Objective: To evaluate the efficacy of adalimumab in the healing of draining fistulas in patients with active Crohn’s disease (CD). Design: A phase III, multicentre, randomised, double-blind, placebo controlled study with an open-label extension was conducted in 92 sites. Patients: A subgroup of adults with moderate to severely active CD (CD activity index 220–450) for ⩾4 months who had draining fistulas at baseline. Interventions: All patients received initial open-label adalimumab induction therapy (80 mg/40 mg at weeks 0/2). At week 4, all patients were randomly assigned to receive double-blind placebo or adalimumab 40 mg every other week or weekly to week 56 (irrespective of fistula status). Patients completing week 56 of therapy were then eligible to enroll in an open-label extension. Main Outcome Measures: Complete fistula healing/closure (assessed at every visit) was defined as no drainage, either spontaneous or with gentle compression. Results: Of 854 patients enrolled, 117 had draining fistulas at both screening and baseline (70 randomly assigned to adalimumab and 47 to placebo). The mean number of draining fistulas per day was significantly decreased in adalimumab-treated patients compared with placebo-treated patients during the double-blind treatment period. Of all patients with healed fistulas at week 56 (both adalimumab and placebo groups), 90% (28/31) maintained healing following 1 year of open-label adalimumab therapy (observed analysis). Conclusions: In patients with active CD, adalimumab therapy was more effective than placebo for inducing fistula healing. Complete fistula healing was sustained for up to 2 years by most patients in an open-label extension trial. ClinicalTrials.gov Identifier: NCT00077779 and NCT00195715.

The similarity of musical scales and consonance judgments across human populations has no generally accepted explanation. Here we present evidence that these aspects of auditory perception arise from the statistical structure of naturally occurring periodic sound stimuli. An analysis of speech sounds, the principal source of periodic sound stimuli in the human acoustical environment, shows that the probability distribution of amplitude-frequency combinations in human utterances predicts both the structure of the chromatic scale and consonance ordering. These observations suggest that what we hear is determined by the statistical relationship between acoustical stimuli and their naturally occurring sources, rather than by the physical parameters of the stimulus per se.

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