Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane.

Background: Anaesthesia may impact long-term cancer survival. In the Cancer and Anaesthesia study, we hypothesised that the hypnotic drug propofol will have an advantage of at least five percentage points in five-year survival over the inhalational anaesthetic sevoflurane for breast cancer surgery. Methods: From 2118 eligible breast cancer patients scheduled for primary curable, invasive breast cancer surgery, 1764 were recruited after ethical approval and individual informed consent to this open label, single-blind, randomised trial at four county- and three university hospitals in Sweden and one Chinese university hospital. Of surveyed patients, 354 were excluded, mainly due to refusal to participate. Patients were randomised by computer at the monitoring organisation to general anaesthesia maintenance with either intravenous propofol or inhaled sevoflurane in a 1:1 ratio in permuted blocks. Data related to anaesthesia, surgery, oncology, and demographics were registered. The primary endpoint was five-year overall survival. Data are presented as Kaplan-Meier survival curves and Hazard Ratios based on Cox univariable regression analyses by both intention-to-treat and per-protocol. EudraCT, 2013-002380-25 and ClinicalTrials.gov, NCT01975064. Findings: Of 1764 patients, included from December 3, 2013, to September 29, 2017, 1670 remained for analysis. The numbers who survived at least five years were 773/841 (91.9% (95% CI 90.1-93.8)) in the propofol group and 764/829 (92.2% (90.3-94.0)) in the sevoflurane group, (HR 1.03 (0.73-1.44); P = 0.875); the corresponding results in the per-protocol-analysis were: 733/798 (91.9% (90.0-93.8)) and 653/710 (92.0% (90.0-94.0)) (HR = 1.01 (0.71-1.44); P = 0.955). Survival after a median follow-up of 76.7 months did not indicate any difference between the groups (HR 0.97, 0.72-1.29; P = 0.829, log rank test). Interpretation: No difference in overall survival was found between general anaesthesia with propofol or sevoflurane for breast cancer surgery. Funding: Swedish Research Council; Uppsala-Örebro Regional Research Council; Västmanland Regional Research Fund; Västmanland Cancer Foundation; Stig and Ragna Gohrton Foundation; Birgit and Henry Knutsson Foundation.

Clonidine Versus Midazolam Premedication and Postoperative Negative Behavioral Changes in Younger Children: A Randomized Controlled Trial.

BACKGROUND: Postoperative negative behavioral changes (NBCs) are common among children, but risk for this is thought to be reduced with premedication. Midazolam has for many years been a standard premedication for children. More recently, the alpha-2 adrenergic agonist clonidine has also become popular as a preanesthetic sedative. We hypothesized that clonidine was superior to midazolam for limiting new NBCs in children as assessed using the Post Hospital Behavior Questionnaire (PHBQ). METHODS: This was a prospective, randomized, controlled, blinded study, including 115 participants aged 24 to 95 months and their parents. The participants underwent ear, nose, or throat outpatient surgery and were randomly allocated to premedication with oral midazolam 0.5 mg/kg or oral clonidine 4 µg/kg. Participants were anesthetized by protocol. At home, later, parents were asked to complete the PHBQ assessment instrument for postoperative NBCs for the participants 1 week, 1 month, and 6 months after the surgery. A secondary outcome, preinduction anxiety, was assessed using modified Yale Preoperative Anxiety Scale (mYPAS). RESULTS: The primary outcome, more than 3 NBCs in an individual case at 1 week, showed no difference in proportions between treatment in the clonidine group compared to the midazolam group, (12/59 or 20% vs 7/56 or 13%, respectively, odds ratio 1.39, 95% confidence interval [CI], 0.75-2.58; P = .32). A secondary result showed a higher preinduction anxiety level in the clonidine compared to the midazolam group (mYPAS >30, 43/59 or 71% vs 12/56 or 21%, respectively; P < .001). CONCLUSIONS: These results did not show a clinical or statistically significant difference, with respect to the primary outcome of behavior changes at 1 week, between the cohorts that received midazolam versus clonidine as a premedication.

Reducing prejudice through priming of control-related words.

We investigated the effect of incidentally presented constructs that imply self-control on activated stereotypes associated with immigrants. To activate immigrant stereotypes, participants responded to a scale that measures people's prejudice toward immigrants. They were then primed, using scrambled sentences, with words that were related to self-control (e.g., control, restrain, self-regulate) or with neutral words. After the priming task, participants evaluated an ambiguous behavior of a target person. On the basis of three experiments, the results showed that participants primed with the control-related words rated the target behavior more positively than those primed with neutral words. The results are discussed in relation to previous research on self-control, automatic influence of activated constructs, and prejudice reduction.