Pediatric obesity: are we under-diagnosing? Assessing pediatric obesity at an urban community health clinic

Pediatric care providers are often discouraged by the scope and magnitude of our current childhood overweight epidemic. Numerous studies have shown the adverse consequences of pediatric obesity, ranging from short-term physical and psychosocial consequences to long-term consequences that manifest in adulthood. In this study we investigated rates of overweight and at-risk for overweight children in a community health center in urban Honolulu, Hawai'i which serves a large multi-cultural and multi-ethnic population with a large presence of Asians and Pacific Islanders. This was done by conducting a chart review of the pediatric patients in the clinic. Twenty-four children had been formally diagnosed and recorded in their charts as obese/overweight during the last 2 years, out of 4,640 pediatric patients seen (less than 0.5%). However, according to this study roughly 140 overweight children are seen monthly at this clinic, indicating a prevalence of more than 50%. Samoan and Micronesian children were found to be primarily impacted.     

Hospitalisation costs of cystic fibrosis

OBJECTIVE: To calculate per-case hospital costs for patients with cystic fibrosis under routine conditions from a healthcare provider's perspective; identify the impact of different cost categories; investigate whether cases with cystic fibrosis can be grouped into homogenous cost groups according to defined severity levels; and determine the value of specific factors as predictors of hospital cost variations. METHODS: All data were collected from cases (n = 131) admitted to an inpatient cystic fibrosis unit under routine conditions during a period of 6 months in 2004. All costs were calculated for the year 2004 and divided into categories with high and low impact on variation in hospitalisation costs between patients. Staff costs for patient care, laboratory costs and drug costs were defined as categories with high impact, thus the individual resource utilisation for each case was measured. Cost categories that were classified as having a low impact were measured as overhead costs. Cases were classified according to two different severity models; within each model, patients were classified according to three severity levels. The diagnosis-related model classifies patients with pulmonary hypertension and global respiratory insufficiency as having severe disease, patients with Pseudomonas aeruginosa as having moderate disease, and patients with no colonisation of the lungs as having mild disease. The lung-function-related model differentiates patients as having mild, moderate and severe disease when patients have forced expiratory volumes in 1 second (FEV(1)) that are > or =70%, between > or =40% and <70%, and <40%, respectively. Analysis of variance tests were performed to investigate the differences of mean costs between the groups. Ordinary least squares regression analysis was used to determine predictors for cost variation. RESULTS: The mean total costs per case were 7326 euro. Almost one-third of the total mean costs were attributable to drug costs (28% of total costs), while shares of staff costs for patient care and laboratory costs (both 9% of total costs) were relatively small. Most of the difference in costs between severity levels was attributable to the variation in overhead costs and drug costs. For both severity models differences in mean total costs of mild and severe cases were statistically significant (p < 0.01 and p < 0.05, respectively) when compared with the mean costs of non-mild and non-severe cases. However, in moderate cases, significant differences compared with cases that were not of moderate severity were only seen for certain cost categories. In the multiple regression model the variables 'diagnosis-related severity' and 'FEV(1)' explained 31% of the variance of 'Ln (total costs per case)' between severity levels (p < or = 0.01). CONCLUSION: This study shows that to a large extent hospitalisation costs for patients with cystic fibrosis vary according to the severity of their disease; drug costs play a major role in these differences. In the light of this variation it seems plausible to create separate reimbursement rates for two or three severity groups. Diagnoses as well as FEV(1) seem suitable criteria for such a classification.     

Human PEPT1 pharmacophore distinguishes between dipeptide transport and binding

The human intestinal oligopeptide transporter (PEPT1) facilitates the absorption of dipeptides, tripeptides, and many peptidomimetic drugs. In this study, a large number of peptides were selected to investigate the structural features required for PEPT1 transport. Binding affinity was determined in a Gly-Sar uptake inhibition assay, whereas functional transport was ranked in a membrane depolarization assay. Although most of the peptides tested could bind to PEPT1, not all were substrates. As expected, single amino acids and tetrapeptides could not bind to or be transported by PEPT1. Dipeptide transport was influenced by charge, hydrophobicity, size, and side chain flexibility. The extent of transport was variable, and unexpectedly, some dipeptides were not substrates of PEPT1. These included dipeptides with two positive charges or extreme bulk in either position 1 or 2. Our results identify key features required for PEPT1 transport in contrast to most previously described pharmacophores, which are based on the inhibition of transport of a known substrate.     

Efficacy and tolerability of capecitabine with weekly paclitaxel for patients with metastatic breast cancer: a phase II report of the SAKK

BACKGROUND: Paclitaxel and capecitabine have proven activity in the treatment of metastatic breast cancer (MBC). Paclitaxel increases the expression of thymidine phosphorylase, the enzyme that activates capecitabine. The purpose of this study was to evaluate the efficacy and tolerability of capecitabine in combination with weekly paclitaxel largely as first-line therapy in patients with MBC. PATIENTS AND METHODS: From April 2002 to September 2004, 19 patients with MBC received oral capecitabine (1,000 mg/m(2) twice daily on days 1-14) plus i.v. paclitaxel (80 mg/m(2) on days 1, 8 and 15) in a 21-day cycle for a maximum of 6 cycles. RESULTS: After a median follow-up of 19.3 months the overall response rate was 63% with 1 complete response (5%) and 11 partial responses (58%). Disease was stabilized in 1 patient (5%) and 3 patients had progressive disease (16%). Three patients were unable to be assessed for response to treatment. Median time to progression was 3.3 months, median time to treatment failure 3.0 months and median overall survival 13.8 months. A substantial number of patients experienced major side effects. The most common treatment-related adverse events were hand-foot syndrome (53%; grade 3: 37%), alopecia (42%; grade 3: 26%), diarrhea (32%; grade 3: 11%) and neurotoxicity (32%; grade 3: 16%). Hematologic toxicities were uncommon. CONCLUSION: The combination of capecitabine and paclitaxel appears to be active in MBC but the safety profile with the dosages used in this trial was unacceptably high and led to a short time to treatment failure. However, based on the efficacy data alternative schedules deserve further evaluation.