The application of population pharmacokinetic analysis to large scale clinical efficacy trials

Summary Results have been presented that demonstrate the ability to conduct population pharmacokinetic analysis as a component of clinical efficacy and safety trials. This method of analysis offers the potential to determine the pharmacokinetics of a drug in the actual patients receiving medication and to evaluate relationships between pharmacokinetics and drug action. However, active involvement in the protocol design, and data collection process are required to ensure the quality of the resultant data set.     

Economic evaluation of treatments for respiratory disease

Considerable quantities of health service resources are being devoted to tackling the problems posed by respiratory diseases and this can be expected to continue as the prevalence of such diseases increases. This paper provides an assessment of the most efficient use of these healthcare resources by reviewing the literature on economic evaluation relating to interventions in the field of respiratory medicine. Currently, this literature largely comprises cost-minimisation studies of both management and educational interventions. Asthma educational interventions, whether targeted at adults or children, appear to be effective in improving patient self-management and adherence to medications, and appear to be associated with a lower overall use of healthcare resources. In terms of management interventions the overall picture is rather less clear although there is some support for the greater efficiency of patient administration of beta-adrenergic agonists by metered dose inhalers over therapist-administered up-draft nebulisation. Two features of respiratory disease make evaluation in this field somewhat unusual: there are alternative methods of delivering therapy to patients, which makes patient compliance an important issue, and since most respiratory diseases are chronic conditions the long-term effectiveness of interventions must be assessed. The scarcity of cost-effectiveness and cost-utility studies in this field may, in part, reflect the difficulties of measuring outcomes in respiratory disease.     

The cellular basis of delirium and its relevance to age-related disorders including Alzheimer's disease.

A wide variety of conditions lead to delirium (i.e., metabolic encephalopathies) in human beings and animals. Despite the varied etiology the clinical consequences are relatively stereotyped which suggests that the diverse insults that cause delirium may act by common metabolic and cellular "final pathways." Related molecular and cellular mechanisms may be involved in aging and Alzheimer's disease, conditions that predispose to the development of delirium. Animal models of delirium better reflect age-related disorders such as Alzheimer's disease than those that impair a single neurotransmitter system such as the cholinergic system; the metabolic encephalopathies produce global cognitive disturbance, which is more typical of these disorders. Thus, research related to delirium has far-reaching implications for normal and abnormal brain function.     

Transparent blocks—an aid in simulation

The use of standard cutouts made of pressed wood¹ and lead solder is advocated for treatment simulation of blocked fields. The advantages offered are the ability to see “through” the block and the capability of planning simple or complex blocking within the limits of existing lead block shapes.     

Recognition of Crohn Disease on Incidental Gastric Biopsy in Childhood

The role of gastric biopsy in the diagnosis of Crohn disease (CD) in the pediatric population has not been well described. We assessed the use of gastric biopsies in the diagnosis of CD using specific histopathologic parameters: granulomata, focal gland injury with neutrophils (glandulitis or glandular abscesses), and/or focal concomitant eosinophilic infiltrates. Multiple (438) consecutive pediatric biopsies with inflammation spanning a 5-year period were identified from archival material in patients ages 2 months to 16 years. A total of 56 CD cases were confirmed using colon biopsies and clinical and radiologic data as the gold standards of diagnosis. Review of hematoxylin and eosin (H&E) slides and Diff-Quik stained slides (negative for Helicobacter pylori) isolated 53 cases which suggested CD on gastric biopsy: 20 cases with granulomata, 14 cases with focal glandulitis and glandular abscesses, and 19 cases of focal glandulitis/glandular abscesses with eosinophilic infiltrates. Seventy-seven percent (43/56) were correctly identified as patients with CD. Twenty-three percent (13/56) of CD cases were not identified primarily because of concurrent H. pylori infection identified on Diff-Quik stain with a superimposed nonspecific diffuse gastritis. The use of Diff-Quik stain to identify H. pylori cases after all other factors are considered was significant (P = 0.0145); a negative stain, combined with the identified histopathologic features indicative of CD, significantly increased the accuracy of CD diagnosis. CD was mimicked by other gastric granulomatous diseases (actinomyces, 1 case; chronic granulomatous disease of childhood, 1 case). Gastric biopsy can be used to identify or support the diagnosis of CD in children in the appropriate clinicopathologic setting.     

Classic Adamantinoma with Osteofibrous Dysplasia-like Foci and Secondary Aneurysmal Bone Cyst

Adamantinoma, a rare bone lesion of the tibia and fibula, has two distinct variants, classic adamantinoma and osteofibrous dysplasia-like adamantinoma. Composite lesions have not been described. Aneurysmal bone cyst is a benign cystic lesion which may also occur in the tibia and fibula. We report an unusual case of classic adamantinoma with osteofibrous dysplasia-like areas and foci of secondary aneurysmal bone cyst with prominent giant cells. A lesion was diagnosed in a 17-year-old girl with a 14-year history of a slowly enlarging left tibial mass and increasing deformity. Pathologically, the predominant pattern was classic adamantinoma, with minor foci of osteofibrous dysplasia-like adamantinoma and areas of secondary aneurysmal bone cyst with abundant multinucleated giant cells. We report the clinical, radiologic, and pathologic features of this case, and summarize lesions associated with secondary aneurysmal bone cyst. To our knowledge, the association of adamantinoma with secondary aneurysmal bone cyst has not been previously reported.