Supporting the management of type 2 diabetes with pharmacist-led reviews: an observational analysis.

OBJECTIVE: Describe and assess the impact of a pharmacist-led patient review programme on the management and control of type 2 diabetes (T2D). DESIGN: Uncontrolled prospective cohort study with before and after intervention data collection. SETTING: General practices within NHS Slough Clinical Commissioning Group (CCG). PARTICIPANTS: 5910 patients with T2D. INTERVENTIONS: Pharmacists reviewed 5910 patients and worked with general practice teams to schedule any of the 9 key care processes recommended by the National Institute for Health and Care Excellence (NICE) that the patients were lacking, to optimise medication and to make other interventions such as providing lifestyle advice. MAIN OUTCOME MEASURES: The proportion of patients receiving the NICE-recommended 9 key care processes and proportion of patients whose glycated haemoglobin (HbA1c), blood pressure (BP) or total cholesterol (TC) readings were over target before and after the intervention period. RESULTS: The proportion of patients receiving all of the NICE-recommended 9 key care processes increased from 46% at project outset in April 2013 to 58% on completion in April 2014 and the percentage of patients achieving HbA1c, BP and TC targets all increased (65% to 70%, 70% to 76%, 78% to 82%, respectively). Quality Outcomes Framework (QOF) data for Slough CCG showed the percentage of diabetic patients achieving target HbA1c, BP and TC readings increased from April 2013 to April 2014, but then diminished in the year after project completion. CONCLUSIONS: The pharmacist-led review increased the number of key care processes administered and improved diabetic control during the year of programme delivery. The improvement abated during the year after, suggesting that such programmes should be ongoing rather than fixed term. The programme combined the strategic drive and project facilitation skills of Slough CCG, the general practice teams' knowledge of their patients and the clinical and information technology skills of an experienced pharmacist team.

Prokineticin 2 is a hypothalamic neuropeptide that potently inhibits food intake.

OBJECTIVE: Prokineticin 2 (PK2) is a hypothalamic neuropeptide expressed in central nervous system areas known to be involved in food intake. We therefore hypothesized that PK2 plays a role in energy homeostasis. RESEARCH DESIGN AND METHODS: We investigated the effect of nutritional status on hypothalamic PK2 expression and effects of PK2 on the regulation of food intake by intracerebroventricular (ICV) injection of PK2 and anti-PK2 antibody. Subsequently, we investigated the potential mechanism of action by determining sites of neuronal activation after ICV injection of PK2, the hypothalamic site of action of PK2, and interaction between PK2 and other hypothalamic neuropeptides regulating energy homeostasis. To investigate PK2's potential as a therapeutic target, we investigated the effect of chronic administration in lean and obese mice. RESULTS: Hypothalamic PK2 expression was reduced by fasting. ICV administration of PK2 to rats potently inhibited food intake, whereas anti-PK2 antibody increased food intake, suggesting that PK2 is an anorectic neuropeptide. ICV administration of PK2 increased c-fos expression in proopiomelanocortin neurons of the arcuate nucleus (ARC) of the hypothalamus. In keeping with this, PK2 administration into the ARC reduced food intake and PK2 increased the release of alpha-melanocyte-stimulating hormone (alpha-MSH) from ex vivo hypothalamic explants. In addition, ICV coadministration of the alpha-MSH antagonist agouti-related peptide blocked the anorexigenic effects of PK2. Chronic peripheral administration of PK2 reduced food and body weight in lean and obese mice. CONCLUSIONS: This is the first report showing that PK2 has a role in appetite regulation and its anorectic effect is mediated partly via the melanocortin system.

A kisspeptin-10 analog with greater in vivo bioactivity than kisspeptin-10.

The kisspeptins are neuropeptides that stimulate the hypothalamo-pituitary-gonadal (HPG) axis. The smallest endogenous kisspeptin, kisspeptin-10 (KP-10), binds to the receptor KISS1R with a similar affinity to the full-length peptide, kisspeptin-54 (KP-54), but is less effective in vivo, possibly because of increased enzymatic breakdown or clearance. The kisspeptin system may have therapeutic potential in the treatment of reproductive disorders and endocrine cancers. We have rationally modified the structure of KP-10 and tested the binding affinity of these analogs for the KISS1R. Those analogs that bound with relatively high affinity to KISS1R were tested for ability to stimulate ERK1/2 phosphorylation in vitro and for their ability to stimulate the HPG axis in vivo. One analog, [dY](1)KP-10, bound to KISS1R with lower affinity to KP-10 and exhibited similar bioactivity in vitro. However, in vivo peripheral administration of [dY](1)KP-10 increased plasma LH and testosterone more potently than KP-10 itself at 20 min postinjection in mice. In addition, 60 min postinjection, 0.15 nmol [dY](1)KP-10 significantly increased total testosterone levels in mice whereas the same dose of KP-10 had no significant effect. Should manipulation of the kisspeptin/KISS1R signaling system prove therapeutically useful, long-lasting analogs such as [dY](1)KP-10 may have greater therapeutic potential than endogenous forms of kisspeptin.