Disambiguating pharmacological mechanisms from placebo in neuropathic pain using functional neuroimaging.

BACKGROUND: A lack of objective outcome measures and overreliance on subjective pain reports in early proof-of-concept studies contribute to the high attrition of potentially effective new analgesics. We studied the utility of neuroimaging in providing objective evidence of neural activity related to drug modulation or a placebo effect in a double-blind, randomized, placebo-controlled, three-way crossover trial. METHODS: We chronically administered pregabalin or tramadol (first-line and second-line analgesics, respectively), recommended for neuropathic pain, in 16 post-traumatic neuropathic pain patients. We measured subjective pain reports, allodynia-evoked neural activity, and brain resting state functional connectivity from patients during the three sessions and resting state data at baseline from patients after washout of their current medication. All data were collected using a 3 T MRI scanner. RESULTS: When compared with placebo only, pregabalin significantly suppressed allodynia-evoked neural activity in several nociceptive and pain-processing areas of the brain, despite the absence of behavioural analgesia. Furthermore, placebo significantly increased functional connectivity between the rostral anterior cingulate and the brainstem, a core component of the placebo neural network. CONCLUSIONS: Functional neuroimaging provided objective evidence of pharmacodynamic efficacy in a proof-of-concept study setting where subjective pain outcome measures are often unreliable. Additionally, we provide evidence confirming the neural mechanism underpinning placebo analgesia as identified in acute experimental imaging studies in patients during the placebo arm of a clinical trial. We explore how brain penetrant active drugs potentially interact with this mechanism. CLINICAL TRIAL REGISTRATION: NCT0061015.

Likely effect of adding flexible sigmoidoscopy to the English NHS Bowel Cancer Screening Programme: impact on colorectal cancer cases and deaths.

BACKGROUND: From 2013, once-only flexible sigmoidoscopy (FS) at age 55 is being phased into the England National Health Service Bowel Cancer Screening Programme (NHSBCSP), augmenting biennial guaiac faecal occult blood testing (gFOBT) at ages 60-74. Here, we project the impact of this change on colorectal cancer (CRC) cases and deaths prevented in England by mid-2030. METHODS: We simulated the life-course of English residents reaching age 55 from 2013 onwards. Model inputs included population numbers, invitation rates and CRC incidence and mortality rates. The impact of gFOBT and FS alone on CRC incidence and mortality were derived from published trials, assuming an uptake of 50% for FS and 57% for gFOBT. For FS plus gFOBT, we assumed the gFOBT effect to be 75% of the gFOBT alone impact. RESULTS: By mid-2030, 8.5 million individuals will have been invited for once-only FS screening. Adding FS to gFOBT screening is estimated to prevent an extra 9627 (-10%) cases and 2207 (-12%) deaths by mid-2030. If FS uptake is 38% or 71%, respectively, an extra 7379 (-8%) or 13 689 (-15%) cases and 1691 (-9%) or 3154 (-17%) deaths will be prevented by mid-2030. CONCLUSIONS: Adding once-only FS at age 55 to the NHSBCSP will prevent ∼10,000 CRC cases and ∼2000 CRC deaths by mid-2030 if FS uptake is 50%. In 2030, one cancer was estimated to be prevented per 150 FS screening episodes, and one death prevented per 900 FS screening episodes. The actual reductions will depend on the FS invitation schedule and uptake rates.

Colposcopy attendance and deprivation: A retrospective analysis of 27,193 women in the NHS Cervical Screening Programme.

BACKGROUND: Attendance for cervical screening is socially graded, but little is known about patterns of attendance for colposcopy following an abnormal screening result. METHODS: Logistic regression was used to regress colposcopy attendance status for 27 193 women against age and area-level deprivation, adjusting for ethnicity. RESULTS: Colposcopy attendance was high at 8 weeks (89%) and 4 months post-referral (94%) but women living in the most deprived areas were significantly less likely to attend. CONCLUSIONS: The high overall attendance rates at colposcopy are encouraging but lower attendance among women in the most income-deprived areas indicates that even when these women attend primary cervical screening, they remain at higher risk of missing out on the benefits of the programme.

Evaluation of a service intervention to improve awareness and uptake of bowel cancer screening in ethnically-diverse areas.

BACKGROUND: Uptake of bowel cancer screening is lowest in London, in populations of lower socio-economic status, and in particular ethnic or religious groups. METHODS: We report on the evaluation of two interventions to improve uptake in an area including populations of low socio-economic status and considerable ethnic diversity. The interventions were face-to-face health promotion on bowel cancer screening at invitees' general practice and health promotion delivered by telephone only. Nine large general practices in East London were chosen at random to offer face-to-face health promotion, and nine other large practices to offer telephone health promotion, with 24 practices of similar size as comparators. Data at practice level were analysed by Mann-Whitney-Wilcoxon tests and grouped-logistic regression. RESULTS: There were 2034 invitees in the telephone intervention practices, 1852 in the face-to-face intervention practices and 5227 in the comparison practices. Median gFOBt kit uptake in the target population (aged 59-70) was 46.7% in the telephone practices, 43.8% in the face-to-face practices and 39.1% in the comparison practices. Significant improvements in the odds of uptake were observed following telephone intervention in both males (OR=1.39, 95% CI=1.20-1.61, P<0.001) and females (OR=1.49, 95% CI=1.29-1.73, P<0.001), while the face-to-face intervention mainly impacted uptake in males (OR=1.23, 95% CI=1.10-1.36), P<0.001) but did not lead to a significant increase in females (OR=1.12, 95% CI=0.96-1.29, P=0.2). CONCLUSIONS: Personally delivered health promotion improved uptake of bowel cancer screening in areas of low socio-economic status and high ethnic diversity. The intervention by telephone appears to be the most effective method.