[Appearances are not deceptive: clinical evidence and new research approaches to open-label placebo]. / Der Schein trügt nicht ­ klinische Evidenz und neue Forschungsansätze zum Open-label-Placebo.

The efficacy of placebo effects is proven in experimental, clinical and meta-analytical studies. However, harnessing placebo effects in clinical treatment contexts is hampered legally and ethically, since it has been considered necessary to conceal the inert nature of a placebo application. Interestingly, the results of recently published small, randomized trials suggest that patients can experience symptom relief after taking pills that they know lack any medication. In particular, these so-called open-label placebos (OLP) improved strongly fluctuating and individually distressing complaints such as gastrointestinal, neurological, psychosomatic and pain symptoms. Although the mechanisms are largely unknown, the open-label placebo application might be a promising way of fostering placebo effects in clinical settings. Initial study protocols already provide schedules for OLP use as an additional treatment in opioid use disorders. Likewise, the reduction of side effects, conversion effects or withdrawal symptoms through OLP applications in pharmacologically active treatments appear to serve as appropriate therapy goals. Further mechanistic studies are urgently needed to investigate the thus far only hypothetically proposed underlying mechanisms of OLP.

Root tear of the meniscus: biomechanical evaluation of an arthroscopic refixation technique.

BACKGROUND: Aim of the current study was to evaluate the structural properties of an arthroscopic refixation technique for meniscal root tears. HYPOTHESIS: Arthroscopic two suture root tear refixation technique using a transtibial approach restores the structural properties of the intact meniscus attachment more closely than a one suture technique. METHODS: Lateral root tear refixation was performed in a porcine knee model. Using a material testing machine, structural properties were determined after a cyclic loading protocol comparing transtibial tunnel reconstruction using one or a double suture technique. Intact posterior horn served as control group. RESULTS: Elongation after cyclic testing was significantly lower for intact and two suture technique when compared to single suture technique. Stiffness was significantly higher for intact constructs with a mean of 53.7 (±6.5) N/m and two suture technique with 44.8 (±9.9) N/m when compared to one suture technique with a mean of 37.1 (±5.4) N/m. In elongation and stiffness, no differences were found between intact and two suture technique. Ultimate failure loads were 325.6 (±77) N for the intact, 273.6 (±45.6) N for two suture technique and 149.8 (±24.3) N for the one suture technique. Both reconstruction techniques showed significantly lower ultimate failure load when compared to the intact control. CONCLUSION: Structural properties of root tear fixation using a transtibial single suture technique showed significantly higher elongation and lower stiffness and failure load after cyclic loading compared to the intact, whereas a two suture technique showed no difference in elongation and stiffness; however, lower failure load.

Determination of a gentamicin loading dose in neonates and infants.

The use of gentamicin as a co-therapy for the treatment of sepsis is common practice in neonates and infants. Gentamicin dosing guidelines have been developed over the past 20 years to accommodate a slower renal elimination rate of gentamicin in the neonatal population. Recently, it has become evident that early attainment of serum gentamicin concentrations > or = 5 micrograms/ml results in a greater therapeutic outcome in septic adult patients. As neonatal immunity is immature and aminoglycosides have an extended elimination half-life in the very young population, reassessment of the initial gentamicin dose has become necessary. Using retrospective data, we determined the amount of gentamicin necessary to effectively "load" a group of neonatal/pediatric patients to achieve initial serum concentrations of 6 or 8 micrograms/ml. One hundred sixty-six patients less than 12 months postnatal age were studied. The mean initial dose delivered was 2.41 mg/kg. Younger patients demonstrated larger gentamicin apparent volumes of distribution and slower elimination half-lives than did older patients. Initial serum gentamicin concentrations calculated from steady-state pharmacokinetic parameters were significantly lower than those seen at steady state. In order to achieve initial serum gentamicin concentrations > 6 micrograms/ml an initial dose of 3 mg/kg would be necessary in the group of patients studied. Younger patients (< or = 34 weeks gestational age) would likely require 4 mg/kg as an initial dose.