Ranking the harm of non-medically used prescription opioids in the UK

A panel of nine experts applied multi-criteria decision analysis (MCDA) to determine the relative overall harm to users and harms to others of street heroin (injected and smoked) and eleven non-medically used prescription opioids. The experts assessed harm scores for each of the 13 opioids on each of 20 harm criteria, weighted the criteria and explored the resulting weighted harm scores for each opioid. Both forms of heroin scored very high: overall harm score of 99 for injected heroin and 72 for smoked heroin on a scale of 0–100. The main feature that distinguishes both forms of street heroin use is that their harm to others is more than five times that of the other eleven opioids. The overall harm score of fentanyl (including injection of fentanyl extracted from patches) and diamorphine (medically prescribed form of heroin) was 54 and 51, respectively, whereas that of orally used opioids ranged from 32 (pethidine) to 11 (codeine-containing pharmaceuticals). Injected street heroin, fentanyl and diamorphine emerged as most harmful to users, with the latter two very low in harm to others. Pethidine, methadone, morphine and oxycodone are also low in harm to others, while moderate in harm to users. We conclude that the overall harms of non-medically used prescription opioids are less than half that of injected street heroin. These data may give a basis for precautionary regulatory measures that should be considered if the rising trend in non-medical use of prescription opioids were to become evident in the UK

“Hot” and “Cold” Cognition in Users of Club Drugs/Novel Psychoactive Substances

Novel psychoactive substances (NPS) are popular “club/party” drugs that first attracted attention in the UK in 2009 and remained legal until the 2016 Psychoactive Substances Act criminalized their distribution. Unlike “traditional” illicit drugs, very little is known about the influence of their analogs on neuropsychological functioning. We characterized the cognitive and emotional profile of NPS/polydrug users using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and EMOTICOM test battery in adult male (aged 20–49 years) recreational users without psychiatric comorbidities (n = 27; “psychonauts”), service users attending a UK specialist “Club Drug” Clinic for problematic use (n = 20) and healthy control volunteers without significant drug-taking histories (n = 35). Tasks were selected to distinguish “hot” cognitive processes that are highly influenced by emotion from “cold” cognitive processes that are largely independent of emotional influence. Both user groups reported significantly higher sensation-seeking traits compared with non-users. Recreational NPS users demonstrated more risk-taking behavior compared with controls and treatment-seeking NPS users showed poorer learning, episodic memory and response inhibition compared with the other two groups. These effects persisted, when controlling for age, intelligence, alcohol and cannabis use severity, nicotine dependence, trait anxiety, depression, childhood adversity, impulsivity, and sensation seeking. Overall, recreational NPS users showed elevated “hot” (emotion-laden) cognition in the absence of “cold” (non-emotional) cognitive deficits, whereas “cold” cognitive dysfunction was pronounced in individuals seeking treatment for problematic NPS use. High trait impulsivity and poor self-control may confer additional risk to NPS/polydrug use severity and separate those seeking treatment from those using NPS recreationally

Heterolytic Scission of Hydrogen Within a Crystalline Frustrated Lewis Pair

We report the heterolysis of molecular hydrogen under ambient conditions by the crystalline frustrated Lewis pair (FLP) 1-{2-[bis (pentafluorophenyOboryl] phenyl -2, 2,6,6-tetrame-thylpiperidine (KCAT). The gas-solid reaction provides an approach to prepare the solvent-free, polycrystalline ion pair KCATH2 through a single crystal to single crystal transformation. The crystal lattice of KCATH2 increases in size relative to the parent KCAT by approximately 2%. Microscopy was used to follow the transformation of the highly colored red/orange KCAT to the colorless KCATH2 over a period of 2 h at 300 K under a flow of H-2 gas. There is no evidence of crystal decrepitation during hydrogen uptake. Inelastic neutron scattering employed over a temperature range from 4-200 K did not provide evidence for the formation of polarized H-2 in a precursor complex within the crystal at low temperatures and high pressures. However, at 300 K, the INS spectrum of KCAT transformed to the INS spectrum of KCATH2. Calculations suggest that the driving force is more favorable in the solid state compared to the solution or gas phase, but the addition of H-2 into the KCAT crystal is unfavorable. Ab Initio methods were used to calculate the INS spectra of KCAT, KCATH2, and a possible precursor complex of H-2 in the pocket between the B and N of crystalline KCAT. Ex-situ NMR showed that the transformation from KCAT to KCATH2 is quantitative and our results suggest that the hydrogen heterolysis process occurs via H-2 diffusion into the FLP crystal with a rate-limiting movement of H-2 from inactive positions to reactive sites.Peer reviewe

Use of contingency management incentives to improve completion of hepatitis B vaccination in people undergoing treatment for heroin dependence: a cluster randomised trial

Background: Poor adherence to treatment diminishes its individual and public health benefit. Financial incentives, provided on the condition of treatment attendance, could address this problem. Injecting drug users are a high-risk group for hepatitis B virus (HBV) infection and transmission, but adherence to vaccination programmes is poor. We aimed to assess whether contingency management delivered in routine clinical practice increased the completion of HBV vaccination in individuals receiving opioid substitution therapy. Methods: In our cluster randomised controlled trial, we enrolled participants at 12 National Health Service drug treatment services in the UK that provided opioid substitution therapy and nurse-led HBV vaccination with a super-accelerated schedule (vaccination days 0, 7, and 21). Clusters were randomly allocated 1:1:1 to provide vaccination without incentive (treatment as usual), with fixed value contingency management (three £10 vouchers), or escalating value contingency management (£5, £10, and £15 vouchers). Both contingency management schedules rewarded on-time attendance at appointments. The primary outcome was completion of clinically appropriate HBV vaccination within 28 days. We also did sensitivity analyses that examined vaccination completion with full adherence to appointment times and within a 3 month window. The trial is registered with Current Controlled Trials, number ISRCTN72794493. Findings: Between March 16, 2011, and April 26, 2012, we enrolled 210 eligible participants. Compared with six (9%) of 67 participants treated as usual, 35 (45%) of 78 participants in the fixed value contingency management group met the primary outcome measure (odds ratio 12·1, 95% CI 3·7–39·9; p<0·0001), as did 32 (49%) of 65 participants in the escalating value contingency management group (14·0, 4·2–46·2; p<0·0001). These differences remained significant with sensitivity analyses. Interpretation: Modest financial incentives delivered in routine clinical practice significantly improve adherence to, and completion of, HBV vaccination programmes in patients receiving opioid substitution therapy. Achievement of this improvement in routine clinical practice should now prompt actual implementation. Drug treatment providers should employ contingency management to promote adherence to vaccination programmes. The effectiveness of routine use of contingency management to achieve long-term behaviour change remains unknown

Improving GHB withdrawal with baclofen: study protocol for a feasibility study for a randomised controlled trial

Background: GHB (gamma-hydroxybutyrate) and its pro-drugs GBL (gamma-butyrolactone) and 1,4-butanediol (1,4-BD) are central nervous system depressants whose street names include ‘G’ and ‘liquid ecstasy’. They are used recreationally predominately for their stimulant and pro-sexual effects or for sedation to help with sleep and/or to ‘come down’ after using stimulant recreational drugs. Although overall population prevalence is low (0.1 %), in some groups such as men who have sex with men, GHB/GBL use may reach 20 %. GHB/GBL dependence may be associated with severe withdrawal with individuals presenting either acutely to emergency departments or to addiction services for support. Benzodiazepines are currently prescribed for GHB/GBL detoxification but do not prevent all complications, such as behavioural disinhibition, that may require hospitalisation or admission to a high dependency /intensive care unit. The GABAB receptor mediates most effects of GHB/GBL and the GABAB agonist, baclofen, has shown promise as an adjunct to benzodiazepines in reducing withdrawal severity when prescribed both during withdrawal and as a 2-day ‘preload’ prior to detoxification. The key aim of this feasibility study is provide information about recruitment and characteristics of the proposed outcome measure (symptom severity, complications including delirium and treatment escalation) to inform an application for a definitive randomised placebo controlled trial to determine the role of baclofen in the management of GHB/GBL withdrawal and whether starting baclofen 2 days earlier improves outcomes further. Methods/design: This is a prospective, randomised, double-blind, placebo-controlled feasibility study that will recruit participants (aged over 18 years) who are GHB/GBL- dependent and wish to undergo planned GHB/GBL detoxification or are at risk of acute withdrawal and are inpatients requiring unplanned withdrawal. We aim to recruit 88 participants: 28 unplanned inpatients and 60 planned outpatients. During detoxification we will compare baclofen 10 mg three times a day with placebo as an adjunct to the usual benzodiazepine regimen. In the planned outpatient arm, we will also compare a 2-day preload of baclofen 10 mg three times a day with placebo. Ratings of GHB/GBL withdrawal, sleep, depression, anxiety as well as GHB/GBL use will be collected. The main data analyses will be descriptive about recruitment and characterising the impact of adding baclofen to the usual benzodiazepine regimen on measures and outcomes of GHB/GBL withdrawal to provide estimates of variability and effect size. A qualitative approach will evaluate research participant and clinician acceptability and data collected to inform cost-effectiveness. Discussion: This feasibility study will inform a randomised controlled trial to establish whether adding baclofen to a benzodiazepine regimen reduces the severity and complications of GHB/GBL withdrawal

Crop Updates 2005 - Lupins and Pulses

This session covers sixty five papers from different authors: 1. 2004 LUPIN AND PULSE INDUSTRY HIGHLIGHTS, Peter White Department of Agriculture 2. BACKGROUND, Peter White Department of Agriculture 2004 REGIONAL ROUNDUP 3. Northern Agricultural Region, Martin Harries, Department of Agriculture 4. Central Agricultural Region, Ian Pritchard, Department of Agriculture 5. Great Southern and Lakes, Rodger Beermier, Department of Agriculture 6. Esperance Port Zone, Mark Seymour, Department of Agriculture, and David Syme, The Grain Pool of WA LUPIN AND PULSE PRODUCTION AGRONOMY AND GENETIC IMPROVEMENT 7. Lupin, Martin Harries, Department of Agriculture 8. Narrow-leafed lupin breeding, Bevan Buirchell, Department of Agriculture 9. Yellow lupin breeding in Western Australia, Kedar Adhikari, Mark Sweetingham and Bevan Buirchell, Department of Agriculture 10. WALAB2000 - First Anthracnose resistant albus lupins, Kedar Adhikari, Bevan Buirchell, MarkSweetingham and Geoff Thomas, Department of Agriculture 11. Improving lupin grain quality and yield through genetic manipulation of key physiological traits, Jon Clements1 and Bevan Buirchell2,1CLIMA, The University of Western Australia 2Department of Agriculture 12. Lupin alkaloids in four Australian species, Shao Fang Wang, Chemistry Centre (WA), CLIMA, The University of Western Australia 13. Improving lupin tolerance to herbicides of metribuzin, isoxaflutole and carfentrazone-ethyl, Ping Si1, Mark Sweetingham12, Bevan Buirchell12, David Bowran2 and Huaan Yang12 , 1CLIMA, The University of Western Australia, 2Department of Agriculture 14. Combined cultural and shielded sprayer herbicide application for weed management, Martin Harries and Mike Baker Department of Agriculture 15. Field testing of lupin seed of various sources with and without post maturity, pre harvest rain for field establishment, Martin Harries, Wayne Parker, Mike Baker, Department of Agriculture 16. Lupin seed rate by wide row spacing, Martin Harries, Bob French, Damien Owen D’arcy, Department of Agriculture 17. How environment influences row spacing response in lupins, Bob French, Department of Agriculture 18. The effect of wider row spacing on lupin architecture, growth and nutrient uptake dynamics, Bill Bowden and Craig Scanlan, Department of Agriculture 19. Fertiliser placement and application rate in wide rows, Martin Harries, Damien Owen D’arcy, Department of Agriculture 20. The pros and cons of cowing lupins in ‘wide’ rows, Wayne Parker, Bob French and Martin Harries, Department of Agriculture 21. Investigation into the influence of row orientation in lupin crops, Jeff Russell1 and Angie Roe2, 1Department of Agriculture, 2Farm Focus Consultants 22. Making the most of Mandelup, Greg Shea and Chris Matthews, Department of Agriculture 23. The effect of wild radish density and lupin cultivars on their competition at Merredin, Shahab Pathan, Abul Hashem and Bob French, Department of Agriculture 24. The potential of pearl lupin (Lupinus mutabilis) for southern Australia, Jon Clements1, Mark Sweetingham2, Bevan Buirchell2, Sofia Sipsas2, Geoff Thomas2, John Quealy1, Roger Jones2, Clive Francis1, Colin Smith2 and Gordon Francis1, 1CLIMA, University of Western Australia 2Department of Agriculture 25. Field pea, Mark Seymour, Department of Agriculture 26. Breeding highlights, Tanveer. Khan and Bob French, Department of Agriculture 27. Variety evaluation, Tanveer Khan, Kerry Regan, Jenny Garlinge and Rod Hunter, Department of Agriculture 28. Large scale field pea variety trials, Martin Harries, Department of Agriculture 29. Kaspa demonstrations, Rodger Beermier, Mark Seymour, Ian Pritchard, Graham Mussell, Department of Agriculture 30. Field pea harvesting demonstration at Merredin, Glen Riethmuller, Greg Shea and Bob French, Department of Agriculture 31. Does Kaspa respond differently to disease, fungicides, time of sowing or seed rate, Mark Seymour, Department of Agriculture 32. Field pea response to foliar Manganese in mallee district, Mark Seymour, Department of Agriculture 33. Kaspa harvesting observations 2004, Mark Seymour, Ian Pritchard, Glen Riethmuller, Department of Agriculture 34. ‘Blackspot Manager’ for understanding blackspot of peas and ascochyta blight management, Moin Salam and Jean Galloway, Department of Agriculture 35. 250,000 ha of field pea in WA – Is it sustainable? Larn McMurray1 and Mark Seymour2, 1South Australian Research and Development Institute, 2Department of Agriculture 36. Desi chickpea, Wayne Parker, Department of Agriculture 37. Breeding highlights, Tanveer Khan1,2 and Kadambot Siddique2,1Department of Agriculture, 2CLIMA, The University of Western Australia 38. Variety evaluation, Tanveer Khan, Kerry Regan, Jenny Garlinge and Rod Hunter, Department of Agriculture 39. Large scale variety testing of desi chickpeas, Martin Harries, Greg Shea, Mike Baker, Dirranie Kirby, Department of Agriculture 40. Desi variety chickpea trial, Martin Harries and Murray Blyth, Department of Agriculture 41. Seeding rates and row spacing of chickpea desi, Martin Harries, MurrayBlyth, Damien Owen D’arcy, Department of Agriculture 42. Molecular characterisation of chickpea wild relatives, Fucheng Shan, Heather Clarke and Kadambot Siddique, CLIMA, The University of Western Australia 43. Plant phosphorus status has a limited influence on the concentration of phosphorus-mobilising carboxylates in the rhizosphere of chickpea, Madeleine Wouterlood, Hans Lambers and Erik Veneklaas, The University of Western Australia 44. Kabuli chickpea, Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 45. ‘Kimberly Large’ A high quality and high yielding new variety for the Ord River Irrigation Area, Kerry Regan1,2, Kadambot Siddique2, Peter White1,2, Peter Smith1 and Gae Plunkett1,1Department of Agriculture, 2CLIMA, University of Western Australia 46. Development of ascochyta resistant and high quality varieties for Australia, Kadambot Siddique1, Kerry Regan1,2, Tim Pope1 and Mike Baker2, 1CLIMA, The University of Western Australia 2Department of Agriculture 47. Towards double haploids in chickpeas and field pea, Janine Croser, Julia Wilson and Kadambot Siddique, CLIMA, The University of Western Australia 48. Crossing chickpea with wild Cicer relatives to introduce resistance to disease and tolerance to environmental stress, Heather Clarke and Kadambot Siddique, CLIMA, The University of Western Australia 49. Faba bean, Peter White, Department of Agriculture 50. Germplasm evaluation, Peter White1,2, Kerry Regan1,2, Tim Pope2, Martin Harries1, Mark Seymour1, Rodger Beermier1 and Leanne Young1, 1Department of Agriculture, 2CLIMA, The University of Western Australia 51. Lentil, Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 52. Variety and germplasm evaluation, Kerry Regan1,2, Tim Pope2, Leanne Young1, Martin Harries1, Murray Blyth1 and Michael Materne3, 1Department of Agriculture, 2CLIMA, University of Western Australia, 3Department of Primary Industries, Victoria 53. Lathyrus species, Kadambot Siddique1, Kerry Regan2, and Colin Hanbury2, 1CLIMA, the University of Western Australia, 2Department of Agricultur

A Bronze Age Round Barrow Cemetery, Pit Alignments, Iron Age Burials, Iron Age Copper Working, and Later Activity at Four Crosses, Llandysilio, Powys.

Excavation undertaken at the Upper Severn valley round barrow cemetery at Four Crosses, Llandysilio between 2004 and 2006 has increased the known barrows and ring-ditches to some 26 monuments, and revealed additional burials. Based on limited dating evidence, and the data from earlier excavations, the majority of the barrows are thought to be constructed in the Bronze Age. The barrows are part of a larger linear cemetery and the landscape setting and wider significance of this linear barrow cemetery are explored within this report. Dating suggests two barrows were later, Iron Age additions. The excavation also investigated Iron Age and undated pit alignments, Middle Iron Age copper working and a small Romano-British inhumation cemetery and field systems. Much of this evidence reflects the continuing importance of the site for ritual and funerary activity

Psychosocial interventions for supporting women to stop smoking in pregnancy

Background: Tobacco smoking remains one of the few preventable factors associated with complications in pregnancy, and has serious long-term implications for women and babies. Smoking in pregnancy is decreasing in high-income countries, but is strongly associated with poverty and is increasing in low- to middle-income countries. Objectives: To assess the effects of smoking cessation interventions during pregnancy on smoking behaviour and perinatal health outcomes. Search methods: In this sixth update, we searched the Cochrane Pregnancy and Childbirth Group's Trials Register (13 November 2015), checked reference lists of retrieved studies and contacted trial authors. Selection criteria: Randomised controlled trials, cluster-randomised trials, and quasi-randomised controlled trials of psychosocial smoking cessation interventions during pregnancy. Data collection and analysis: Two review authors independently assessed trials for inclusion and trial quality, and extracted data. Direct comparisons were conducted in RevMan, with meta-regression conducted in STATA 14. Main results: The overall quality of evidence was moderate to high, with reductions in confidence due to imprecision and heterogeneity for some outcomes. One hundred and two trials with 120 intervention arms (studies) were included, with 88 trials (involving over 28,000 women) providing data on smoking abstinence in late pregnancy. Interventions were categorised as counselling, health education, feedback, incentives, social support, exercise and dissemination. In separate comparisons, there is high-quality evidence that counselling increased smoking cessation in late pregnancy compared with usual care (30 studies; average risk ratio (RR) 1.44, 95% confidence interval (CI) 1.19 to 1.73) and less intensive interventions (18 studies; average RR 1.25, 95% CI 1.07 to 1.47). There was uncertainty whether counselling increased the chance of smoking cessation when provided as one component of a broader maternal health intervention or comparing one type of counselling with another. In studies comparing counselling and usual care (largest comparison), it was unclear whether interventions prevented smoking relapse among women who had stopped smoking spontaneously in early pregnancy. However, a clear effect was seen in smoking abstinence at zero to five months postpartum (11 studies; average RR 1.59, 95% CI 1.26 to 2.01) and 12 to 17 months (two studies, average RR 2.20, 95% CI 1.23 to 3.96), with a borderline effect at six to 11 months (six studies; average RR 1.33, 95% CI 1.00 to 1.77). In other comparisons, the effect was unclear for most secondary outcomes, but sample sizes were small. Evidence suggests a borderline effect of health education compared with usual care (five studies; average RR 1.59, 95% CI 0.99 to 2.55), but the quality was downgraded to moderate as the effect was unclear when compared with less intensive interventions (four studies; average RR 1.20, 95% CI 0.85 to 1.70), alternative interventions (one study; RR 1.88, 95% CI 0.19 to 18.60), or when smoking cessation health education was provided as one component of a broader maternal health intervention. There was evidence feedback increased smoking cessation when compared with usual care and provided in conjunction with other strategies, such as counselling (average RR 4.39, 95% CI 1.89 to 10.21), but the confidence in the quality of evidence was downgraded to moderate as this was based on only two studies and the effect was uncertain when feedback was compared to less intensive interventions (three studies; average RR 1.29, 95% CI 0.75 to 2.20). High-quality evidence suggests incentive-based interventions are effective when compared with an alternative (non-contingent incentive) intervention (four studies; RR 2.36, 95% CI 1.36 to 4.09). However pooled effects were not calculable for comparisons with usual care or less intensive interventions (substantial heterogeneity, I2 = 93%). High-quality evidence suggests the effect is unclear in social support interventions provided by peers (six studies; average RR 1.42, 95% CI 0.98 to 2.07), in a single trial of support provided by partners, or when social support for smoking cessation was provided as part of a broader intervention to improve maternal health. The effect was unclear in single interventions of exercise compared to usual care (RR 1.20, 95% CI 0.72 to 2.01) and dissemination of counselling (RR 1.63, 95% CI 0.62 to 4.32). Importantly, high-quality evidence from pooled results demonstrated that women who received psychosocial interventions had a 17% reduction in infants born with low birthweight, a significantly higher mean birthweight (mean difference (MD) 55.60 g, 95% CI 29.82 to 81.38 g higher) and a 22% reduction in neonatal intensive care admissions. However the difference in preterm births and stillbirths was unclear. There did not appear to be adverse psychological effects from the interventions. The intensity of support women received in both the intervention and comparison groups has increased over time, with higher-intensity interventions more likely to have higher-intensity comparisons, potentially explaining why no clear differences were seen with increasing intervention intensity in meta-regression analyses. Among meta-regression analyses: studies classified as having 'unclear' implementation and unequal baseline characteristics were less effective than other studies. There was no clear difference between trials implemented by researchers (efficacy studies), and those implemented by routine pregnancy staff (effectiveness studies), however there was uncertainty in the effectiveness of counselling in four dissemination trials where the focus on the intervention was at an organisational level. The pooled effects were similar in interventions provided for women classified as having predominantly low socio-economic status, compared to other women. The effect was significant in interventions among women from ethnic minority groups; however not among indigenous women. There were similar effect sizes in trials with biochemically validated smoking abstinence and those with self-reported abstinence. It was unclear whether incorporating use of self-help manuals or telephone support increased the effectiveness of interventions. Authors' conclusions: Psychosocial interventions to support women to stop smoking in pregnancy can increase the proportion of women who stop smoking in late pregnancy and the proportion of infants born low birthweight. Counselling, feedback and incentives appear to be effective, however the characteristics and context of the interventions should be carefully considered. The effect of health education and social support is less clear. New trials have been published during the preparation of this review and will be included in the next update