Diabetes Text-Message Self-Management Support Program (SMS4BG): A Pilot Study.

BACKGROUND: The increasing prevalence of diabetes and costly long-term complications associated with poor glycemic control are issues facing health services worldwide. Diabetes self-management, with the support of health care providers, is critical for successful outcomes, however, frequent clinical contact is costly. Text messages via short message service (SMS) have the advantage of instant transmission at low cost and, given the ubiquity of mobile phones, may be the ideal platform for the delivery of diabetes self-management support. A tailored text message-based diabetes support intervention called Self-Management Support for Blood Glucose (SMS4BG) was developed. The intervention incorporates prompts around diabetes education, management, and lifestyle factors (healthy eating, exercise, and stress management), as well as blood glucose monitoring reminders, and is tailored to patient preferences and clinical characteristics. OBJECTIVE: To determine the usability and acceptability of SMS4BG among adults with poorly controlled diabetes. METHODS: Adults (aged 17 to 69 years) with type 1 (n=12) or type 2 diabetes (n=30), a hemoglobin A1c (HbA1c) over 70 mmol/mol (8.6%), and who owned a mobile phone (n=42) were recruited to take part in a 3-month pilot study of SMS4BG. At registration, participants selected the modules they would like to receive and, where appropriate, the frequency and timing of blood glucose monitoring reminders. Patient satisfaction and perceptions of the usability of the program were obtained via semistructured phone interviews conducted at completion of the pilot study. HbA1c was obtained from patient records at baseline and completion of the pilot study. RESULTS: Participants received on average 109 messages during the 3-month program with 2 participants withdrawing early from the study. Follow-up interviews were completed with 93% of participants with all reporting SMS4BG to be useful and appropriate to their age and culture. Participants reported a range of perceived positive impacts of SMS4BG on their diabetes and health behaviors. HbA1c results indicated a positive impact of the program on glycemic control with a significant decrease in HbA1c from baseline to follow-up. CONCLUSIONS: A tailored text message-based intervention is both acceptable and useful in supporting self-management in people with poorly controlled diabetes. A randomized controlled trial of longer duration is needed to assess the efficacy and sustainability of SMS4BG.

The polymorphism of progesterone: stabilization of a 'disappearing' polymorph by co-crystallization.

Progesterone has been known to be polymorphic for over 70 years, and crystallization conditions for the production of both experimentally characterized polymorphs have been repeatedly reported in the literature up to 1975. Nevertheless, our attempts to produce crystals of the metastable form 2 suitable for single crystal X-ray diffraction failed until the structurally related molecule pregnenolone was introduced as an additive into the crystallization solution. Accurate low temperature crystal structures were obtained for forms 1 and 2, pregnenolone and a newly discovered pregnenolone-progesterone co-crystal, which appeared concomitantly with progesterone forms 1 and 2. Computational work based on the experimental crystal structures and those generated by a search for low energy structures showed that the crystallization of enantiomerically pure progesterone results in a more strained conformation compared with the racemate due to the rotation of the acetyl and 21-methyl groups. The role of impurities or additives in influencing crystallization outcome is discussed.

Search for a predicted hydrogen bonding motif--a multidisciplinary investigation into the polymorphism of 3-azabicyclo[3.3.1]nonane-2,4-dione.

The predictions of the crystal structure of 3-azabicyclo[3.3.1]nonane-2,4-dione submitted in the 2001 international blind test of crystal structure prediction (CSP2001) led to the conclusion that crystal structures containing an alternative hydrogen bonded dimer motif were energetically competitive with the known catemer-based structure. Here we report an extensive search for a dimer-based crystal structure. Using an automated polymorph screen a new catemer-based metastable polymorph (form 2) and two new catemer-based solvates were found, and concurrent thermal studies reproduced form 2 and identified a plastic phase (form 3), whose powder X-ray diffraction pattern was consistent with the cubic space group I23 (a = 7.5856(1) A). Computational studies on the monomer showed that the imide N-H was a weak hydrogen bond donor, rationalizing the occurrence of the plastic phase which involved the breaking of all hydrogen bonds, and modeling of small clusters showed that dimers could easily reorganize to give the catemer. FTIR spectra confirmed the weakness of the hydrogen bond, with the solute showing no self-assembly in solution. It is concluded that the weakness of the N-H donor, coupled with the globular shape of the molecule, allows unusually facile transformation between alternative hydrogen bonding motifs during aggregation and nucleation.

Toward the Prediction of Organic Hydrate Crystal Structures.

Lattice energy minimization studies on four ordered crystal structures of ice and 22 hydrates of approximately rigid organic molecules (along with 11 corresponding anhydrate structures) were used to establish a model potential scheme, based on the use of a distributed multipole electrostatic model, that can reasonably reproduce the crystal structures. Transferring the empirical repulsion-dispersion potentials for organic oxygen and polar hydrogen atoms to water appears more successful for modeling ice phases than using common water potentials derived from liquid properties. Lattice energy differences are reasonable but quite sensitive to the exact conformation of water and the organic molecule used in the rigid molecule modeling. This potential scheme was used to test a new approach of predicting the crystal structure of 5-azauracil monohydrate (an isolated site hydrate) based on seeking dense crystal packings of 66 5-azauracil···water hydrogen-bonded clusters, derived from an analysis of hydrate hydrogen bond geometries involving the carbonyl- and aza-group acceptors in the Cambridge Structural Database. The known structure was found within 5 kJ mol(-1) of the global minimum in static lattice energy and as the third most stable structure, within 1 kJ mol(-1), when thermal effects at ambient temperature were considered. Thus, although the computational prediction of whether an organic molecule will crystallize in a hydrated form poses many challenges, the prediction of plausible structures for hydrogen-bonded monohydrates is now possible.

Racemic progesterone: predicted in silico and produced in the solid state.

A computational prediction that mixing the synthetic mirror image of progesterone with its natural form would produce a specific racemic crystal structure was validated.

5-Fluorouracil and thymine form a crystalline solid solution.

The crystal structure of a 5-fluorouracil-thymine [5-fluoropyrimidine-2,4(1H,3H)-dione-5-methylpyrimidine-2,4(1H,3H)-dione, C(4)H(3)FN(2)O(2)xC(5)H(6)N(2)O(2)] solid solution has been determined. Both of the crystallographically independent sites can accommodate either 5-fluorouracil or thymine molecules, leading to occupational disorder [C(5-x)H(6-3x)F(x)N(2)O(2)xC(5-y)H(6-3x)F(y)N(2)O(2), with x = 0.52 and y = 0.7 for determination (I), x = 0.55 and y = 0.69 for (II), and x = 0.67 and y = 0.76 for (III)]. The 5-fluorouracil-thymine ratio in the crystal structure is influenced by the 5-fluorouracil-thymine ratio in the crystallization solution, though it does not exactly mirror it. The crystal structure comprises interpenetrating hydrogen-bonded nets, containing four independent hydrogen bonds.

Kinetic insights into the role of the solvent in the polymorphism of 5-fluorouracil from molecular dynamics simulations.

We investigate the fundamental factors controlling polymorphism in 5-fluorouracil by performing molecular dynamics simulations of solutions of the compound in water, nitromethane, and wet nitromethane. Analysis of the effect of solvent on the initial aggregation of 5-fluorouracil molecules shows that the strong binding of water to the 5-fluorouracil molecule hinders the formation of the doubly hydrogen-bonded dimer and, by default, promotes close hydrophobic F...F interactions that are a feature of the unusual (Z' = 4) structure of form I. In contrast, doubly hydrogen-bonded dimers are observed to form readily in solution in dry nitromethane, consistent with the crystallization of the doubly hydrogen-bonded ribbon structure of form II from this solvent. When nitromethane is doped with water, the water forms hydrogen bonds to the solute, interfering with the formation of the doubly hydrogen-bonded dimers, which is consistent with the crystallization of form I from this hygroscopic solvent when it is not dried. Overall, the molecular dynamics simulations provide an atomistic picture of how solvent-solute interactions can significantly affect the initial association of 5-fluorouracil molecules to the extent that they determine the polymorphic outcome of the crystallization.

A new polymorph of 5-fluorouracil found following computational crystal structure predictions.

A new polymorph of 5-fluorouracil has been obtained following a manual polymorph screen inspired by a computational crystal structure prediction search. It corresponds to the structure that was predicted to be the global minimum in lattice energy. The difficulty of crystallizing this simple structure with a rational hydrogen-bonding motif can be rationalized from the differential solvation of the functional groups.