Influence of Referral Pathway on Ebola Virus Disease Case-Fatality Rate and Effect of Survival Selection Bias.

Case-fatality rates in Ebola treatment centers (ETCs) varied widely during the Ebola virus disease (EVD) outbreak in West Africa. We assessed the influence of referral pathway on ETC case-fatality rates with a retrospective cohort of 126 patients treated at the Mathaska ETC in Port Loko, Sierra Leone. The patients consisted of persons who had confirmed EVD when transferred to the ETC or who had been diagnosed onsite. The case-fatality rate for transferred patients was 46% versus 67% for patients diagnosed onsite (p = 0.02). The difference was mediated by Ebola viral load at diagnosis, suggesting a survival selection bias. Comparisons of case-fatality rates across ETCs and clinical management strategies should account for potential survival selection bias.

No significant influence of OCT1 genotypes on the pharmacokinetics of morphine in adult surgical patients.

We investigated the impact of genetic variants in OCT1 (SLC22A1) on morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) pharmacokinetics in adult patients scheduled for major surgery. Blood samples were taken before and 5, 10, 15, 30, 45, 60 and 90 min after a bolus of morphine (0.15 mg/kg). Patients were genotyped for the genetic variants (rs12208357, rs34059508, rs72552763 and rs34130495) in OCT1. Eighty-six patients completed the trial. The mean difference (95% confidence interval) for dose adjusted morphine, M3G and M6G AUC was 0.9 (-0.7-2.4), -5.9 (-11.8 to -0.03) and -1.1 (-2.5-0.4) h/L*10-6 , respectively, in patients with two reduced function alleles compared to patients with no reduced function alleles in OCT1. Accordingly, the (AUCM3G/Dose )/(AUCmorphine/Dose ) and (AUCM6G/Dose )/(AUCmorphine/Dose ) ratio was reduced, -1.8 (-3.2 to -0.4) and -0.4 (-0.7 to -0.03), respectively, when comparing the same groups. OCT1 variants had no influence on the experience of pain, adverse events or the number of PCA doses used. In conclusion, genetic variants in OCT1 had a small and clinically unimportant impact on the exposure of morphine after intravenous administration. Our results do not support pre-emptive genotyping for OCT1 prior to morphine administration in patients scheduled for major surgery.

[Central pontin myelinolysis]. / Central pontinmyelinolyse og hyponatriæmi.

Initially central pontin myelinolysis was associated with alcoholism and later with hyponatraemia and particularly the correction rate. The diagnosis is made by characteristic symptoms and cerebral MRI with areas of hyperintensity on T2-weighted images. Outcome varies, mortality is high and most survivors have some degree of neurological deficit. There is no treatment and supportive therapy remains the only option with possible recovery within 6-8 weeks. Hyponatraemia can safely be corrected at a rate of no more than 10 mmol/l within the first 24 hours and 18 mmol/l within 48 hours.

[Development of central pontin myelinolysis in a patient with light hyponatraemia]. / Udvikling af central pontinmyelinolyse hos en patient med kun let hyponatriæmi.

Central pontin myelinolysis has since the 1970s been correlated with hyponatraemia. A 56-year-old woman was admitted to hospital after a few days of diminished capacity and acute disorientation and respiratory distress. Initially, her alcohol overconsumption was not recognised. She presented with only a light hyponatraemia and sepsis. Following fluid resuscitation she developed hypernatraemia and was later diagnosed with osmotic demyelination syndrome. Despite several weeks of therapy the outcome was fatal.