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Dicarba cyclic peptide analogues of the cystine-containing octapeptides octreotide, lanreotide, and vapreotide, all known somatostatin analogues, have been synthesized via an on-resin homogeneous metal-catalysed sequence involving ruthenium-catalysed ring-closing metathesis followed by rhodium-catalysed hydrogenation. Key words: dicarba-analogues of cystine-containing peptides, octreotide, vapreotide, and lanreotide; tandem ring-closing metathesis and hydrogenation. Des peptides cycliques dicarbones analogues de la cystine contenant les octapeptides octreotide, lanreotide et vapreotide, tous connus comme etant des analogues de la somatostatine, ont ete synthetises sur resine via une serie de catalyses homogenes impliquant une metathese de fermeture de cycle catalysee par du ruthenium et une hydrogenation catalysee par du rhodium. Mots cles : analogues dicarbones de la cystine contenant des peptides, octreotide, vapreotide et lanreotide; reaction tandem de fermeture de cycle par metathese et hydrogenation.

Objectives: To evaluate the effectiveness of a self help approach to smoking cessation in pregnancy., Design: Pragmatic cluster randomised controlled trial with community midwife as the unit of randomisation., Setting: Three NHS hospital trusts in England., Participants: 1527 women who smoked at the start of pregnancy., Intervention: A series of five self help booklets comprising a step by step programme to increase motivation for quitting smoking and to teach strategies for cessation and relapse prevention. The first booklet was given to the women by a midwife at the earliest opportunity in antenatal care, together with a booklet for partners, family members, and friends. The remaining four booklets were mailed directly to the women., Main Outcome Measures: The primary outcome was smoking cessation validated by cotinine measurement at the end of the second trimester of pregnancy. Other outcomes were self reported smoking status and cigarette consumption among daily smokers. Qualitative data exploring the acceptability of the intervention and the way that smoking cessation advice was delivered in both trial arms were also collected., Results: Smoking cessation rates were low: the cotinine validated rates were 18.8% (113/600) in the intervention group and 20.7% (144/695) in the normal care group (difference 1.9%, 95% confidence intervals -3.5% to 7.3%). Self reported quit rates were higher. In the intervention group, 156 (25.6%) women reported not smoking for at least seven days, compared with 207 (29.1%) in the normal care group. In both groups, median self reported daily cigarette consumption among daily smokers was 10 cigarettes per day. Pregnant women and midwives approved of the intervention, but the way in which it was delivered varied considerably. For the primary smoking outcome, the degree of clustering at the midwife level was non-trivial (intracluster correlation coefficient 0.031)., Conclusion: The self help intervention was acceptable but ineffective when implemented during routine antenatal care. More intensive and complex interventions, appropriately targeted and tailored, need to be developed and evaluated. Validated smoking cessation rates among pregnant women are substantially lower than the self reported rates on which current smoking policy is based.