Role for Maternal Asthma in Severe Human Metapneumovirus Lung Disease Susceptibility in Children.

BACKGROUND: Severity of human metapneumovirus (hMPV) lower respiratory illness (LRTI) is considered similar to that observed for respiratory syncytial virus (RSV). However, differences in severity between these pathogens have been noted, suggesting the degree of illness may vary in different populations. Moreover, a potential association between hMPV and asthma also suggests that hMPV may preferentially affect asthmatic subjects. METHODS: In a population-based surveillance study in children aged <2 years admitted for severe LRTI in Argentina, nasopharyngeal aspirates were tested by RT-PCR for hMPV, RSV, influenza A, and human rhinovirus. RESULTS: Of 3947 children, 383 (10%) were infected with hMPV. The hospitalization rate for hMPV LRTI was 2.26 per 1000 children (95% confidence interval [CI], 2.04-2.49). Thirty-nine (10.2%) patients infected with hMPV experienced life-threatening disease (LTD; 0.23 per 1000 children; 95% CI, .16-.31/1000), and 2 died (mortality rate 0.024 per 1000; 95% CI, .003-.086). In hMPV-infected children birth to an asthmatic mother was an increased risk for LTD (odds ratio, 4.72; 95% CI, 1.39-16.01). We observed a specific interaction between maternal asthma and hMPV infection affecting risk for LTD. CONCLUSIONS: Maternal asthma increases the risk for LTD in children <2 years old hospitalized for severe hMPV LRTI.

Respiratory Failure and Death in Vulnerable Premature Children With Lower Respiratory Tract Illness.

BACKGROUND: Efforts to better understand the risk factors associated with respiratory failure (RF) and fatal lower respiratory tract infection (LRTI) in premature children in developing countries are necessary to elaborate evidenced-based preventive interventions. We aim to characterize the burden of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) LRTI in premature children and determine risk factors for RF and fatal illness in a vulnerable population. METHODS: This is a prospective, population-based, cross-sectional study. Subjects with severe LRTI were enrolled during respiratory season. Risk factors for RF and death in premature infants were investigated. RESULTS: A total of 664 premature children participated. Infant's hospitalization rate due to LRTI was 82.6/1000 (95% confidence interval [CI], 68.6-96.7/1000). Infant's RSV and hMPV rates were 40.9/1000 (95% CI, 36.3-45.6/1000) and 6.6/1000 (95% CI, 3.9-9.2/1000), respectively. The RF rate was 8.2/1000 (95% CI, 4.9-11.5/1000). The LRTI mortality was 2.2/1000 (95% CI, 0.7-3.7/1000); for RSV, the rate was 0.8/1000 (95% CI, 0-1.7/1000) with a case-fatality ratio of 1.8%. Never breastfeeding, malnutrition, younger than 6 months, congenital heart disease, and lower hematocrit were risk factors for RF. Experiencing pneumonia, pneumothorax, sepsis, or apnea were clinical determinants of poor outcomes. CONCLUSIONS: Premature children under 2 years old in vulnerable environments experience RF and death more often than term counterparts. Modifiable risk factors associated with poor outcomes should prompt evidence-based interventions.

Pharmacokinetics, Safety, and Antiviral Effects of Multiple Doses of the Respiratory Syncytial Virus (RSV) Fusion Protein Inhibitor, JNJ-53718678, in Infants Hospitalized With RSV Infection: A Randomized Phase 1b Study.

BACKGROUND: This phase 1b study evaluated the pharmacokinetics, safety, and antiviral effects of the respiratory syncytial virus (RSV)-specific fusion inhibitor JNJ-53718678 (JNJ-8678) in hospitalized RSV-infected patients aged > 1 to ≤24 months. METHODS: Patients categorized by age (cohort 1: ≥6 to ≤24 months; cohort 2: ≥3 to < 6 months; cohort 3: > 1 to < 3 months) were randomized to oral JNJ-8678 or placebo once daily for 7 days. Dose increases followed data review committee recommendations (cohort 1: 2/6/8/9 mg/kg; cohort 2: 1.5/4.5/6 mg/kg; cohort 3: 1/3/5 mg/kg). Cohort 1 included a 9 mg/kg dose, as target exposures were not reached at lower doses. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modeling. Safety was assessed by adverse events (AEs), laboratory tests, and electrocardiograms. To assess antiviral effects, RSV RNA viral load from nasal swabs was quantified over time using reverse-transcription quantitative polymerase chain reaction. RESULTS: Patients received JNJ-8678 (n = 37) or placebo (n = 7). Pharmacokinetic parameters were similar at the highest doses for cohorts 1-3 (area under the plasma concentration-time curve from time of administration up to 24 hours postdosing at day 7: 35 840, 34 980, and 39 627 ng × hour/mL, respectively). Two grade 3 AEs were reported (both bronchiolitis; 1 JNJ-8678, 1 placebo), reported as serious AEs; all other AEs were grade 1 or 2. Two additional serious AEs were reported (rhinitis [JNJ-8678]; pneumonia [placebo]). No deaths, grade 4 AEs, or AEs leading to discontinuation were reported. Median RSV viral load change from baseline in JNJ-8678 vs placebo by day 3 was -1.98 vs -0.32 log10 copies/mL. CONCLUSIONS: In RSV-infected infants, JNJ-8678 was well tolerated. Target exposures were reached and antiviral activity was observed. CLINICAL TRIALS REGISTRATION: NCT02593851.

[Seroprevalence of anti-Mycoplasma pneumoniae antibodies in otherwise healthy children]. / Seroprevalencia de anticuerpos anti-Mycoplasma pneumoniae en niños menores de 12 años.

INTRODUCTION: Mycoplasma pneumoniae (Mypn) infection could be occurring at an earlier age due to social pheno mena such as attending daycare centers more frequently and earlier than decades ago. OBJECTIVE: to estimate the prevalence of anti-Mypn antibodies in children aged 0-12 years, and to explore whether age, attendance to daycare center/school, overcrowding or the presence of children aged below 12 years in the households increase the risk of seropositivity. PATIENTS AND METHOD: Cross-sectional stu dy including healthy children aged 0-12 years which required blood draws for routine laboratory tests. In all cases, the aforementioned variables were recorded and anti-Mypn IgG was determined by enzyme immunoassay. The association between predictors and seropositivity was assessed in a logistic regression model. RESULTS: We included 232 patients (average age 56.4 ± 40.0 months). 56.9% attended a daycare center/school, 63.8% co-habited with children under 12 years old, and 15.9% lived in overcrowded households. The prevalence of anti-Mypn antibodies was 14.6%. There were no significant differences between seropositive and seronegative children regarding age (63.1 ± 40.7 vs. 55.4 ± 41.3 months), school/day-care attendance (64.7% vs. 55.5%), overcrowding (14.7% vs. 14.9%), or co-habiting with children (64.7% vs. 63.6%). Age was not an independent predictor of seropositivity in the multivariate model. CONCLUSION: The prevalence of anti-Mypn antibodies in children was 14.6% and age was not a predictor of seropositivity.

Mortality due to Respiratory Syncytial Virus. Burden and Risk Factors.

RATIONALE: Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization and an important cause of death in infants in the developing world. The relative contribution of social, biologic, and clinical risk factors to RSV mortality in low-income regions is unclear. OBJECTIVES: To determine the burden and risk factors for mortality due to RSV in a low-income population of 84,840 infants. METHODS: This was a prospective, population-based, cross-sectional, multicenter study conducted between 2011 and 2013. Hospitalizations and deaths due to severe lower respiratory tract illness (LRTI) were recorded during the RSV season. All-cause hospital deaths and community deaths were monitored. Risk factors for respiratory failure (RF) and mortality due to RSV were assessed using a hierarchical, logistic regression model. MEASUREMENTS AND MAIN RESULTS: A total of 2,588 (65.5%) infants with severe LRTI were infected with RSV. A total of 157 infants (148 postneonatal) experienced RF or died with RSV. RSV LRTI accounted for 57% fatal LRTI tested for the virus. A diagnosis of sepsis (odds ratio [OR], 17.03; 95% confidence interval [CI], 13.14-21.16 for RF) (OR, 119.39; 95% CI, 50.98-273.34 for death) and pneumothorax (OR, 17.15; 95% CI, 13.07-21.01 for RF) (OR, 65.49; 95% CI, 28.90-139.17 for death) were the main determinants of poor outcomes. CONCLUSIONS: RSV was the most frequent cause of mortality in low-income postneonatal infants. RF and death due to RSV LRTI, almost exclusively associated with prematurity and cardiopulmonary diseases in industrialized countries, primarily affect term infants in a developing world environment. Poor outcomes at hospitals are frequent and associated with the cooccurrence of bacterial sepsis and clinically significant pneumothoraxes.

[Scientific production from public hospitals of the City of Buenos Aires, 2017]. / Producción científica de los hospitales públicos de la Ciudad de Buenos Aires, 2017.

The number of publications in the scientific literature coming from an institution is an indicator of its scientific production. The scientific production of the hospitals of the Government of the City of Buenos Aires (GCBA) has been evaluated previously, but without discriminating how much of that production corresponded to other academic institutions settled there (University of Buenos Aires, UBA, National Council of Scientific Research and Techniques, CONICET). Our objective was to evaluate the publications included in PubMed that correspond to hospitals of the GCBA, describe their main characteristics, and discriminate the contribution of other academic institutions (UBA and CONICET). It is a cross-sectional study based on a PubMed search, using the name of each of the 34 GCBA hospitals, CONICET and UBA in the "affiliation" field. In total, 2727 publications from GCBA hospitals were identified (4.6% of Argentine publications); 73.9% in English, 78.9% in relation to humans, 37.2% in the last 5 years; 6.4% with high level of evidence (clinical trials and meta-analysis), and 28.4% including children. Compared to the national total, the GCBA publications include fewer works in English, more research in humans, more clinical trials and more research in children. Of the publications corresponding to hospitals of the GCBA, 90.4% did not share the affiliation with CONICET or with UBA. In conclusion, the GCBA hospitals generated 4.6% of the total Argentine publications in PubMed; and 90% of these was not shared with UBA or CONICET. Publications from GCBA institutions include more clinical trials and research in children.

[Correlation between results of the residency admission test and of pediatric certification test in Buenos Aires, Argentina]. / Relación entre el desempeño en el examen de ingreso a la residencia y en el de especialización en pediatría en la Ciudad de Buenos Aires.

In the city of Buenos Aires (CABA), pediatric residents enter the residency program after taking a unified admission test. After completion of the program and passing a final test, the Universidad de Buenos Aires (UBA) provides a professional certification. The objective of this study is to determine if the results obtained in the residency admission test (RAT) and those of the professional certification test (PCT) correlated. This is a cross-sectional study, that included all subjects who passed the pediatrics RAT in CABA in 2004-2009, and that attended the pediatric PCT of the UBA. The score for each subject in both tests was obtained and the corresponding correlation was calculated. Results were divided in quintiles, and the proportion of subjects who improved their position in the PCT with respect to the RAT was calculated. Data from 303 subjects was obtained. The RAT showed a median of 45.0 (over 60 maximum) (IC-range: 43.0-48.7), and the PCT showed a median of 6 points (over 10 max.)(IC-range: 6-8). A significative correlation between results in RAT and PCT was observed (r = 0.37, p < 0.001). Based on their position in the RAT, 43.8% of subjects improved their position in the PCT, without differences between residents attending pediatric and general hospitals (45.6 vs. 31.5%; p = 0.1). In the case of pediatric residents, results of the residency admission test correlate with those obtained in the professional certification test.

[The Use of the Objective Structured Clinical Examination for Paediatric residents in the City of Buenos Aires]. / Aplicación del Examen Clínico Objetivo Estructurado en la residencia de Pediatría de la Ciudad de Buenos Aires.

INTRODUCTION: The Objective Structured Clinical Examination (OSCE) is considered the reference standard for competence evaluation, but its use in Latin America is limited. The City of Buenos Aires Government (CBAG) administers a Paediatric residency system that includes 400 residents distributed in 13 hospitals, sharing an admission system and education program. We aim to describe the experience of administering an OSCE for evaluating all the Paediatric residents of the CBAG. SUBJECTS AND METHOD: Descriptive study, including all paediatric residents of the CBAG, belonging to 13 hospitals (2 paediatric and 11 general), ending their first year of training. The OSCE included 10 stations. RESULTS: Eighty-five residents participated in the OSCE, and 88.2% (95% CI 79.7-93.5) passed the examination. There were no significant differences in the pass rate between residents from paediatric hospitals and from general hospitals (89.5 vs. 85.7%; OR=1.4; 95% CI 0.4-5.5; P=.8). CONCLUSIONS: In 2015, the OSCE was administered to all paediatric residents of the CBAG for the first time. This experience allowed identifying weaknesses in the education system, in order to develop strategies to overcome them.

Macronutrients during pregnancy and life-threatening respiratory syncytial virus infections in children.

RATIONALE: Respiratory syncytial virus (RSV) is an important cause of hospitalization and death in infants worldwide. Most RSV deaths occur in developing countries, where burden and risk factors for life-threatening illness are unclear. OBJECTIVES: We defined the burden of life-threatening (O(2) saturation [O(2) sat] ≤ 87%) and fatal RSV infection, and characterized risk factors for life-threatening disease in hospitalized children. Special emphasis was placed on studying the impact of dietary habits during pregnancy. We hypothesized that dietary preferences, differing from those of our remote ancestors, would negatively impact children's pulmonary health. For instance, a diet rich in carbohydrates is a signature of recent millennia and typical of low-income populations, heavily burdened by life-threatening RSV disease. METHODS: Prospective study in a catchment population of 56,560 children under 2 years of age during the RSV season in Argentina. All children with respiratory signs and O(2) sat less than 93% on admission were included. MEASUREMENTS AND MAIN RESULTS: Among 1,293 children with respiratory infections, 797(61.6%) were infected with RSV: 106 of these had life-threatening disease; 1.9 per 1,000 children (95% confidence interval [CI], 1.5-2.2/1,000) under 24 months. A total of 22 hospitalized children died (9 RSV(+)), 26 died at home due to acute respiratory infection (14 attributed to RSV); all were under 12 months old. The annual attributable mortality rate for RSV was 0.7 per 1,000 infants (95% CI, 0.4-1.1/1,000). Life-threatening disease was dose-dependently associated with carbohydrate ingestion during pregnancy (adjusted odds ratio from 3.29 [95% CI, 1.15-9.44] to 7.36 [95% CI, 2.41-22.5] versus the lowest quartile). CONCLUSIONS: Life-threatening and fatal RSV infections are a heavy burden on infants in the developing world. Diets rich in carbohydrates during pregnancy are associated with these severe outcomes.

Waiting for the next winter. Outpatient pediatric visits for respiratory infections before, during, and after the COVID-19 pandemic in the city of Buenos Aires.

INTRODUCTION: During the COVID-19 pandemic, pediatric visits due to acute lower respiratory infections (ALRIs) decreased, but most reports are from hospitalized patients. There is little information on this phenomenon in outpatients, who are the majority in ALRI. We evaluated the impact of the COVID-19 pandemic on ALRI-related outpatient visits in the City of Buenos Aires. METHODS: Observational study including all outpatient visits of children under 2 years of age to the public health system of the City of Buenos Aires, between 1 January 2018 and 31 December 2022. We analyzed the total number of visits and the ALRI-related visits, and their distribution throughout the study period. RESULTS: A total of 704,426 visits were registered, 7.38% of them due to ALRI. ALRI-related visits decreased from the implementation of a national lockdown (2020) and increased again as the restriction measures decreased, particularly the return to full school attendance (2021). In general, the proportion of ALRI-related visits was significantly higher in the cold months than in the warm ones (9.8% vs. 5.5%; odds ratio: 1.76, 95% confidence interval: 1.73-1.79; p < .001). This difference was observed before (2018 and 2019) and after the pandemic (2022), but not in 2020-2021. The peak of ALRI-related visits occurred in the cold months in pre-pandemic years (2018-2019), did not appear in 2020, reappeared delayed in 2021, and recovered seasonality in 2022. CONCLUSION: Outpatient ALRI-related visits decreased significantly in the city of Buenos Aires during the COVID-19 pandemic and currently seem to have recovered their magnitude and seasonality.

Impact of the SARS-CoV-2 pandemic on the body mass index of children seen in the City of Buenos Aires. / Impacto de la pandemia por SARS-CoV-2 en el índice de masa corporal de niños asistidos en la Ciudad Autónoma de Buenos Aires.

Introduction. Childhood overweight and obesity are a public health problem. The onset of the COVID-19 pandemic may have contributed to this condition. The body mass index (BMI) Z-score has been accepted as an indicator for overweight and obesity diagnosis and follow-up. Objective. To assess whether the prevalence of overweight and obesity and the BMI Z-score in children aged 2 to 5 years increased during the pandemic. Population and methods. Retrospective, cohort study. Patients included were those seen at public health care facilities in the City of Buenos Aires (CABA), who were aged 2 to 5 years, had weight and height values recorded at 2 different visits, before and after the establishment of the preventive and mandatory social isolation policy. Patients' nutritional status (BMI Z-score) and the variation in this indicator between both visits were recorded. Results. A total of 3866 subjects were assessed; their average age was 3.4 ± 0.8 years; 48.1% were girls. The average interval between both visits was 14.3 ± 2.5 months. The prevalence of overweight/ obesity increased from 12.6% (95% CI: 11.6-13.6) to 20.9% (95% CI: 19.6-22.2), p < 0.001, and so did the BMI Z-score (0.4 ± 1.1 versus 0.8 ± 1.3, p < 0.001). Conclusion. The prevalence of overweight and obesity and the BMI Z-score in children aged 2 to 5 years increased significantly during the pandemic.

Introducción. El sobrepeso y la obesidad infantil constituyen un problema de salud pública. El inicio de la pandemia por COVID-19 pudo haber favorecido esta patología. El puntaje Z del índice de masa corporal (Z-IMC) es un indicador aceptado para su diagnóstico y seguimiento. Objetivo. Evaluar si la prevalencia de sobrepeso y obesidad, y el Z-IMC en niños de 2 a 5 años aumentó durante la pandemia. Población y métodos. Estudio de cohorte retrospectiva. Se incluyeron pacientes asistidos en efectores públicos de salud del Gobierno de la Ciudad Autónoma de Buenos Aires (GCABA), de 2 a 5 años de edad, con registro de peso y talla en dos consultas, antes y después de haber comenzado el aislamiento social preventivo y obligatorio (ASPO). Se registró estado nutricional (Z-IMC) y variación del Z-IMC entre ambas consultas. Resultados. Se evaluaron 3866 sujetos, edad promedio 3,4 ± 0,8 años; el 48,1 % fueron mujeres. El intervalo promedio entre consultas fue 14,3 ± 2,5 meses. La prevalencia de sobrepeso/obesidad aumentó del 12,6 % (IC95% 11,6-13,6) al 20,9 % (IC95% 19,6-22-2); p <0,001, al igual que el Z-IMC (0,4 ± 1,1 vs. 0,8 ± 1,3; p <0,001). Conclusión. La prevalencia de sobrepeso y obesidad, y el Z-IMC en niños de 2 a 5 años aumentó significativamente durante la pandemia.

Thirty-day readmissions in children with complex chronic conditions.

INTRODUCTION: The rate of hospital readmission within 30 days of discharge is a quality indicator in health care. Paediatric patients with complex chronic conditions have high readmission rates. Failure in the transition between hospital and home care could explain this phenomenon. OBJECTIVES: To estimate the incidence rate of 30-day hospital readmission in paediatric patients with complex chronic conditions, estimate how many are potentially preventable and explore factors associated with readmission. MATERIALS AND METHOD: Cohort study including hospitalised patients with complex chronic conditions aged 1 month to 18 years. Patients with cancer or with congenital heart disease requiring surgical correction were excluded. The outcomes assessed were 30-day readmission rate and potentially preventable readmissions. We analysed sociodemographic, geographic, clinical and transition to home care characteristics as factors potentially associated with readmission. RESULTS: The study included 171 hospitalizations, and 28 patients were readmitted within 30 days (16.4%; 95% CI, 11.6%-22.7%). Of the 28 readmissions, 23 were potentially preventable (82.1%; 95% CI, 64.4%-92.1%). Respiratory disease was associated with a higher probability of readmission. There was no association between 30-day readmission and the characteristics of the transition to home care. CONCLUSIONS: The 30-day readmission rate in patients with complex chronic disease was 16.4%, and 82.1% of readmissions were potentially preventable. Respiratory disease was the only identified risk factor for 30-day readmission.

ATP-P2X7R pathway activation limits the Tfh cell compartment during pediatric RSV infection.

Background: Follicular helper T cells (Tfh) are pivotal in B cell responses. Activation of the purinergic receptor P2X7 on Tfh cells regulates their activity. We investigated the ATP-P2X7R axis in circulating Tfh (cTfh) cells during Respiratory Syncytial Virus (RSV) infection. Methods: We analyzed two cohorts: children with RSV infection (moderate, n=30; severe, n=21) and healthy children (n=23). We utilized ELISA to quantify the levels of PreF RSV protein-specific IgG antibodies, IL-21 cytokine, and soluble P2X7R (sP2X7R) in both plasma and nasopharyngeal aspirates (NPA). Additionally, luminometry was employed to determine ATP levels in plasma, NPA and supernatant culture. The frequency of cTfh cells, P2X7R expression, and plasmablasts were assessed by flow cytometry. To evaluate apoptosis, proliferation, and IL-21 production by cTfh cells, we cultured PBMCs in the presence of Bz-ATP and/or P2X7R antagonist (KN-62) and a flow cytometry analysis was performed. Results: In children with severe RSV disease, we observed diminished titers of neutralizing anti-PreF IgG antibodies. Additionally, severe infections, compared to moderate cases, were associated with fewer cTfh cells and reduced plasma levels of IL-21. Our investigation revealed dysregulation in the ATP-P2X7R pathway during RSV infection. This was characterized by elevated ATP levels in both plasma and NPA samples, increased expression of P2X7R on cTfh cells, lower levels of sP2X7R, and heightened ATP release from PBMCs upon stimulation, particularly evident in severe cases. Importantly, ATP exposure decreased cTfh proliferative response and IL-21 production, while promoting their apoptosis. The P2X7R antagonist KN-62 mitigated these effects. Furthermore, disease severity positively correlated with ATP levels in plasma and NPA samples and inversely correlated with cTfh frequency. Conclusion: Our findings indicate that activation of the ATP-P2X7R pathway during RSV infection may contribute to limiting the cTfh cell compartment by promoting cell death and dysfunction, ultimately leading to increased disease severity.

CROCuS, a Phase II Study Evaluating the Antiviral Activity, Clinical Outcomes, and Safety of Rilematovir in Children Aged ≥ 28 Days and ≤ 3 Years with Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus.

BACKGROUND: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children aged ≤ 5 years and adults aged ≥ 60 years worldwide. Despite this, RSV-specific therapeutic options are limited. Rilematovir is an investigational, orally administered inhibitor of RSV fusion protein-mediated viral entry. OBJECTIVE: To establish the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir (low or high dose) in children aged ≥ 28 days and ≤ 3 years with RSV disease. METHODS: CROCuS was a multicenter, international, double-blind, placebo-controlled, randomized, adaptive phase II study, wherein children aged ≥ 28 days and ≤ 3 years with confirmed RSV infection who were either hospitalized (Cohort 1) or treated as outpatients (Cohort 2) were randomized (1:1:1) to receive rilematovir (low or high dose) or placebo. Study treatment was administered daily as an oral suspension from days 1 to 7, with dosing based on weight and age groups. The primary objective was to establish antiviral activity of rilematovir by evaluating the area under the plasma concentration-time curve of RSV viral load in nasal secretions from baseline through day 5. Severity and duration of RSV signs and symptoms and the safety and tolerability of rilematovir were also assessed through day 28 (± 3). RESULTS: In total, 246 patients were randomized, treated, and included in the safety analysis population (Cohort 1: 147; Cohort 2: 99). Of these, 231 were included in the intent-to-treat-infected analysis population (Cohort 1: 138; Cohort 2: 93). In both cohorts, demographics were generally similar across treatment groups. In both cohorts combined, the difference (95% confidence interval) in the mean area under the plasma concentration-time curve of RSV RNA viral load through day 5 was - 1.25 (- 2.672, 0.164) and - 1.23 (- 2.679, 0.227) log10 copies∙days/mL for the rilematovir low-dose group and the rilematovir high-dose group, respectively, when compared with placebo. The estimated Kaplan-Meier median (95% confidence interval) time to resolution of key RSV symptoms in the rilematovir low-dose, rilematovir high-dose, and placebo groups of Cohort 1 was 6.01 (4.24, 7.25), 5.82 (4.03, 8.18), and 7.05 (5.34, 8.97) days, respectively; in Cohort 2, estimates were 6.45 (4.81, 9.70), 6.26 (5.41, 7.84), and 5.85 (3.90, 8.27) days, respectively. A similar incidence of adverse events was reported in patients treated with rilematovir and placebo in Cohort 1 (rilematovir: 61.9%; placebo: 58.0%) and Cohort 2 (rilematovir: 50.8%; placebo: 47.1%), with most reported as grade 1 or 2 and none leading to study discontinuation. The study was terminated prematurely, as the sponsor made a non-safety-related strategic decision to discontinue rilematovir development prior to full recruitment of Cohort 2. CONCLUSIONS: Data from the combined cohort suggest that rilematovir has a small but favorable antiviral effect of indeterminate clinical relevance compared with placebo, as well as a favorable safety profile. Safe and effective therapeutic options for RSV in infants and young children remain an unmet need. CLINICAL TRIAL REGISTRATION: EudraCT Number: 2016-003642-93; ClinicalTrials.gov Identifier: NCT03656510. First posted date: 4 September, 2018.

Pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in Argentina.

BACKGROUND: While the Northern Hemisphere experiences the effects of the 2009 pandemic influenza A (H1N1) virus, data from the recent influenza season in the Southern Hemisphere can provide important information on the burden of disease in children. METHODS: We conducted a retrospective case series involving children with acute infection of the lower respiratory tract or fever in whom 2009 H1N1 influenza was diagnosed on reverse-transcriptase polymerase-chain-reaction assay and who were admitted to one of six pediatric hospitals serving a catchment area of 1.2 million children. We compared rates of admission and death with those among age-matched children who had been infected with seasonal influenza strains in previous years. RESULTS: Between May and July 2009, a total of 251 children were hospitalized with 2009 H1N1 influenza. Rates of hospitalization were double those for seasonal influenza in 2008. Of the children who were hospitalized, 47 (19%) were admitted to an intensive care unit, 42 (17%) required mechanical ventilation, and 13 (5%) died. The overall rate of death was 1.1 per 100,000 children, as compared with 0.1 per 100,000 children for seasonal influenza in 2007. (No pediatric deaths associated with seasonal influenza were reported in 2008.) Most deaths were caused by refractory hypoxemia in infants under 1 year of age (death rate, 7.6 per 100,000). CONCLUSIONS: Pandemic 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza in previous years.

[Scientific research in public health institutions of the City of Buenos Aires]. / La investigación científica en las instituciones de salud del Gobierno de la Ciudad de Buenos Aires.

Hospitals with academic activities offer better services to their patients. The Government of Buenos Aires City (GBAC) has an important network of health facilities, but there is little information regarding their academic activities. Our aim was to estimate the proportion of articles included in MEDLINE originated in GBAC hospitals, to evaluate their contribution regarding the whole country (Argentina), and to describe some characteristics of these papers. It is a cross-sectional study based on a MEDLINE search, using the name of each of the 33 GBAC hospitals in the "affiliation" field. Among 22 million references, 1781 belonged to GBAC hospitals (4.4% of all references from Argentina); 66.5% were in English, 83.7% were related to humans, 30.1% were from the last 5 years, 8.3% included high level scientific evidence research (meta-analysis or randomized controlled trials), and 31.1% included research in children. Regarding the rest of the references from Argentina, those from GBAC hospitals included less papers in English (66.5% vs. 90.0%; OR: 0.22; p < 0.0001), less recent papers (30.1% vs. 34.6%; OR: 0.81; p < 0.0001), more research in humans (83.7% vs. 37.3%; OR: 8.65; p < 0.0001), more randomized controlled trials (8.0% vs. 2.8%; OR: 2,9; p < 0.0001), and more research in children (31.1% vs. 9.2%; OR: 4.44; p < 0.0001). GBAC hospitals contributed with 4.4% of references attributed to Argentina in MEDLINE. References from GBAC hospitals were less recent, and included more randomized controlled trials and research in children.

[Exclusive breastfeeding and disease evolution in hospitalized infants with bronchiolitis]. / Lactancia materna exclusiva y evolución de la enfermedad en lactantes hospitalizados por bronquiolitis.

Bronchiolitis is the main reason for hospitalization in infancy. Breastfeeding is a protective factor aga inst infections, however, although there is evidence that breastfeeding could prevent hospitalizations due to bronchiolitis, its effect in patients already hospitalized because of this disease is less clear. OBJECTIVE: To evaluate if there are differences in the evolution of patients hospitalized due to bronchiolitis fed with exclusive breastfeeding (EBF) vs. breast milk substitutes (BMS). PATIENTS AND METHOD: Prospec tive cohort study. Children hospitalized due to bronchiolitis aged from 1 to 6 months were included. Evolution was compared with respect to days of hospitalization, days of oxygen therapy, requirement of high-flow nasal cannula (HFNC), presence of associated pneumonia, transfer to intensive care, and death. RESULTS: During the study period, 131 infants hospitalized due to bronchiolitis met the selection criteria, 54 were fed with EBF, 29 with BMS, and 48 received mixed feeding. The EBF group required significantly fewer days of oxygen therapy (5.1 ± 2.4 vs. 6.6 ± 3.5; p < 0.02) and hospitalization (7.0 ± 2.4 vs. 8.4 ± 3.6; p < 0.04) than the BMS group. Although males in the BMS group required on average more days of hospitalization and oxygen therapy, this difference was not statistically significant. No deaths were recorded in the groups studied. CONCLUSION: Patients fed with EBF required fewer days of oxygen therapy and hospitalization than those who received BMS.

[Circulation dynamics of respiratory syncytial virus and its relationship with ambient temperature. 25-year series in Buenos Aires] / Dinámica de circulación de virus sincicial respiratorio y su relación con la temperatura ambiental. Serie de 25 años en Buenos Aires.

Objective: To evaluate changes in RSV seasonality in the last 25 years and their correlation with the mean annual temperature. Methods: Cross-sectional study, based on RSV and temperature data from the City of Buenos Aires (1995-2019). For each year, we describe the beginning, end, and duration of the RSV season and the correlation with the mean annual temperature. Results: We identified 10,183 RSV infections. The duration of the RSV season decreased significantly (1995: 29 weeks vs. 2019: 18 weeks; R: 0.6 (p< 0.001)), due to an earlier ending (1995: week 45 vs. 2019: week 34; 0.6 (p<0.001)). No correlation was observed between mean annual temperature and the duration, start, or end of the RSV season. Conclusion: In the last 25 years, the duration of the RSV season has been significantly shortened due to an earlier ending, without correlation with temperature.

Introducción: El cambio climático global podría alterar la circulación del virus sincicial respiratorio (VSR). Objetivo: Evaluar modificaciones en la circulación de VSR en los últimos 25 años y su correlación con la temperatura ambiente. Métodos: Estudio transversal, utilizando registros de VSR y temperatura de la Ciudad de Buenos Aires (1995-2019). Para cada año, describimos inicio, fin y duración de la temporada de VSR y evaluamos su correlación con la temperatura media anual. Resultados: Se identificaron 10183 infecciones por VSR. La duración de la temporada disminuyó significativamente (1995: 29 semanas vs. 2019: 18 semanas; R: 0.6 (p< 0,001)), debido a una finalización más precoz (1995: semana 45 vs. 2019: semana 34; 0,6 (p<0,001)). No se observó correlación entre temperatura media anual y duración, comienzo ni finalización de la temporada de VSR. Conclusión: En los últimos 25 años, la duración de la temporada de VSR se acortó significativamente, sin correlación con la temperatura.

Impacto de la contaminación ambiental en las consultas por enfermedad respiratoria en niños menores de 2 años.

Introducción: La contaminación del aire incrementaría el riesgo de infección respiratoria aguda (IRA) en pediatría. Objetivo: evaluar el impacto de la contaminación del aire en las consultas por IRA realizadas en efectores del Gobierno de la Ciudad de Buenos Aires. Método: estudio ecológico, de series temporales. Fuentes de información: Agencia de Protección Ambiental, Servicio Meteorológico Nacional e Historia de Salud Integral del Sistema de Gestión Hospitalaria. Población: Pacientes menores de 2 años que consultaron por IRA a un efector del GCBA y que residían en una comuna con monitoreo ambiental continuo, durante el 2018. Variables de predicción: Niveles diarios de CO, NO2, PM10 de las estaciones de monitoreo ambiental continuo de la Ciudad Autónoma de Buenos Aires. Variables de resultado: número de consultas totales y por IRA. Variables a controlar: efector, sexo y temperatura media. Se construyó una definición operativa para seleccionar en la base de datos a las consultas objeto de estudio. Resultados: Se registraron 80.287 consultas, 24.847 por IRA (30%). Las consultas por IRA tuvieron correlación positiva en la estación "Córdoba" con el N2O (RR: 1,13 [1,00-1,28]). El número de consultas por IRA en los meses fríos fue mayor que en los cálidos (19,9% vs 11,9%; RR:1,67 [1,61-1,72]). Conclusión: Los valores promedios de PM10 y N2O muestran correlación con el número de las consultas totales y por infección respiratoria aguda, respectivamente. Las consultas se incrementaron durante el invierno.