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An international double-blind randomized placebo controlled study evaluated the safety and efficacy of four doses of a new sustained release naloxone capsule to treat Opioid Induced Constipation (OIC). Methods Forty patients taking opioids for noncancer related pain, and experiencing OIC, were randomized into 4 cohorts of 10 patients. A multiple ascending dose design was used to evaluate the safety and efficacy of 2.5 mg, 5 mg, 10 mg, and 20 mg naloxone sustained release (NSR) capsules vs placebo. Drug was given once-daily for 3 weeks followed by twice daily (bid) dosing between weeks 4 and 6. Results The incidence of treatment emergent adverse events was highest in the placebo group. The incidence of adverse events among the four active treatment groups were similar. There were no serious adverse events. The number of severe events was low overall but highest in the placebo group. Significant improvements were seen in Spontaneous Bowel Movements with 5 mg, 10 mg, and 20 mg NSR capsules. Mean change in SBMs from baseline of 2.21 ( P = 0.052), 2.37 ( P = 0.032); 4.11 ( P = 0.0005); 5.19 (<0.0001) was noted with NSR 2.5 mg, 5 mg, 10 mg, and 20 mg, respectively, when taken once daily, compared with 1.38 ( P = 0.2) for patients on placebo therapy. No changes in subjective or objective measures of opioid withdrawal as measured by the Subjective Opioid Withdrawal Scale or Clinical Opioid Withdrawal Scale were observed. There was no increase in patient reported pain as measured daily using a visual analogue scale. Conclusions This Phase II study has shown that using a new sustained release formulation to deliver oral naloxone to the colon allows successful treatment of OIC without comprising the desired opioid effects. [ABSTRACT FROM AUTHOR]

Objectives. Cardiovascular disease (CVD) is responsible for 50% of the excess mortality for patients with RA. This study aimed to evaluate a novel 8-week cognitive behavioural patient education intervention designed to effect behavioural change with regard to modifiable CVD risk factors in people with RA.Methods. This was a non-blinded randomized controlled trial with a delayed intervention arm. Participants were randomly assigned to receive the cognitive behavioural education intervention or a control information leaflet at a ratio of 1:1. The primary outcome measure was patient’s knowledge of CVD in RA; secondary measures were psychological measures relating to effecting behaviour change, actual behaviour changes and clinical risk factors. Data were collected at baseline, 2 and 6 months.Results. A total of 110 participants consented (52 in the intervention group and 58 in the control group) to participate in the study. At 6 months, those in the intervention group had significantly higher knowledge scores (P < 0.001); improved behavioural intentions to increase exercise (P < 0.001), eat a low-fat diet (P = 0.01) and lose weight (P = 0.06); and lower mean diastolic blood pressure by 3.7 mmHg, whereas the control group’s mean diastolic blood pressure increased by 0.8 mmHg. There was no difference between the groups on actual behaviours.Conclusions. Patient education has a significant role to play in CVD risk factor modification for patients with RA, and the detailed development of this programme probably contributed to its successful results. It is disappointing that behaviours, as we measured them, did not change. The challenge, as always, is how to translate behavioural intentions into action. Larger studies, powered specifically to look at behavioural changes, are required.Trial registration. National Institute for Health Research, UKCRN 4566. [ABSTRACT FROM PUBLISHER]

Objective. MTX is widely used to treat synovitis in PsA without supporting trial evidence. The aim of our study was to test the value of MTX in the first large randomized placebo-controlled trial (RCT) in PsA.Methods. A 6-month double-blind RCT compared MTX (15 mg/week) with placebo in active PsA. The primary outcome was PsA response criteria (PsARC). Other outcomes included ACR20, DAS-28 and their individual components. Missing data were imputed using multiple imputation methods. Treatments were compared using logistic regression analysis (adjusted for age, sex, disease duration and, where appropriate, individual baseline scores).Results. Four hundred and sixty-two patients were screened and 221 recruited. One hundred and nine patients received MTX and 112 received placebo. Forty-four patients were lost to follow-up (21 MTX, 23 placebo). Twenty-six patients discontinued treatment (14 MTX, 12 placebo). Comparing MTX with placebo in all randomized patients at 6 months showed no significant effect on PsARC [odds ratio (OR) 1.77, 95% CI 0.97, 3.23], ACR20 (OR 2.00, 95% CI 0.65, 6.22) or DAS-28 (OR 1.70, 95% CI 0.90, 3.17). There were also no significant treatment effects on tender and swollen joint counts, ESR, CRP, HAQ and pain. The only benefits of MTX were reductions in patient and assessor global scores and skin scores at 6 months (P = 0.03, P < 0.001 and P = 0.02, respectively). There were no unexpected adverse events.Conclusions. This trial of active PsA found no evidence for MTX improving synovitis and consequently raises questions about its classification as a disease-modifying drug in PsA.Trial registration. Current Controlled Trials, www.controlled-trials.com, ISRCTN:54376151. [ABSTRACT FROM AUTHOR]