This study sought to assess clinical characteristics and differences in outcomes between children with Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) osteomyelitis or septic arthritis and whether initial antibiotic regimen affects patient outcomes. We analyzed records of children ages 15 days to 18 years admitted between 2009 and 2016 to two tertiary children’s hospitals who were diagnosed with an osteoarticular infection and had a microorganism identified. A total of 584 patients met inclusion criteria, of which 365 (62.5%) had a microbiological diagnosis. MSSA was the most common pathogen identified (45.5%), followed by MRSA (31.2%). Compared to MSSA, patients with MRSA had a higher initial C-reactive protein and longer hospitalization. Patients whose initial antibiotic regimens included vancomycin had a longer hospitalization than those initiated on clindamycin without vancomycin, even after removing sicker patients admitted to the pediatric intensive care unit. While MRSA was associated with increased severity of osteoarticular infections compared to MSSA, the incidence of MRSA has been declining at our institution. Patients with longer lengths of stay were more likely to be on vancomycin. Clindamycin should be considered in the initial antibiotic regimen for osteomyelitis and septic arthritis with ongoing surveillance of local microbiology and outcomes.

Background: Neural tube defects are common birth defects resulting in severe morbidity and mortality; they can largely be prevented with periconceptional maternal intake of folic acid. Understanding the occurrence of neural tube defects and their contribution to mortality in settings where their burden is highest could inform prevention and health-care policy. We aimed to estimate the mortality attributed to neural tube defects in seven countries in sub-Saharan Africa and southeast Asia. Methods: This analysis used data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network and health and demographic surveillance systems from South Africa, Mozambique, Bangladesh, Kenya, Mali, Ethiopia, and Sierra Leone. All stillbirths and infants and children younger than 5 years who died, who were enrolled in CHAMPS, whose families consented to post-mortem minimally invasive tissue sampling (MITS) between Jan 1, 2017, and Dec 31, 2021, and who were assigned a cause of death by a determination of cause of death panel as of May 24, 2022, were included in this analysis, regardless the cause of death. MITS and advanced diagnostic methods were used to describe the frequency and characteristics of neural tube defects among eligible deaths, identify risk factors, and estimate the mortality fraction and mortality rate (per 10 000 births) by CHAMPS site. Findings: Causes of death were determined for 3232 stillbirths, infants, and children younger than 5 years, of whom 69 (2%) died with a neural tube defect. Most deaths with a neural tube defect were stillbirths (51 [74%]); 46 (67%) were neural tube defects incompatible with life (ie, anencephaly, craniorachischisis, or iniencephaly) and 22 (32%) were spina bifida. Deaths with a neural tube defect were more common in Ethiopia (adjusted odds ratio 8·09 [95% CI 2·84–23·02]), among female individuals (4·40 [2·44–7·93]), and among those whose mothers had no antenatal care (2·48 [1·12–5·51]). Ethiopia had the highest adjusted mortality fraction of deaths with neural tube defects (7·5% [6·7–8·4]) and the highest adjusted mortality rate attributed to neural tube defects (104·0 per 10 000 births [92·9–116·4]), 4–23 times greater than in any other site. Interpretation: CHAMPS identified neural tube defects, a largely preventable condition, as a common cause of death among stillbirths and neonatal deaths, especially in Ethiopia. Implementing interventions such as mandatory folic acid fortification could reduce mortality due to neural tube defects. Funding: Bill & Melinda Gates Foundation.

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The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) research group was formed over a decade ago to improve the interpretation of micronutrient biomarkers in settings with inflammation. The BRINDA inflammation adjustment method uses regression correction to adjust for the confounding effects of inflammation on select micronutrient biomarkers and has provided important insights to micronutrient research, policy, and programming. However, users may face challenges when applying the BRINDA inflammation adjustment methods to their own data due to varying guidance on the adjustment approach for different biomarkers and the need to develop statistical programming to conduct these analyses. This may result in lost opportunities to have results of micronutrient data readily available during critical decision-making periods. Our research objectives are to 1) provide an all-in-one summary of the BRINDA method in adjusting multiple micronutrient biomarkers for inflammation, 2) evaluate whether malaria as a binary variable should be included in the BRINDA inflammation adjustment method, and 3) present standardized and user-friendly BRINDA adjustment R package and SAS macro. This paper serves as a practical guidebook for the BRINDA inflammation adjustment approach and aids users to use the BRINDA R package and SAS to streamline their analyses.

Background: It is unclear whether 25(OH)D concentrations in children and female adults may be influenced by inflammation and thus require adjustment when estimating the population prevalence of vitamin D deficiency. Objectives: We examined correlations between inflammation biomarkers, CRP or alpha-1-acid glycoprotein (AGP), and serum 25(OH)D concentrations among preschool children (PSC; 6–59 mo) and nonpregnant females of reproductive age (FRA; 15–49 y). Methods: We analyzed cross-sectional data from 6 nationally representative nutrition surveys (Afghanistan, Cambodia, Pakistan, UK, USA, and Vietnam) conducted among PSC (n = 9880) and FRA (n = 14,749) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project. Rank correlations between CRP or AGP and 25(OH)D concentrations were examined while taking into account complex survey design effects. Results: Among both PSC and FRA, correlations between inflammation and vitamin D biomarkers were weak and inconsistent across surveys. For PSC, correlation coefficients between CRP and 25(OH)D concentrations ranged from −0.04 to 0.08, and correlations between AGP and 25(OH)D ranged from 0.01 to 0.05. Correlation coefficients between CRP and 25(OH)D for FRA ranged from −0.11 to 0.14, and correlations between AGP and 25(OH)D concentrations ranged from −0.05 to 0.01. Conclusions: Based on the weak and inconsistent correlations between CRP or AGP and 25(OH)D, there is no rationale to adjust for these inflammation biomarkers when estimating population prevalence of vitamin D deficiency in PSC or FRA.

Anemia remains an important global health problem. Inexpensive, accurate, and noninvasive solutions are needed to monitor and evaluate anemia in resource-limited settings. We evaluated the performance of multiple point-of-care hemoglobin devices, including a novel noninvasive smartphone application tested on Apple® and Android® cell phones, Masimo Pronto®, and HemoCue® Hb-301 and Hb-801, against a gold-standard hematology analyzer (reference hemoglobin) using venous blood. We examined correlations between hemoglobin devices and reference hemoglobin, device accuracy (average bias, Bland-Altman plots, clinical performance) and classification bias (sensitivity, specificity) among 299 refugees (10mo-65y) in Atlanta, GA. Semi-structured interviews (n = 19) with participants and staff assessed usability and acceptability. Mean reference hemoglobin was 13.7 g/dL (SD:1.8) with 12.5% anemia. Noninvasive hemoglobin devices were not well correlated with reference hemoglobin (Apple® R2 = 0.08, Android® R2 = 0.11, Masimo Pronto® R2 = 0.29), but stronger correlations were reported with HemoCue® Hb-301 (R2 = 0.87) and Hb-801 (R2 = 0.88). Bias (SD) varied across each device: Apple®: -1.6 g/dL (2.0), Android®: -0.7 g/dL (2.0), Masimo Pronto®: -0.4 g/dL (1.6), HemoCue® Hb-301: +0.4 g/dL (0.7) and HemoCue® Hb-801: +0.2 g/dL (0.6). Clinically acceptable performance (within ± 1 g/dL of reference hemoglobin) was higher for the invasive devices (HemoCue® Hb-301: 90.3%; HemoCue® Hb-801: 93.4%) compared to noninvasive devices (Apple®: 31.5%; Android®: 34.6%; Masimo Pronto®: 49.5%). Sensitivity and specificity were 63.9% and 48.2% for Apple®, 36.1% and 67.6% for Android®, 45.7% and 85.3% for Masimo Pronto®, 54.3% and 97.6% for HemoCue® Hb-301, and 66.7% and 97.6% for HemoCue® Hb-801. Noninvasive devices were considered easy to use and were the preferred method by participants. Among the only studies to compare multiple point-of-care approaches to hemoglobin testing, the diagnostic ability of HemoCue® was comparable to reference hemoglobin, while noninvasive devices had high user acceptability but considerable biases. Improvements in noninvasive device performance and further testing in anemic populations are recommended before broader use.

Background: In the management of pediatric osteomyelitis or septic arthritis, delay in treatment may affect outcome, while receipt of antibiotics prior to culture may affect culture results. We aimed to determine if pathogen identification decreased in cultures that were pretreated with antibiotics. Methods: We conducted a retrospective cohort study of 584 hospitalized children between 30 days and 18 years of age admitted to two tertiary children’s hospitals. Logistic regression assessed the effect of antibiotic duration on blood, bone, joint aspirate, and “other” culture positivity. Results: Overall, 42% of blood cultures, 70% of bone cultures, 39% of joint cultures, and 70% of “other” cultures were positive. Compared with children who did not receive antibiotics prior to culture, there were no significant differences in odds of a positive culture in children whose cultures were pretreated with antibiotics for any of the culture types [OR (95% CI) 0.90 (0.56–1.44) for blood cultures, 0.77 (0.25–2.34) for bone cultures, 0.71 (0.39–1.28) for joint cultures, 1.18 (0.58–2.41) “for other” cultures; all p > 0.05]. Furthermore, the duration (hours) of antibiotics in the pretreated cultures was also not a significant predictor of culture positivity (OR ranged from 0.99–1.00 for all cultures, p > 0.05). Conclusions: Culture positivity was not associated with antibiotic pretreatment in any of the samples, even for longer duration of antibiotics prior to culture, though the small sample size of subgroups is an important limitation. In pediatric patients hospitalized with osteomyelitis and/or septic arthritis, early initiation of antibiotics may not affect culture positivity.

Importance: Anemia, defined as low hemoglobin (Hb) concentration insufficient to meet an individual's physiological needs, is the most common blood condition worldwide. Objective: To evaluate the current World Health Organization (WHO) Hb cutoffs for defining anemia among persons who are apparently healthy and to assess threshold validity with a biomarker of tissue iron deficiency and physiological indicator of erythropoiesis (soluble transferrin receptor [sTfR]) using multinational data. Design, Setting, and Participants: In this cross-sectional study, data were collected and evaluated from 30 household, population-based nutrition surveys of preschool children aged 6 to 59 months and nonpregnant women aged 15 to 49 years during 2005 to 2016 across 25 countries. Data analysis was performed from March 2020 to April 2021. Exposure: Anemia defined according to WHO Hb cutoffs. Main Outcomes and Measures: To define the healthy population, persons with iron deficiency (ferritin <12 ng/mL for children or <15 ng/mL for women), vitamin A deficiency (retinol-binding protein or retinol <20.1 μg/dL), inflammation (C-reactive protein >0.5 mg/dL or α-1-acid glycoprotein >1 g/L), or known malaria were excluded. Survey-specific, pooled Hb fifth percentile cutoffs were estimated. Among individuals with Hb and sTfR data, Hb-for-sTfR curve analysis was conducted to identify Hb inflection points that reflect tissue iron deficiency and increased erythropoiesis induced by anemia. Results: A total of 79950 individuals were included in the original surveys. The final healthy sample was 13445 children (39.9% of the original sample of 33699 children; 6750 boys [50.2%]; mean [SD] age 32.9 [16.0] months) and 25880 women (56.0% of the original sample of 46251 women; mean [SD] age, 31.0 [9.5] years). Survey-specific Hb fifth percentile among children ranged from 7.90 g/dL (95% CI, 7.54-8.26 g/dL in Pakistan) to 11.23 g/dL (95% CI, 11.14-11.33 g/dL in the US), and among women from 8.83 g/dL (95% CI, 7.77-9.88 g/dL in Gujarat, India) to 12.09 g/dL (95% CI, 12.00-12.17 g/dL in the US). Intersurvey variance around the Hb fifth percentile was low (3.5% for women and 3.6% for children). Pooled fifth percentile estimates were 9.65 g/dL (95% CI, 9.26-10.04 g/dL) for children and 10.81 g/dL (95% CI, 10.35-11.27 g/dL) for women. The Hb-for-sTfR curve demonstrated curvilinear associations with sTfR inflection points occurring at Hb of 9.61 g/dL (95% CI, 9.55-9.67 g/dL) among children and 11.01 g/dL (95% CI, 10.95-11.09 g/dL) among women. Conclusions and Relevance: Current WHO cutoffs to define anemia are higher than the pooled fifth percentile of Hb among persons who are outwardly healthy and from nearly all survey-specific estimates. The lower proposed Hb cutoffs are statistically significant but also reflect compensatory increased erythropoiesis. More studies based on clinical outcomes could further confirm the validity of these Hb cutoffs for anemia..

In the original publication of this article [Paganelli CR, Kassebaum N, Strong K, et al. Guidance for Systematic Integration of Undernutrition in Attributing Cause of Death in Children. Clin Infect Dis. Volume 73, Issue Supplement_5, 15 December 2021, Pages S374.S381, https://doi.org/10.1093/ cid/ciab851], there were a number of minor errors which have been corrected in the originally published version of this manuscript. In Table 1 on the Moderate Wasting line, 'WLZ score below -2 but above -3' should read 'WLZ score below -2 but above or equal to -3'. In the MITS ANTHROPOMETRY section, the statement on WHO growth standards for children -5 years of age has been corrected to ?5 years of age'. In the section Objective 1: Establish Guidance for When to Include Severe and Moderate Wasting and Stunting in Death Certification and in Part 1 (Causal Chain) or Part 2 (Contributing Condition), the reference to Figure 1 has been corrected to reference Figure 2. The Figure 2 reference at the end of this section has been removed. The access date has been added to Reference 37.

Minimally invasive tissue sampling (MITS) is increasingly being used to better understand causes of death in low-resource settings. Undernutrition (eg, wasting, stunting) is prevalent among children globally and yet not consistently coded or uniformly included on death certificates in MITS studies when present. Consistent and accurate attribution of undernutrition is fundamental to understanding its contribution to child deaths. In May 2020, members of the MITS Alliance Cause of Death Technical Working Group convened a panel of experts in public health, child health, nutrition, infectious diseases, and MITS to develop guidance for systematic integration of undernutrition, as assessed by anthropometry, in cause of death coding, including as part of the causal chain or as a contributing condition, in children <5 years of age. The guidance presented here will support MITS and other researchers, public health practitioners, and clinicians with a systematic approach to assigning and interpreting undernutrition in death certification.