Systematic review on efficacy and safety of empirical versus pre-emptive antifungal therapy among children with febrile neutropenia reveals paucity of data.

BACKGROUND: Two approaches are used to manage invasive fungal disease (IFD) in febrile neutropenic patients viz. empirical therapy (without attempting to confirm the diagnosis), or pre-emptive therapy (after screening tests for IFD). OBJECTIVE: This systematic review was undertaken to compare these approaches in children. METHODS: We searched PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Clinical Trial Registries and grey literature, for randomized controlled trials (RCT) comparing empirical versus pre-emptive antifungal therapy in children with FN suspected to have IFD. We used the Cochrane Risk of bias 2 tool for quality assessment, and evaluated the certainty of evidence using the GRADE approach. RESULTS: We identified 7989 citations. Stepwise screening identified only one relevant RCT that administered empirical (n = 73) or pre-emptive (n = 76) antifungal therapy. There were no significant differences in all-cause mortality (RR 1.56, 95% CI: 0.46, 5.31), IFD mortality (RR 1.04, 95% CI:0.15, 7.20) and other clinically important outcomes such as duration of fever, duration of hospitalization and proportion requiring ICU admission. There were no safety data reported. The number of days of antifungal therapy was significantly lower in the pre-emptive therapy arm. The certainty of evidence for all outcomes was 'moderate'. CONCLUSIONS: This systematic review highlighted the paucity of data, comparing empirical versus pre-emptive antifungal therapy in children with febrile neutropenia having suspected invasive fungal disease. Data from a single included trial suggests that both approaches may be comparable in research settings. Robust trials are warranted to address the gap in existing knowledge about the optimal approach in clinical practice.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Tracheobronchial abnormalities on computed tomography angiography in children with congenital heart disease.

OBJECTIVES: To evaluate the assortment of tracheobronchial abnormalities on computed tomography angiography (CTA) in children with congenital heart disease (CHD). METHODS: In this study approved by the Institute ethics committee, CTA studies of 182 children (age range: 2 days-8 years) with CHD, performed from July 2021 to March 2023 were analyzed. Two pediatric radiologists independently assessed the tracheobronchial airways (from the trachea to lobar bronchi) for developmental and branching anomalies and airway compromise (narrowing). In cases which demonstrated airway compromise, the extent and the cause of airway narrowing were evaluated, and the etiology were divided into extrinsic and intrinsic causes. Interobserver agreement between the two radiologists was calculated using kappa statistics. RESULTS: One hundred children demonstrated normal airway anatomy and no luminal narrowing. Airway narrowing was observed in 63 (34.6%) children (κ: 0.954), and developmental airway anomalies were seen in 32 (17.5%) children (κ: 0.935). Of the 63 children with airway narrowing, 47 (25.8%) children had extrinsic cause for narrowing, 11 (6%) children had intrinsic causes for narrowing, and 5 (2.7%) children had both intrinsic and extrinsic causes attributing to airway compromise. Significant airway narrowing (>50% reduction) was seen in 35 (19.2%) children (κ: 0.945). CONCLUSION: Tracheobronchial airway abnormalities are frequently associated in children with CHD and need to be appraised preoperatively. Cross-sectional imaging with CTA provides excellent information on tracheobronchial airway anatomy and caliber as well as delineates the possible etiology of airway narrowing, thus accurately diagnosing airway anomalies.

A multimethods randomized trial found that plain language versions improved adults understanding of health recommendations.

OBJECTIVES: To make informed decisions, the general population should have access to accessible and understandable health recommendations. To compare understanding, accessibility, usability, satisfaction, intention to implement, and preference of adults provided with a digital "Plain Language Recommendation" (PLR) format vs. the original "Standard Language Version" (SLV). STUDY DESIGN AND SETTING: An allocation-concealed, blinded, controlled superiority trial and a qualitative study to understand participant preferences. An international on-line survey. 488 adults with some English proficiency. 67.8% of participants identified as female, 62.3% were from the Americas, 70.1% identified as white, 32.2% had a bachelor's degree as their highest completed education, and 42% said they were very comfortable reading health information. In collaboration with patient partners, advisors, and the Cochrane Consumer Network, we developed a plain language format of guideline recommendations (PLRs) to compare their effectiveness vs. the original standard language versions (SLVs) as published in the source guideline. We selected two recommendations about COVID-19 vaccine, similar in their content, to compare our versions, one from the World Health Organization (WHO) and one from Centers for Disease Control and Prevention (CDC). The primary outcome was understanding, measured as the proportion of correct responses to seven comprehension questions. Secondary outcomes were accessibility, usability, satisfaction, preference, and intended behavior, measured on a 1-7 scale. RESULTS: Participants randomized to the PLR group had a higher proportion of correct responses to the understanding questions for the WHO recommendation (mean difference [MD] of 19.8%, 95% confidence interval [CI] 14.7-24.9%; P < 0.001) but this difference was smaller and not statistically significant for the CDC recommendation (MD of 3.9%, 95% CI -0.7% to 8.3%; P = 0.096). However, regardless of the recommendation, participants found the PLRs more accessible, (MD of 1.2 on the seven-point scale, 95% CI 0.9-1.4%; P < 0.001) and more satisfying (MD of 1.2, 95% CI 0.9-1.4%; P < 0.001). They were also more likely to follow the recommendation if they had not already followed it (MD of 1.2, 95% CI 0.7-1.8%; P < 0.001) and share it with other people they know (MD of 1.9, 95% CI 0.5-1.2%; P < 0.001). There was no significant difference in the preference between the two formats (MD of -0.3, 95% CI -0.5% to 0.03%; P = 0.078). The qualitative interviews supported and contextualized these findings. CONCLUSION: Health information provided in a PLR format improved understanding, accessibility, usability, and satisfaction and thereby has the potential to shape public decision-making behavior.

Assessment of Blood Lead Level of School Children in 10 Cities of India: A Cross-Sectional Study.

OBJECTIVES: To assess the blood lead level (BLL) of school children in 10 cities of India. METHODS: This multi-centric cross-sectional study enrolled participants from randomly selected schools. Data on demographic details, socioeconomic status (SES) and anthropometric indicators was collected. Samples were collected for assessment of lead level in blood. Inductively coupled plasma-optical emission spectrometry technique was used to assess BLL. RESULTS: From April 2019 through February 2020, 2247 participants were recruited from sixty schools (62.6% government schools) with equal gender distribution. The overall median (interquartile range) BLL was 8.8 (4.8, 16.4) µg/dl. The highest median (interquartile range) BLL was in Manipal 30.6 (23.0, 46.7) and lowest in Dibrugarh 4.8 (3.2, 7.0). Overall, 82.5% of participants had BLL above ≤4 µg/dl. Significant negative correlation was observed between BLL and SES (correlation= -0.24, p <0.001), anthropometric indicators (correlation= -0.11, p <0.001), hemoglobin level (correlation= -0.045, p = 0.03) and multivariate regression model showed association with gender, SES and anthropometric indicators. CONCLUSIONS: BLL are elevated in urban school going children and there is intercity variation. Hence, urgent focus is needed to reduce exposure to lead in India.

Maternally transmitted anti-measles antibodies, and susceptibility to disease among infants in Chandigarh, India: A prospective birth cohort study.

Prior to the age of measles vaccination, infants are believed to be protected against measles by passively transferred maternal antibodies. However, the quantity and quality of such protection have not been well established in the Indian setting. We undertook this study to characterize the transfer and decline in maternal anti-measles antibodies among infants, and determine their susceptibility to measles. In this population-based, birth-cohort study, we enrolled pregnant women and their newborn infants, from a catchment area of 30 Anganwadis in Chandigarh, India. We collected maternal blood at delivery, and infant blood samples at birth, and 3, 6, and 9 months of age. Anti-measles IgG antibodies were measured using quantitative ELISA. We assessed antibody decline using log-linear models. In total, 428 mother-infant dyads were enrolled, and data from 413 dyads were analyzed. At birth, 91.5% (95% CI: 88.8, 94.2) of infants had protective antibody levels, which declined to 26.3% (95% CI: 21.0%, 31.9) at 3 months, 3.4% (95% CI: 0.9, 5.9) at 6 months, and 2.1% (95% CI: 0.1, 4.1) at 9 months. Younger mothers transferred lower levels of antibodies to their infants. We concluded that the majority of infants are susceptible to measles as early as three months of age, much earlier than their eligibility to receive measles vaccination.

Association of dietary intake with micronutrient deficiency in Indian school children: a cross-sectional study.

Adequate nutrition is necessary during childhood and early adolescence for adequate growth and development. Hence, the objective of the study was to assess the association between dietary intake and blood levels of minerals (calcium, iron, zinc, and selenium) and vitamins (folate, vitamin B12, vitamin A, and vitamin D) in urban school going children aged 6-16 years in India, in a multicentric cross-sectional study. Participants were enrolled from randomly selected schools in ten cities. Three-day food intake data was collected using a 24-h dietary recall method. The intake was dichotomised into adequate and inadequate. Blood samples were collected to assess levels of micronutrients. From April 2019 to February 2020, 2428 participants (50⋅2 % females) were recruited from 60 schools. Inadequate intake for calcium was in 93⋅4 % (246⋅5 ± 149⋅4 mg), iron 86⋅5 % (7⋅6 ± 3⋅0 mg), zinc 84⋅0 % (3⋅9 ± 2⋅4 mg), selenium 30⋅2 % (11⋅3 ± 9⋅7 mcg), folate 73⋅8 % (93⋅6 ± 55⋅4 mcg), vitamin B12 94⋅4 % (0⋅2 ± 0⋅4 mcg), vitamin A 96⋅0 % (101⋅7 ± 94⋅1 mcg), and vitamin D 100⋅0 % (0⋅4 ± 0⋅6 mcg). Controlling for sex and socioeconomic status, the odds of biochemical deficiency with inadequate intake for iron [AOR = 1⋅37 (95 % CI 1⋅07-1⋅76)], zinc [AOR = 5⋅14 (95 % CI 2⋅24-11⋅78)], selenium [AOR = 3⋅63 (95 % CI 2⋅70-4⋅89)], folate [AOR = 1⋅59 (95 % CI 1⋅25-2⋅03)], and vitamin B12 [AOR = 1⋅62 (95 %CI 1⋅07-2⋅45)]. Since there is a significant association between the inadequate intake and biochemical deficiencies of iron, zinc, selenium, folate, and vitamin B12, regular surveillance for adequacy of micronutrient intake must be undertaken to identify children at risk of deficiency, for timely intervention.

Plain Language vs Standard Format for Youth Understanding of COVID-19 Recommendations: A Randomized Clinical Trial.

Importance: To ensure that youths can make informed decisions about their health, it is important that health recommendations be presented for understanding by youths. Objective: To compare understanding, accessibility, usability, satisfaction, intention to implement, and preference of youths provided with a digital plain language recommendation (PLR) format vs the original standard language version (SLV) of a health recommendation. Design, Setting, and Participants: This pragmatic, allocation-concealed, blinded, superiority randomized clinical trial included individuals from any country who were 15 to 24 years of age, had internet access, and could read and understand English. The trial was conducted from May 27 to July 6, 2022, and included a qualitative component. Interventions: An online platform was used to randomize youths in a 1:1 ratio to an optimized digital PLR or SLV format of 1 of 2 health recommendations related to the COVID-19 vaccine; youth-friendly PLRs were developed in collaboration with youth partners and advisors. Main Outcomes and Measures: The primary outcome was understanding, measured as the proportion of correct responses to 7 comprehension questions. Secondary outcomes were accessibility, usability, satisfaction, preference, and intended behavior. After completion of the survey, participants indicated their interest in completing a 1-on-1 semistructured interview to reflect on their preferred digital format (PLR or SLV) and their outcome assessment survey response. Results: Of the 268 participants included in the final analysis, 137 were in the PLR group (48.4% female) and 131 were in the SLV group (53.4% female). Most participants (233 [86.9%]) were from North and South America. No significant difference was found in understanding scores between the PLR and SLV groups (mean difference, 5.2%; 95% CI, -1.2% to 11.6%; P = .11). Participants found the PLR to be more accessible and usable (mean difference, 0.34; 95% CI, 0.05-0.63) and satisfying (mean difference, 0.39; 95% CI, 0.06-0.73) and had a stronger preference toward the PLR (mean difference, 4.8; 95% CI, 4.5-5.1 [4.0 indicated a neutral response]) compared with the SLV. No significant difference was found in intended behavior (mean difference, 0.22 (95% CI, -0.20 to 0.74). Interviewees (n = 14) agreed that the PLR was easier to understand and generated constructive feedback to further improve the digital PLR. Conclusions and Relevance: In this randomized clinical trial, compared with the SLV, the PLR did not produce statistically significant findings in terms of understanding scores. Youths ranked it higher in terms of accessibility, usability, and satisfaction, suggesting that the PLR may be preferred for communicating health recommendations to youths. The interviews provided suggestions for further improving PLR formats. Trial Registration: ClinicalTrials.gov Identifier: NCT05358990.

Equity issues rarely addressed in the development of COVID-19 formal recommendations and good practice statements: a cross-sectional study.

BACKGROUND AND OBJECTIVE: To identify COVID-19 actionable statements (e.g., recommendations) focused on specific disadvantaged populations in the living map of COVID-19 recommendations (eCOVIDRecMap) and describe how health equity was assessed in the development of the formal recommendations. METHODS: We employed the place of residence, race or ethnicity or culture, occupation, gender or sex, religion, education, socio-economic status, and social capital-Plus framework to identify statements focused on specific disadvantaged populations. We assessed health equity considerations in the evidence to decision frameworks (EtD) of formal recommendations for certainty of evidence and impact on health equity criteria according to the Grading of Recommendations, Assessment, Development, and Evaluations criteria. RESULTS: We identified 16% (124/758) formal recommendations and 24% (186/819) good practice statements (GPS) that were focused on specific disadvantaged populations. Formal recommendations (40%, 50/124) and GPS (25%, 47/186) most frequently focused on children. Seventy-six percent (94/124) of the recommendations were accompanied with EtDs. Over half (55%, 52/94) of those considered indirectness of the evidence for disadvantaged populations. Considerations in impact on health equity criterion most frequently involved implementation of the recommendation for disadvantaged populations (17%, 16/94). CONCLUSION: Equity issues were rarely explicitly considered in the development COVID-19 formal recommendations focused on specific disadvantaged populations. Guidance is needed to support the consideration of health equity in guideline development during health emergencies.