Regulating in the Global Village: The Case of Non-Invasive Pre-Natal Tests

In the context of the global village, this paper focuses on the development of Non-Invasive Prenatal Testing (NIPT)—a test that provides clinicians and prospective parents with an easy, early and safe opportunity to obtain potentially reliable genetic and health information about the future child. In the first part of the article, we identify various concerns relating to NIPT, now released into an environment that is remarkably difficult to regulate. For example, we question whether the online information about NIPT upon which women might rely will be reliable and up-to-date, whether women might use Internet suppliers to work round local legal restrictions, and whether the stored test results might impact on future children. In the second part of the article, whilst recognising the limited opportunities for making effective regulatory interventions in the global village, we suggest some possible responses to the particular concerns about NIPT identified in the paper

In ordinary times, in extraordinary times: Consent, newborn screening, genetics and pandemics

Against the backdrop of newborn genetic screening and pandemics, this article examines disputes between parents, acting as proxies for their children, and healthcare professionals. While some will support parents, others will push-back against proxy consent and the right to veto actions that are proposed by the professionals. Whereas in ordinary times, such a push-back might seek to displace or downgrade parental rights (e.g. by appealing to professional duty or the optimisation of health) or to de-centre or dilute consent, in extraordinary times, rights and consent are superseded by appeals to responsibility, solidarity, and even “states of exception”

Testing Times Ahead: Non-Invasive Prenatal Testing and the Kind of Community that We Want to Be

This article reviews the Nuffield Council on Bioethics’ report on Non‐Invasive Prenatal Testing (NIPT); and introduces two general questions provoked by the report – concerning, respectively, the nature and extent of the informational interests that are to be recognised in today's ‘information societies’ and the membership of today's ‘genetic societies’. The article also considers the role and nature of the Nuffield Council. While the Council's report identifies a range of individual and collective interests that are relevant to determining the legitimate uses of NIPT, we argue that it should put these interests into an order of importance; we sketch how this might be done; and we suggest that, failing such a prioritisation of interests, the Council should present its reflections in a way that engages public debate around a number of options rather than making firm recommendation

Pathologic response to neoadjuvant treatment in locally advanced rectal cancer and impact on outcome

BACKGROUND: Downstaging and pathologic complete response (pCR) after chemoradiotherapy (CRT) may improve progression-free survival and overall survival (OS) after curative therapy of locally advanced adenocarcinoma of rectum. The purpose of this study is to evaluate the pathologic response subsequent to neoadjuvant chemoradiation in locally advanced rectal adenocarcinoma and any impact of response on oncological outcome [disease-free survival (DFS), OS]. METHODS: A total of 127 patients with histologically-proven rectal adenocarcinoma, locally advanced, were treated with preoperative radiotherapy and concurrent 5-fluorouracil (5 FU), and followed by curative surgery. Pathologic response to neoadjuvant treatment was evaluated by comparing pathologic TN (tumour and nodal) staging (yp) with pre-treatment clinical staging. DFS and OS were compared in patients with: pCR, partial pathologic response and no response to neoadjuvant therapy. RESULTS: 14.96% (19 patients) had a pCR, 58.27% [74] showed downstaging and 26.77% [34] had no change in staging. At follow-up (range, 4-9 years, median 6 years 2 months or 74 months), 17.32% [22] showed recurrence: 15.74% [20] distant metastasis, 1.57% [2] pelvic failure. 10.5% [2] of the patients with pCR showed distant metastasis, none showed local recurrence. In the downstaged group, nine developed distant failure and two had local recurrence (14.86%). Distant failure was seen in 26.47% [9] of those with no response to neoadjuvant treatment. DFS and OS rates for all groups were 82.67% and 88.97% respectively. Patients with pCR showed 89.47% DFS and 94.7% OS. In partial responders, DFS was 85.1% and OS was 90.5%. In non-responders, DFS and OS were 73.5% and 82.3% respectively. Patients with pCR had a significantly greater probability of DFS and OS than non-responders. Rectal cancer-related death was 11.02% [14]: one patient (5.26%) with pCR, 9.47% [7] in the downstaged group and 17.64% [6] of non-responders. CONCLUSIONS: The majority of patients showed some response to neoadjuvant treatment. Findings of this study indicate tumour response to neoadjuvant CRT improves the long-term outcome, with a better result in patients with pCR

Observer agreement for small bowel ultrasound in Crohn’s disease:results from the METRIC trial

Purpose: To prospectively evaluate interobserver agreement for small bowel ultrasound (SBUS) in newly diagnosed and relapsing Crohn’s disease. Methods: A subset of patients recruited to a prospective trial comparing the diagnostic accuracy of MR enterography and SBUS underwent a second SBUS performed by one of a pool of six practitioners, who recorded the presence, activity and location of small bowel and colonic disease. Detailed segmental mural and extra-mural observations were also scored. Interobserver variability was expressed as percentage agreement with a construct reference standard, split by patient cohort, grouping disease as present or absent. Prevalence adjusted bias adjusted kappa (PABAK), and simple percentage agreement between practitioners, irrespective of the reference standard, were calculated. Results: Thirty-eight patients (11 new diagnosis, 27 relapse) were recruited from two sites. Overall percentage agreement for small bowel disease presence against the consensus reference was 82% (52–95% (95%CI)), kappa coefficient (κ) 0.64, (substantial agreement) for new diagnosis and 81%, κ 0.63 (substantial agreement) for the relapsing cohort. Agreement for colonic disease presence was 64%, κ 0.27 (fair agreement) in new diagnosis and 78%,κ 0.56 (moderate agreement) in the relapsing cohort. Simple agreement between practitioners was 84% and 87% for small bowel and colonic disease presence respectively. Practitioners agreed on small bowel disease activity in 24/27 (89%) where both identified disease. Kappa agreement for detailed mural observations ranged from κ 0.00 to 1.00. Conclusion: There is substantial practitioner agreement for small bowel disease presence in newly diagnosed and relapsing CD patients, supporting wider dissemination of enteric US.</p

Observer agreement for small bowel ultrasound in Crohn’s disease:results from the METRIC trial

Purpose: To prospectively evaluate interobserver agreement for small bowel ultrasound (SBUS) in newly diagnosed and relapsing Crohn’s disease. Methods: A subset of patients recruited to a prospective trial comparing the diagnostic accuracy of MR enterography and SBUS underwent a second SBUS performed by one of a pool of six practitioners, who recorded the presence, activity and location of small bowel and colonic disease. Detailed segmental mural and extra-mural observations were also scored. Interobserver variability was expressed as percentage agreement with a construct reference standard, split by patient cohort, grouping disease as present or absent. Prevalence adjusted bias adjusted kappa (PABAK), and simple percentage agreement between practitioners, irrespective of the reference standard, were calculated. Results: Thirty-eight patients (11 new diagnosis, 27 relapse) were recruited from two sites. Overall percentage agreement for small bowel disease presence against the consensus reference was 82% (52–95% (95%CI)), kappa coefficient (κ) 0.64, (substantial agreement) for new diagnosis and 81%, κ 0.63 (substantial agreement) for the relapsing cohort. Agreement for colonic disease presence was 64%, κ 0.27 (fair agreement) in new diagnosis and 78%,κ 0.56 (moderate agreement) in the relapsing cohort. Simple agreement between practitioners was 84% and 87% for small bowel and colonic disease presence respectively. Practitioners agreed on small bowel disease activity in 24/27 (89%) where both identified disease. Kappa agreement for detailed mural observations ranged from κ 0.00 to 1.00. Conclusion: There is substantial practitioner agreement for small bowel disease presence in newly diagnosed and relapsing CD patients, supporting wider dissemination of enteric US.</p