Fractional flow reserve derived from computed tomography coronary angiography in the assessment and management of stable chest pain: the FORECAST randomized trial.

AIMS: Fractional flow reserve (FFRCT) using computed tomography coronary angiography (CTCA) determines both the presence of coronary artery disease and vessel-specific ischaemia. We tested whether an evaluation strategy based on FFRCT would improve economic and clinical outcomes compared with standard care. METHODS AND RESULTS: Overall, 1400 patients with stable chest pain in 11 centres were randomized to initial testing with CTCA with selective FFRCT (experimental group) or standard clinical care pathways (standard group). The primary endpoint was total cardiac costs at 9 months. Secondary endpoints were angina status, quality of life, major adverse cardiac and cerebrovascular events, and use of invasive coronary angiography. Randomized groups were similar at baseline. Most patients had an initial CTCA: 439 (63%) in the standard group vs. 674 (96%) in the experimental group, 254 of whom (38%) underwent FFRCT. Mean total cardiac costs were higher by £114 (+8%) in the experimental group, with a 95% confidence interval from -£112 (-8%) to +£337 (+23%), though the difference was not significant (P = 0.10). Major adverse cardiac and cerebrovascular events did not differ significantly (10.2% in the experimental group vs. 10.6% in the standard group) and angina and quality of life improved to a similar degree over follow-up in both randomized groups. Invasive angiography was reduced significantly in the experimental group (19% vs. 25%, P = 0.01). CONCLUSION: A strategy of CTCA with selective FFRCT in patients with stable angina did not differ significantly from standard clinical care pathways in cost or clinical outcomes, but did reduce the use of invasive coronary angiography.

Patterning of motor neurons by retinoic acid in the chick embryo hindbrain in vitro.

Motor neurons are found throughout the developing chick hindbrain, while somatic motor (SM) neurons develop only in rhombomeres 5 to 8 (r5-8), and in r1. In r2-8 neuroepithelial explants from stage 7-10 embryos cultured in collagen gels, we found that motor neurons were generated throughout r2-8, while SM neuron differentiation was restricted to r5-8, as in vivo. Exposure of such explants to retinoic acid (RA) resulted in SM neuron differentiation throughout r2-8, while inclusion of the mesoderm and endoderm suppressed this effect. In explants with mesoderm/endoderm, RA-dependent SM neuron differentiation in rostral rhombomeres was restored by the application of an inhibitor of the RA-degrading enzyme CYP26. We found that the mesoderm/endoderm (either with or without RA) induced Cyp26 expression in the neuroepithelium in vitro, suggesting that the modulatory effect of CYP26 on RA-dependent patterning might be dependent on local signals.

Epilepsy and pregnancy: Report of an Epilepsy Research Foundation Workshop.

Pregnancy in women with epilepsy (WWE) is known to be associated with a higher risk of congenital malformations than is associated with pregnancy in non-epileptic women. Several factors have been identified to account for the increased risk, including the direct teratogenic effects of antiepileptic drug (AED) therapy, indirect effects of these drugs by interfering with folate metabolism, genetic abnormalities in drug or folate metabolism, and possibly an arrhythmogenic effect of maternal drug therapy on the embryonic heart, leading to ischaemia in developing tissues. A harmful effect of maternal seizures on the developing embryo has not been proven, although seizures and status epilepticus account for most of the excess maternal mortality in women with epilepsy. Abrupt withdrawal of drug therapy by the mother may be an important contributory factor. Less is known about the psychomotor development of children born to mothers with epilepsy because few studies have been designed to follow their progress throughout childhood. Retrospective studies suggest that impaired cognitive development may be associated with maternal drug therapy, particularly valproate. There is an urgent need to evaluate these risks and, with this in mind, several prospective registers have been set up to collect data from pregnancies in women with epilepsy.