ABSTRACT. Objective. Respiratory syncytial virus (RSV) bronchiolitis is a common cause of hospitalizations in children and has been increasingly identified as a risk factor in the development of asthma. Little is known about what determines the severity of RSV bronchiolitis, which may be helpful in the initial assessment of these children.Design. We evaluated a variety of environmental and host factors that may contribute to the severity of RSV bronchiolitis in the RSV Bronchiolitis in Early Life prospective cohort study. Severity of bronchiolitis was based on the quantization of lowest O 2 saturation and the length of stay. These factors included the child's and family's demographics, presence of household allergens (dust mite, cat, dog, and cockroach), peripheral blood eosinophil count, immunoglobulin E level, infant feeding, prior illnesses, exposure to intrauterine and postnatal cigarette smoke, and family history of atopy.Patients. We prospectively enrolled 206 hospitalized infants, all under 12 months old (4.0 ؎ 3.3 months old), with their first episode of severe RSV bronchiolitis (mean O 2 saturation: 91.6 ؎ 7.3%; length of stay: 2.5 ؎ 2.5 days; presence of radiographic opacities: 75%). Patients were excluded for a variety of reasons including previous wheezing, regular use of bronchodilator or antiinflammatory medications, any preexisting lung disease including asthma, chronic lung disease of prematurity/bronchopulmonary dysplasia, or cystic fibrosis; gastroesophageal reflux disease on medical therapy; or congenital anomalies of the chest or lung.Results. Age was found to be a significant factor in the severity of infection. The younger an infant was, the more severe the infection tended to be as measured by the lowest oxygen (O 2 ) saturation. We also found that infants exposed to postnatal cigarette smoke from the mother had a lower O 2 saturation than those not exposed. However, there was no significant difference in RSV bronchiolitis severity between infants exposed only to intrauterine smoke and those infants never exposed to cigarette smoke. Infants with a family history of atopy, especially a maternal history of asthma or hay fever, had a higher O 2 saturation. Although a history of maternal atopy seemed to be protective, there was no association between allergens and bronchiolitis severity, although 25% of households had elevated allergen levels. Black infants demonstrated less severe RSV bronchiolitis than their white counterparts. Multivariate analysis revealed age, race, maternal atopy, and smoking to be associated with severity of RSV bronchiolitis.Conclusion. R espiratory syncytial virus (RSV) infection is very common in early life: Ͼ95% of children have been infected by 2 years of age. RSV infections are responsible for ϳ100 000 hospital admissions in the United States annually, mostly affecting infants. 1 Of RSV-related admissions, 7% to 21% will require ventilatory support because of respiratory insufficiency. 2-4 Therefore, RSV infection imposes a significant burden on children early in ...

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The largest portion of the cost for asthma healthcare is due to hospitalizations. Improved methods of healthcare delivery for patients with asthma are needed to prevent readmissions. From 1996 to 1999, 96 adult subjects (predominantly young African American women) hospitalized with an asthma exacerbation, who had a history of frequent healthcare use, were randomized to an asthma nurse specialist intervention (n ϭ 50) or a usual care group (n ϭ 46) for 6 months. Our aim was to decrease rates of readmissions within 6 months of hospital discharge, to reduce cost, and to improve health-related quality of life. Our results demonstrate a 60% reduction in total hospitalizations (31 readmissions in the intervention group and 71 in the control group, p ϭ 0.04), with no significant change in emergency department visits. Readmissions for asthma were reduced by 54% (21 vs. 42 in the control group; p ϭ 0.04). We found a marked reduction in lost work or school days: 246 versus 1,040 days in the control group (p ϭ 0.02). The intervention resulted in a substantial reduction in direct and indirect healthcare costs, saving $6,462 per patient (p ϭ 0.03). A brief intervention program focusing on high healthcare users with asthma can result in improved asthma control and reduced hospital use with substantial cost savings.

Purpose: FLASH radiotherapy (RT) can potentially reduce normal tissue toxicity while preserving tumoricidal effectiveness to improve the therapeutic ratio. The key of FLASH for sparing normal tissues is to irradiate Accepted Article This article is protected by copyright. All rights reserved tissues with an ultra-high dose rate (i.e., ≥40Gy/s), for which proton RT can be used. However, currently available treatment plan optimization method only optimizes the dose distribution and does not directly optimize the dose rate. The contribution of this work to FLASH proton RT is the development of a novel treatment optimization method, i.e., simultaneous dose and dose rate optimization (SDDRO), to optimize tissue-receiving dose rate distribution as well as dose distribution. Methods: Distinguished from existing methods, SDDRO accounts for dose rate constraint and optimizes dose rate distribution. In terms of mathematical formulation, SDDRO is a constrained optimization problem with dose-volume constraint on dose distribution, minimum dose rate constraint on dose-averaged tissue-receiving dose rates, minimum monitor-unit constraint on spot weight, and maximum intensity constraint on beam intensity. In terms of optimization algorithm, SDDRO is solved by iterative convex relaxation and alternating direction method of multipliers. SDDRO algorithms are presented for both scenarios with either constant or variable beam intensity. Results: SDDRO was compared with intensity modulated proton therapy (IMPT) (dose optimization alone, and no dose rate optimization) using three lung cases. SDDRO substantially improved the dose rate distribution compared to IMPT, e.g., increasing of the region-of-interest (ROI) volume (ROI=CTV_10mm: the ring sandwiched by 10mm outer and inner expansion of CTV boundary) receiving at least 40Gy/s from ~30-50% to at least 98%, and the lung volume receiving at least 40Gy/s from ~30-40% to ~70-90%. Moreover, both dose and dose rate distributions from SDDRO were further considerably improved via the combined use of hypofractionation and multiple beams. Conclusions: We have developed a joint dose and dose rate optimization method for FLASH proton RT, namely SDDRO, which is first-of-its-kind to the best of our knowledge. The results suggest that (1) SDDRO can substantially improve the FLASH-dose-rate coverage (e.g., in terms of dose-rate volume histogram) compared to IMPT for the purpose of normal tissue sparing while preserving the dose distribution and (2) the combination of hypofractionation and multiple beams can further considerably improve the SDDRO plan quality in terms of both dose and dose rate distribution.