the aim was to examine cross-sectional association between moderate alcohol consumption and total brain volume in a cohort of participants in early middle-age, unconfounded by age-related neuronal change. 353 participants aged 39 to 45 years reported on their alcohol consumption using the AUDit-c measure. participants with alcohol abuse were excluded. Brain MRi was analyzed using a fully automated method. Brain volumes were adjusted by intracranial volume expressed as adjusted total brain volume (aTBV). AUDIT-C mean of 3.92 (SD 2.04) indicated moderate consumption. In a linear regression model, alcohol consumption was associated with smaller atBV (B = − 0.258, p < .001). When sex and current smoking status were added to the model, the association remained significant. Stratified by sex, the association was seen in both males (B = − 0.258, p = 0.003) and females (B = − 0.214, p = 0.011). Adjusted for current smoking, the association remained in males (B = − 0.268, p = 0.003), but not in females. When alcohol consumption increased, total brain volume decreased by 0.2% per one AUDIT-C unit already at 39-45 years of age. Moderate alcohol use is associated with neuronal changes in both males and females suggesting health risks that should not be overlooked. Alcohol abuse is harmful to the brain, but the effects of moderate consumption, and the earliest age when the harmful effects appear, are less known. Volume changes of small parts of the brain, e.g. hippocampus 1 and the ventricles 2,3 , have been associated with moderate consumption, but the relationship of alcohol consumption and total brain volume is contradictory. Methodological differences in imaging technology and in estimating alcohol consumption may make the results difficult to compare and interpret. In addition, most previous studies of global brain values have included participants in late middle-age or old age. However, the rate of age-related brain volume does not occur in a linear fashion, but the decrease accelerates towards old age making the effect of age difficult to control in statistical analysis. Studying younger participants and groups with less age heterogeneity would be helpful. We found ten studies 4-13 which used volumetry, voxel-based morphometry or brain age estimates for analyzing the association of large brain structures and alcohol consumption in moderate drinkers (Table 1). Two of these studies included middle-aged participants in their forties to sixties 4,5 , two mainly over 65-year-olds 6,7 , and six report on participants of a wide age range 8-13. Findings in the middle-aged were conflicting. Decreased 4 and increased 5 volume of white matter, and increased volume of gray matter and ventricular size were associated with moderate drinking in males, but no associations were found in females. Studies of participants over 65 years found either larger 6 or smaller 7 whole brain volumes associated with drinking. Studies of a wider age range have found decreased volumes 8-10 or no association 11,12 with consumption. The most recent stud...

BackgroundDexketoprofen has been shown to provide efficient analgesia and an opioid-sparing effect after orthopedic surgery. In this dose-finding study, we evaluated the analgesic efficacy and opioid-sparing effect of dexketoprofen administered intravenously (i.v.) after laparoscopic cholecystectomy (LCC).MethodsTwenty-four patients undergoing LCC were randomized to receive dexketoprofen 10 or 50 mg i.v. 15 min before the end of the surgery. Subjects were provided with 0.2 mg/kg of oxycodone at anesthesia induction. In the recovery room, pain was assessed with an 11-point numerical rating scale (NRS; score of 0 = no pain, score of 10 = most severe pain) every 10 min. When the NRS score was ≥3/10 at rest or ≥5/10 at wound compression, a plasma sample was taken for analysis of oxycodone [to determine the minimum effective concentration (MEC)], its metabolites, and dexketoprofen. After that, subjects were titrated with oxycodone 2 or 3 mg i.v. every 10 min until the NRS score was <3/10 at rest and <5/10 at wound compression. At this point, a second plasma sample was taken for analysis of oxycodone [minimum effective analgesic concentration (MEAC)], its metabolites, and dexketoprofen.ResultsAt the onset of pain, the plasma oxycodone concentrations (MEC) were similar in the two groups: median 60 ng/mL (range 37–73) in the 10 mg group and median 52 ng/mL (range 24–79) in the 50 mg group. At the time of pain relief, the MEACs were 98 ng/mL (range 59–150) in the 10 mg group and 80 ng/mL (range 45–128) in the 50 mg group. The total doses of oxycodone needed to achieve pain relief were similar: 0.11 mg/kg (range 0–0.33) in the 10 mg group and 0.08 mg/kg (range 0–0.24) in the 50 mg group. Eleven subjects developed mild desaturation or a decreased respiratory rate after oxycodone titration.ConclusionIn the present double-blinded, randomized clinical trial, the need for a rescue opioid analgesic, oxycodone, was similar with the two dose levels of dexketoprofen—10 and 50 mg i.v.—after LCC.

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