This is the first prospective multicenter study confirming the hypothesis that children with clinically relevant NMI face an increased risk for severe RSV-disease. It seems reasonable to include NMI as a cofactor into the decision algorithm of passive immunization.

Drug delivery to brain tumors has been a controversial subject. Some believe the blood-brain barrier is not important, while others believe it is the major obstacle in treatment and have devised innovative approaches to circumvent it. These approaches can be divided into two categories: those that attempt to increase drug delivery of intravascularly administered drugs by manipulating either the drugs or capillary permeability, and those that attempt to increase drug delivery by local administration. Several strategies have been developed to increase the fraction of intravascular drug reaching the tumor, including intraarterial administration, barrier disruption, new ways of packaging drugs, and, most recently, inhibiting drug ef ux from tumor. When given intravascularly, all drugs have a common drawback: the body acts as a sink, and, even in the best situations, only a small fraction of administered drug actually reaches the tumor. A consequence is that systemic toxicity is usually the dose-limiting factor. When given locally, such as into the cerebrospinal uid or directly into the tumor, 100% of an administered dose is delivered to the target site. However, local delivery is associated with variable and unpredictable spatial distribution and variation in drug concentration. The major dose-limiting factor of most local delivery methods will be neurotoxicity. The relative advantages and disadvantages of the different methods of circumventing the blood-brain barrier are presented in this review, and special attention is given to convection-enhanced delivery, which has particular promise for the local delivery of large therapeutic agents such as monoclonal antibodies, antisense oligonucleotides, or viral vectors. Neuro-Oncology 2, 45-59, 2000 (Posted to Neuro-Oncology [serial online], Doc. 99-30, December 14, 1999 IntroductionThe delivery of drugs to brain tumors has long been a controversial problem. In 1977, Vick et al. wrote in an editorial: "We believe that there is compelling evidence to suggest that the 'blood-brain barrier,' as it is generally conceived, is not one of the factors impeding the success of brain tumor chemotherapy." They went on to say that "dosage, route of administration, tumor cell uptake, metabolic fate within tumor cells, and the washout or sink effect of the extracellular space and CSF are the issues that will have to be studied" (Vick et al., 1977). Some clinicians have agreed with Vick et al. (Donelli et al., 1992;Stewart, 1994); however, on the whole, the belief that the BBB 3 and BTB prevent drugs from reaching brain tumors in suf cient concentrations to kill the tumor cells has motivated numerous attempts to increase the amount of drug that reaches the tumor. Many innovative methods have been used to try to increase drug delivery including, most recently, a method in which drugs are infused directly into brain tumors, a method referred to as convection-enhanced delivery (CED) Laske et al., 1997a;Lieberman et al., 1995). This review Neuro-Oncology n J AN UA RY 2 0 00 45Neuro-Oncology

Objective:Infants with chronic lung disease of infancy (CLDI) are at high risk for severe respiratory syncytial virus (RSV) illness requiring hospitalization. Palivizumab was first licensed in 1998 for the prevention of RSV disease in high-risk infants, including those with CLDI. We performed a retrospective cohort study of all hospitalized children with CLDI aged <2 years between 1998 and 2008 in the USA to determine trends in rates of hospitalizations due to RSV (RSVH) since the launch of palivizumab.Materials and methods:Data from the United States National Hospital Discharge Survey, a multistage systematic survey sample of US hospitals, were assembled. We defined RSVH using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes of 079.6 (RSV), 466.11 (acute bronchiolitis due to RSV), and 480.1 (pneumonia due to RSV). Quarterly rates of RSVH were assessed for children with CLDI (ICD-9-CM code 770.7) and calculated between 1998 and 2008. Because RSV may be miscoded, the analysis was repeated after expanding the definition of RSVH to include all acute bronchitis and acute bronchiolitis (ABH) (ICD-9-CM = 466). Trends were described using linear regression with seasonal indicators included in the model.Results:On average, about 966 RSVH (range 98–1373 RSVH) per year were found for children <2 years with CLDI in the USA between 1998 and 2008. Over the 11-year period, the predicted rate of RSVH statistically significantly decreased by 48% (from 93.78 to 49.06 RSVH per 1 million children) (P = 0.013). Addition of ABH resulted in a nonstatisically significant decrease of 32% over the 10-year period (P = 0.102).Conclusion:These results suggest that there has been a decrease in the rate of RSVH in infants with CLDI between 1998 and 2008. The reasons for this decrease may include improved neonatal intensive care unit and outpatient management of CLDI, and possibly increased use of palivizumab in this high-risk population.

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