The Child and Adolescent Psychiatry Trials Network (CAPTN)

OBJECTIVE: The current generation of clinical trials in pediatric psychiatry often fails to maximize clinical utility for practicing clinicians, thereby diluting its impact. METHOD: To attain maximum clinical relevance and acceptability, the Child and Adolescent Psychiatry Trials Network (CAPTN) will transport to pediatric psychiatry the practical clinical trials model widely used in other areas of medicine. RESULTS: CAPTN, a collaborative effort of the Duke Clinical Research Institute and the American Academy of Child and Adolescent Psychiatry, will conduct large, simple "practical" trials that provide generalizable answers to important clinical questions without bias. "Large" in this case means the random allocation of thousands of patients in hundreds of clinical centers to different treatments as they are delivered in community settings. "Simple" means that the number and type of data elements (and, hence, subject and investigator burden) is small and straightforward so as not to discourage provider or patient participation and to maximize the number of subjects per dollar spent. CONCLUSION: With 200 to 400 child and adolescent psychiatrists each participating in two or three practical clinical trials over 4 years, CAPTN promises to advance both the evidence base and research capacity in child and adolescent psychiatry.     

Stabilization effect of resin on the production of potent proteasome inhibitor NPI-0052 during submerged fermentation of Salinispora tropica

Addition of acrylic resin Amberlite XAD-7 during the fermentation of Salinispora tropica significantly enhanced the production of NPI-0052 by 69 fold. Examination of the time course of resin addition to the Salinispora tropica fermentation demonstrated that the increase in the production of NPI-052 is due to the stabilization effect by resin but not the removal of an end product feedback repression. Delay in resin addition to the fermentation led to decreases in the production of NPI-0052 to the amounts that are synthesized prior to the resin addition.     

Revascularization after segmental resection of lower extremity soft tissue sarcomas

BACKGROUND AND OBJECTIVES: Limb salvage surgery combined with vascular reconstruction has replaced amputation as the preferred treatment of soft tissue sarcomas involving major vascular structures of the extremities. We describe our experience with soft tissue sarcomas involving major vascular structures and examine outcomes according to the type of graft selected for arterial reconstruction. We also examine the effect of venous reconstruction on post-operative edema. METHODS: This retrospective review includes 14 patients with lower extremity soft-tissue sarcomas that encased major vessels, requiring combined limb-preserving tumor resection and revascularization with a synthetic or autogenous saphenous vein graft. Edema in patients with and without venous reconstruction was compared. The incidence of infection, wound dehiscence, and graft thrombosis were compared according to arterial graft type. RESULTS: There was no significant difference in edema in patients with venous reconstruction and those without. There was also no significant difference in infection and graft thrombosis in patients with synthetic grafts and those with autogenous saphenous vein grafts. Wound dehiscence occurred more often in patients with synthetic grafts (P = 0.029). CONCLUSIONS: Although this study was small, these results suggest that further studies are needed to determine the roles that vascular graft selection and venous reconstruction play in clinical outcome.     

Core Rewarming via Warm Lavage Liquid Ventilation in a Swine Model of Hypothermia-associated Ventricular Fibrillation

OBJECTIVES: To determine whether warm lavage liquid ventilation (LV) would provide rapid cardiopulmonary rewarming in swine with severe hypothermia and ventricular fibrillation. METHODS: Intubated common swine (n = 3; mean +/- SEM weight 26+/-1.2 kg) were cooled to a mean aortic temperature of 26.4+/-0.9 degrees C. Ventricular fibrillation was induced by transthoracic electrical shock. Rewarming was initiated by continuous endotracheal instillation of warm (44 degrees C) pre-oxygenated, perfluorocarbon liquid at 5 mL/kg/min. Endotracheal instillation of perfluorocarbon occurred while standard gas ventilation continued. Manual chest compressions were performed throughout the 30-minute rewarming process. Outcome measures were the absolute and relative rates of change of all temperatures. RESULTS: After 30 minutes of warm lavage LV, the mean aortic and pulmonary artery temperatures increased by 6.6+/-0.6 degrees C, respectively. Esophageal, nasal, and rectal temperatures did not change significantly. In one animal, normal sinus rhythm spontaneously returned after 16 minutes of rewarming. CONCLUSIONS: During cardiac arrest, warm lavage liquid ventilation may produce rapid cardiopulmonary rewarming.     

Long‐term medical costs and resource utilization in systemic lupus erythematosus and lupus nephritis: A five‐year analysis of a large medicaid population

Objective

To estimate the long‐term direct medical costs and health care utilization for patients with systemic lupus erythematosus (SLE) and a subset of SLE patients with nephritis.

Methods

Patients with newly active SLE were found in the MarketScan Medicaid Database (1999–2005), which includes all inpatient, outpatient, emergency department, and pharmaceutical claims for more than 10 million Medicaid beneficiaries. The date a patient became newly active was defined as the earliest observed SLE diagnosis code, with a 6‐month clean period prior to the diagnosis. This method identified 2,298 patients with a consecutive followup of 5 years. A reference group of patients without SLE was constructed using propensity score matching. Nephritis was assessed based on diagnosis and procedure codes involving the kidney.

Results

Mean annual medical costs for SLE patients totaled $16,089 at year 1, which is significantly greater (by $6,831) than that for reference patients. Costs decreased slightly at year 2 but then increased yearly at an average rate of 16% through year 5, to $23,860. SLE patients without nephritis (n = 1,809) had costs $967–3,756 higher than the reference patients. SLE patients with nephritis (n = 489) had costs $13,228–34,907 greater than the reference group. Inpatient visits for the nephritis subgroup were 0.6–1.0 per capita, which are approximately twice the rate for all SLE patients and 3 to 4 times higher than the reference group.

Conclusion

SLE is a costly condition to treat. Medical expenses incurred by SLE patients increase steadily over time, particularly for patients with nephritis.     

Thermal and pH stability of "beta-benzyme"

The thermal and pH stability of "beta-benzyme", an artificial chymotrypsin based on beta-cyclodextrin, has been studied and compared with the stability of real chymotrypsin. Artificial chymotrypsin is vastly superior to real chymotrypsin with regard to both temperature and pH stability. The reasons for this increased stability are discussed.     

Hyperinsulinemia in obesity: Lack of relation to gastric emptying of glucose solution or to plasma somatostatin levels

To investigate some factors that may be related to the hyperinsulinemia of obesity, we measured fractional gastric emptying rates and changes of circulating levels of glucose, insulin, and somatostatin-like immunoreactivity (SLI) following the intragastric instillation of glucose in age-matched obese and nonobese Pima Indians with normal glucose tolerance. Results for the nonobese Pimas were also compared with findings for age- and weight-matched Caucasians with normal glucose tolerance. The levels of fasting plasma insulin and the integrated insulin response to glucose were significantly greater (P < 0.01) in obese than in nonobese Pimas. Mean rates of fractional gastric emptying, both in the basal state and after the glucose load, were similar for the three groups. The fractional gastric emptying rates after a glucose load were strongly correlated with the integrated responses of both plasma glucose and insulin in the nonobese Caucasians (r = 0.88, 0.90; P < 0.01) but not in either Pima group. There were no significant differences in peripheral plasma SLI for any of the three groups, either in the basal state or after the glucose load. These findings suggest that the hyperinsulinemia of established obesity is not mediated by alterations in the gastric emptying rate of liquids or by peripheral plasma SLI concentrations. They do not, however, exclude defects in gastric emptying of solid foods. Nor do they exclude the possibility that gastric or D-cell abnormalities exist during the period of fat accumulation but recede after obesity is established.