SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

Synthesis and characterization of N-t-BOC protected pyrrole-sulfur oligomers and polymers

The synthesis and characterization of a new class of pyrrole-sulfur compounds is described. These compounds are designed to be precursors for an organic analogue of poly(sulfur nitride). Poly(N-t-BOC-2.5-pyrrolyl sulfide) was prepared from N-t-BOC-2,5-dibromopyrrole by first lithiating this compound with n-BuLi, followed by the addition of bis(p-tosyl) sulfide. Similarly, bis(N-t-BOC-2-pyrrolyl) sulfide was prepared starting from N-t-BOC-2-bromopyrrole. Subsequent selective oxidation with one or two equivalents of m-CPBA quantitatively gave bis(N-t-BOC-2-pyrrolyl) sulfoxide and -sulfone, respectively. Thermal deprotection of the t-BOC groups of the oligomers and the polymer resulted in decomposition of these compounds; the lauer is presumably due to a combination of sulfur-extrusion and polymerization

π-dimers of pyrrole-thiophene oligomer cation radicals

\u3cp\u3eThe redox states of phenyl end-capped oligomers containing pyrrole and thiophene units are characterized with optical absorption and EPR spectroscopy. The spectra give direct evidence for the π-dimerization of the corresponding cation radicals in solution.\u3c/p\u3

Infrared detectors with poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonic acid) (PEDOT/PSS) as the active material

Large area (3×3mm2) infrared detectors which present a fast rise of their output upon pulsed excitation can be made by using PEDOT/PSS with a low surface resistance. Thus, the action of the infrared sensitive device is based on a change in resistance after photo-excitation of charge carriers in PEDOT/PS via their low-energy absorption features. The absence of any measurable delay in the response of the device is consistent with the view that the charges on the polymer chain are responsible for the absorption of infrared radiation

Infrared detectors with poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonic acid) (PEDOT/PSS) as the active material

Large area (3×3mm2) infrared detectors which present a fast rise of their output upon pulsed excitation can be made by using PEDOT/PSS with a low surface resistance. Thus, the action of the infrared sensitive device is based on a change in resistance after photo-excitation of charge carriers in PEDOT/PS via their low-energy absorption features. The absence of any measurable delay in the response of the device is consistent with the view that the charges on the polymer chain are responsible for the absorption of infrared radiation

Synthesis and (Non)linear Optical Properties of a Series of Donor-Oligopyrrole-Acceptor Molecules,

The Pd-catalyzed cross-coupling reaction involving organostannanes (Stille reaction) is applied to prep. a series of N-t-BOC-protected D-p-A oligopyrroles. After purifn., oligomers with one to four pyrrole units inserted between a 4-nitrophenyl and a 4-methoxyphenyl group are isolated in yields between 20 and 47%. Only minor differences in the linear optical properties are obsd. for the four oligomers. The charge-transfer band around lmax = 365 nm shows a small, unexpected, hypsochromic shift, while the p-p* band around lmax = 285 nm shows a small, expected, bathochromic shift upon elongation of the mol. Their nonlinear optical properties, however, show a surprising proceeding; going from the D-p-A oligomer with one pyrrole unit to that with three pyrrole units, the hyperpolarizability, as measured by hyper-Rayleigh scattering, increases addnl. with the no. of pyrrole units within the oligomer, up to 277 * 10-30 esu in case of the trimer. On the basis of the assumption that both transitions contribute to the hyperpolarizability, a better conjugated D-p-A oligomer with a bithienyl spacer inserted between a 2-(4-nitrophenyl)-5-pyrrolyl and a 2-(4-methoxyphenyl)-5-pyrrolyl group is prepd. analogously. This mol. shows only one combined absorption at lmax = 378 nm for both the charge transfer and the p-p* band, while the hyperpolarizability is as high as 440 * 10-30 esu. These data, showing a very favorable transparency-hyperpolarizability tradeoff, are explained in terms of the contribution of two transitions that are superimpose