The oral NK(1) antagonist aprepitant for the prevention of acute and delayed chemotherapy-induced nausea and vomiting: Pooled data from 2 randomised, double-blind, placebo controlled trials

In this work, data from two phase III studies were pooled to further evaluate the NK(1) antagonist aprepitant for prevention of cisplatin induced nausea and vomiting. One thousand and forty three patients receiving cisplatin (> or = 70 mg/m2) were randomised to receive either a control regimen (32 mg intravenous ondansetron [O] and 20 mg oral dexamethasone [D] on day 1; 8 mg D twice daily on days 2-4) or an aprepitant (A) regimen (125 mg A plus 32 mg O and 12 mg D on day 1, 80 mg A and 8 mg D once daily on days 2-3, and 8 mg D on day 4). The primary endpoint was no emesis and no rescue therapy. Potential correlations between acute and delayed emesis were assessed, as were frequency of emetic episodes by time interval and effects on nausea and quality of life as measured by the functional living index emesis (FLIE) questionnaire. In the aprepitant group, there was statistically significantly less nausea over the study period as well as higher functioning on the FLIE questionnaire in both the nausea and vomiting domains. Patients without acute emesis were more likely to have no emesis in the delayed phase. Compared with control, the aprepitant regimen improved prevention of delayed emesis by 16% points in patients without acute emesis, and by 17% points in patients with acute emesis. Among patients who did not have complete response, the frequency of emesis at various intervals over 5 days was consistently lower in patients receiving aprepitant. Analyses of this combined Phase III population further characterized the clinical profile of the aprepitant regimen, showing that delayed emesis is correlated with, but not entirely dependent on, the presence of acute emesis, and that aprepitant has a favorable effect against nausea throughout 5 days postchemotherapy. In addition, even among patients who had emesis or needed rescue therapy, aprepitant was associated with a lower frequency of these events compared with the control regimen.     

Minimally invasive treatment of esophageal cancer: laparoscopic staging to robotic esophagectomy

Minimally invasive surgical (MIS) procedures have become commonplace in modern surgical practice. The term minimally invasive surgery has been and continues to be interchangeably applied to describe laparoscopic, laparoscopic-assisted, thoracoscopic, and telesurgical (robotic) procedures. Minimally invasive surgical procedures for the treatment of benign and malignant disorders of the esophagus are being developed, refined, and clinically applied in parallel with the exponential availability of novel technologies and instrumentation. Herein, we review the progression from laparoscopic/thoracoscopic esophagectomy to telesurgical esophagectomy, presently termed minimally invasive esophagectomy, and describe the telesurgical procedure as well as early the clinical outcome experience.     

Low doses of lithium carbonate reduce melatonin light sensitivity in healthy volunteers

Sensitivity of the pineal hormone melatonin to bright light at night has been posited as a putative marker of affective disorders. Research demonstrates melatonin supersensitivity to light in bipolar disorder, however the role that lithium carbonate plays in this response is unclear. This study assessed the effect of lithium on nocturnal melatonin secretion and sensitivity to light in healthy adults. Ten participants, tested on two nights, had blood samples drawn between 20:00 and 02:30 hours. On testing nights participants were exposed to 200 lux of light between 24:00 and 01:00 hours. Participants took 250 mg of lithium daily for 5 d between testing nights. The results indicated that lithium had a significant effect on sensitivity to light but not on overall melatonin synthesis. This finding has implications on the true magnitude of the melatonin light response in people with bipolar disorder and may elucidate possible mechanisms of action of lithium.     

Antiemetic efficacy of the neurokinin-1 antagonist, aprepitant, plus a 5HT3 antagonist and a corticosteroid in patients receiving anthracyclines or cyclophosphamide in addition to high-dose cisplatin: analysis of combined data from two Phase III randomized clinical trials

BACKGROUND: The tendency of chemotherapeutic regimens to cause vomiting is dependent on the individual drugs in the regimen. The authors analyzed data combined from 2 Phase III trials to assess the effect of the neurokinin-1 (NK(1)) antagonist aprepitant combined with a 5HT(3) antagonist plus a corticosteroid in a subpopulation receiving > 1 emetogenic chemotherapeutic agent. METHODS: In the current study, 1043 cisplatin-naive patients (42% were women) receiving cisplatin-based (> or = 70 mg/m(2)) chemotherapy were assigned randomly to a control regimen (ondansetron [O] 32 mg intravenously and dexamethasone [D] 20 mg orally on Day 1; D 8 mg twice daily on Days 2-4) or an aprepitant (A) regimen (A 125 mg orally plus O 32 mg and D 12 mg on Day 1; A 80 mg and D 8 mg once daily on Days 2-3; and D 8 mg on Day 4). Randomization was stratified for use of concomitant chemotherapy and female gender. The primary end point was complete response (no vomiting and no rescue therapy) on Days 1-5 (0-120 hours). Data were analyzed by a modified intent-to-treat approach, and logistic regression was used to make treatment comparisons among patients receiving the most frequently coadministered emetogenic concomitant chemotherapy (Hesketh level > or = 3). RESULTS: Among the approximately 13% of patients (n = 81 for A; n = 80 for control) who received additional emetogenic chemotherapy (doxorubicin or cyclophosphamide), the aprepitant regimen provided a 33 percentage-point improvement in the complete response rate compared with the control regimen. Among the general population, the advantage with aprepitant was 20 percentage points. CONCLUSIONS: The current analysis of > 1000 patients from 2 large randomized trials showed that in the subpopulation at increased risk of chemotherapy-induced nausea and vomiting due to concomitant emetogenic chemotherapy, the addition of aprepitant to standard antiemetics improved protection to an even greater extent than in the general study population.     

Robots in general surgery: present and future

Robotic surgery is an emerging technology. We began to use this technique in 2000, after it was approved by the Food and Drug Administration. Our preliminary experience was satisfactory. We report 4 years' experience of using this technique in our institution. Between August 2000 and December 2004, 399 patients underwent robotic surgery using the Da Vinci system. We performed 110 gastric bypass procedures, 30 Lap band, 59 Heller myotomies, 12 Nissen fundoplications, 6 epiphrenic diverticula, 18 total esophagectomies, 3 esophageal leiomyoma resections, 1 pyloroplasty, 2 gastrojejunostomies, 2 transduodenal sphincteroplasties, 10 adrenalectomies and 145 living-related donor nephrectomies. Operating times for fundoplications and Lap band were longer. After the learning curve, the operating times and morbidity of the remaining procedures were considerably reduced. Robot-assisted surgery allows advanced laparoscopic procedures to be performed with enhanced results given that it reduces the learning curve as measured by operating time and morbidity.     

Responsiveness of health-related quality of life outcome measures in cardiac rehabilitation: comparison of cardiac rehabilitation outcome measures

Assessment instruments that are not responsive to change are unsuitable as outcome tools in cardiac rehabilitation because they underestimate the psychosocial benefits of program attendance. Nine questionnaires were assessed for responsiveness with the standardized response mean (SRM). Questionnaires were allocated into 3 batteries, and each battery was completed by cardiac rehabilitation and comparison participants at 2 time points (411 and 375 participants in total, respectively). There was a high degree of variability in the responsiveness of instrument subscales. The positive affect subscale of the Global Mood Scale (J. Denollet, 1993a) was the most responsive (SRM = 0.62). Further information on the comparative responsiveness of psychosocial scales is important to optimize instrument selection for outcome studies.     

Pyoderma gangrenosum--an unusual differential diagnosis for acute infection

Pyoderma gangrenosum rarely occurs in the breast and has only previously been reported in the literature in response to trauma. We describe a case occurring spontaneously in the breast that was initially mistaken for an infection.     

Endoscopic treatment of gastroesophageal reflux

The treatment of gastroesophageal reflux (GERD) has improved dramatically in recent years. The new endoluminal treatments may bring a relatively simple, minimally invasive therapy that can be simultaneously applied in patients with GERD undergoing diagnostic upper endoscopy. Although the initial results are promising, these new techniques are generating some controversy and require further evaluation with randomized studies and longer follow-ups to define their precise role in the long-term management of the gastroesophageal reflux disease.     

A decrease in physical activity affects appetite, energy, and nutrient balance in lean men feeding ad libitum

BACKGROUND: It is not clear how decreased activity quantitatively affects energy balance (EB) in subjects feeding ad libitum. OBJECTIVE: We assessed the effect of an imposed sedentary routine on appetite, energy intake (EI), EB, and nutrient balance in lean men for 7 d. DESIGN: Six men with a mean (+/-SD) age of 23.0 +/- 2.3 y, weight of 69.2 +/- 11.4 kg, and height of 1.76 +/- 0.07 m were each studied twice during a sedentary [1.4 x resting metabolic rate (RMR)] and a moderately active (1.8 x RMR) regimen. During each treatment, they resided in the whole-body indirect calorimeter for the 7 d and had ad libitum access to a medium-fat diet of constant, measurable composition. Meal size, frequency, and composition were continually monitored. Motivation to eat was recorded during waking hours. Subjects were weighed in light clothing each morning, and their weight was corrected to nude. RESULTS: Energy expenditure was 9.7 and 12.8 MJ/d [P < 0.01; SE of the difference between means (SED) = 0.41] during the sedentary and active regimens, respectively. EI was 13.5 and 14.4 MJ/d (P = 0.463, SED = 1.06), respectively. There was no regimen effect on hunger, appetite, or body weight. By day 7, cumulative EB was 26.3 and 11.1 MJ, respectively. CONCLUSIONS: Reducing a level of physical activity from 1.8 to 1.4 x RMR can markedly affect EB. A sedentary routine does not induce a compensatory reduction of EI and leads to a significantly positive EB, most of which is stored as fat.