Development of a core outcome set for evaluative research into paediatric cerebral visual impairment (CVI), in the UK and Eire.

OBJECTIVES: Cerebral visual impairment (CVI) comprises a heterogeneous group of brain-related vision problems. A core outcome set (COS) represents the most important condition-specific outcomes according to patients, carers, professionals and researchers. We aimed to produce a COS for studies evaluating interventions for children with CVI, to increase the relevance of research for families and professionals and thereby to improve outcomes for affected children. DESIGN: We used methods recommended by the Core Outcome Measures in Effectiveness Trials Initiative. These included a proportionate literature review of outcomes used in previous studies; qualitative interviews with children and families; a two-round Delphi survey involving parents, children and professionals and a consensus meeting to ratify the most important outcomes. SETTING: Telephone interviews and online Delphi surveys of participants who all lived in UK or Eire. PARTICIPANTS: Eighteen parents and six young people were interviewed. Delphi participants (n=80 did both rounds) included professionals working with children who have CVI (teachers, orthoptists, ophthalmologists, optometrists, qualified teachers for visually impaired, family members (parents and siblings) and affected children. RESULTS: The literature review included 13 studies yielding 37 outcomes. Qualitative interviews provided 22 outcomes. After combining and refining similar items, the first round contained 23 outcomes and the second 46. At the consensus meeting, 5 attendees recommended 27 outcomes for inclusion in the CVI COS, of which 15 were ratified as most important, including 4 related to vision; 1 to family well-being; 1 to adults around the child being informed about CVI and the rest to the child's abilities to engage with people and surroundings. CONCLUSIONS: Good engagement from participants led to the development of a COS. Future research will be useful to identify the best ways to measure COS items and potentially to update this COS as more interventions for CVI are developed. TRIAL REGISTRATION NUMBER: ISRCTN13762177.

Developing the WCRF International/University of Bristol Methodology for Identifying and Carrying Out Systematic Reviews of Mechanisms of Exposure-Cancer Associations.

Background: Human, animal, and cell experimental studies; human biomarker studies; and genetic studies complement epidemiologic findings and can offer insights into biological plausibility and pathways between exposure and disease, but methods for synthesizing such studies are lacking. We, therefore, developed a methodology for identifying mechanisms and carrying out systematic reviews of mechanistic studies that underpin exposure-cancer associations.Methods: A multidisciplinary team with expertise in informatics, statistics, epidemiology, systematic reviews, cancer biology, and nutrition was assembled. Five 1-day workshops were held to brainstorm ideas; in the intervening periods we carried out searches and applied our methods to a case study to test our ideas.Results: We have developed a two-stage framework, the first stage of which is designed to identify mechanisms underpinning a specific exposure-disease relationship; the second stage is a targeted systematic review of studies on a specific mechanism. As part of the methodology, we also developed an online tool for text mining for mechanism prioritization (TeMMPo) and a new graph for displaying related but heterogeneous data from epidemiologic studies (the Albatross plot).Conclusions: We have developed novel tools for identifying mechanisms and carrying out systematic reviews of mechanistic studies of exposure-disease relationships. In doing so, we have outlined how we have overcome the challenges that we faced and provided researchers with practical guides for conducting mechanistic systematic reviews.Impact: The aforementioned methodology and tools will allow potential mechanisms to be identified and the strength of the evidence underlying a particular mechanism to be assessed. Cancer Epidemiol Biomarkers Prev; 26(11); 1667-75. ©2017 AACR.

Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? A systematic review and meta-analysis.

PURPOSE: To establish whether the association between milk intake and prostate cancer operates via the insulin-like growth factor (IGF) pathway (including IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3). METHODS: Systematic review, collating data from all relevant studies examining associations of milk with IGF, and those examining associations of IGF with prostate cancer risk and progression. Data were extracted from experimental and observational studies conducted in either humans or animals, and analyzed using meta-analysis where possible, with summary data presented otherwise. RESULTS: One hundred and seventy-two studies met the inclusion criteria: 31 examining the milk-IGF relationship; 132 examining the IGF-prostate cancer relationship in humans; and 10 animal studies examining the IGF-prostate cancer relationship. There was moderate evidence that circulating IGF-I and IGFBP-3 increase with milk (and dairy protein) intake (an estimated standardized effect size of 0.10 SD increase in IGF-I and 0.05 SD in IGFBP-3 per 1 SD increase in milk intake). There was moderate evidence that prostate cancer risk increased with IGF-I (Random effects meta-analysis OR per SD increase in IGF-I 1.09; 95% CI 1.03, 1.16; n = 51 studies) and decreased with IGFBP-3 (OR 0.90; 0.83, 0.98; n = 39 studies), but not with other growth factors. The IGFBP-3 -202A/C single nucleotide polymorphism was positively associated with prostate cancer (pooled OR for A/C vs. AA = 1.22; 95% CI 0.84, 1.79; OR for C/C vs. AA = 1.51; 1.03, 2.21, n = 8 studies). No strong associations were observed for IGF-II, IGFBP-1 or IGFBP-2 with either milk intake or prostate cancer risk. There was little consistency within the data extracted from the small number of animal studies. There was additional evidence to suggest that the suppression of IGF-II can reduce tumor size, and contradictory evidence with regards to the effect of IGFBP-3 suppression on tumor progression. CONCLUSION: IGF-I is a potential mechanism underlying the observed associations between milk intake and prostate cancer risk.