L. La Colla

Pharmacokinetic model-driven remifentanil administration in the morbidly obese: the 'critical weight' and the 'fictitious height', a possible solution to an unsolved problem?

In response to an issue we have recently raised, the two main manufacturers of infusion pumps have decided to update their software for target-controlled infusion (TCI) of remifentanil. For this opioid, the ‘Minto’ pharmacokinetic parameter set is incorporated into infusion pumps. Unfortunately, lean body mass (LBM), which is a covariate for important pharmacokinetic parameters in thismodel, is defined by an equation that appears to be flawed at high values of total bodyweight (TBW), i.e. for morbidly obese patients. Lean body mass is calculated from bodyweight in kilograms and height (Ht) in centimeters in men and women according to equations 1 and 2, respectively:

Beneficial Effects of Humidified, Warmed Carbon Dioxide Insufflation During Laparoscopic Bariatric Surgery: A Randomized Clinical Trial. What if Sample Size Calculation Made Difference?

Sir: We read with interest the article published by Dr. Savel and colleagues [1]. While the authors are to be commended for their aim to conduct a prospective, randomized double-blind trial about the effect of warm and humidified carbon dioxide insufflation on postoperative pain and morphine requirements, there seems to be some issues with the study design. In particular, even though this trial appears to be adequately designed and analyzed, it does not seem to be adequately powered. In fact, in order for a particular finding to be claimed as significant (or not), the study should be adequately powered. The authors state their primary endpoints were visual analogic pain scores (VAS) and morphine requirements. They refer to an older article [2] but, unfortunately, seem to have failed sample size calculation. Nowhere in this reference article is the variability (SD) in morphine requirement at 24 h 10 mg. Considering a more reasonable variability (SD) of 30 mg and considering a clinically significant difference of 10 mg, a total of 193 patients per group would have been required (considering the “standard” α error of 0.05 and a power of 0.8) in this study. As for VAS, the authors did not perform any sample size calculation, and therefore, it is almost impossible to perform a pre-study sample size calculation. However, assuming a mean VAS value of 2.5±1.8 at 24 h [3] and considering a reduction of 1.8 clinically significant, more than 30 patients per group would have been required. It is also possible to perform a post hoc sample size calculation or power analysis on the statistical tests they have used from their data. In particular, considering a mean VAS value of 3.8±1.7 in the control group (Table 2), and a difference of 1.3, their test had a power of only 0.52 to detect such difference (considering an α error of 0.05). Appropriate sample size calculation and power is mandatory to draw adequate conclusions. In this case, the authors state no differences in opioid requirements and postoperative pain exists between the 2 groups. Are we sure it is really so? We hope our observations are useful to other authors planning surgical trials. “Editor’s Note: “Dr. Savel was invited to respond to this Letter-to-the Editor and declined.”

Continuous Infusion of Intraperitoneal Bupivacaine After Laparoscopic Surgery: A Randomized Controlled Trial—What about Statistical Power and Analysis?

Sir: We read with interest the article published by Dr. Sherwinter and colleagues [1]. While the authors are to be commended for their aim to conduct a prospective, randomized, double-blind trial about the effect of intraperitoneal local anesthetic infusion on postoperative pain and opioid requirements in obesity surgery, there seems to be some issues with both the design of the study and the statistical analysis. As for study design, the major issue is that this study does not seem to be adequately powered. In fact, in order for a particular finding to be claimed as significant (or not), the study must have enough power. The authors state that the aim of this study is to evaluate visual analogic pain scores (VAS) and morphine requirements after intraperitoneal infusion of bupivacaine. As for morphine, they refer to a study which evaluates the effect of warmed and humidified carbon dioxide insufflation in laparoscopic surgery [2]. Assuming a standard deviation of 25 (and not 10 as the authors wrongly assume), more than 130 patients per group would have been required (considering the “standard” α error of 0.05 and a power of 0.8) to detect an 11-mg difference in morphine requirement at 48 h. Moreover, it is interesting that the authors choose a study where patient-controlled analgesia was provided via an infusion pump, whereas they decided to perform a nurse-based administration of morphine. Maybe they could have chosen another study for sample size calculation? As for VAS, the authors did not perform any sample size calculation, and therefore, it is almost impossible to perform a pre-study sample size calculation. However, it is possible to perform a post hoc sample size calculation or power analysis on the statistical tests they have used from their data. In particular, considering a mean VAS value of 3.5±2.4 in the control group and a difference of 1.7, their test had a power of only 0.47 to detect such difference (considering an α error of 0.05). Another critical point is the statistical analysis. Despite its existence for many years, the importance of nonlinear mixed-effects modeling in pain studies has been recently reasserted [3]. Nowhere is the importance of a method which accounts for both interindividual variability (e.g., unique sensitivity to pain) able to characterize the time course of pain in different patients and intraindividual variability (various sources of “noise”) as critical as in pain OBES SURG (2009) 19:817–818 DOI 10.1007/s11695-009-9826-6

Clinical investigation of the novel iron‐chelating agent, CP94, to enhance topical photodynamic therapy of nodular basal cell carcinoma: when statistics make a difference

licular ostia. The diagnosis of cicatricial alopecia was suggested by scalp dermoscopy that showed diminished hair follicle density with loss of follicular ostia and absence of signs of inflammation or traction. The absence of yellow dots or perifollicular keratosis and erythema excluded alopecia areata and frontal fibrosing alopecia. Our series confirms Goldberg’s opinion that CMA can occur in the absence of traction and points out the importance of dermoscopy in the diagnosis of hair disorders. This noninvasive technique allows immediate differential diagnosis between CMA and other diseases affecting the scalp margin, such as alopecia areata and frontal fibrosing alopecia.