Which treatment for whom for ADHD? Moderators of treatment response in the MTA

Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators.     

Immune regulation and CNS autoimmune disease

The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity and duration of the tissue directed injury. Convergence of research, involving direct manipulation of specific cells and molecular mediators in animal models and in vitro analysis of human immune and neural cells and tissues, is providing increasing insight into the role of these immune regulatory functions and their potential to serve as therapeutic targets.     

Suits happen

Does your agency have enough malpractice insurance to protect you if you're involved in a lawsuit? Many EMTs are taking matters into their own hands.     

A plasma factor enhances activity of vitamin K-dependent coagulation proteins

A plasma factor, "coagulopoietin", present in animals with depleted vitamin K-dependent coagulation factors, appears to enhance activity of these factors in normal animals. We have investigated the effects of "coagulopoietin" on synthesis of certain coagulation proteins by the isolated rat liver perfused for eight hours. Liver donor rats received plasma injections from vitamin K-deficient rats or from normal rats 24 hr before sacrifice. Coagulation activity of Factor VII and Factor II in liver perfusate samples was measured with a coagulation assay; Factor II synthesis was also measured by rocket immunoelectrophoresis and by activation with E. carinatus venom. Cumulative hepatic synthesis of Factor VII coagulation activity was increased by 43% when rat liver donors received vitamin K-deficient rat plasma compared to normal rat plasma. Cumulative synthesis of Factor II coagulation activity was increased by 51%, but synthesis of the protein measured immunologically or by activation with venom was not affected. The "coagulopoietin" factor in these studies appears to increase measurable coagulation factor activity without increasing total protein synthesis.     

Kinetic study of smoking marijuana

Six subjects each smoked a 1% marijuana cigarette and 2 hr later smoked a second one. Plasma levels of delta-9-tetrahydrocannabinol were measured for 9 hr with a radioimmunoassay. Heart rate and self-reported "high" were measured for 2 hr after each cigarette. All three measures showed a rapid increase after the start of smoking with Cmax occurring before the end of smoking. There was a strong correlation between decrease in heart rate and plasma levels from 10 min after smoking until 120 min. All pharmacodynamic response measures returned to baseline values within approximately 2 hr.     

Failure of Nonoperative Management of Isolated Superior Mesenteric Artery Dissection

A case of isolated dissection of the superior mesenteric artery is presented here. This rare condition was confirmed angiographically in a 46-year-old man with persistent abdominal pain. He was treated initially with anticoagulation alone. One year later, he developed recurrent symptoms and had radiologic documentation of progression of the condition. Operative repair was performed and recovery was uneventful. This case demonstrates a failure of the nonoperative approach to this rare condition and suggests that disease progression may be inevitable. Early surgical correction may ease operative management.     

Bisulfite-containing propofol: is it a cost-effective alternative to Diprivan for induction of anesthesia?

Propofol (Diprivan(TM); AstraZeneca, Wilmington, DE) is a commonly used drug for the induction of general anesthesia in the ambulatory setting. With the availability of a new bisulfite-containing generic formulation of propofol, questions have arisen regarding its cost effectiveness and safety compared with Diprivan(TM). Two hundred healthy outpatients were randomly assigned, according to a double-blinded protocol, to receive either Diprivan(TM) or bisulfite-containing propofol 1.5 mg/kg IV as part of a standardized induction sequence. Maintenance of anesthesia consisted of either desflurane (4%-8% end-tidal) or sevoflurane (1%-2% end-tidal) in combination with a remifentanil infusion (0.125 microg x kg(-1) x min(-1) IV). Patient assessments included pain on injection, induction time, hemodynamic and bispectral electroencephalographic changes during induction, emergence time, and incidence of postoperative nausea and vomiting. The two propofol groups were comparable demographically, and the induction times and bispectral index values during the induction were also similar. However, the bisulfite-containing formulation was associated with less severe pain on injection (5% vs 11%), with fewer patients recalling pain on injection after surgery (38% vs. 51%, P<0.05). None of the patients manifested allergic-type reactions after the induction of anesthesia. The acquisition cost (average wholesale price in US dollars) of a 20-mL ampoule of Diprivan(TM) was $15 compared with $13 for the bisulfite-containing propofol formulation. Therefore, we concluded that the bisulfite-containing formulation of propofol is a cost-effective alternative to Diprivan(TM) for the induction of outpatient anesthesia. Implications: Bisulfite-containing propofol and Diprivan(TM) (AstraZeneca, Wilmington, DE) were similar with respect to their induction characteristics; however, the generic formulation was associated with a smaller incidence of injection pain. Assuming that the drug costs are similar, these data suggest that the bisulfite-containing formulation of propofol is a cost-effective alternative to Diprivan(TM).     

Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial.

PURPOSE: Ifosfamide, carboplatin, etoposide, and vincristine, alone and in combination, are highly active against small-cell lung cancer (SCLC). This trial was designed to investigate whether survival could be improved by a regimen of all four drugs (ICE-V) compared with standard chemotherapy in patients with SCLC and good performance status, and to assess the patients' quality of life (QL). PATIENTS AND METHODS: Patients were randomly assigned to receive six cycles of either ICE-V at 4-week intervals without dose reduction or standard chemotherapy administered according to local practice. The recommended standard control regimens were cyclophosphamide, doxorubicin, and etoposide; and cisplatin and etoposide. RESULTS: A total of 402 patients were randomly assigned, and 350 (87%) patients have died. Overall survival was longer in the ICE-V group (hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P = .0049), median survival was 15.6 months in the ICE-V group and 11.6 months in the control group, and 2-year survival rates were 20% and 11%, respectively. There was no evidence that the relative survival benefit for ICE-V was less in extensive-stage than in limited-stage patients. An increased rate of septicemia was reported in the ICE-V group (15% v 7% in the control group), but this did not result in an increase in reported treatment-related deaths (four patients [2%] in both groups). The findings on QL were broadly similar in both groups, with some benefit in favor of ICE-V. CONCLUSION: Compared with standard chemotherapy, the ICE-V regimen improves overall survival without QL penalties, despite an increased but manageable level of toxicity.     

Langerhans' cell histiocytosis in patients older than 21 years

In this retrospective review of 541 patients with Langerhans' cell histiocytosis, 211 (39%) patients were older than 21 years of age, whereas 330 (61%) were younger than 21 years of age. The adult patients had a mean age of 32 years (range, 21-69 years) with 159 (75%) men and 52 (25%) women, whereas the pediatric patients consisted of 176 (55%) boys and 144 (45%) girls. This male predominance in adults was statistically significant. Three adults had the Hand-Schuller-Christian variant, whereas the remaining adults (208) had eosinophilic granuloma. The rib accounted for 25% of the adult lesions and only 8% of the pediatric lesions. Spine involvement was less common in the adult group (3% versus 10%) and was predominantly thoracic. The adult patients had 40 (77%) diaphyseal lesions, 12 (23%) metaphyseal lesions, and no epiphyseal lesions. The pediatric patients had 75 (54%) diaphyseal, 59 (42%) metaphyseal, and five (4%) epiphyseal lesions. Radiographic evaluation revealed similar margin and matrix patterns in both groups, with a geographic lesion without sclerotic borders being the most common pattern. Langerhans' cell histiocytosis is considered a pediatric disease. However, this study showed a significant number (39%) of patients older than 21 years of age with this condition.