution (9 of 17 queried GHAs). Respondents from LMICs were more likely to gain virtual access through another organization for all 17 queried VGHAs. HIC respondents had significantly more access to global health funding through their own organization (p < 0.01) and more flexibility for using funds. There were significant differences and trends between respondent groups in different resource environments in terms of accessibility to and interest in different virtual global health activities, both during and after the pandemic. CONCLUSIONS: Our results highlight the need to examine accessibility to virtual global health activities within partnerships between high- and low- to middle-income countries. While virtual activities may bridge existing gaps in global health education and partnerships, further study on priorities and agenda setting for such initiatives, with special attention to power dynamics and structural barriers, are necessary to ensure meaningful virtual global health engagement moving forward.

Short Research Article: RESEED - the perceived impact of an enhanced usual care model of a novel, teacher-led, task-shifting initiative for child mental health.

BACKGROUND: Task-shifted, teacher-led care may begin to bridge the child mental health care gap in low- and middle-income countries by improving mental health literacy. We explore the perceived impact of RESEED (Responding to Students' Emotions through Education), an abbreviated version of Tealeaf (Teachers Leading the Frontlines). METHODS: After classroom implementation of tools from a 3-day training on child mental health and cognitive behavioral techniques in Darjeeling, India, 29 teachers participated in focus group discussions (FGDs). RESULTS: Inductive content analyses of FGDs demonstrated RESEED's acceptability, positive overall impact, and barriers. CONCLUSIONS: Stepped levels of teacher-led care may support child mental health in resource-limited settings through mental reframing.

Evaluation of Vector-Enabled Xenosurveillance in Rural Guatemala.

Surveillance methods that permit rapid detection of circulating pathogens in low-resource settings are desperately needed. In this study, we evaluated a mosquito bloodmeal-based surveillance method ("xenosurveillance") in rural Guatemala. Twenty households from two villages (Los Encuentros and Chiquirines) in rural southwest Guatemala were enrolled and underwent weekly prospective surveillance from August 2019 to December 2019 (16 weeks). When febrile illness was reported in a household, recently blood-fed mosquitoes were collected from within dwellings and blood samples taken from each member of the household. Mosquitoes were identified to species and blood sources identified by sequencing. Shotgun metagenomic sequencing was used to identify circulating viruses. Culex pipiens (60.9%) and Aedes aegypti (18.6%) were the most abundant mosquitoes collected. Bloodmeal sources were most commonly human (32.6%) and chicken (31.6%), with various other mammal and avian hosts detected. Several mosquito-specific viruses were detected, including Culex orthophasma virus. Human pathogens were not detected. Therefore, xenosurveillance may require more intensive sampling to detect human pathogens in Guatemala and ecologically similar localities in Central America.

Effects of Maternal HIV Infection on Early Kaposi Sarcoma-Associated Herpesvirus Seroconversion in a Kenyan Mother-Infant Cohort.

BACKGROUND: We identified whether maternal human immunodeficiency virus (HIV) infection during pregnancy affects transplacental transfer of Kaposi sarcoma-associated herpesvirus (KSHV)-specific antibodies and subsequent infant infection. METHODS: We followed pregnant Kenyan women through delivery and their infants until age 2 years. Children were classified as HIV-exposed uninfected (HEU) or HIV-unexposed uninfected (HUU) based on maternal HIV status. Maternal venous and cord blood at delivery and child venous blood every 6 months were tested for antibodies to 20 KSHV antigens by multiplex bead-based immunoassay. Multiple comparisons were adjusted using false discovery rate (FDR). RESULTS: Maternal HIV infection was significantly associated with decreased transplacental transfer of antibodies against all KSHV antigens and lower cord blood levels for 8 antigens at FDR P < .10. Neither birth to 6-month antibody level changes nor 6-month levels differed in HEU and HUU, except for ORF50. By age 24 months, 74% of children KSHV seroconverted but HEU and HUU did not differ in time to seroconversion nor 2-year seropositivity after adjustment for child malaria infection. CONCLUSIONS: Maternal HIV infection reduced a child's initial KSHV antibody levels but did not affect age of infection. Regardless of HIV exposure in utero, KSHV seroconversion in Kenyan children occurred early; associated factors must be identified.

Cumulative Febrile, Respiratory, and Gastrointestinal Illness Among Infants in Rural Guatemala and Association With Neurodevelopmental and Growth Outcomes.

BACKGROUND: Infectious disease exposures in early life are increasingly recognized as a risk factor for poor subsequent growth and neurodevelopment. We aimed to evaluate the association between cumulative illness with neurodevelopment and growth outcomes in a birth cohort of Guatemalan infants. METHODS: From June 2017 to July 2018, infants 0-3 months of age living in a resource-limited region of rural southwest Guatemala were enrolled and underwent weekly at-home surveillance for caregiver-reported cough, fever, and vomiting/diarrhea. They also underwent anthropometric assessments and neurodevelopmental testing with the Mullen Scales of Early Learning (MSEL) at enrollment, 6 months, and 1 year. RESULTS: Of 499 enrolled infants, 430 (86.2%) completed all study procedures and were included in the analysis. At 12-15 months of age, 140 (32.6%) infants had stunting (length-for-age Z [LAZ] score < -2 SD) and 72 (16.7%) had microcephaly (occipital-frontal circumference [OFC] < -2 SD). In multivariable analysis, greater cumulative instances of reported cough illness (beta = -0.08/illness-week, P = 0.06) and febrile illness (beta = -0.36/illness-week, P < 0.001) were marginally or significantly associated with lower MSEL Early Learning Composite (ELC) Score at 12-15 months, respectively; there was no association with any illness (cough, fever, and/or vomiting/diarrhea; P = 0.27) or with cumulative instances of diarrheal/vomiting illness alone ( P = 0.66). No association was shown between cumulative instances of illness and stunting or microcephaly at 12-15 months. CONCLUSIONS: These findings highlight the negative cumulative consequences of frequent febrile and respiratory illness on neurodevelopment during infancy. Future studies should explore pathogen-specific illnesses, host response associated with these syndromic illnesses, and their association with neurodevelopment.

COVID-19 Attitudes and Vaccine Hesitancy among an Agricultural Community in Southwest Guatemala: A Cross-Sectional Survey.

Despite offering free-of-charge COVID-19 vaccines starting July 2021, Guatemala has one of the lowest vaccination rates in Latin America. From 28 September 2021 to 11 April 2022, we conducted a cross-sectional survey of community members, adapting a CDC questionnaire to evaluate COVID-19 vaccine access and hesitancy. Of 233 participants ≥ 12 years, 127 (55%) received ≥1 dose of COVID-19 and 4 (2%) reported prior COVID-19 illness. Persons ≥ 12 years old who were unvaccinated (n = 106) were more likely to be female (73% vs. 41%, p < 0.001) and homemakers (69% vs. 24%, p < 0.01) compared with vaccinated participants (n = 127). Among those ≥18 years, the main reported motivation for vaccination among vaccinated participants was to protect the health of family/friends (101/117, 86%); on the other hand, 40 (55%) unvaccinated persons reported little/no confidence in public health institutions recommending COVID-19 vaccination. Community- and/or home-based vaccination programs, including vaccination of families through the workplace, may better reach female homemakers and reduce inequities and hesitancy.

Differences in parental vaccine confidence and attitudes by health system in Guatemala and their impact on immunization timeliness.

OBJECTIVE: The objectives of this study were to evaluate parental confidence and attitudes towards immunization in urban Guatemala between private versus public health systems and their impact on vaccination timeliness in their children. METHODS: A cross-sectional survey was conducted in parents 6-18-month-old children who attended well-child outpatient clinics from two health systems (public employee-based insurance and private health care) in Guatemala City from November 2017 through August 2018. Parental demographics, household characteristics, food insecurity, vaccine hesitancy using the WHO SAGE Vaccine Hesitancy Scale, and information on parental use of social media platforms and vaccine information sources were collected. RESULTS: Five hundred-three parents were surveyed, most of them mothers. Only 9 parents reported they had previously refused a vaccine for their child: 8 (3.2 %) from private clinics and 1 (0.4 %) from the public clinic (p = 0.02). Significantly more children attending private clinics (226, 90.4 %) were shown to have a delay in any of their vaccines scheduled for the first 2 years of life compared to those in the public clinic (169, 66.8 %; p < 0.01). Children of parents having a college degree (84.5 vs 70.1 %; p < 0.001), earning more than US$ 1,000 per month (81.5 vs 70.7 %; p < 0.001), and having a computer at home (81.4 vs 70.2; p = 0.007) were more likely to have any delays in the scheduled vaccines. Parents seeking care at private clinics were 1.14 times more at risk of delaying a vaccine compared to those at the public clinic, adjusted for other covariates (p = 0.03, 95 % CI: 1.01, 1.28). CONCLUSIONS: In Guatemala, children receiving immunizations at private clinics were significantly more likely than those attending public clinics to be delayed in their immunization schedule and to remain more days without the recommended protection, especially for third doses of the primary vaccine series.

Limitations introduced by a low participation rate of SARS-CoV-2 seroprevalence data.

BACKGROUND: There has been a large influx of COVID-19 seroprevalence studies, but comparability between the seroprevalence estimates has been an issue because of heterogeneities in testing platforms and study methodology. One potential source of heterogeneity is the response or participation rate. METHODS: We conducted a review of participation rates (PR) in SARS-CoV-2 seroprevalence studies collected by SeroTracker and examined their effect on the validity of study conclusions. PR was calculated as the count of participants for whom the investigators had collected a valid sample, divided by the number of people invited to participate in the study. A multivariable beta generalized linear model with logit link was fitted to determine if the PR of international household and community-based seroprevalence studies was associated with the factors of interest, from 1 December 2019 to 10 March 2021. RESULTS: We identified 90 papers based on screening and were able to calculate the PR for 35 out of 90 papers (39%), with a median PR of 70% and an interquartile range of 40.92; 61% of the studies did not report PR. CONCLUSIONS: Many SARS-CoV-2 seroprevalence studies do not report PR. It is unclear what the median PR rate would be had a larger portion not had limitations in reporting. Low participation rates indicate limited representativeness of results. Non-probabilistic sampling frames were associated with higher participation rates but may be less representative. Standardized definitions of participation rate and data reporting necessary for the PR calculations are essential for understanding the representativeness of seroprevalence estimates in the population of interest.

Anthropometric proxies for child neurodevelopment in low-resource settings: length- or height-for-age, head circumference or both?

Stunting (<-2 SD of length- or height-for-age on WHO growth curves) is the most used predictor of child neurodevelopmental (ND) risk. Occipitofrontal head circumference (OFC) may be an equally feasible, but more direct and robust predictor. We explored association of the two measurements with ND outcome, separately and combined, and examined if cutoffs are more efficacious than continuous measures in predicting ND risk. Infants and young children in rural Guatemala (n = 642; age range = 0.1-35.9 months) were enrolled in a prospective natural history study, and their ND was tested using the Mullen Scales of Early Learning (MSEL) longitudinally. Length- or height-for-age and OFC-for-age were calculated. We performed age-adjusted multivariable regression analyses to explore the association between 1) length or height and ND, 2) OFC and ND, and 3) both length or height and OFC combined, with ND; concurrently, predictively, and longitudinally, as continuous variables and using WHO z-score cutoffs. Continuous length- or height-for-age and OFC z-scores were more strongly associated with MSEL than the traditional -2 SD WHO cutoff. The combination of height-for-age z-score and OFC z-score was consistently, strongly associated with the MSEL Early Learning Composite concurrently (p-values 0.0004-0.11), predictively (p-value 0.001-0.07), with the exception of the 18-24 months age group which had very few records, and in the longitudinal model (p-value <0.0001-0.004). The combination of continuous length- or height-for-age and OFC shows additional utility in estimating ND risk in infants and young children. Measurement of OFC may improve precision of prediction of ND risk in infants and young children.

The Impact of Altitude at Birth on Perinatal Respiratory Support for Neonates with Trisomy 21.

OBJECTIVE: Both high altitude and trisomy 21 (T21) status can negatively impact respiratory outcomes. The objective of this study was to examine the association between altitude and perinatal respiratory support in neonates with T21 compared with those without T21. STUDY DESIGN: This retrospective cohort study used the United States all-county natality files that included live, singleton, in-hospital births from 2015 to 2019. Descriptive statistics for neonates with and without the primary outcome of sustained assisted ventilation (>6 hours) were compared using t-tests and Chi-squared analyses. Multivariable logistic regression was used to determine the association between respiratory support and the presence of T21, and included an interaction term to determine whether the association between respiratory support and the presence of T21 was modified by elevation at delivery. RESULTS: A total of 17,939,006 neonates, 4,059 (0.02%) with T21 and 17,934,947 (99.98%) without, were included in the study. The odds of requiring sustained respiratory support following delivery were 5.95 (95% confidence interval [CI]: 5.31, 6.66), 4.06 (95% CI: 2.39, 6.89), 2.36 (95% CI: 1.64, 3.40), and 5.04 (95% CI: 1.54, 16.54) times as high for neonates with T21 than without T21 when born at low, medium, high, and very high elevations, respectively. The odds of requiring immediate ventilation support following delivery were 5.01 (95% CI: 4.59, 5.46), 5.90 (95% CI: 4.16, 8.36), 2.86 (95% CI: 2.15, 3.80), and 12.08 (95% CI: 6.78, 21.51) times as high for neonates with T21 than without T21 when born at low, medium, high, and very high elevation, respectively. CONCLUSION: Neonates with T21 have increased odds of requiring respiratory support following delivery when compared with neonates without T21 at all categories of altitude. However, the odds ratios did not increase monotonically with altitude which indicates additional research is critical in understanding the effects of altitude on neonates with T21. KEY POINTS: · Neonates with T21 have an increased need for perinatal respiratory support at all altitudes.. · The odds of needing perinatal respiratory support did not increase monotonically with elevation.. · Additional research is critical to understanding the effects of altitude on neonates with T21..

Clinical and Economic Impact of COVID-19 on Agricultural Workers, Guatemala1.

We evaluated clinical and socioeconomic burdens of respiratory disease in banana farm workers in Guatemala. We offered all eligible workers enrollment during June 15-December 30, 2020, and annually, then tracked them for influenza-like illnesses (ILI) through self-reporting to study nurses, sentinel surveillance at health posts, and absenteeism. Workers who had ILI submitted nasopharyngeal swab specimens for testing for influenza virus, respiratory syncytial virus, and SARS-CoV-2, then completed surveys at days 0, 7, and 28. Through October 10, 2021, a total of 1,833 workers reported 169 ILIs (12.0 cases/100 person-years), and 43 (25.4%) were laboratory-confirmed infections with SARS-CoV-2 (3.1 cases/100 person-years). Workers who had SARS-CoV-2‒positive ILIs reported more frequent anosmia, dysgeusia, difficulty concentrating, and irritability and worse clinical and well-being severity scores than workers who had test result‒negative ILIs. Workers who had positive results also had greater absenteeism and lost income. These results support prioritization of farm workers in Guatemala for COVID-19 vaccination.

Investigating transmission of SARS-CoV-2 using novel face mask sampling: a protocol for an observational prospective study of index cases and their contacts in a congregate setting.

INTRODUCTION: This study aims to measure how transmission of SARS-CoV-2 occurs in communities and to identify conditions that lend to increased transmission focusing on congregate situations. We will measure SARS-CoV-2 in exhaled breath of asymptomatic and symptomatic persons using face mask sampling-a non-invasive method for SARS-CoV-2 detection in exhaled air. We aim to detect transmission clusters and identify risk factors for SARS-CoV-2 transmission in presymptomatic, asymptomatic and symptomatic individuals. METHODS AND ANALYSIS: In this observational prospective study with daily follow-up, index cases and their respective contacts are identified at each participating institution. Contact definitions are based on Centers for Disease Control and Prevention and local health department guidelines. Participants will wear masks with polyvinyl alcohol test strips adhered to the inside for 2 hours daily. The strips are applied to all masks used over at least 7 days. In addition, self-administered nasal swabs and (optional) finger prick blood samples are performed by participants. Samples are tested by standard PCR protocols and by novel antigen tests. ETHICS AND DISSEMINATION: This study was approved by the Colorado Multiple Institutional Review Board and the WHO Ethics Review Committee. From the data generated, we will analyse transmission clusters and risk factors for transmission of SARS-CoV-2 in congregate settings. The kinetics of asymptomatic transmission and the evaluation of non-invasive tools for detection of transmissibility are of crucial importance for the development of more targeted control interventions-and ultimately to assist with keeping congregate settings open that are essential for our social fabric. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (#NCT05145803).

Challenges and lessons learned from the rapid operationalization of a prospective cohort to study the natural history and neurodevelopmental outcomes of postnatal Zika virus infection among infants and children in rural Guatemala.

During the course of the 2015-2017 outbreak of Zika virus (ZIKV) in the Americas, the emerging virus was recognized as a congenital infection that could damage the developing brain. As the Latin American ZIKV outbreak advanced, the scientific and public health community questioned if this newly recognized neurotropic flavivirus could affect the developing brain of infants and young children infected after birth. We report here the study design, methods and the challenges and lessons learned from the rapid operationalization of a prospective natural history cohort study aimed at evaluating the potential neurological and neurodevelopmental effects of postnatal ZIKV infection in infants and young children, which had become epidemic in Central America. This study enrolled a cohort of 500 mothers and their infants, along with nearly 400 children 1.5-3.5 years of age who were born during the initial phase of the ZIKV epidemic in a rural area of Guatemala. Our solutions and lessons learned while tackling real-life challenges may serve as a guide to other researchers carrying out studies of emerging infectious diseases of public health priority in resource-constrained settings.

Teacher, caregiver, and student acceptability of teachers delivering task-shifted mental health care to students in Darjeeling, India: a mixed methods pilot study.

Background: The acceptability of teachers delivering task-shifted mental health care to their school-aged students is understudied. Here, we evaluate teachers', students', and caregivers' acceptability of Tealeaf (Teachers Leading the Frontlines), an alternative system of care in which teachers are trained and supervised to deliver transdiagnostic, non-manualized task-shifted care to their students. Methods: In a 2019 single-arm, mixed methods, pragmatic acceptability pilot study in Darjeeling, India, 13 teachers delivered task-shifted child mental health care to 26 students in need. Teachers delivered care through using a transdiagnostic, non-manualized therapy modality, "education as mental health therapy" (Ed-MH). Measured with validated scales, teachers' and students' acceptability were compared after teacher training (PRE) and at the end of intervention (POST) using paired t tests. Teachers (n = 7), students (n = 7), and caregivers (n = 7) completed semi-structured interviews POST. Results: Teachers' quantitative measures indicated moderate acceptability PRE and POST and did not change PRE to POST. Children's measures showed acceptability PRE and POST but decreased PRE to POST. Teachers and caregivers universally expressed acceptability in interviews. Facilitators of acceptability included impact, trust of teachers, and teachers' ability to make adaptations. Conditions required for acceptability included supervision and teachers emphasizing academics benefits over mental health benefits to caregivers. Barriers to acceptability included a lack of teacher time and stigma. Interviewed students universally were unaware of receiving care; teachers intentionally avoided singling them out. Conclusion: Teachers, caregivers, and children found teacher delivering task-shifted care acceptable, a key factor in care adoption and sustainability, though interviewed children were unaware of receiving care.Trial registration The trial was registered on January 01, 2018 with Clinical Trials Registry-India (CTRI), Reg. No. CTRI/2018/01/011471, Ref. No. REF/2017/11/015895. http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=21129&EncHid=&modid=&compid=%27,%2721129det%27. Supplementary Information: The online version contains supplementary material available at 10.1007/s44192-022-00024-z.

Repeated Rapid Active Sampling Surveys Demonstrated a Rapidly Changing Zika Seroprevalence among Children in a Rural Dengue-endemic Region in Southwest Guatemala during the Zika Epidemic (2015-2016).

Although Central America is largely dengue virus (DENV)-endemic, the 2015-2016 Zika virus (ZIKV) pandemic brought new urgency to develop surveillance approaches capable of characterizing the rapidly changing disease burden in resource-limited settings. We conducted a pediatric DENV surveillance study in rural Guatemala, including serial cross-sectional surveys from April through September 2015 (Survey 1), in October-November 2015 (Survey 2), and January-February 2016 (Survey 3). Serum underwent DENV IgM MAC ELISA and polymerase chain reaction testing. Using banked specimens from Surveys 2 and 3, we expanded testing to include DENV 1-4 and ZIKV microneutralization (MN50), DENV NS1 IgG ELISA, and ZIKV anti-NS1 antibody Blockage of Binding (BoB) ELISA testing. Demographic risk factors for ZIKV BoB positivity were explored using multivariable generalized linear regression models. Of Survey 2 and 3 samples available (N = 382), DENV seroprevalence slightly increased (+1%-10% depending on the assay) during the surveillance period and increased with age. In contrast, ZIKV seroprevalence consistently increased over the 3-month period, including from 6% to 34% (P < 0.0001) and 10%-37% (P < 0.0001) using the MN50 ≥100 and BoB ELISA assays, respectively. Independent risk factors for ZIKV seropositivity included older age (prevalence ratio (PR)/year = 1.12, 95% confidence interval (CI) = 1.07-1.17) and primary caregiver literacy (PR = 2.80, CI = 1.30-6.06). Rapid active surveillance (RAS) surveys demonstrated a nearly 30% increase in ZIKV prevalence and a slight (≤ 10%) increase in DENV seroprevalence from October to November 2015 to January to February 2016 in rural southwest Guatemala, regardless of serologic assay used. RAS surveys may be a useful "off-the-shelf" tool to characterize arboviruses and other emerging pathogens rapidly in resource-limited settings.

Association Between Lysine Reduction Therapies and Cognitive Outcomes in Patients With Pyridoxine-Dependent Epilepsy.

BACKGROUND AND OBJECTIVES: Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is a developmental epileptic encephalopathy characterized by seizure improvement after pyridoxine supplementation. Adjunct lysine reduction therapies reduce the accumulation of putative neurotoxic metabolites with the goal to improve developmental outcomes. Our objective was to examine the association between treatment with lysine reduction therapies and cognitive outcomes. METHODS: Participants were recruited from within the International Registry for Patients with Pyridoxine-Dependent Epilepsy from August 2014 through March 2021. The primary outcome was standardized developmental test scores associated with overall cognitive ability. The relationship between test scores and treatment was analyzed with multivariable linear regression using a mixed-effects model. A priori, we hypothesized that treatment in early infancy with pyridoxine and lysine reduction therapies would result in a normal developmental outcome. A sub-analysis was performed to evaluate the association between cognitive outcome and lysine reduction therapies initiated in the first six months of life. RESULTS: A total of 112 test scores from 60 participants were available. On average, treatment with pyridoxine and lysine reduction therapies was associated with a non-significant increase of 6.9 points (95% CI -2.7 to 16.5) on developmental testing compared to treatment with pyridoxine alone. For the sub-analysis, a total of 14 developmental testing scores were available from 8 participants. On average, treatment with pyridoxine and lysine reduction therapies in the first six months of life was associated with a significant increase of 21.9 points (95% CI 1.7 to 42.0) on developmental testing. DISCUSSION: Pyridoxine and lysine reduction therapies at any age was associated with mild improvement in developmental testing and treatment in early infancy was associated with a clinically significant increase in developmental test scores. These results provide insight into the mechanism of intellectual and developmental disability in PDE-ALDH7A1 and emphasize the importance of treatment in early infancy with both pyridoxine and lysine reduction therapies. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in PDE-ALDH7A1, pyridoxine plus lysine reduction therapies compared to pyridoxine alone is not significantly associated with overall higher developmental testing scores, but treatment in the first six months of life is associated with significantly higher developmental testing scores.

Vital sign predictors of severe influenza among children in an emergent care setting.

BACKGROUND: Decisions regarding the evaluation of children with influenza infection rely on the likelihood of severe disease. The role of early vital signs as predictors of severe influenza infection in children is not well known. Our objectives were to determine the value of vital signs in predicting hospitalization/recurrent emergency department (ED) visits due to influenza infection in children. METHODS: We conducted a prospective study of children aged 6 months to 8 years of age with influenza like illness evaluated at an ED/UC from 2016-2018. All children underwent influenza testing by PCR. We collected heart rate, respiratory rate and temperature, and converted heart rate (HR) and respiratory rate (RR) to z-scores by age. HR z scores were further adjusted for temperature. Our primary outcome was hospitalization/recurrent ED visits within 72 hours. Vital sign predictors with p< 0.2 and other clinical covariates were entered into a multivariable logistic regression model to determine odds ratios (OR) and 95% CI; model performance was assessed using the Brier score and discriminative ability with the C statistic. RESULTS: Among 1478 children, 411 (27.8%) were positive for influenza, of which 42 (10.2%) were hospitalized or had a recurrent ED visit. In multivariable analyses, adjusting for age, high-risk medical condition and school/daycare attendance, higher adjusted respiratory rate (OR 2.09, 95%CI 1.21-3.61, p = 0.0085) was a significant predictor of influenza hospitalization/recurrent ED visits. CONCLUSIONS: Higher respiratory rate adjusted for age was the most useful vital sign predictor of severity among young children with PCR-confirmed influenza.

Detection of SARS-CoV-2 in exhaled air using non-invasive embedded strips in masks.

BACKGROUND: SARS-CoV-2 emerged in 2019 and resulted in a pandemic causing millions of infections worldwide. Gold-standard for SARS-CoV-2 detection uses quantitative RT-qPCR on respiratory secretions to detect viral RNA (vRNA). Acquiring these samples is invasive, can be painful for those with xerostomia and other health conditions, and sample quality can vary greatly. Frequently only symptomatic individuals are tested even though asymptomatic individuals can have comparable viral loads and efficiently transmit virus. METHODS: We utilized a non-invasive approach to detect SARS-CoV-2 in individuals, using polyvinyl alcohol (PVA) strips embedded in KN95 masks. PVA strips were tested for SARS-CoV-2 vRNA via qRT-PCR and infectious virus. RESULTS: We show efficient recovery of vRNA and infectious virus from virus-spiked PVA with detection limits comparable to nasal swab samples. In infected individuals, we detect both human and SARS-CoV-2 RNA on PVA strips, however, these levels are not correlated with length of time mask was worn, number of times coughed or sneezed, or level of virus in nasal swab samples. We successfully cultured and deep-sequenced PVA-associated virus. CONCLUSIONS: These results demonstrate the feasibility of using PVA-embedded masks as a non-invasive platform for detecting SARS-CoV-2 in exhaled air in COVID-positive individuals regardless of symptom status.