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Objectives: Extubation failure (EF) in PICU patients is reintubation within 48, 72, or 96 hours of planned extubation (EF48, EF72, and EF96, respectively). Standardized sedation protocols, extubation readiness testing, and noninvasive respiratory support are used to improve efficient liberation from mechanical ventilation (MV). We therefore aimed to review EF rates, time to failure, and the use of noninvasive respiratory support after extubation, 2017-2021., Design: Retrospective analysis of patients admitted to PICUs contributing to the Virtual Pediatric Systems (VPS, LLC) database, 2017-2021., Setting: One hundred thirty-six participating PICUs., Patients: All patients admitted to participating PICUs between January 1, 2017, and December 31, 2021, who had MV and met inclusion criteria for planned extubation., Interventions: None., Measurements and Main Results: There were 111,229 planned extubations with 5,143 reintubations within 48 hours. The EF48, EF72, and EF96 rates were 4.6%, 5.3%, and 5.8%, respectively. Higher rates of EF were associated with age younger than 6 months, underlying genetic conditions, medical comorbidities, or cardiac surgery. Failed extubation was also associated with higher Pediatric Risk of Mortality III scores, longer duration of MV, and longer PICU and hospital lengths of stay. From 2017 to 2021, there was an increase in the use of high-flow nasal cannula oxygen therapy after extubation from 16.6% to 20.2%., Conclusions: In the VPS 2017-2021 dataset, we have found that the overall EF rates (EF48-EF96) have improved over this 5-year period. We are not able to assess the clinical benefit of this change, but it is evident that over the same period, there has been a concomitant increase in the use of postextubation noninvasive respiratory support. Further work is needed to look at the interaction of these effects in contemporary PICU practice., Competing Interests: Drs. Soto-Campos, Palumbo, and Rice received funding from Virtual Pediatric Systems, LLC. Drs. Soto-Campos and Palumbo disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: This study sought to estimate the overall cumulative incidence and odds of Hospital-acquired venous thromboembolism (VTE) among critically ill children with and without exposure to invasive ventilation. In doing so, we also aimed to describe the temporal relationship between invasive ventilation and hospital-acquired VTE development., Methods: We performed a retrospective cohort study using Virtual Pediatric Systems (VPS) data from 142 North American pediatric ICUs among children < 18 y of age from January 1, 2016-December 31, 2022. After exclusion criteria were applied, cohorts were identified by presence of invasive ventilation exposure. The primary outcome was cumulative incidence of hospital-acquired VTE, defined as limb/neck deep venous thrombosis or pulmonary embolism. Multivariate logistic regression was used to determine whether invasive ventilation was an independent risk factor for hospital-acquired VTE development., Results: Of 691,118 children studied, 86,922 (12.4%) underwent invasive ventilation. The cumulative incidence of hospital-acquired VTE for those who received invasive ventilation was 1.9% and 0.12% for those who did not ( P < .001). The median time to hospital-acquired VTE after endotracheal intubation was 6 (interquartile range 3-14) d. In multivariate models, invasive ventilation exposure and duration were each independently associated with development of hospital-acquired VTE (adjusted odds ratio 1.64 [95% CI 1.42-1.86], P < .001; and adjusted odds ratio 1.03 [95% CI 1.02-1.03], P < .001, respectively)., Conclusions: In this multi-center retrospective review from the VPS registry, invasive ventilation exposure and duration were independent risk factors for hospital-acquired VTE among critically ill children. Children undergoing invasive ventilation represent an important target population for risk-stratified thromboprophylaxis trials., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

The concept of "remission" in asthma has been around for a long time and it has been a controversial topic. Despite the attempts of some studies to characterize this entity, the discussion continues. In the case of asthma there is still no clear definition, either in terms of its meaning or the parameters that should be included or whether it should be divided into clinical or complete remission. To help defining these controversial concepts, SEPAR has advocated the multidisciplinary working group REMAS (REMission in ASthma). Following the Delphi methodology and with the involvement of more than 120 specialists in asthma management, this group has arrived at a consensus on the definitions of remission in asthma and establishing the criteria and characteristics that will be of use in future studies evaluating the efficacy or effectiveness of treatments., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: The use of monoclonal antibody (mAb)-based therapies is becoming the new standard of care for severe uncontrolled asthma (SUA). Even though patients may qualify for one or more of these targeted treatments, based on different clinical criteria, a global vision of mAb prescription management in a large sample of hospitals is not well characterised in Spain.The objective was to give a global vision of mAb prescription management in a large sample of hospitals in Spain., Materials and Methods: We used an aggregate data survey method to interview pulmonology specialists in a large sample of Spanish centres (90). The following treatment-related information was obtained on patients treated with mAbs: specific mAbs prescribed, treatment interruption, switch and restart and the reasons for these treatment changes., Results: mAb prescription was more frequent in females (13.3% females vs 7.4% males; p  < 0.001). There were no differences in prevalence by hospital complexity level. In contrast, there were differences by geographical area. Omalizumab was the most prescribed mAb (6.2%), followed by mepolizumab (2.9%). Discontinuation of Omalizumab (due to a lack of effectivity) and switches from this mAb to mepolizumab were more frequent. Very few restarts to the first treatment were observed after a switch from ≥2 mAbs., Conclusions: Omalizumab appeared as the most prescribed mAb in SUA but was also the most withdrawn; a specific and objective characterisation of patients with SUA, along with asthma phenotyping, and together with further evaluation of safety and effectiveness profiles, will lead to future progress in the management of SUA with mAbs., (© 2023 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Background: Monoclonal antibodies (mABs) have become available to treat more efficiently patients with severe uncontrolled asthma (SUA). However, the use of mABs is lower than expected given the prevalence of SUA, with significant disparities in the use of these treatments., Objective: To evaluate the proportion of patients with SUA treated with mABs in Spain, and to analyze some of the factors that could determine these prescription patterns., Methods: An analysis was performed on the data provided from the Hospitals National Health System (NHS) 2018 catalogue where Chest Diseases Department and a Hospital Pharmacy were available. Random sampling was performed to determine the sample size, stratifying proportionally by geographic area and hospital level. Characteristics of the participating sites, as well as the prescribing of mABs were collected, which included geographic area, hospital levels, prescribing medical specialities, types of clinics, and mABs prescribed., Results: Data from 90 hospitals were analyzed (Response rate 64.3%). Level 4 hospitals, the Canary Islands geographical area, and the presence of a high complexity Asthma Healthcare Unit (ACU) were associated with a higher probability that the SUA was treated with mABs., Conclusion: The map of the prescribing of mABs for SUA in Spain shows a significant variation by geographic area, hospital level, type of clinic, and the accreditation level of the ACUs. At the current time, there appears to be significant under-prescribing of these treatments.

Severe asthma is a heterogeneous syndrome with several clinical variants and often represents a complex disease requiring a specialized and multidisciplinary approach, as well as the use of multiple drugs. The prevalence of severe asthma varies from one country to another, and it is estimated that 50% of these patients present a poor control of their disease. For the best management of the patient, it is necessary a correct diagnosis, an adequate follow-up and undoubtedly to offer the best available treatment, including biologic treatments with monoclonal antibodies. With this objective, this consensus process was born, which began in its first version in 2018, whose goal is to offer the patient the best possible management of their disease in order to minimize their symptomatology. For this 2020 consensus update, a literature review was conducted by the authors. Subsequently, through a two-round interactive Delphi process, a broad panel of asthma experts from SEPAR and the regional pulmonology societies proposed the recommendations and conclusions contained in this document., (© 2022 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Objective: To evaluate the relationship between pediatric intensive care unit (PICU) severity-adjusted length of stay (LOS) and 24-h unplanned readmission rate., Data Source: Data were obtained from a 10-year cohort from 2009 to 2018 from the Virtual Pediatric Systems (VPS, LLC) database., Study Design: In this retrospective study, standardized LOS ratio was computed for each PICU as the ratio of the sum of actual LOS divided by the predicted LOS for each PICU using VPS predictive LOS model. Correlation between standardized LOS ratios and 24-h unplanned readmission rates were computed using Pearson's correlation coefficient., Principal Findings: There was practically no relationship between standardized LOS ratio and 24-h readmission rate (R 2  = 0.05)., Data Collection/extraction Methods: Not Applicable., Conclusions: Severity-adjusted LOS has no relationship with 24-h unplanned readmission rate. These findings suggest that the relationship between PICU severity-adjusted LOS and 24-h unplanned readmission rate should not be used as a balancing quality measure., (© 2022 Health Research and Educational Trust.)

Background: Reslizumab is an anti-interleukin 5 monoclonal antibody that has demonstrated to reduce the risk of severe exacerbations and to improve symptoms, lung function, and quality of life in randomized controlled trials that included patients with severe eosinophilic uncontrolled asthma (SEUA) and a history of severe exacerbations., Objective: The aim of the present study was to evaluate the effectiveness of add-on reslizumab in a cohort of patients with SEUA under real-life conditions., Methods: This was a multi-centre, retrospective, real-life study that included subjects with SEUA treated with reslizumab in 44 asthma units throughout Spain. Eligible patients were those who had received at least one dose of reslizumab as part of normal clinical practice. The primary endpoint was complete asthma control at 52 weeks, defined as absence of severe exacerbations, ACT ≥20 and no maintenance oral corticosteroids (OCS). Demographic, clinical, and functional data were collected at baseline (T0), after four to six months (T1); after 12 months (T2) and beyond 12 months of therapy (T3)., Results: Treatment with reslizumab achieved complete asthma control in 40% of the 208 included SEUA patients and led to a significant reduction in exacerbations (from 3.0; IQR: 2.0-4.0 at V0 to 0.0; IQR: 0.0-0.0 at V2), maintenance OCS use (from 54.8% (95% CI: 48.0-61.6 at T0 to 18.5% (95% CI: 12.5-24.5 at T2) and a meaningful improvement in symptoms in the entire treated population: ACT increased from 12.8 ± 4.5 at V0 to 20.0 ± 5.1 at V2 (p < 0.001). Most of the improvement achieved at 12 months was obtained at 4-6 months. The retention (continuation) rate of reslizumab was 75% through 2 years (95CI%: 1.9-2.1). Overall, reslizumab showed an adequate safety profile., Conclusion: Reslizumab is an effective therapy for SEUA with adequate safety profile in real-life conditions., Competing Interests: Luis A Pérez de Llano declares to have received grants and/or fees for consultancy or speeches from Novartis, Astra-Zeneca, GSK, Teva, Boehringer-Ingelheim, Chiesi, Sanofi, MSD, FAES, Techdow Pharma, Leo Pharma, Gebro, Gilead, Menarini, Mundipharma, and Esteve. Borja G Cosío declares he has received speaking or advisory fees, or economic aid to attend congresses from Astra-Zeneca, GSK, Novartis, Chiesi, Mundipharma, Menarini, Sanofi, TEVA, Boehringer-Ingelheim, and Rovi. Ignacio Lobato Astiárraga declares he has received speaker fees, consulting fees from Astra-Zeneca, GlaxoSmithKline, Novartis, Chiesi, Sanofi, Boehringer, SEPAR, and Teva. Gregorio Soto Campos declares he has received speaker fees, consulting fees from ALK, Astra-Zeneca, Bial, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi, and Teva. Miguel Ángel Tejedor Alonso declares that there is no relevant conflict of interest. Nuria Marina Malanda declares she has received speaker fees, consulting fees from Astra-Zeneca, Sanofi, GlaxoSmithKline, Chiesi, Pfizer, Novartis, and Teva. Alicia Padilla Galo declares she has received speaking or advisory fees, or economic aid to attend congresses from Novartis, Teva, Astra-Zeneca, GlaxoSmithKline, and ALK. Isabel Urrutia Landa declares she has received speaking or advisory fees, or economic aid to attend congresses from Astra-Zeneca, Sanofi, GlaxoSmithKline, Chiesi, Bial Aristegui, Teva, Novartis, ALK, Boehringer-Ingelheim, and Mundi Pharma. Francisco Javier Michel de la Rosa has received speaker fees and/or consulting fees and/or support attend Congresses from the following: Astra-Zeneca, Boehringer-Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Grifols, Menarini, Novartis, Sanofi Aventis, and Teva. Ismael García-Moguel declares he has received speaking or advisory fees, or economic aid to attend congresses from Astra-Zeneca, Sanofi, GlaxoSmithKline, Chiesi, Mundipharma, Allergy therapeutics, Novartis, Stallergenes Greer, and Teva. The authors report no other conflicts of interest in this work., (© 2022 Pérez de Llano et al.)

Objectives: Firearm-related injury is the second leading cause of injury and death for children 1-18 years old in United States. The objective of our study was to analyze the outcomes of children admitted to the PICU with firearm injuries., Design: Retrospective study., Setting: PICUs in United States contributing data to Virtual Pediatric Systems, LLC, from January 2009 to December 2017., Patients: Children age 1 month to 18 years old admitted to the PICU with firearm injury, identified by external cause of injury E-codes and International Classification of Diseases, 9th Edition, and International Classification of Diseases, 10th Edition, codes were identified., Interventions: None., Measurements and Main Results: There were 1,447 cases identified of which 175 (12%) died in the PICU. Unintentional firearm injury (67.7%) and assault with a firearm injury (20%) comprised 90% of the cases. Males comprised 78% of the cohort (1,122) and race distribution included 45% Black (646), 27% White (390), and 12% Hispanic (178). Among the children who died in the PICU, 55% were 13-18 years old. Children attempting suicide with a firearm were more likely to die in the PICU as compared to the other causes of firearm injury. Based on their Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores at discharge, there is high morbidity in children with firearm injuries., Conclusions: Mortality rate of children with firearm injury admitted to the PICU is high. Children admitted to the PICU with suicide attempt with a firearm carried the highest mortality. Further studies may help further define the epidemiology of firearm injuries in children and plan interventions to minimize these unnecessary deaths., Competing Interests: Dr. Soto-Campos received funding from Virtual Pediatric Systems (VPS), LLC; he disclosed that he is an employee of VPS, LLC. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To investigate the change in rate of invasive procedures (endotracheal intubation, central venous catheters, arterial catheters, and peripheral inserted central venous catheters) performed in PICUs per admission over time. Secondarily, to investigate the change in type of respiratory support over time., Design: Retrospective study of prospectively collected data using the Virtual Pediatric Systems (VPS; LLC, Los Angeles, CA) database., Setting: North American PICUs., Patients: Patients admitted from January 2009 to December 2017., Interventions: None., Measurements and Main Results: There were 902,624 admissions from 161 PICUs included in the analysis. Since 2009, there has been a decrease in rate of endotracheal intubations, central venous catheters placed, and arterial catheters placed and an increase in the rate of peripheral inserted central venous catheter insertion per admission over time after controlling for severity of illness and unit level effects. As compared to 2009, the incident rate ratio for 2017 for endotracheal intubation was 0.90 (95% CI, 0.83-0.98; p = 0.017), for central venous line placement 0.69 (0.63-0.74; p < 0.001), for arterial catheter insertion 0.85 (0.79-0.92; p < 0.001), and for peripheral inserted central venous catheter placement 1.14 (1.03-1.26; p = 0.013). Over this time period, in a subgroup with available data, there was a decrease in the rate of invasive mechanical ventilation and an increase in the rate of noninvasive respiratory support (bilevel positive airway pressure/continuous positive airway pressure and high-flow nasal oxygen) per admission., Conclusions: Over 9 years across multiple North American PICUs, the rate of endotracheal intubations, central catheter, and arterial catheter insertions per admission has decreased. The use of invasive mechanical ventilation has decreased with an increase in noninvasive respiratory support. These data support efforts to improve exposure to invasive procedures in training and structured systems to evaluate continued competency., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Introduction: A Spanish real-world study in patients with severe persistent asthma who achieved asthma control after a one-year treatment with omalizumab highlighted the phenotypic heterogeneity of these patients (FENOMA study). In this subanalysis, we describe the clinical improvement in patients with severe allergic asthma in this study (positive skin test and IgE level 30-1500 IU/mL); n=240., Patients and Methods: FENOMA was an observational, multicentre, retrospective study in 345 patients achieving asthma control according to Spanish guidelines (GEMA). Baseline demographic and asthma-related characteristics were collected. Outcomes analyzed were those included in asthma control definition plus changes in background treatments and in blood eosinophil count (%) and exhaled nitric oxide fraction [FeNO]., Results: At baseline, patients were aged 45.4±15.0 years; 67% were women. Median (Q1;Q3) IgE levels were 302.5 (154.0; 553.5) IU/mL. After one-year treatment with omalizumab: 43.3% of patients had daytime symptoms vs 97.7% before treatment and 49.6% stopped taking oral corticosteroids. FEV 1 increased a median of 12.0 (4.0; 23.0)%; P <0.0001. The number of non-severe asthma exacerbations decreased a median of -4.0 (-7.0; 2.0); P <0.0001. Median unplanned visits to primary care or specialists and days of school/workplace absenteeism decreased from 4.9 (2.0; 6.0), 1.0 (0.0; 3.0) and 0.0 (0.0; 14.0) to 0.0 (0.0; 1.0), 0.0 (0.0; 0.0) and 0.0 (0.0; 0.0), respectively. Median eosinophil blood count and FeNO decreased from 5.0 (3:0; 8.0)% to 3.0 (2.0; 5.5)% and from 36.0 (23:0; 53.0) ppb to 20.0 (13.0; 34.0) ppb, respectively., Conclusion: This study highlights the asthma control achieved by patients with severe allergic asthma treated with omalizumab, with relevant benefits on the burden of the disease both on patients and the healthcare system., Competing Interests: S Cabrejos reports personal fees from Novartis, GSK, ALK Abelló, Stallergenes, HAL Allergy, Astra Zeneca, Inmunotek, and Diater collaborations. A Moreira is currently a Medical Advisor at Novartis Farmacéutica S.A. A Ramirez is currently a Medical Communication Advisor at Novartis Farmacéutica S.A. S Quirce reports personal fees and non-financial supports from ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Novartis, Sanofi, and Teva (for the organization of educational events, advisory boards, and received speakers’ honoraria). G Soto Campos reports personal fees (advisory boards and speakers´ honoraria) from AstraZeneca, Boehringer Ingelheim, Novartis, GSK, Chiesi, Bial and Menarini. I Dávila reports payment for lectures including service on speakers´ bureaus from ALK-Abelló, Astra-Zeneca, Chiesi, Diater, GSK, Leti, Novartis, Sanofi, Stallergenes, Teva; consultancy from Allergy therapeutics, ALK-Abello, Astra-Zeneca, GSK, Merck, Novartis, Sanofi, and Stallergenes; grants from Merck and Thermo Fisher diagnostics. P Campo reports speaker fees from Bial and Novartis; advisory boards for Astra-Zeneca and GSK. The authors report no other conflicts of interest in this work., (© 2020 Cabrejos et al.)

Background: The appropriate identification of asthma phenotypes of responders to omalizumab would optimize the selection of treatment., Objective: To describe the most frequent clinical phenotypes in patients with severe asthma responding to omalizumab and their clinical and pulmonary function improvement., Methods: This was an observational, retrospective, multicenter study. Adult patients with severe asthma, who achieved good control after the first year of treatment with omalizumab were included. Omalizumab was prescribed according to clinical routine practice. Responders were assigned to one pre-established phenotype based on the most predominant one before they had started treatment with omalizumab, all according to the physician's criteria. Data about asthma symptoms, number of non-severe asthma exacerbations, medication intake (inhaled and oral corticosteroids and rescue medication), lung function, high fractional exhaled nitric oxide (FeNO) and peripheral eosinophils counts were recorded., Results: Among the 345 patients included, the main phenotypes were severe asthma with frequent exacerbations (29.9%), early-onset allergic asthma (23.8%), severe steroid-dependent asthma (18.8%), and severe eosinophilic asthma (13.6%). Clinical and respiratory changes observed after first year of treatment with omalizumab included: reduction in asthma symptoms, reduction in the use and dose of corticosteroids and need for rescue therapy, improvement of pulmonary function, reduction in the number of episodes of non-severe asthma exacerbations regardless of the duration of severe disease since the diagnosis. Increased blood levels of peripheral eosinophils and high FeNO levels were found at baseline., Conclusion: Several heterogeneous severe asthma phenotypes were observed as good responders to omalizumab., (Copyright © 2019. Published by Elsevier Ltd.)

Objectives: The use of mortality prediction scores in clinical trials in the PICU is essential for comparing patient groups. Because of the decline in PICU mortality over the last decades, leading to a shift toward later deaths, recent trials use 90-day mortality as primary outcome for estimating mortality and survival more accurately. This study assessed and compared the performance of two frequently used PICU mortality prediction scores for prediction of PICU and 90-day mortality., Design: This secondary analysis of the randomized controlled Early versus Late Parenteral Nutrition in the Pediatric Intensive Care Unit trial compared the discrimination (area under the receiver operating characteristic curve) and calibration of the Pediatric Index of Mortality 3 and the Pediatric Risk of Mortality III scores for prediction of PICU and 90-day mortality., Setting: Three participating PICUs within academic hospitals in Belgium, the Netherlands, and Canada., Patients: One-thousand four-hundred twenty-eight critically ill patients 0-17 years old., Interventions: None., Measurements and Main Results: Although Pediatric Index of Mortality 3 only includes information available at the time of PICU admission, thus before any intervention in the PICU, it showed good discrimination (area under the receiver operating characteristic curve, 0.894; 95% CI, 0.892-0.896) and good calibration (no deviation from the diagonal, p = 0.58) for PICU mortality. Pediatric Risk of Mortality III, which involves the worst values for the evaluated variables during the first 24 hours of PICU stay, was statistically more discriminant (area under the receiver operating characteristic curve, 0.920; 95% CI, 0.918-0.921; p = 0.04) but poor in calibration (significant deviation from the diagonal; p = 0.04). Pediatric Index of Mortality 3 and Pediatric Risk of Mortality III discriminated equally well between 90-day mortality and survival (area under the receiver operating characteristic curve, 0.867; 95% CI, 0.866-0.869 and area under the receiver operating characteristic curve, 0.882; 95% CI, 0.880-0.884, respectively, p = 0.77), but Pediatric Risk of Mortality III was not well calibrated (p = 0.04), unlike Pediatric Index of Mortality 3 (p = 0.34)., Conclusions: Pediatric Index of Mortality 3 performed better in calibration for predicting PICU and 90-day mortality than Pediatric Risk of Mortality III and is not influenced by intervention or PICU quality of care. Therefore, Pediatric Index of Mortality 3 seems a better choice for use in clinical trials with 90-day mortality as primary outcome.

Objectives: To determine the relationship between PICU volume and severity-adjusted mortality in a large, national dataset., Design: Retrospective cohort study., Setting: The VPS database (VPS, LLC, Los Angeles, CA), a national multicenter clinical PICU database., Patients: All patients with discharge dates between September 2009 and March 2012 and valid Pediatric Index of Mortality 2 and Pediatric Risk of Mortality III scores, who were not transferred to another ICU and were seen in an ICU that collected at least three quarters of data., Interventions: None., Measurements and Main Results: Anonymized data received included ICU mortality, hospital and patient demographics, and Pediatric Index of Mortality 2 and Pediatric Risk of Mortality III scores. PICU volume/quarter was determined (VPS sites submit data quarterly) per PICU and was divided by 100 to assess the impact per 100 discharges per quarter (volume). A mixed-effects logistic regression model accounting for repeated measures of patients within ICUs was performed to assess the association of volume on severity-adjusted mortality, adjusting for patient and unit characteristics. Multiplicative interactions between volume and severity of illness were also modeled. We analyzed 186,643 patients from 92 PICUs, with an overall ICU mortality rate of 2.6%. Volume ranged from 0.24 to 8.89 per ICU per quarter; the mean volume was 2.61. The mixed-effects logistic regression model found a small but nonlinear relationship between volume and mortality that varied based on the severity of illness. When severity of illness is low, there is no clear relationship between volume and mortality up to a Pediatric Index of Mortality 2 risk of mortality of 10%; for patients with a higher severity of illness, severity of illness-adjusted mortality is directly proportional to a unit's volume., Conclusions: For patients with low severity of illness, ICU volume is not associated with mortality. As patient severity of illness rises, higher volume units have higher severity of illness-adjusted mortality. This may be related to differences in quality of care, issues with unmeasured confounding, or calibration of existing severity of illness scores.

Background: Volumetric capnography dead-space measurements (physiologic dead-space-to-tidal-volume ratio [VD/VT] and alveolar VD/VT) are considered more accurate than the more readily available time-based capnography dead-space measurement (end-tidal alveolar dead-space fraction [AVDSF]). We sought to investigate the correlation between volumetric capnography and time-based capnography dead-space measurements., Methods: This was a single-center prospective cohort study of 65 mechanically ventilated children with arterial lines. Physiologic VD/VT, alveolar VD/VT, and AVDSF were calculated with each arterial blood gas using capnography data., Results: We analyzed 534 arterial blood gases from 65 children (median age 4.9 y, interquartile range 1.7-12.8). The correlation between physiologic VD/VT and AVDSF (r = 0.66, 95% CI 0.59-0.72) was weaker than the correlation between alveolar VD/VT and AVDSF (r = 0.8, 95% CI 0.76-0.85). The correlation between physiologic VD/VT and AVDSF was weaker in children with low PaO2 /FIO2 (< 200 mm Hg), low exhaled VT (< 100 mL), a pulmonary reason for mechanical ventilation, or large airway VD (> 3 mL/kg). All 3 dead-space measurements were highly correlated (r > 0.7) in children without hypoxemia (PaO2 /FIO2 > 300 mm Hg), mechanically ventilated for a neurologic or cardiac reason, or on significant inotropes or vasopressors., Conclusions: In mechanically ventilated children without significant hypoxemia or with cardiac output-related dead-space changes, physiologic VD/VT was highly correlated with AVDSF and alveolar VD/VT. In children with significant hypoxemia, physiologic VD/VT was poorly correlated with AVDSF. Alveolar VD/VT and AVDSF correlated well in most tested circumstances. Therefore, AVDSF may be useful in most children for alveolar dead-space monitoring., (Copyright © 2015 by Daedalus Enterprises.)

Objective: Comparison of clinical outcomes is imperative in the evaluation of healthcare quality. Risk adjustment for children undergoing cardiac surgery poses unique challenges, due to its distinct nature. We developed a risk-adjustment tool specifically focused on critical care mortality for the pediatric cardiac surgical population: the Pediatric Index of Cardiac Surgical Intensive care Mortality score., Design: Retrospective analysis of prospectively collected pediatric critical care data., Setting: Pediatric critical care units in the United States., Patients: Pediatric cardiac intensive care surgical patients., Interventions: Prospectively collected data from consecutive patients admitted to ICUs were obtained from The Virtual PICU System (VPS, LLC, Los Angeles, CA), a national pediatric critical care database. Thirty-two candidate physiologic, demographic, and diagnostic variables were analyzed for inclusion in the development of the Pediatric Index of Cardiac Surgical Intensive care Mortality model. Multivariate logistic regression with stepwise selection was used to develop the model., Measurements and Main Results: A total of 16,574 cardiac surgical patients from the 55 PICUs across the United States were included in the analysis. Thirteen variables remained in the final model, including the validated Society of Thoracic Surgeons-European Association of Cardio-Thoracic Surgery Congenital Heart Surgery Mortality (STAT) score and admission time with respect to cardiac surgery, which identifies whether the patient underwent the index surgical procedure before or after admission to the ICU. Pediatric Index of Cardiac Surgical Intensive Care Mortality (PICSIM) performance was compared with the performance of Pediatric Risk of Mortality-3 and Pediatric Index of Mortality-2 risk of mortality scores, as well as the STAT score and STAT categories by calculating the area under the curve of the receiver operating characteristic from a validation dataset: PICSIM (area under the curve = 0.87) performed better than Pediatric Index of Mortality-2 (area under the curve = 0.81), Pediatric Risk of Mortality-3 (area under the curve = 0.82), STAT score (area under the curve = 0.77), STAT category (area under the curve = 0.75), and Risk Adjustment for Congenital Heart Surgery-1 (area under the curve = 0.74)., Conclusions: This newly developed mortality score, PICSIM, consisting of 13 risk variables encompassing physiology, cardiovascular condition, and time of admission to the ICU showed better discrimination than Pediatric Index of Mortality-2, Pediatric Risk of Mortality-3, and STAT score and category for mortality in a multisite cohort of pediatric cardiac surgical patients. The introduction of the variable "admission time with respect to cardiac surgery" allowed prediction of mortality when patients are admitted to the ICU either before or after the index surgical procedure.

Objective: ICU resources may be overwhelmed by a mass casualty event, triggering a conversion to Crisis Standards of Care in which critical care support is diverted away from patients least likely to benefit, with the goal of improving population survival. We aimed to devise a Crisis Standards of Care triage allocation scheme specifically for children., Design: A triage scheme is proposed in which patients would be divided into those requiring mechanical ventilation at PICU presentation and those not, and then each group would be evaluated for probability of death and for predicted duration of resource consumption, specifically, duration of PICU length of stay and mechanical ventilation. Children will be excluded from PICU admission if their mortality or resource utilization is predicted to exceed predetermined levels ("high risk"), or if they have a low likelihood of requiring ICU support ("low risk"). Children entered into the Virtual PICU Performance Systems database were employed to develop prediction equations to assign children to the exclusion categories using logistic and linear regression. Machine Learning provided an alternative strategy to develop a triage scheme independent from this process., Setting: One hundred ten American PICUs, Subjects: : One hundred fifty thousand records from the Virtual PICU database., Interventions: None., Measurements and Main Results: The prediction equations for probability of death had an area under the receiver operating characteristic curve more than 0.87. The prediction equation for belonging to the low-risk category had lower discrimination. R for the prediction equations for PICU length of stay and days of mechanical ventilation ranged from 0.10 to 0.18. Machine learning recommended initially dividing children into those mechanically ventilated versus those not and had strong predictive power for mortality, thus independently verifying the triage sequence and broadly verifying the algorithm., Conclusion: An evidence-based predictive tool for children is presented to guide resource allocation during Crisis Standards of Care, potentially improving population outcomes by selecting patients likely to benefit from short-duration ICU interventions.

Background: Patients with type 2 diabetes (T2DM) are at risk of long-term vascular complications. In trials, exenatide once weekly (ExQW), a GLP-1R agonist, improved glycemia, weight, blood pressure (BP), and lipids in patients with T2DM. We simulated potential effects of ExQW on vascular complications, survival, and medical costs over 20 years versus standard therapies., Patients and Methods: The Archimedes model was used to assess outcomes for ~25,000 virtual patients with T2DM (NHANES 1999-2006 [metformin ± sulfonylureas, age 57 years, body mass index 33 kg/m(2), weight 94 kg, duration T2DM 9 years, hemoglobin A1c [A1C] 8.1%]). The effects of three treatment strategies were modeled and compared to moderate-adherence insulin therapy: advancement to high-adherence insulin at A1C ≥ 8% (treat to target A1C < 7%) and addition of pioglitazone (PIO) or ExQW from simulation start. ExQW effects on A1C, weight, BP, and lipids were modeled from clinical trial data. Costs, inflated to represent 2010 $US, were derived from Medicare data, Drugstore.com, and publications. As ExQW was investigational, we omitted ExQW, PIO, and insulin pharmacy costs., Results: By year 1, ExQW treatment decreased A1C (~1.5%), weight (~2 kg), and systolic BP (~5 mmHg). PIO and high-adherence insulin decreased A1C by ~1%, increased weight, and did not affect systolic BP. After 20 years, A1C was ~7% with all strategies. ExQW decreased rates of cardiovascular and microvascular complications more than PIO or high-adherence insulin versus moderate-adherence insulin. Over 20 years, ExQW treatment resulted in increased quality-adjusted life-years (QALYs) of ~0.3 years/person and cost savings of $469/life-year versus moderate adherence insulin. For PIO or high-adherence insulin, QALYs were virtually unchanged, and costs/life-year versus moderate-adherence insulin increased by $69 and $87, respectively., Conclusions: This long-term simulation demonstrated that ExQW treatment may decrease rates of cardiovascular and some microvascular complications of T2DM. Increased QALYs, and decreased costs were also projected.

Background: All the community acquired pneumonia followed up in an outpatient clinic were prospectively studied in order to determine: etiology, clinical-radiological characteristics and its progression with diagnostic and therapeutic protocols., Patients and Method: We arranged clinical evaluation protocols, etiological diagnosis by means of serology (in the first visit and three weeks later); and when necessary, by means of fiberbronchoscopy (protected microbiological brush), as well as clinical and radiological progression (up to three visits) after empirical treatment., Results: Initially, 240 patients were included, of which 221 were fully followed up. Etiological diagnosis was obtained in 86 patients (39%). The bacteria most frequently isolated was Coxiella burnetii (12.2%), followed up Mycoplasma pneumoniae and Legionella pneumophila. Two cases of Strepcococus pneumoniae were diagnosed. The most frequent radiological onset was alveolar infiltrate (86%). The initial empiric treatment were macrolids (71%) or second generation cephalosporines (22%). Most patients presented a favourable clinical and radiological progression. Only 2 patients needed admission to the hospital (< 1%)., Conclusions: In community acquired pneumonias studied in our outpatient clinic we found a high number of "atypical" agents. Treatment with macrolids or second generation cephalosporines are appropriate for these patients.

Objective: To study the prevalence os smoking in school children in Sevilla and the influence of personal and social environment on smoking patterns., Methods: This study was part of a preventative anti-smoking campaign in schools. Students filled in anonymous questionnaires based on the World Health Organization survey instrument for population attitudes and habits., Results: We surveyed 3385 students between 10 and 19 years of age at 47 schools in Seville and 28 villages in the surrounding province. Current smoking was reported by 19.1% of the students; slightly more girls (19.8%) than boys (18.3%) smoked. Smoking was related to having an older brother or sister who smoked and particularly to having friends who smoked (OR 20.5). The adolescents reported that parents were less permissive than the rest of their environment. Smokers associated tobacco with values such as independence and freedom; they believed that smoking might have an impact on health, although their conviction was less strong than that of non-smokers, regular smokers had high expectations of continuing., Conclusions: We found a high proportion of smokers among students of both sexes. Starting and continuing to smoke during adolescence is considerably influenced by the social environment of peers and is possibly affected by messages of independence and freedom transmitted through tobacco industry advertising.

Background: The aim of this study was to prospectively evaluate the clinical and gasometric evolution and the side effects of two treatment schedules in the exacerbations of patients with chronic obstructive pulmonary disease (COPD): 500 mg/24 h of azithromycin (AZM) for three days versus 500 mg/12 h of acetyl cefuroxime (ACF) for 10 days., Patients and Methods: Patients were randomized included into each therapeutic schedule. The patients were seen three times (days 1 and 4, and at 15-21 days) to evaluate clinical symptoms scores. Forced spirometry and arterial gasometry were performed the first and the last time the patients were seen. The number of patients requiring admission during follow up and the secondary effects of each antibiotic were quantified., Results: A total de 50 patients were treated with AZM and 51 with ACF. The evolution of the symptoms was similar although with a trend to greater improvement in those treated with AZM. This improvement was significant for the characteristics of expectoration (p < 0.05). Functional and gasometric evolution was similar in the two schedules. Three patients treated with AZM required hospital admission, as did 5 treated with ACF. A greater number of secondary effects were observed in patients treated with ACF (18%) than in those receiving AZM (10%), with gastrointestinal side effects being the most commonly observed., Conclusions: Treatment with short schedule of AZM may have the same activity as longer schedule of ACF, with fewer secondary effects thereby suggesting that AZM may be an effective alternative in the treatment of exacerbations in patients with COPD.