Mobilizing a Statewide Network to Provide Ebola Education and Support.

BACKGROUND: Healthcare providers require the latest information and procedures when a public health emergency arises. During the fall of 2014, when the Ebola virus was first identified in a patient in the United States, education about Ebola virus disease (EVD) and procedures for its identification and control needed widespread and immediate dissemination to healthcare providers. In addition, there was a need to allay fears and reassure the public and providers that a process was in place to manage Ebola should it arrive in Arkansas. The state health department engaged multiple interest groups and provided a variety of educational and management activities. The Arkansas Department of Health and the only academic medical center in the state began offering time-consuming, one-on-one education over the phone, which reached too few providers. A solution was needed to educate many providers across the state in the protocols for identification, isolation, and management of patients with EVD. In response, the Arkansas Department of Health and the University of Arkansas for Medical Sciences leveraged the interactive video and Webinar capabilities of the state's telemedicine network to educate both providers and the public of this public health emergency. MATERIALS AND METHODS: Six interactive video events were staged over 5 days in October 2014. RESULTS: In six events, 82 individual healthcare facilities (67 of which were hospitals) and 378 providers attended via the Webinar option, whereas 323 healthcare professionals received continuing education credits. CONCLUSIONS: A statewide videoconferencing infrastructure can be successfully mobilized to provide timely public health education and communication to healthcare providers and the public in multiple disciplines and practice settings.

Postcard intervention for repeat self-harm: randomised controlled trial.

BACKGROUND: Self-harm and suicidal behaviour are common reasons for emergency department presentation. Those who present with self-harm have an elevated risk of further suicidal behaviour and death. AIMS: To examine whether a postcard intervention reduces self-harm re-presentations in individuals presenting to the emergency department. METHOD: Randomised controlled trial conducted in Christchurch, New Zealand. The intervention consisted of six postcards mailed during the 12 months following an index emergency department attendance for self-harm. Outcome measures were the proportion of participants re-presenting with self-harm and the number of re-presentations for self-harm in the 12 months following the initial presentation. RESULTS: After adjustment for prior self-harm, there were no significant differences between the control and intervention groups in the proportion of participants re-presenting with self-harm or in the total number of re-presentations for self-harm. CONCLUSIONS: The postcard intervention did not reduce further self-harm. Together with previous results this finding suggests that the postcard intervention may be effective only for selected subgroups.

Anticancer metallohelices: nanomolar potency and high selectivity.

A range of new helicate-like architectures have been prepared via highly diastereoselective self-assembly using readily accessible starting materials. Six pairs of enantiomers [Fe2L3]Cl4·nH2O (L = various bidentate ditopic ligands NN-NN) show very good water solubility and stability. Their activity against a range of cancer cell lines in vitro is structure-dependent and gives IC50 values as low as 40 nM. In an isogenic pair of HCT116 colorectal cancer cells, preferential activity was observed against cell lines that lack functional p53. Selectivity is also excellent, and against healthy human retinal pigment epithelial (ARPE19) and lung fibroblast (WI38) cells IC50 values are nearly three orders of magnitude higher. Cisplatin is unselective in the same tests. The compounds also appear to have low general toxicity in a number of models: there is little if any antimicrobial activity against methicillin-resistant Staphylococcus aureus and Escherichia coli; Acanthamoeba polyphaga is unaffected at 25 µg mL-1 (12.5 µM); Manduca sexta larvae showed clear evidence of systemic distribution of the drug, and rather than any observation of adverse effects they exhibited a significant mean weight gain vs. controls. Investigation of the mode of action revealed no significant interaction of the molecules with DNA, and stimulation of substantial cell death by apoptosis.

Asymmetric triplex metallohelices with high and selective activity against cancer cells.

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail 'triplex' strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 p53(++), causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli.

Optically pure heterobimetallic helicates from self-assembly and click strategies.

Single diastereomer, diamagnetic, octahedral Fe(II) tris chelate complexes are synthesised that contain three pendant pyridine proligands pre-organised for coordination to a second metal. They bind Cu(I) and Ag(I) with coordination geometry depending on the identity of the metal and the detail of the ligand structure, but for example homohelical (ΔFe,ΔCu) configured systems with unusual trigonal planar Cu cations are formed exclusively in solution as shown by VT-NMR and supported by DFT calculations. Similar heterobimetallic tris(triazole) complexes are synthesised via clean CuAAC reactions at a tris(alkynyl) complex, although here the configurations of the two metals differ (ΔFe,ΛCu), leading to the first optically pure heterohelicates. A second series of Fe complexes perform less well in either strategy as a result of lack of preorganisation.

Origins of stereoselectivity in optically pure phenylethaniminopyridine tris-chelates M(NN')3(n+) (M = Mn, Fe, Co, Ni and Zn).

One-pot reactions of 2-pyridinecarboxaldehyde, chiral phenylethanamines and Fe(II) give single diastereomer fac diimine complexes at thermodynamic equilibrium so that no chiral separations are required (d.r. > 200 : 1). The origins of this stereoselectivity are partly steric and partly a result of the presence of three sets of inter-ligand parallel-offset π-stacking interactions. Mn(II), Co(II), Co(III), Ni(II) and Zn(II) give similar fac structures, alongside the imidazole analogues for Fe(II). While most of the complexes are paramagnetic, the series of molecular structures allows us to assess the influence of the π-stacking present, and there is a strong correlation between this and the M-N bond length. Fe(II) is close to optimal. For the larger Zn(II) ion, very weak π-stacking leads to poorer measured stereoselectivity (NMR) but this is improved with increased solvent polarity. The mechanism of stereoselection is further investigated via DFT calculations, chiroptical spectroscopy and the use of synthetic probes.

A phase III, multicenter, randomized, placebo-controlled clinical trial of topical aminocaproic acid (Caprogel) in the management of traumatic hyphema.

OBJECTIVE: To determine the safety and efficacy of topical aminocaproic acid (Caprogel) in the management of traumatic hyphema. DESIGN: Multicenter, randomized, double-masked, placebo-controlled clinical trial. PARTICIPANTS: A total of 51 patients participated in this trial (power = 36%, 2-tailed test). INTERVENTION: Patients presenting with traumatic hyphema were randomly assigned to 5-day treatment with topical aminocaproic acid or a placebo gel. Patients were monitored daily with ocular examination and vital sign testing for the 5 days of treatment and at 24 and 48 hours after treatment. General physical examination and laboratory testing were performed at baseline and day 5. MAIN OUTCOME MEASURES: The main efficacy variable was the rate of rebleeding. Secondary efficacy variables included time to hyphema clearance, intraocular pressure, time to secondary hemorrhage, and visual acuity. Safety variables included adverse events, vital signs, and laboratory measurements. RESULTS: Rebleeding occurred in 30% of the placebo group (8 of 27; 95% confidence interval [CI] = 14-50%), versus 8% of the treatment group (2 of 24; 95% CI = 1-27%), for an estimated continuity-corrected difference in percentage of patients with bleeding of 17% (95% CI = -3-38%). Secondary efficacy variables were similar in the groups, except that there was a trend towards more visual improvement in the topical aminocaproic acid group (54%) than in the placebo group (30%) at the last measurement (P = 0.08). Adverse events were similar. CONCLUSIONS: This study provides evidence that topical aminocaproic acid is safe and demonstrates trends towards reducing the rebleeding rate in the management of traumatic hyphema. However, because the study was terminated before complete enrollment, more definitive recommendations will require a larger trial.