Changing Health-Related Behaviors 2: On Improving the Value of Health Spending.

The quantity of health spending does not equate directly to the quality of healthcare. Social spending and nonmedical determinants of health impact on health outcomes. The value of health spending in the United States is limited by the high cost of goods and labor, and administrative costs, high use of low-level care, and lack of basic healthcare coverage in a substantial minority of the population. There are additional reasons for differences in the value of health spending as revealed by a comparison of Canada and Australia, where similar spending per capita results in better health system performance in Australia than in Canada. Within Canada, there are large differences between provinces in the value of health spending. Overutilization of health resources occurs when an intervention is not indicated, or of low value, or is provided at the wrong time. The Choosing Wisely Initiative is a solution for overutilization of low-value care. Recognition of the reality that effective treatments are often applied inconsistently and inappropriately has spurred the development of a science concerned with improvement of quality of care.

Engineering of a GLP-1 analogue peptide/anti-PCSK9 antibody fusion for type 2 diabetes treatment.

Type 2 diabetes (T2D) is a complex and progressive disease requiring polypharmacy to manage hyperglycaemia and cardiovascular risk factors. However, most patients do not achieve combined treatment goals. To address this therapeutic gap, we have developed MEDI4166, a novel glucagon-like peptide-1 (GLP-1) receptor agonist peptide fused to a proprotein convertase subtilisin/kexin type 9 (PCSK9) neutralising antibody that allows for glycaemic control and low-density lipoprotein cholesterol (LDL-C) lowering in a single molecule. The fusion has been engineered to deliver sustained peptide activity in vivo in combination with reduced potency, to manage GLP-1 driven adverse effects at high dose, and a favourable manufacturability profile. MEDI4166 showed robust and sustained LDL-C lowering in cynomolgus monkeys and exhibited the anticipated GLP-1 effects in T2D mouse models. We believe MEDI4166 is a novel molecule combining long acting agonist peptide and neutralising antibody activities to deliver a unique pharmacology profile for the management of T2D.

Synthesis and SAR of aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors.

The development of a series of novel aminopyrimidines as inhibitors of c-Jun N-terminal kinases is described. The synthesis, in vitro inhibitory values for JNK1, JNK2 and CDK2, and the in vitro inhibitory value for a c-Jun cellular assay are discussed.

Novel optical detection system for in vivo identification and localization of cervical intraepithelial neoplasia.

A noncontact optical detection system is developed for the in vivo identification and localization of high-grade cervical intraepithelial neoplasia (CIN 2,3). Diagnostic scans of the entire human cervix are performed following acetic acid application employing three integrated optical measurements: laser-induced fluorescence spectroscopy, white light diffuse reflectance spectroscopy, and video imaging. Full cervical scans comprising 499 interrogation locations at 1-mm spatial resolution are completed in 12 s. Diffuse reflectance and fluorescence spectra with signal-to-noise ratios of better than 100-to-1 are collected between 360 and 720 nm in increments of 1 nm, with an inherent spectral resolution of 8 nm. Glare reduction and optical vignetting are handled with a novel illumination scheme and subsequent spectral arbitration algorithms. The system is designed and found to be well below acceptable safe optical exposure levels. Typical reproducibility across multiple systems is approximately 5%, providing reliable and accurate detection of in vivo cervical neoplasia in normal clinical use.