Enhancing the use of opioids in pain management: antinociceptive potentiation with opioid agonist/antagonist combinations.

While opioids are the most effective and widely used class of drug for the management of moderate to severe pain, their use may be limited by adverse effects that are unpleasant and potentially dangerous. Research is increasingly directed towards strategies to improve the use of opioids in pain management, investigating methods by which the analgesia afforded by an opioid may be enhanced, while minimising adverse effects. One approach that has produced promising findings in animal studies and some clinical reports is the combination of an opioid agonist and "ultra-low" (nanomole) doses of an opioid antagonist. A recent animal study reported that antinociception may be significantly enhanced with the combination of the partial opioid agonist/antagonist buprenorphine and ultra-low doses of the antagonist naloxone. The central aim of the studies described herein was to investigate the effect of this drug combination on response to experimental nociceptive stimuli and the incidence and severity of adverse effects among healthy volunteers. The first study established normative responses to two commonly used nociceptive tests, the cold pressor and electrical stimulation tests, in 100 healthy volunteers. The effect of buprenorphine on nociceptive test performance had not previously been determined, therefore a dose-ranging study of buprenorphine was conducted to establish a doseresponse relationship. The subsequent two studies investigated the effect of a range of buprenorphine:naloxone IV dose ratios (5:1, 10:1, 12.5:1, 15:1, 20:1 and 25:1) on nociception and adverse effects among healthy volunteers. These studies are the first to investigate the combination of buprenorphine and ultra-low dose antagonist in humans, and the first to assess the agonist:antagonist combination in an experimental model of human nociception. Antinociception was significantly enhanced with the combination of buprenorphine and naloxone in the 12.5:1 and 15:1 ratios. Moreover, this enhanced antinociception occurred without a simultaneous increase in adverse effects and indeed with a reduction in the severity of some effects. An agent that produces greater analgesia and reduces adverse effects has the potential to overcome some of the barriers that limit the use of opioids in pain management. The current findings indicate that further investigation of this drug combination is warranted.Thesis (Ph.D.) -- University of Adelaide, Dept. of Clinical and Experimental Pharmacology, 200

Sprouting suppression and mushroom production after inoculation of Juglans x intermedia stumps with edible fungi species

Removal of stumps and suppression of sprouts after harvesting by conventional methods, such as using heavy machinery or herbicides, alters the physico-chemical characteristics of soil, may cause environmental damage and can be very costly. In this study, the performance of inoculation with edible fungi as a biological alternative for stump degradation, has been examined in walnut plantations of five Spanish provinces. Stumps were inoculated with two species of edible fungi: Pleurotus ostreatus (Jacq. Ex Fr.) P. Kumm and Lentinula edodes (Berk) Pené. Compared with untreated controls, the two biological treatments resulted in a significant and evident reduction of the sprouting probability, which was stronger than the result obtained with chemical treatments. Inoculated stumps also produced edible sporocarps, averaging 15.58 g per stump during the first year. This article constitutes the basis for the development of a sustainable, environmentally friendly and cost-effective product, which is a bioeconomy-based solution for stump degradation in intensive plantations

Cost-effectiveness of 13-valent pneumococcal conjugate vaccination in Mongolia.

OBJECTIVE: The Ministry of Health (MOH), Mongolia, is considering introducing 13-valent pneumococcal conjugate vaccine (PCV13) in its national immunization programme to prevent the burden of disease caused by Streptococcus pneumoniae. This study evaluates the cost-effectiveness and budget impact of introducing PCV13 compared to no PCV vaccination in Mongolia. METHODS: The incremental cost-effectiveness ratio (ICER) of introducing PCV13 compared to no PCV vaccination was assessed using an age-stratified static multiple cohort model. The risk of various clinical presentations of pneumococcal disease (meningitis, pneumonia, non-meningitis non-pneumonia invasive pneumococcal disease and acute otitis media) at all ages for thirty birth cohorts was assessed. The analysis considered both health system and societal perspectives. A 3+0 vaccine schedule and price of US$3.30 per dose was assumed for the baseline scenario based on Gavi, the Vaccine Alliance's advance market commitment tail price. RESULTS: The ICER of PCV13 introduction is estimated at US$52 per disability-adjusted life year (DALY) averted (health system perspective), and cost-saving (societal perspective). Although indirect effects of PCV have been well-documented, a conservative scenario that does not consider indirect effects estimated PCV13 introduction to cost US$79 per DALY averted (health system perspective), and US$19 per DALY averted (societal perspective). Vaccination with PCV13 is expected to cost around US$920,000 in 2016, and thereafter US$820,000 every year. The programme is likely to reduce direct disease-related costs to MOH by US$440,000 in the first year, increasing to US$510,000 by 2025. CONCLUSION: Introducing PCV13 as part of Mongolia's national programme appears to be highly cost-effective when compared to no vaccination and cost-saving from a societal perspective at vaccine purchase prices offered through Gavi. Notwithstanding uncertainties around some parameters, cost-effectiveness of PCV introduction for Mongolia remains robust over a range of conservative scenarios. Availability of high-quality national data would improve future economic analyses for vaccine introduction

Implementation of a national school-based Human Papillomavirus (HPV) vaccine campaign in Fiji: knowledge, vaccine acceptability and information needs of parents.

BACKGROUND: In 2008 Fiji implemented a nationwide Human Papillomavirus (HPV) vaccine campaign targeting all girls aged 9-12 years through the existing school-based immunisation program. Parents of vaccine-eligible girls were asked to provide written consent for vaccination. The purpose of this study was to describe parents' knowledge, experiences and satisfaction with the campaign, the extent to which information needs for vaccine decision-making were met, and what factors were associated with vaccine consent. METHODS: Following vaccine introduction, a cross-sectional telephone survey was conducted with parents of vaccine-eligible girls from randomly selected schools, stratified by educational district. Factors related to vaccine consent were explored using Generalised Estimating Equations. RESULTS: There were 560 vaccine-eligible girls attending the participating 19 schools at the time of the campaign. Among these, 313 parents could be contacted, with 293 agreeing to participate (93.6%). Almost 80% of participants reported having consented to HPV vaccination (230/293, 78.5%). Reported knowledge of cervical cancer and HPV prior to the campaign was very low. Most respondents reported that they were satisfied with their access to information to make an informed decision about HPV vaccination (196/293, 66.9%). and this was very strongly associated with provision of consent. Despite their young age, the vaccine-eligible girls were often involved in the discussion and decision-making. Most consenting parents were satisfied with the campaign and their decision to vaccinate, with almost 90% indicating they would consent to future HPV vaccination. However, negative media reports about the vaccine campaign created confusion and concern. Local health staff were cited as a trusted source of information to guide decision-making. Just over half of the participants who withheld consent cited vaccine safety fears as the primary reason (23/44, 52.3%). CONCLUSION: This is the first reported experience of HPV introduction in a Pacific Island nation. In a challenging environment with limited community knowledge of HPV and cervical cancer, media controversy and a short lead-time for community education, Fiji has implemented an HPV vaccine campaign that was largely acceptable to the community and achieved a high level of participation. Community sensitisation and education is critical and should include a focus on the local health workforce and the vaccine target group

Implementation of a national school-based Human Papillomavirus (HPV) vaccine campaign in Fiji: knowledge, vaccine acceptability and information needs of parents

BACKGROUND: In 2008 Fiji implemented a nationwide Human Papillomavirus (HPV) vaccine campaign targeting all girls aged 9–12 years through the existing school-based immunisation program. Parents of vaccine-eligible girls were asked to provide written consent for vaccination. The purpose of this study was to describe parents’ knowledge, experiences and satisfaction with the campaign, the extent to which information needs for vaccine decision-making were met, and what factors were associated with vaccine consent. METHODS: Following vaccine introduction, a cross-sectional telephone survey was conducted with parents of vaccine-eligible girls from randomly selected schools, stratified by educational district. Factors related to vaccine consent were explored using Generalised Estimating Equations. RESULTS: There were 560 vaccine-eligible girls attending the participating 19 schools at the time of the campaign. Among these, 313 parents could be contacted, with 293 agreeing to participate (93.6 %). Almost 80 % of participants reported having consented to HPV vaccination (230/293, 78.5 %). Reported knowledge of cervical cancer and HPV prior to the campaign was very low. Most respondents reported that they were satisfied with their access to information to make an informed decision about HPV vaccination (196/293, 66.9 %). and this was very strongly associated with provision of consent. Despite their young age, the vaccine-eligible girls were often involved in the discussion and decision-making. Most consenting parents were satisfied with the campaign and their decision to vaccinate, with almost 90 % indicating they would consent to future HPV vaccination. However, negative media reports about the vaccine campaign created confusion and concern. Local health staff were cited as a trusted source of information to guide decision-making. Just over half of the participants who withheld consent cited vaccine safety fears as the primary reason (23/44, 52.3 %). CONCLUSION: This is the first reported experience of HPV introduction in a Pacific Island nation. In a challenging environment with limited community knowledge of HPV and cervical cancer, media controversy and a short lead-time for community education, Fiji has implemented an HPV vaccine campaign that was largely acceptable to the community and achieved a high level of participation. Community sensitisation and education is critical and should include a focus on the local health workforce and the vaccine target group.This work was funded by the Australian Aid Program. Helen Marshall acknowledges support of the National Health and Medical Research Council of Australia: Career Development Fellowship (1084951)

Supporting local planning and budgeting for maternal, neonatal and child health in the Philippines.

BACKGROUND: Responsibility for planning and delivery of health services in the Philippines is devolved to the local government level. Given the recognised need to strengthen capacity for local planning and budgeting, we implemented Investment Cases (IC) for Maternal, Neonatal and Child Health (MNCH) in three selected sub-national units: two poor, rural provinces and one highly-urbanised city. The IC combines structured problem-solving by local policymakers and planners to identify key health system constraints and strategies to scale-up critical MNCH interventions with a decision-support model to estimate the cost and impact of different scaling-up scenarios. METHODS: We outline how the initiative was implemented, the aspects that worked well, and the key limitations identified in the sub-national application of this approach. RESULTS: Local officials found the structured analysis of health system constraints helpful to identify problems and select locally appropriate strategies. In particular the process was an improvement on standard approaches that focused only on supply-side issues. However, the lack of data available at the local level is a major impediment to planning. While the majority of the strategies recommended by the IC were incorporated into the 2011 plans and budgets in the three study sites, one key strategy in the participating city was subsequently reversed in 2012. Higher level systemic issues are likely to have influenced use of evidence in plans and budgets and implementation of strategies. CONCLUSIONS: Efforts should be made to improve locally-representative data through routine information systems for planning and monitoring purposes. Even with sound plans and budgets, evidence is only one factor influencing investments in health. Political considerations at a local level and issues related to decentralisation, influence prioritisation and implementation of plans. In addition to the strengthening of capacity at local level, a parallel process at a higher level of government to relieve fund channelling and coordination issues is critical for any evidence-based planning approach to have a significant impact on health service delivery

Pneumococcal carriage in children in Ulaanbaatar, Mongolia before and one year after the introduction of the 13-valent pneumococcal conjugate vaccine.

BACKGROUND: Nasopharyngeal carriage of Streptococcus pneumoniae precedes disease, is the source of pneumococcal community spread, and the mechanism for herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few PCV impact studies in low- and middle-income countries, particularly in Asia. In 2016, Mongolia introduced the 13-valent PCV (PCV13) in a phased manner using a 2 + 1 schedule, with catch-up. We aimed to assess the impact of PCV13 introduction on nasopharyngeal pneumococcal carriage and density in children in Mongolia. METHODS: We conducted two cross-sectional carriage surveys (pre- and one year post-PCV) at community health clinics in two districts of the capital city, Ulaanbaatar in both May-July 2015 and 2017. The study analysis included 961 children too young to be vaccinated (5-8 weeks old) and 989 children eligible for vaccination (12-23 months old). Pneumococci were detected by quantitative real-time PCR and molecular serotyping performed using DNA microarray. FINDINGS: One year post-PCV introduction, PCV13 serotype carriage reduced by 52% in 12-23 month olds (adjusted prevalence ratio [aPR] 0.48 [95% confidence interval [CI] 0.39-0.59]), with evidence of non-PCV13 serotype replacement (aPR 1.55 [95% CI 1.30-1.85]), compared with the pre-PCV period. In 5-8 week olds, PCV13 serotype carriage reduced by 51% (aPR 0.49 [95% CI 0.33-0.73]) with no significant change in non-PCV13 serotype carriage (aPR 1.10 [95% CI 0.83-1.46]). An increase was observed in both PCV13 and non-PCV13 pneumococcal density post-PCV introduction. Antimicrobial resistance (AMR) genes were common, with 82.3% of samples containing at least one of the 10 AMR genes assessed. CONCLUSION: This study demonstrates substantive PCV13 impact on pneumococcal carriage one year post-vaccine introduction in Mongolia. The reductions in PCV13 serotype carriage are likely to result in reductions in pneumococcal disease including indirect effects. Increases in non-PCV13 serotypes require further monitoring

Providing oxygen to children in hospitals: a realist review

OBJECTIVE: To identify and describe interventions to improve oxygen therapy in hospitals in low-resource settings, and to determine the factors that contribute to success and failure in different contexts. METHODS: Using realist review methods, we scanned the literature and contacted experts in the field to identify possible mechanistic theories of how interventions to improve oxygen therapy systems might work. Then we systematically searched online databases for evaluations of improved oxygen systems in hospitals in low- or middle-income countries. We extracted data on the effectiveness, processes and underlying theory of selected projects, and used these data to test the candidate theories and identify the features of successful projects. FINDINGS: We included 20 improved oxygen therapy projects (45 papers) from 15 countries. These used various approaches to improving oxygen therapy, and reported clinical, quality of care and technical outcomes. Four effectiveness studies demonstrated positive clinical outcomes for childhood pneumonia, with large variation between programmes and hospitals. We identified factors that help or hinder success, and proposed a practical framework depicting the key requirements for hospitals to effectively provide oxygen therapy to children. To improve clinical outcomes, oxygen improvement programmes must achieve good access to oxygen and good use of oxygen, which should be facilitated by a broad quality improvement capacity, by a strong managerial and policy support and multidisciplinary teamwork. CONCLUSION: Our findings can inform practitioners and policy-makers about how to improve oxygen therapy in low-resource settings, and may be relevant for other interventions involving the introduction of health technologies

The EUropean-VGOS Project

In Spring 2018 the Bonn correlation centre\ua0started a collaboration with the three European stations\ua0of Wettzell, Onsala and Yebes, equipped with\ua0both S/X- and broadband systems, to perform VGOS-like test sessions. The aim is to verify and develop further\ua0the processing chain for VGOS experiments end-to-end, from the scheduling to the analysis of the derived\ua0observables. We will present the current status of\ua0the project

Determining the pneumococcal conjugate vaccine coverage required for indirect protection against vaccine-type pneumococcal carriage in low and middle-income countries: a protocol for a prospective observational study

Pneumococcal conjugate vaccines (PCVs) prevent disease through both direct protection of vaccinated individuals and indirect protection of unvaccinated individuals by reducing nasopharyngeal (NP) carriage and transmission of vaccine-type (VT) pneumococci. While the indirect effects of PCV vaccination are well described, the PCV coverage required to achieve the indirect effects is unknown. We will investigate the relationship between PCV coverage and VT carriage among undervaccinated children using hospital-based NP pneumococcal carriage surveillance at three sites in Asia and the Pacific.We are recruiting cases, defined as children aged 2-59 months admitted to participating hospitals with acute respiratory infection in Lao People's Democratic Republic, Mongolia and Papua New Guinea. Thirteen-valent PCV status is obtained from written records. NP swabs are collected according to standard methods, screened using lytA qPCR and serotyped by microarray. Village-level vaccination coverage, for the resident communities of the recruited cases, is determined using administrative data or community survey. Our analysis will investigate the relationship between VT carriage among undervaccinated cases (indirect effects) and vaccine coverage using generalised estimating equations.Ethical approval has been obtained from the relevant ethics committees at participating sites. The results are intended for publication in open-access peer-reviewed journals and will demonstrate methods suitable for low- and middle-income countries to monitor vaccine impact and inform vaccine policy makers about the PCV coverage required to achieve indirect protection