Backgroundγ-Hydroxybutyrate (GHB) is a drug of abuse with dose-dependent sedative effects. Systematic data on the acute toxicity of GHB from emergency department (ED) presentations over a long period of time are currently missing from the literature. The present study described the clinical features of GHB toxicity.MethodsRetrospective case series of GHB intoxications seen in an urban ED.ResultsFrom January 2002 to September 2015, 78 GHB-related intoxication cases were recorded (71 % male patients). The mean ± SD age was 29 ± 8 years. The co-use of alcohol and/or other illicit drugs was reported in 65 % of the cases. Neurological symptoms other than central nervous system depression included agitation (40 %) and clonus (21 %). The most frequent reasons for admission were coma (64 %) and agitation (23 %). The median time to regain consciousness was 90 min (range, 3–400 min). Sudden recovery was reported in 25 cases (32 %). Coma was not significantly associated with polyintoxication. Coma occurred in 77 % of the alcohol co-users and in 62 % ofthe non-alcohol users (p=0.052). The mean recovery time in comatose patients was 142 min in patients with co-use of alcohol compared with 89 min in patients without alcohol co-use (p=0.07). Alcohol co-use was not significantly associated with nausea/vomiting (p=0.07). The co-use of stimulants was not significantly associated with non-responsive coma (Glasgow Coma Scale = 3) or mean recovery time. Analytical confirmation of GHB was available in 37 cases (47 %), with additional quantitative analysis in 20 cases. The median GHB concentration was 240 mg/L (range, 8.3–373 mg/L). Intoxication was severe in 72 % of the cases. No fatalities occurred, and 72 % of the patients were discharged directly home from the ED.DiscussionThere were trend associations between alcohol co-use and frequency and length of coma and nausea/vomiting which did not reach the significance level (all p=0.05-0.07) but may nevertheless be clinically relevant. As the exact time of use is not always known, and co-use of other substances can affect the severity of poisoning, no definitive conclusions can be drawn regarding the association between GHB concentration and severity.ConclusionImpaired consciousness and agitation were typical findings of GHB intoxication. The co-use of alcohol and/or other illicit substances is common but was not significantly associated with the severity of the intoxications in our study.

Background Ovarian cancer (OC) is the fifth most common malignant female cancer with a high mortality, mainly because of aggressive high-grade serous carcinomas (HGSOC), but also due to absence of specific early symptoms and effective detection strategies. The CXCL12-CXCR4 axis is considered to have a prognostic impact and to serve as potential therapeutic target. Therefore we investigated the role of pCXCR4 and CXCR4 expression of the tumor cells and of tumor infiltrating immune cells (TIC) in high-grade serous OC and their association with the recurrence-free (RFS) and overall survival (OS). Methods A tissue microarray of 47 primary high grade ovarian serous carcinomas and their recurrences was stained with primary antibodies directed against CXCR4 and pCXCR4. Beside the evaluation of the absolute tumor as well as TIC expression in primary and recurrent cancer biopsies the corresponding ratios for pCXCR4 and CXCR4 were generated and analyzed. The clinical endpoints were response to chemotherapy, OS as well as RFS. Results Patients with a high pCXCR4/CXCR4 TIC ratio in primary cancer biopsies showed a significant longer RFS during the first two years (p = 0.025). However, this effect was lost in the long-term analysis including a follow-up period of 5 years (p = 0.128). Interestingly, the Multivariate Cox regression analysis showed that a high pCXCR4/CXCR4 TIC ratio in primary cancer independently predicts longer RFS (HR 0.33; 95CI 0.13 - 0.81; p = 0.015). Furthermore a high dichotomized distribution of CXCR4 positive tumor expression in recurrent cancer biopsies showed a significantly longer 6-month RFS rate (p = 0.018) in comparison to patients with low CXCR4 positive tumor expression. However, this effect was not independent of known risk factors in a Multivariate Cox regression (HR 0.57; 95CI 0.24 - 1.33; p = 0.193). Conclusions To the best of our knowledge we show for the first time that a high pCXCR4/CXCR4 TIC ratio in primary HGSOC biopsies is indicative for better RFS and response to chemotherapy. Highlights • We observed a significant association between high pCXCR4/CXCR4 TIC ratio and better RFS in primary cancer biopsies, especially during the early postoperative follow-up and independent of known risk factors for recurrence. • High CXCR4 tumor expression in recurrent HGSOC biopsies might be indicative for sensitivity to chemotherapy. We found evidence that at the beginning of the disease (early follow-up) the role of the immune response seems to be the most crucial factor for progression. On the other hand in recurrent/progressive disease the biology of the tumor itself becomes more important for prognosis. • We explored for the first time the predictive and prognostic role of pCXCR4/CXCR4 TIC ratio in high-grade serous ovarian cancer.

Background Speaking-up is a method of assertive communication that increases patient safety but often encounters barriers. Numerous studies describe programs introducing speaking-up with varying success; the common denominator seems to be the need for a multimodal and sustained approach to achieve the required change in behavior and culture for safer health care. Methods Before implementing a 22-month multistep program for establishing and strengthening speaking-up at our institution, we assessed perceived safety culture using the “Safety Attitudes Questionnaire.” After program completion, participants completed parts of the same Safety Attitudes Questionnaire relevant to speaking-up, and preresult and postresult were compared. In addition, levels of speaking-up and assertive communication were compared with a Swiss benchmark using results from the “Speaking-up About Patient Safety Questionnaire.” Results Safety Attitudes Questionnaire scores were significantly higher after program completion in 2 of 3 answered questions (median [first quartile, third quartile), 5.0 [4.0, 5.0] versus 4.0 [4.0, 5.0], P = 0.0002, and 5.0 [4.0, 5.0] versus 4.0 [4.0, 4.0] P = 0.002; n = 34). Our composite score on the Speaking-up About Patient Safety Questionnaire was significantly higher (mean ± SD, 5.9 ± 0.7 versus 5.2 ± 1.0; P < 0.001) than the benchmark (n = 65). Conclusions A long-term multimodal program for speaking-up was successfully implemented. Attitude and climate toward safety generally improved, and postprogram perceived levels of assertive communication and speaking-up were higher than the benchmark. These results support current opinion that multimodal programs and continued effort are required, but that speaking-up can indeed be strengthened.

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