Economic return of clinical trials performed under the pediatric exclusivity program.

CONTEXT: In 1997, Congress authorized the US Food and Drug Administration (FDA) to grant 6-month extensions of marketing rights through the Pediatric Exclusivity Program if industry sponsors complete FDA-requested pediatric trials. The program has been praised for creating incentives for studies in children and has been criticized as a "windfall" to the innovator drug industry. This critique has been a substantial part of congressional debate on the program, which is due to expire in 2007. OBJECTIVE: To quantify the economic return to industry for completing pediatric exclusivity trials. DESIGN AND SETTING: A cohort study of programs conducted for pediatric exclusivity. Nine drugs that were granted pediatric exclusivity were selected. From the final study reports submitted to the FDA (2002-2004), key elements of the clinical trial design and study operations were obtained, and the cost of performing each study was estimated and converted into estimates of after-tax cash outflows. Three-year market sales were obtained and converted into estimates of after-tax cash inflows based on 6 months of additional market protection. Net economic return (cash inflows minus outflows) and net return-to-costs ratio (net economic return divided by cash outflows) for each product were then calculated. MAIN OUTCOME MEASURES: Net economic return and net return-to-cost ratio. RESULTS: The indications studied reflect a broad representation of the program: asthma, tumors, attention-deficit/hyperactivity disorder, hypertension, depression/generalized anxiety disorder, diabetes mellitus, gastroesophageal reflux, bacterial infection, and bone mineralization. The distribution of net economic return for 6 months of exclusivity varied substantially among products (net economic return ranged from -$8.9 million to $507.9 million and net return-to-cost ratio ranged from -0.68 to 73.63). CONCLUSIONS: The economic return for pediatric exclusivity is variable. As an incentive to complete much-needed clinical trials in children, pediatric exclusivity can generate lucrative returns or produce more modest returns on investment.

Variation in pediatric traumatic brain injury outcomes in the United States.

OBJECTIVE: To ascertain the degree of variation, by state of hospitalization, in outcomes associated with traumatic brain injury (TBI) in a pediatric population. DESIGN: A retrospective cohort study of pediatric patients admitted to a hospital with a TBI. SETTING: Hospitals from states in the United States that voluntarily participate in the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. PARTICIPANTS: Pediatric (age ≤ 19 y) patients hospitalized for TBI (N=71,476) in the United States during 2001, 2004, 2007, and 2010. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Primary outcome was proportion of patients discharged to rehabilitation after an acute care hospitalization among alive discharges. The secondary outcome was inpatient mortality. RESULTS: The relative risk of discharge to inpatient rehabilitation varied by as much as 3-fold among the states, and the relative risk of inpatient mortality varied by as much as nearly 2-fold. In the United States, approximately 1981 patients could be discharged to inpatient rehabilitation care if the observed variation in outcomes was eliminated. CONCLUSIONS: There was significant variation between states in both rehabilitation discharge and inpatient mortality after adjusting for variables known to affect each outcome. Future efforts should be focused on identifying the cause of this state-to-state variation, its relationship to patient outcome, and standardizing treatment across the United States.

Vascular access, fluid resuscitation, and blood transfusion in pediatric trauma.

Trauma care in the general population has largely become protocol-driven, with an emphasis on fast and efficient treatment, good team communication at all levels of care including prehospital care, initial resuscitation, intensive care, and rehabilitation. Most available literature on trauma care has focused on adults, allowing the potential to apply concepts from adult care to pediatric care. But there remain issues that will always be specific to pediatric patients that may not translate from adults. Several new devices such as intraosseous (IO) needle systems and techniques such as ultrasonography to cannulate central and peripheral veins have become available for integration into our pre-existing trauma care system for children. This review will focus specifically on the latest techniques and evidence available for establishing intravenous access, rational approaches to fluid resuscitation, and blood product transfusion in the pediatric trauma patient.

Acquired epidermodysplasia verruciformis syndrome in HIV-infected pediatric patients: Prospective treatment trial with topical glycolic acid and human papillomavirus genotype characterization

SCOPUS: ar.j

The biocompatibility of resin-modified glass-ionomer cements for dentistry

OBJECTIVES: The biological effects of resin-modified glass-ionomer cements as used in clinical dentistry are described, and the literature reviewed on this topic. METHODS: Information on resin-modified glass-ionomers and on 2-hydroxyethyl methacrylate (HEMA), the most damaging substance released by these materials, has been collected from over 50 published papers. These were mainly identified through Scopus. RESULTS: HEMA is known to be released from these materials and has a variety of damaging biological properties, ranging from pulpal inflammation to allergic contact dermatitis. These are therefore potential hazards from resin-modified glass-ionomers. However, clinical results with these materials that have been reported to date are generally positive. CONCLUSIONS/SIGNIFICANCE: Resin-modified glass-ionomers cannot be considered biocompatible to nearly the same extent as conventional glass-ionomers. Care needs to be taken with regard to their use in dentistry and, in particular, dental personnel may be at risk from adverse effects such as contact dermatitis and other immunological responses.

Water sorption/desorption in polyacid-modified composite resins for dentistry

The water sorption and desorption behaviour of three commercial polyacid-modified composite resins used in clinical dentistry have been studied in detail. Cured specimens of each material were subjected to two successive water uptake cycles in an atmosphere of 93% relative humidity, with one intervening desorption cycle in a desiccating atmosphere over concentrated sulfuric acid. Specimens were found to absorb and desorb water according Fick's law until Mt/M(infinity) values of approximately 0.5. Diffusion rates for uptake varied between cycles, ranging from 2.37-4.53 x 10(-9 )cm(2) s(-1) for 1st cycle to 0.85-2.72 x 10(-8 )cm(2 )s(-1) for 2nd cycle. Desorption rates were similar to those for 2nd cycle sorption, and ranged from 0.86 to 5.47 x 10(-8 )cm(2 )s(-1). Equilibration times for 1st cycle water uptake were greater than for 2nd cycle sorption and for desorption and overall the behaviour of polyacid-modified composites in a high humidity atmosphere was similar to that of conventional composites in water. It is concluded that the hydrophilic components of the former do not bring about an enhanced rate of water transport.

Polyacid-modified composite resins ("compomers") and their use in clinical dentistry

OBJECTIVES: This paper describes the chemistry and properties of polyacid-modified composite resins ("compomers") designed for use in clinical dentistry, and reviews the literature in this area. METHODS: Information has been obtained from over 50 published articles appearing in the dental and biomaterials literature, with studies being principally identified through MedLine. RESULTS: Published work shows that polyacid-modified composite resins constitute a discrete class of polymeric repair material for use in dentistry. Their distinction is that they contain hydrophilic components, and these cause water to be drawn into the material following cure. This triggers an acid-base reaction, and gives the materials certain clinically-desirable properties (fluoride release, buffering capability) that are also associated with glass-ionomer cements. The water uptake leads to a decline in certain, though not all, physical properties. However, clinical studies have shown these materials to perform acceptably in a variety of applications (Class I, Class II and Class V cavities, as fissure sealants and as orthodontic band cements), especially in children's teeth. CONCLUSIONS/SIGNIFICANCE: Polyacid-modified composite resins constitute a versatile class of dental repair material, whose bioactivity confers clinical advantages, and which are particularly useful in children's dentistry.