Characterization of NGFFYamide Signaling in Starfish Reveals Roles in Regulation of Feeding Behavior and Locomotory Systems

Neuropeptides in deuterostomian invertebrates that have an Asn-Gly motif (NG peptides) have been identified as orthologs of vertebrate neuropeptide-S (NPS)-type peptides and protostomian crustacean cardioactive peptide (CCAP)-type neuropeptides. To obtain new insights into the physiological roles of NG peptides in deuterostomian invertebrates, here we have characterized the NG peptide signaling system in an echinoderm—the starfish Asterias rubens. The neuropeptide NGFFYamide was identified as the ligand for an A. rubens NPS/CCAP-type receptor, providing further confirmation that NG peptides are orthologs of NPS/CCAP-type neuropeptides. Using mRNA in situ hybridization, cells expressing the NGFFYamide precursor transcript were revealed in the radial nerve cords, circumoral nerve ring, coelomic epithelium, apical muscle, body wall, stomach, and tube feet of A. rubens, indicating that NGFFYamide may have a variety of physiological roles in starfish. One of the most remarkable aspects of starfish biology is their feeding behavior, where the stomach is everted out of the mouth over the soft tissue of prey. Previously, we reported that NGFFYamide triggers retraction of the everted stomach in A. rubens and here we show that in vivo injection of NGFFYamide causes a significant delay in the onset of feeding on prey. To investigate roles in regulating other aspects of starfish physiology, we examined the in vitro effects of NGFFYamide and found that it causes relaxation of acetylcholine-contracted apical muscle preparations and induction of tonic and phasic contraction of tube feet. Furthermore, analysis of the effects of in vivo injection of NGFFYamide on starfish locomotor activity revealed that it causes a significant reduction in mean velocity and distance traveled. Interestingly, experimental studies on mammals have revealed that NPS is an anxiolytic that suppresses appetite and induces hyperactivity in mammals. Our characterization of the actions of NGFFYamide in starfish indicates that NPS/NG peptide/CCAP-type signaling is an evolutionarily ancient regulator of feeding and locomotion

Study protocol: national research partnership to improve primary health care performance and outcomes for Indigenous peoples

Background Strengthening primary health care is critical to reducing health inequity between Indigenous and non-Indigenous Australians. The Audit and Best practice for Chronic Disease Extension (ABCDE) project has facilitated the implementation of modern Continuous Quality Improvement (CQI) approaches in Indigenous community health care centres across Australia. The project demonstrated improvements in health centre systems, delivery of primary care services and in patient intermediate outcomes. It has also highlighted substantial variation in quality of care. Through a partnership between academic researchers, service providers and policy makers, we are now implementing a study which aims to 1) explore the factors associated with variation in clinical performance; 2) examine specific strategies that have been effective in improving primary care clinical performance; and 3) work with health service staff, management and policy makers to enhance the effective implementation of successful strategies. Methods/Design The study will be conducted in Indigenous community health centres from at least six States/Territories (Northern Territory, Western Australia, New South Wales, South Australia, Queensland and Victoria) over a five year period. A research hub will be established in each region to support collection and reporting of quantitative and qualitative clinical and health centre system performance data, to investigate factors affecting variation in quality of care and to facilitate effective translation of research evidence into policy and practice. The project is supported by a web-based information system, providing automated analysis and reporting of clinical care performance to health centre staff and management. Discussion By linking researchers directly to users of research (service providers, managers and policy makers), the partnership is well placed to generate new knowledge on effective strategies for improving the quality of primary health care and fostering effective and efficient exchange and use of data and information among service providers and policy makers to achieve evidence-based resource allocation, service planning, system development, and improvements of service delivery and Indigenous health outcomes.Ross Bailie, Damin Si, Cindy Shannon, James Semmens, Kevin Rowley, David J Scrimgeour, Tricia Nage, Ian Anderson, Christine Connors, Tarun Weeramanthri, Sandra Thompson, Robyn McDermott, Hugh Burke, Elizabeth Moore, Dallas Leon, Richard Weston, Haylene Grogan, Andrew Stanley and Karen Gardne

Impact of cost of medicines for chronic conditions on low income households in Australia

Objectives To determine the cost of medicines for selected chronic illnesses and the proportion of discretionary income this would potentially displace for households with different pharmaceutical subsidy entitlements and incomes. Methods We analysed household income and expenditure data for 9,774 households participating in two Australian surveys in 2009-10. The amount of \u27discretionary\u27 income available to households after basic living and health care expenditure was modelled for households with high pharmaceutical subsidies: pensioner and non-pensioner concessional (social security entitlements); and households with general pharmaceutical subsidies and low, middle or high incomes. We calculated the proportion of discretionary income that would be needed for medicines if one household member had diabetes or acute coronary syndrome, or if one member also had two co-existing illnesses (gastro-oesophageal reflux disease and depression, or asthma and osteoarthritis). Results Pensioner and low income households had little discretionary income after basic living and health care expenditure (AUD$92 and$164/week, respectively). Medicines for the specified illnesses ranged from $11-$42/month for high subsidy households and $34-$186/month for low subsidy households. Costs reduced substantially once patients reached the annual pharmaceutical cap (safety net), prior to which medicine costs would displace the equivalent of 1%-10% of discretionary income for most household types. However, low income households would have to forego the equivalent of between 5%-26% of their discretionary income for between 7 and 9 months of the year before receiving additional subsidies. Conclusions Prescription medicines for chronic conditions pose a substantial financial burden to many households, particularly those with low incomes and general pharmaceutical subsidies. Policies are needed to minimize the cost burden of prescription medicines, particularly for low-income working households

Have increases in co-payments for medicines further burdened Australians in remote and disadvantaged areas?

Published abstract of the 28th ICPE 2012 Background: To determine whether the national declines in prescription medicine use occurring after the Co-payments for publically-subsidised medicines in Australia were increased by 21% in 2005. Use of many medicines fell at the national-level after this rise in co-payments. Objectives: To determine whether the 21% increase copayments impacted on all areas of Australia or was specific to remote and disadvantaged areas. Methods: Observed dispensing of proton pump inhibitors (PPIs) and statins were obtained for 1392 statistical local areas (SLA) of Australia in 2004 and 2006. Ratios of observed/expected dispensing (dispensing ratios) for each SLA were calculated. Expected dispensing was based on national dispensing rates and age-standardised to each SLA. Expected dispensing for 2006 was based on pre-2005 prescription trends. Mean dispensing ratios for each medicine and year were calculated for all remoteness and disadvantage groups. Generalised regression models compared the percentage change in dispensing ratios from 2004 to 2006. Results: Between 2004 and 2006 PPIs dispensing fell significantly in major cities (-13.7%, 95% CI = -17.3 to - 9.8), inner regional (-14.0, 95% CI = -19.5 to -8.2), outer regional (-14.6%, 95% CI = -19.9 to -9.0) and remote areas (-9.4%, 95% CI = -16.4 to -1.8). Statins dispensing fell in all groups but the most remote (range 6–7%).When focussing on disadvantage, PPI dispensing fell significantly in all groups (range 12–15%). Statins dispensing did not fall significantly in the most disadvantaged areas (-2.9%, 95% CI = -8.6–3.2) but did in the least and second-least disadvantaged areas (-6.5%, 95% CI = -11.3 to -1.5, and -5.8, 95% CI = -10.5 to -0.9, respectively). Dispensing of PPIs and statins in the most remote and disadvantaged areas remained substantially below levels expected for Australia after the 21% co-payments increase. Conclusions: The findings suggest that the 2005 21% in patient co-payments adversely impacted on prescription medicine use in all areas of Australia and was not specific to remote or disadvantaged areas. Indeed, dispensing of statins fell significantly in all areas but the most remote and disadvantaged, and the existing gap in dispensing of PPIs and statins was not widened by the co-payments increase. PPIs, which are used at above-prevalence rates in Australia and have cheaper over-the-counter substitutes available, were more sensitive to co-payment increases than statins

From the city to the bush: Increases in patient co-payments for medicines have impacted on medicine use across Australia

Aim. To determine whether the national declines in prescription medicine use occurring after the 2005 21% increase in co-payments affected all areas of Australia or were specific to remote and disadvantaged areas. Methods. Observed dispensing of proton pump inhibitors (PPIs) and statins were obtained for 1392 statistical local areas (SLA) of Australia in 2004 and 2006. Expected dispensing was based on national dispensing rates and was age standardised to each SLA. Expected dispensing for 2006 was based on pre-2005 prescription trends. Ratios of observed to expected dispensing (dispensing ratios) for each SLA were calculated. Mean dispensing ratios for each medicine and year were calculated for all remoteness and disadvantage groups. Generalised regression models compared the percentage change in dispensing ratios from 2004 to 2006. Results. Between 2004 and 2006 PPI dispensing fell significantly in major cities (-13.7%, 95% CI less than or equal to -17.3 - 9.8), inner regional (-14.0, 95%CI less than or equal to -19.5 - 8.2), outer regional (-14.6%, 95%CI less than or equal to -19.9 - 9.0) and remote areas (-9.4%, 95%CI less than or equal to -16.4 - 1.8). Statin dispensing fell in all groups but the most remote (range 6-7%). When focussing on disadvantage, PPI dispensing fell significantly in all groups (range 12-15%). Statins dispensing did not fall significantly in the most disadvantaged areas (-2.9%, 95%CI less than or equal to -8.6-3.2) but did in the least (-6.5%, -11.3 - 1.5) and second-least (-5.8, -10.5 - 0.9) disadvantaged areas. Dispensing of PPIs and statins in the most remote and disadvantaged areas remained substantially below levels expected for Australia after the 21% co-payments increase. Conclusions. The findings suggest that the 2005 21% in patient co-payments adversely affected prescription medicine use in all areas of Australia and was not specific to remote or disadvantaged areas. Indeed, dispensing of statins fell significantly in all but the most remote and disadvantaged areas, and the existing gap in dispensing of PPIs and statins was not widened by the co-payments increase. PPIs, which are used at above-prevalence rates in Australia and have cheaper over-the-counter substitutes available, were more sensitive to co-payment increases than were statins. What is known about the topic? Despite high levels of chronic illness in geographically remote and socially disadvantaged areas of Australia, prescription medicine use is generally lowest in these areas. In 2005, co-payments for publically subsidised medicines increased by 21%. After this increase, utilisation of many medicines fell at the national level. It is not known whether these falls in utilisation were specific to remote or disadvantaged areas or if decreases occurred across all areas of Australia. What does this paper add? Between 2004 and 2006 PPI dispensing decreased significantly across all remoteness groups (major cities, inner regional, outer regional and remote areas) and statin dispensing fell significantly in all but remote areas. When focusing on disadvantage groups, dispensing of PPIs fell across Australia, and statins fell significantly in all but the most disadvantaged areas. What are the implications for practitioners? The effect of the 2005 21% increase in co-payments was not specific to remote or disadvantaged areas and was associated with decreases in dispensing across Australia

The impact of co-payment increases on dispensings of government-subsidised medicines in Australia

Purpose: Patient co-payments for medicines subsidised under the Australian Pharmaceutical Benefits Scheme (PBS) increased by 24% in January 2005. We investigated whether this increase and two related co-payment changes were associated with changes in dispensings of selected subsidised medicines in Australia. Method: We analysed national aggregate monthly prescription dispensings for 17 medicine categories, selected to represent a range of treatments (e.g. for diabetes, cardiovascular diseases, gout). Trends in medication dispensings from January 2000 to December 2004 were compared with those from January 2005 to September 2007 using segmented regression analysis. Results: Following the January 2005 increase in PBS co-payments, significant decrease in dispensing volumes were observed in 12 of the 17 medicine categories (range: 3.2-10.9%), namely anti-epileptics, anti-Parkinson\u27s treatments, combination asthma medicines, eye-drops, glaucoma treatments, HmgCoA reductase inhibitors, insulin, muscle relaxants, non-aspirin antiplatelets, osteoporosis treatments, proton-pump inhibitors (PPIs) and thyroxine. The largest decrease was observed for medicines used in treating asymptomatic conditions or those with over-the-counter (OTC) substitutes. Decrease in dispensings to social security beneficiaries was consistently greater than for general beneficiaries following the co-payment changes (range: 1.8-9.4% greater, p = 0.028). Conclusions: The study findings suggest that recent increase in Australian PBS co-payments have had a significant effect on dispensings of prescription medicines. The results suggest large increase in co-payments impact on patients\u27 ability to afford essential medicines. Of major concern is that, despite special subsidies for social security beneficiaries in the Australian system, the recent co-payment increase has particularly impacted on utilisation for this group