Enhancing Immunogenicity of a 3’aminomethylnicotine-DT-Conjugate Anti-Nicotine Vaccine With CpG Adjuvant in Mice and Non-Human Primates.

Enhancing immunogenicity of a 3’aminomethylnicotine-DT-conjugate anti-nicotine vaccine with CpG adjuvant in mice and non-human primates.

Int Immunopharmacol. 2013 Apr 2;
McCluskie MJ, Pryde DC, Gervais DP, Stead DR, Zhang N, Benoit M, Robertson K, Kim IJ, Tharmanathan T, Merson JR, Davis HL

Tobacco smoking is one of the most preventable causes of morbidity and mortality, but current smoking cessation treatments have relatively poor long term efficacy. Anti-nicotine vaccines offer a novel mechanism of action whereby anti-nicotine antibodies (Ab) in circulation prevent nicotine from entering the brain, thus avoiding the reward mechanisms that underpin nicotine addiction. Since antibody responses are typically long lasting, such vaccines could potentially lead to better long-term smoking cessation outcomes. Clinical trials of anti-nicotine vaccines to date have not succeeded, although there was evidence that very high anti-nicotine Ab titers could lead to improved smoking cessation outcomes, suggesting that achieving higher titers in more subjects might result in better efficacy overall. In this study, we evaluated CpG (TLR9 agonist) and aluminum hydroxide (Al(OH)3) adjuvants with a model anti-nicotine antigen comprising trans-3’aminomethylnicotine (3’AmNic) conjugated to diphtheria toxoid (DT). Anti-nicotine Ab titers were significantly higher in both mice and non-human primates (NHP) when 3’AmNic-DT was administered with CpG/Al(OH)3 than with Al(OH)3 alone, and affinity was enhanced in mice. CpG also improved functional responses, as measured by nicotine brain levels in mice after intravenous administration of radiolabeled nicotine (30% versus 3% without CpG), or by nicotine binding capacity of NHP antisera (15-fold higher with CpG). Further improvement should focus on maximizing Ab function, which takes into account both titer and avidity, and this may require improved conjugate design in addition to adjuvants. HubMed – addiction


ZNF804A and cortical thickness in schizophrenia and bipolar disorder.

Psychiatry Res. 2013 Apr 4;
Bergmann O, Haukvik UK, Brown AA, Rimol LM, Hartberg CB, Athanasiu L, Melle I, Djurovic S, Andreassen OA, Dale AM, Agartz I

ZNF804A SNP rs1344706 confers genome-wide risk for schizophrenia and bipolar disorder. Both disorders affect cortical thickness. To determine if single nucleotide polymorphisms (SNPs) across ZNF804A are associated with cortical thinning, we investigated 63 SNPs (including rs1344706) in 365 psychosis patients and healthy controls. Results show no significant associations. HubMed – addiction


Ultra-rapid screening for substance-use disorders: The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST-Lite).

Drug Alcohol Depend. 2013 Apr 2;
Ali R, Meena S, Eastwood B, Richards I, Marsden J

BACKGROUND: The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST 3.0; index test) is a structured interview for alcohol, tobacco, cannabis, stimulants, sedatives and opioid use disorders in general medical settings. Perceived administration time deters routine use. This study releases a short-form: the ASSIST-Lite. METHODS: Diagnostic accuracy study among 2082 adults recruited from general medical (70%) and specialist mental health/addiction treatment services (22%). Current DSM-IV substance dependence (MINI International Neuropsychiatric Interview) and moderate-severe tobacco dependence (Fagerstrom Nicotine Dependence Test) were reference standards. Exploratory factor and item-response theory models re-calibrated ordinal test items. Items for the ASSIST-Lite were selected by diagnostic accuracy evaluation (area under the receiver-operating characteristic [AUC] curve [?0.7]), sensitivity, specificity, positive and negative predictive values [PVP, NVP], kappa, likelihood ratios [LR+, LR-], and clinical utility index [CU+, CU-]). RESULTS: For each substance an item pair was selected (AUC [0.8-1.0], sensitivity [0.8-1.0], specificity [0.7-0.8], PVP [0.8-1.0], NVP [0.7-1.0], kappa [0.5-0.9], LR+ [2.5-5.9], LR- [0.0-0.2], CU+ [0.7-0.9], and CU- [0.5-0.8]). Gender, age and recruitment setting (specialist mental health versus general medical) did not moderate accuracy, with the exception of opioids (AUC <0.7, participants ?59 years). Male opioid users had more severe substance involvement scores that females (differential item functioning analysis, P=0.00). There was no evidence of differential accuracy between countries (AUC range, 0.8-1.0). CONCLUSION: The ASSIST-Lite is an ultra-rapid screener which has been optimised for general medical settings. Optionally, a criterion question can be added to capture hazardous drinking, and to capture use of another type of mood-altering substance. HubMed – addiction


Improving access to analgesic drugs for patients with cancer in sub-Saharan Africa.

Lancet Oncol. 2013 Apr; 14(4): e176-82
O’Brien M, Mwangi-Powell F, Adewole IF, Soyannwo O, Amandua J, Ogaja E, Okpeseyi M, Ali Z, Kiwanuka R, Merriman A

WHO expects the burden of cancer in sub-Saharan Africa to grow rapidly in coming years and for incidence to exceed 1 million per year by 2030. As a result of late presentation to health facilities and little access to diagnostic technology, roughly 80% of cases are in terminal stages at the time of diagnosis, and a large proportion of patients have moderate to severe pain that needs treatment with opioid analgesics. However, consumption of opioid analgesics in the region is low and data suggest that at least 88% of cancer deaths with moderate to severe pain are untreated. Access to essential drugs for pain relief is limited by legal and regulatory restrictions, cultural misperceptions about pain, inadequate training of health-care providers, procurement difficulties, weak health systems, and concerns about diversion, addiction, and misuse. However, recent initiatives characterised by cooperation between national governments and local and international non-governmental organisations are improving access to pain relief. Efforts underway in Uganda, Kenya, and Nigeria provide examples of challenges faced and innovative approaches adopted and form the basis of a proposed framework to improve access to pain relief for patients with cancer across the region. HubMed – addiction