Successful and unsuccessful recruitment and retainment strategies in a UK multicentre drug trial for a rare chronic pain condition which performed above target.

INTRODUCTION: Recruitment into trials in rare chronic pain conditions can be challenging, so such trials consequently are underpowered or fail. METHODS: Drawing from our experience in conducting, to date, the largest academic trial in a rare chronic pain condition, complex regional pain syndrome, we have identified recruitment and retention strategies for successful trial conduct. RESULTS: We present 13 strategies grouped across the categories of 'setting the recruitment rate', 'networking', 'patient information', 'trial management' and 'patient retention'. Moreover, six recruitment risks are also discussed. A conservative recruitment estimate, based on audits of newly referred patients to the trial centres without taking into account availability of 'old' patients or recruitment from outside centres, and assuming a 55% patient refusal rate yielded accurate numbers. CONCLUSION: Appreciation of these identified recruitment challenges and opportunities may contribute to supporting prospective investigators when they design clinical trials for chronic pain patient population groups where it has been historically difficult to conduct high-quality and robust clinical trials.

Possible association between response inhibition and a variant in the brain-expressed tryptophan hydroxylase-2 gene.

UNLABELLED: The ability to inhibit a response is an important component of normal behavioral control and is an aspect of psychopathology when diminished. Converging evidence implicates the serotonergic neurotransmitter system in response inhibition circuitry. OBJECTIVES: The present study examined potential associations between serotonergic genetic markers and response inhibition as indexed by Stop Task performance. METHODS: College-age participants (N=199) completed self-report questionnaires, the computerized Stop Task, and donated buccal cells for genetic analyses. Statistics were analyzed by ANOVA. RESULTS: Stop Signal reaction time was not associated with allelic variation at a monoamine oxidase A promoter length polymorphism or a serotonin 1B terminal autoreceptor polymorphism (G861C). An intronic genetic marker of the neuronal tryptophan hydroxylase-2 (the rate-limiting enzyme for serotonin biosynthesis) gene, however, was associated with the Stop Signal reaction time. Individuals homozygous for the T variant at an intron-8 polymorphism had the longest Stop Signal reaction time (i.e. greater impulsivity, P=0.01), and this effect was stronger in males (P=0.01) than in females (P=0.10). CONCLUSIONS: A genotype at an intron-8 tryptophan hydroxylase-2 polymorphism was associated with response inhibition as indexed by the Stop Task. These results, if replicated, would implicate dorsal raphe serotonin neurons in response inhibition. It may be that individuals with the T/T genotype may have reduced tryptophan hydroxylase-2 function and correspondingly lower central serotonin levels; however, further investigation of the reported association is required.

Stereotactic breast biopsy: an audit of 18 months at BreastScreen Auckland.

Stereotactic biopsy has become a widely used technique for marnmographically detected lesions that are clinically and sonographically occult. Vacuum-assisted (mammotome) biopsy on a dedicated prone stereotactic unit has further increased ease of biopsy and utility of the technique. Results of an 18-month audit in the national breast screening programme (BreastScreen Auckland and North) in the Auckland region demonstrates results comparable with those achieved elsewhere. Of a total of 399 stereotactic biopsies, 23 were excluded as they were 14-G core biopsies rather than 11-G mammotome biopsies. Of 376 mammotome biopsies, 10 (2%) failed, 266 (70.7%) were benign, 39 (10.3%) were atypical ductal hyperplasia (ADH) and 70 (18.6%) were malignant. Of these, 14.6% were ductal carcinoma in situ (DCIS) and 4% were invasive carcinomas. All cases diagnosed as ADH underwent formal excision biopsy. Of the 39 cases, 33 demonstrated benign disease or residual ADH only on excision (84.6%) and six (15.4%) patients were upgraded: five to DCIS and one to invasive carcinoma. The significant complication rate was 0.5%. Indications for biopsy were calcification in 89% of cases, mass lesions in 10.6% of cases and architectural distortion in 0.2% of cases. The failure rate of 2% compares with hookwire biopsy series. Practical issues and protocols have been presented.