SummaryBackgroundIntrahepatic cholestasis of pregnancy, characterised by maternal pruritus and increased serum bile acid concentrations, is associated with increased rates of stillbirth, preterm birth, and neonatal unit admission. Ursodeoxycholic acid is widely used as a treatment without an adequate evidence base. We aimed to evaluate whether ursodeoxycholic acid reduces adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.MethodsWe did a double-blind, multicentre, randomised placebo-controlled trial at 33 hospital maternity units in England and Wales. We recruited women with intrahepatic cholestasis of pregnancy, who were aged 18 years or older and with a gestational age between 20 weeks and 40 weeks and 6 days, with a singleton or twin pregnancy and no known lethal fetal anomaly. Participants were randomly assigned 1:1 to ursodeoxycholic acid or placebo, given as two oral tablets a day at an equivalent dose of 500 mg twice a day. The dose could be increased or decreased at the clinician's discretion, to a maximum of four tablets and a minimum of one tablet a day. We recommended that treatment should be continued from enrolment until the infant's birth. The primary outcome was a composite of perinatal death (in-utero fetal death after randomisation or known neonatal death up to 7 days after birth), preterm delivery (<37 weeks' gestation), or neonatal unit admission for at least 4 h (from birth until hospital discharge). Each infant was counted once within this composite. All analyses were done according to the intention-to-treat principle. The trial was prospectively registered with the ISRCTN registry, number 91918806.FindingsBetween Dec 23, 2015, and Aug 7, 2018, 605 women were enrolled and randomly allocated to receive ursodeoxycholic acid (n=305) or placebo (n=300). The primary outcome analysis included 304 women and 322 infants in the ursodeoxycholic acid group, and 300 women and 318 infants in the placebo group (consent to use data was withdrawn for 1 woman and 2 infants). The primary composite outcome occurred in 74 (23%) of 322 infants in the ursodeoxycholic acid group and 85 (27%) of 318 infants in the placebo group (adjusted risk ratio 0·85 [95% CI 0·62–1·15]). Two serious adverse events were reported in the ursodeoxycholic acid group and six serious adverse events were reported in the placebo group; no serious adverse events were regarded as being related to treatment.InterpretationTreatment with ursodeoxycholic acid does not reduce adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy. Therefore, its routine use for this condition should be reconsidered.FundingNational Institute for Health Research Efficacy and Mechanism Evaluation Programme.

ObjectiveTo determine accuracy, safety and acceptability of the FreeStyle Libre Flash Glucose Monitoring System in the paediatric population.Design, setting and patientsEighty-nine study participants, aged 4–17 years, with type 1 diabetes were enrolled across 9 diabetes centres in the UK. A factory calibrated sensor was inserted on the back of the upper arm and used for up to 14 days. Sensor glucose measurements were compared with capillary blood glucose (BG) measurements. Sensor results were masked to participants.ResultsClinical accuracy of sensor results versus BG results was demonstrated, with 83.8% of results in zone A and 99.4% of results in zones A and B of the consensus error grid. Overall mean absolute relative difference (MARD) was 13.9%. Sensor accuracy was unaffected by patient factors such as age, body weight, sex, method of insulin administration or time of use (day vs night). Participants were in the target glucose range (3.9–10.0 mmol/L) ∼50% of the time (mean 12.1 hours/day), with an average of 2.2 hours/day and 9.5 hours/day in hypoglycaemia and hyperglycaemia, respectively. Sensor application, wear/use of the device and comparison to self-monitoring of blood glucose were rated favourably by most participants/caregivers (84.3–100%). Five device related adverse events were reported across a range of participant ages.ConclusionsAccuracy, safety and user acceptability of the FreeStyle Libre System were demonstrated for the paediatric population. Accuracy of the system was unaffected by subject characteristics, making it suitable for a broad range of children and young people with diabetes.Trial registration numberNCT02388815.

We present a two-stage genomewide scan for osteoarthritis-susceptibility loci, using 481 families that each contain at least one affected sibling pair. The first stage, with 272 microsatellite markers and 297 families, involved a sparse map covering 23 chromosomes at intervals of approximately 15 cM. Sixteen markers that showed evidence of linkage at nominal P