Asthma management : implementation of short-acting beta agonist guidelines in Western Australia:a unique collaboration

Background: The Respiratory Health Network in Western Australia developed the Asthma Model of Care in 2010 which incorporates best practice guidelines. At the same time short-acting beta agonist guidelines (SABA) were developed by stakeholder consensus at University of Western Australia (UWA) and incorporated the use of an Asthma Action Plan Card. Objective: To report on the implementation of a key component of the WA Asthma Model of Care, the SABA guidelines that incorporate the Asthma Action Plan card. Methods: Implementation strategies included lectures, direct pharmacy detailing, media releases, and information packs (postal and electronic). Groups targeted included pharmacists, consumers and medical practitioners. Results: State-based (n=18) and national (n=6) professional organisations were informed about the launch of the guidelines into practice in WA. In the four-month implementation period more than 47,000 Asthma Action Plan Cards were distributed, primarily to community pharmacies. More than 500 pharmacies were provided with information packs or individual detailing. More than 10,000 consumers were provided with information about the guidelines. Conclusions and implications: The collaboration of stakeholders in this project allowed for widespread access to various portals which, in turn, resulted in a multifaceted approach in disseminating information. Ongoing maintenance programs are required to sustain and build on the momentum of the implementation program and to ultimately address patient outcomes and practice change, which would be the longer-term goals of such a project. Future research will seek to ascertain the impact of the card on patient outcomes in WA.

Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder:protocol for a systematic review and meta-analysis

INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

GIP(Lys16PAL) and GIP(LyS37PAL):novel long-acting acylated analogues of glucose-dependent insulinotropic polypeptide with improved antidiabetic potentia

Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. GIP(Lys16PAL) and GIP(Lys37PAL) were resistant to dipeptidyl peptidase IV (DPP IV) degradation. In vitro studies demonstrated that GIP analogues retained their ability to activate the GIP receptor through production of cAMP and to stimulate insulin secretion. Intraperitoneal administration of GIP analogues to obese diabetic (ob/ob) mice significantly decreased the glycemic excursion and elicited increased and prolonged insulin responses compared to native GIP. A protracted glucose-lowering effect was observed 24 h following GIP(Lys37PAL) administration. Once a day injection for 14 days decreased nonfasting glucose, improved glucose tolerance, and enhanced the insulin response to glucose. These data demonstrate that fatty acid derivatized GIP peptides represent a novel class of long-acting stable GIP analogues for therapy of type 2 diabetes. © 2006 American Chemical Society.

Fatty acid derivatised analogues of glucose-dependent insulinotropic polypeptide with improved antihyperglycaemic and insulinotropic properties

C-terminal acylation of Lys(37) with myristic (MYR; tetradecanoic acid), palmitic (PAL; hexadecanoic acid) and stearic (octadecanoic acid) fatty acids with or without N-terminal acetylation was employed to develop long-acting analogues of the glucoregulatory hormone, glucose-dependent insulinotropic polypeptide (GIP). All GIP analogues exhibited resistance to dipeptidylpeptidase-IV (DPP-IV) and significantly improved in vitro cAMP production and insulin secretion. Administration of GIP analogues to ob/ob mice significantly lowered plasma glucose-GIP(Lys(37)MYR), N-AcGIP(Lys(37)MYR) and GIP(Lys(37)PAL) increased plasma insulin concentrations. GIP(Lys(37)MYR) and N-AcGIP(Lys(37)MYR) elicited protracted glucose-lowering effects when administered 24h prior to an intraperitoneal glucose load. Daily administration of GIP(Lys(37)MYR) and N-AcGIP(Lys(37)MYR) to ob/ob mice for 24 days decreased glucose and significantly improved plasma insulin, glucose tolerance and beta-cell glucose responsiveness. Insulin sensitivity, pancreatic insulin content and triglyceride levels were not changed. These data demonstrate that C-terminal acylation particularly with myristic acid provides a class of stable, longer-acting forms of GIP for further evaluation in diabetes therapy.

A key role for transmembrane prolines in calcitonin receptor-like receptor agonist binding and signalling:implications for family B G-protein-coupled receptors

Calcitonin receptor like-receptor is a family B G-protein coupled receptor (GPCR). It requires receptor activity modifying protein (RAMP) 1 to give a calcitonin gene-related peptide (CGRP) receptor. Little is known of how members of this receptor family function. Proline residues often form important kinks in alpha-helices. Therefore, all proline residues within the transmembrane helices of the receptor (Pro241, Pro244 in helix 4, Pro275 in helix 5, Pro321 and Pro331 in helix 6) were mutated to alanine. Pro241 Pro275, and Pro321 are highly conserved throughout all family B GPCRs. The binding of CGRP and its ability to stimulate cAMP production were investigated in mutant and wild-type receptors after transient transfection into COS-7 cells with RAMP1. The P321A mutation significantly decreased the pEC(50) for CGRP and reduced its affinity but did not change cell-surface expression. Antagonist binding [CGRP(8-37) and 1-piperidinecarboxamide N-[2-[[5amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl]pentyl]amino]-1-[(3 5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quina zolinyl) (BIBN4096BS)] was little altered by the mutation. Adrenomedullin-mediated signaling was disrupted when P321A was coexpressed with RAMP1, RAMP2, or RAMP3. The P331A mutant produced a moderate reduction in CGRP binding and receptor activation. Mutation of the other residues had no effect on receptor function. Thus, Pro321 and Pro331 are required for agonist binding and receptor activation. Modeling suggested that Pro321 induces a bend in helix 6, bringing its C terminus near that of helix 3, as seen in many family A GPCRs. This is abolished in P321A. P321A-I325P predicted to restore this conformation, showed wild-type activation. Modeling can also rationalize the effects of transmembrane proline mutants previously reported for another family B GPCR, the VPAC(1) receptor.

High sensitivity sensors utilising characteristics of dispersion-turning-point of long-period gratings in B/Ge co-doped fibre

Systematically investigated the waveguide dispersion characteristics of LPFGs. It has been revealed that the coupled cladding modes resonating in the dispersion-turning-point region are intrinsically sensitive to the external perturbation. Thus, LPFG-based application devices requiring good stability should avoid this region. On the other hand, this mode ultra-sensitive-zone can be explored to realise sensors and tuneable filters of high efficiency.

Super-high temperature sensitivity of long-period gratings in B/Ge co-doped fiber

Long period fiber grating (LPFG) can be used as active gain controlling device in EDFA. However, LPFGs fabricated in the standard telecom fiber only have a typical temperature sensitivity of 3-10nm/100°C, which may not be sufficient for implementing tuneable filters capable of wide tuning range and high tuning efficiency. In this paper, we report a theoretical and experimental investigation of thermal properties of LPFGs fabricated in B/Ge co-doped optical fiber. We have found that the temperature sensitivity of the LPFGs in the B/Ge fiber is considerably increased compared with those produced in the standard fiber. The LPFGs written in the B/Ge fiber have achieved, on average, one order of magnitude higher sensitivity than that of the LPFGs produced in the standard telecom fiber. We have also identified that the thermal response of LPFG is strongly dependent on the order of the coupled resonant cladding mode. The maximum sensitivity of 1.75nm/°C achieved by the 10th cladding mode of the 240μm LPFG is nearly 24 times that of the minimum value (0.075nm/C) exhibited by the 30th mode of the 34μm LPFG. Such devices may lead to high-efficiency and low-cost thermal/electrical tunable loss filters or sensors with extremely high temperature resolution.

High-temperature sensitivity of long-period gratings in B-Ge codoped fiber

We report an investigation of thermal properties of long-period fiber gratings (LPFGs) of various periods fabricated in the conventional B-Ge codoped fiber. It has been found that the temperature sensitivity of the LPFGs produced in the B-Ge fiber can be significantly enhanced as compared with the standard telecom fiber. A total of 27.5-nm spectral shift was achieved from only 10 °C change in temperature for an LPFG with 240-μm period, demonstrating a first ever reported high sensitivity of 2.75 nm/°C. Such an LPFG may lead to high-efficiency and low-cost thermal/electrical tunable loss filters or sensors with extremely high-temperature resolution. The nonlinear thermal response of the supersensitive LPG was also reported and first explained.