Ipilimumab, a monoclonal antibody against cytotoxic T lymphocyte antigen 4 (CTLA-4), has been shown to improve survival in patients with advanced metastatic melanoma. It also enhances immunity to NY-ESO-1, a cancer/testis antigen expressed in a subset of patients with melanoma. To characterize the association between immune response and clinical outcome, we first analyzed NY-ESO-1 serum antibody by ELISA in 144 ipilimumab-treated patients with melanoma and found 22 of 140 (16%) seropositive at baseline and 31 of 144 (22%) seropositive following treatment. These NY-ESO-1-seropositive patients had a greater likelihood of experiencing clinical benefit 24 wk after ipilimumab treatment than NY-ESO-1-seronegative patients (P = 0.02, relative risk = 1.8, two-tailed Fisher test). To understand why some patients with NY-ESO-1 antibody failed to experience clinical benefit, we analyzed NY-ESO-1-specific CD4 + and CD8 + T-cell responses by intracellular multicytokine staining in 20 NY-ESO-1-seropositive patients and found a surprising dissociation between NY-ESO-1 antibody and CD8 responses in some patients. NY-ESO-1-seropositive patients with associated CD8 + T cells experienced more frequent clinical benefit (10 of 13; 77%) than those with undetectable CD8 + T-cell response (one of seven; 14%; P = 0.02; relative risk = 5.4, two-tailed Fisher test), as well as a significant survival advantage (P = 0.01; hazard ratio = 0.2, time-dependent Cox model). Together, our data suggest that integrated NY-ESO-1 immune responses may have predictive value for ipilimumab treatment and argue for prospective studies in patients with established NY-ESO-1 immunity. The current findings provide a strong rationale for the clinical use of modulators of immunosuppression with concurrent approaches to favor tumor antigen-specific immune responses, such as vaccines or adoptive transfer, in patients with cancer.

Naloxone is effective in preventing PCA opioid-related side effects. Naloxone infusion at 0.25 microg x kg(-1) x h(-1) not only attenuates these side effects but appears to reduce postoperative (beyond 4-8 h) opioid requirements. This dosing regimen can be prepared with 400 microg naloxone in 1,000 ml crystalloid given in 24 h to a patient weighing 70 kg.

The pharmacokinetics of remifentanil were studied in children from birth to 18 yr. Remifentanil was found to have age-related changes in clearance and volume of distribution, but not half-life. The increased clearance observed in young infants is in contrast to other opioids.

Meperidine was initially synthesized as an anticholinergic agent but was soon discovered to have analgesic properties. Although meperidine's anticholinergic effects were demonstrated in vivo, the anticholinergic effects on the biliary and renal tracts have not been demonstrated in vivo. Studies have clearly demonstrated that meperidine is no more efficacious in treating biliary or renal tract spasm than comparative mu opioids. The initial studies demonstrating the analgesic efficacy of meperidine were mostly case reports and not double-blind, randomized, controlled trials in specific populations. Subsequent comparative studies failed to demonstrate any advantages of meperidine over comparable doses of other analgesics. Meperidine was portrayed in practice and teaching as having unique clinical advantages. The analgesic effects of meperidine are not pronounced, and, in addition, meperidine use is complicated by unique side effects including serotonergic crisis and normeperidine toxicity. Meperidine's poor efficacy, toxicity, and multiple drug interactions have resulted in a movement to replace meperidine with more efficacious and less toxic opioid analgesics.

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Anesthesia-based pain services are facilitating improvements in the quality of care of surgical patients by developing and directing institution-wide perioperative analgesia programs that include interdisciplinary collaborations. However, the impact of anesthesia-based pain services has not been evaluated in a systematic fashion. This prospective multisite study (n = 23 hospitals) utilized a standardized approach to evaluate the quality of pain care provided to patients who were and who were not cared for by an anesthesia-based pain service. A total of 5837 patients were evaluated using a standardized survey that consisted of a medical record review and a patient interview. The data were collected as part of the hospitals' quality improvement activities. Forty-nine percent of the patients were cared for by an anesthesia-based pain service. Patients who received pain service care reported significantly lower pain intensity scores; had lower levels of pain in the postoperative period; had a lower incidence of pruritus, sedation, and nausea; and experienced significantly less pain than expected. In addition, these patients were more likely to receive patient education about postoperative pain management; were more satisfied with their postoperative pain management; and were discharged sooner from the hospital. The findings from this study demonstrate that the care provided by anesthesia-based pain services has a significant impact on patient outcomes.

In a randomized controlled trial at Duke University and University of North Carolina Hospitals, 143 two to six year old children undergoing elective ambulatory surgery were randomized into a control group who received routine preoperative teaching or an intervention group who received an interactive teaching book. Changes in behaviour were measured by a Vernon behavioural questionnaire preoperatively and again two weeks postoperatively. A Global Mood Score was assessed in the preoperative holding area, at arrival into the operating room, and at the time of mask induction. The children in the control group were significantly more aggressive postoperatively than the intervention group (P < 0.05). Children who received the interactive teaching book exhibited higher levels of anxiety on the day of surgery, but fewer behavioural changes two weeks following surgery. Parents in the intervention group reported that preoperative teaching helped their child (87%) and themselves (83%).