The Effect of Dietary Supplementation on Aggressive Behaviour in Australian Adult Male Prisoners: A Feasibility and Pilot Study for a Randomised, Double Blind Placebo Controlled Trial.

This study aimed to assess the feasibility of conducting a nutrition trial in adult male prisoners. Adult male prisoners were recruited for a 16-week randomised control trial comparing the effect of ingestion of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) and multivitamin supplements versus placebo on aggressive behaviour. The baseline and post-intervention assessments from the participant blood samples were the erythrocyte n-3 LCPUFA levels as well as measures of aggressive behaviour determined through institutional records of misconduct (IRM), the Inmate Behaviour Observation Scale (IBOS), and questionnaires. A total of 136 adult male prisoners consented to the study with a retention rate of 60%, and 93% of blood samples were successfully collected. The IRM and IBOS scores were collected for 100% of participants, whilst 82-97% of participants completed the questionnaires. From the baseline data, the Odds Ratio shows that prisoners are 4.3 times more likely to have an IBOS >2 if they are below the 6% cut off on the omega-3 index. Both groups improved across all outcome measures and, at the current sample size, no significant differences were seen between them. A power calculation suggests a total sample size of 600 participants is required to detect the effects of this dietary supplementation, and that this supplementation study is feasible in a Correctional Centre. Important criteria for the exclusion and consideration of logistics and compliance are presented.

Correction: Baseline Omega-3 Index Correlates with Aggressive and Attention Deficit Disorder Behaviours in Adult Prisoners.

[This corrects the article DOI: 10.1371/journal.pone.0120220.].

Baseline omega-3 index correlates with aggressive and attention deficit disorder behaviours in adult prisoners.

BACKGROUND: There is emerging evidence that the supplementation of omega-3 contributes to a decrease in aggressive behaviour in prison populations. A challenge of such research is achieving statistical power against effect sizes which may be affected by the baseline omega-3 index. There are no published data on the blood omega-3 index with studies of this kind to assess the variability of the blood omega-3 index in conjunction with aggression and attention deficit assessments. OBJECTIVE: To determine if the variance of the omega-3 index is correlated with aggressive and attention deficit behaviour in a prison population. DESIGN: 136 adult male prisoners were recruited from South Coast Correctional Centre (SCCC), NSW Australia. A 7 point categorisation was used to quantify levels of aggressive behaviour (4 weeks) from individual SCCC case notes, whereby higher scores correspond to increasingly aggressive behaviour. Study participants completed the Aggression Questionnaire (AQ) and the Brown's Attention Deficit Disorder Scales (BADDS), provided a blood sample for erythrocyte fatty acid analysis using gas chromatography and the omega-3 index was calculated. RESULTS: The baseline omega-3 index ranged from 2.3% to 10.3%, indicating that some participants already had substantial omega-3 intake, however a median of 4.7% indicated a lower overall omega-3 intake than the general Australian population. Assessment of aggressive and attention deficit behaviour shows that there were negative correlations between baseline omega-3 index and baseline aggression categorisation scores (r = -0.21, P = 0.016); total AQ score (r = -0.234, P = 0.011); Anger (r = -0.222 p = 0.016); Hostility AQ (r = -0.239, P = 0.009); indirect aggression (r = -0.188 p = 0.042); total BADDS (r = -0.263, p = 0.005); Activation (r = -0.224, p = 0.016); Attention (r = -0.192, p = 0.043); Effort (r = -0.253, p = 0.007); Affect (r = -0.330, p = 0.000) and Memory (r = -0.240, p = 0.010). CONCLUSIONS: There is a high variability in omega-3 status of a NSW prison population, and inmates with lower omega-3 index were more aggressive and had higher ADD scores.

Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses.

BACKGROUND: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. METHODS: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). RESULTS: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m(2). MTD was 10 mg/m(2); DLTs at 12 (2/4 patients) and 10 mg/m(2) (3/12) included thrombocytopenia and febrile neutropenia; diarrhoea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1-10 mg/m(2). Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. CONCLUSIONS: TP300 had predictable hematologic toxicity, and diarrhoea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage. TRIAL REGISTRATION: EU-CTR2006-001345-33.

A phase I pharmacokinetic and pharmacodynamic study of the farnesyl transferase inhibitor BMS-214662 in combination with cisplatin in patients with advanced solid tumors.

PURPOSE: BMS-214662 is a potent and selective inhibitor of the farnesyl transferase enzyme with in vitro and in vivo antitumor activity. The aims of this study were to characterize the toxicities and to determine the pharmacokinetic profiles of BMS-214662 when administered in combination with cisplatin, and to determine the constitutive farnesyltransferase activity as a surrogate pharmacodynamic end point. EXPERIMENTAL DESIGN: Twenty-nine patients with advanced solid malignancy, refractory to conventional therapy, and with adequate hematological, renal, and hepatic function were treated with escalating doses of BMS-214662 administered as a 1-h infusion, followed after an interval of 30 min by 75 mg/m(2) cisplatin administered as a 4-h infusion and repeated every 21 days. Blood and urine samples for pharmacokinetic and pharmacodynamic analyses were collected during the first cycle of treatment only. RESULTS: Dose-limiting toxicities occurred in 4 of 9 patients enrolled at the 225 mg/m(2) BMS-214662 dose cohort, and included elevation of hepatic transaminases, nausea, vomiting, diarrhea, and renal failure. There was no apparent pharmacokinetic interaction between the two drugs at the recommended dose levels, and a dose-dependent inhibition of farnesyltransferase activity was observed, which returned to control levels within 24 h of drug administration. There were no objective responses, but disease stabilization was observed in 15 patients, including 4 patients with stable disease after 6 cycles of treatment. CONCLUSIONS: A dose of 200 mg/m(2) of BMS-214662 administered as a 1-h infusion with 75 mg/m(2) cisplatin over 4 h is the recommended dose for additional studies.