Developing a core outcome set for fistulising perianal Crohn's disease

OBJECTIVE: Lack of standardised outcomes hampers effective analysis and comparison of data when comparing treatments in fistulising perianal Crohn's disease (pCD). Development of a standardised set of outcomes would resolve these issues. This study provides the definitive core outcome set (COS) for fistulising pCD. DESIGN: Candidate outcomes were generated through a systematic review and patient interviews. Consensus was established via a three-round Delphi process using a 9-point Likert scale based on how important they felt it was in determining treatment success culminating in a final consensus meeting. Stakeholders were recruited nationally and grouped into three panels (surgeons and radiologists, gastroenterologists and IBD specialist nurses, and patients). Participants received feedback fromtheir panel(in the second round) andall participants(in the third round) to allow refinement of their scores. RESULTS: A total of 295 outcomes were identified from systematic reviews and interviews that were categorised into 92 domains. 187 stakeholders (response rate 78.5%) prioritised 49 outcomes through a three-round Delphi study.The final consensus meeting of 41 experts and patients generated agreement on an eight domain COS. The COS comprised three patient-reported outcome domains (quality of life, incontinence and a combined score of patient priorities) and five clinician-reported outcome domains (perianal disease activity, development of new perianal abscess/sepsis, new/recurrent fistula, unplanned surgery and faecal diversion). CONCLUSION: A fistulising pCD COS has been produced by all key stakeholders. Application of the COS will reduce heterogeneity in outcome reporting, thereby facilitating more meaningful comparisons between treatments, data synthesis and ultimately benefit patient care

The association between treatment adherence to nicotine patches and smoking cessation in pregnancy: a secondary analysis of a randomised controlled trial

IntroductionIn non-pregnant ‘quitters’, adherence to nicotine replacement therapy (NRT) increases smoking cessation. We investigated relationships between adherence to placebo or NRT patches and cessation in pregnancy, including an assessment of reverse causation and whether any adherence: cessation relationship is moderated when using nicotine or placebo patches. MethodsUsing data from 1050 pregnant trial participants, regression models investigated associations between maternal characteristics, adherence and smoking cessation. ResultsAdherence during the first month was associated with lower baseline cotinine concentrations (beta -0.08, 95%CI -0.15 to -0.01) and randomisation to NRT (beta 2.59, 95%CI 1.50 to 3.68). Adherence during both treatment months was associated with being randomised to NRT (beta 0.51, 95%CI 0.29 to 0.72) and inversely associated with higher nicotine dependence. Adherence with either NRT or placebo was associated with cessation at one month (OR 1.11, 95%CI 1.08 to 1.13) and delivery (OR 1.06, 95%CI 1.03 to 1.09), but no such association was observed in the subgroup where reverse causation was not possible. Amongst all women, greater adherence to nicotine patches was associated with increased cessation (OR 2.47, 95%CI 1.32 to 4.63) but greater adherence to placebo was not (OR 0.98, 95%CI: 0.44 to 2.18). ConclusionWomen who were more adherent to NRT were more likely to achieve abstinence; more nicotine dependent women probably showed lower adherence to NRT because they relapsed to smoking more quickly. The interaction between nicotine-containing patches and adherence for cessation suggests that the association between adherence with nicotine patches and cessation may be partly causal

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Developing a core outcome set for fistulising perianal Crohn's disease

Objective Lack of standardised outcomes hampers effective analysis and comparison of data when comparing treatments in fistulising perianal Crohn’s disease (pCD). Development of a standardised set of outcomes would resolve these issues. This study provides the definitive core outcome set (COS) for fistulising pCD. Design Candidate outcomes were generated through a systematic review and patient interviews. Consensus was established via a three-round Delphi process using a 9-point Likert scale based on how important they felt it was in determining treatment success culminating in a final consensus meeting. Stakeholders were recruited nationally and grouped into three panels (surgeons and radiologists, gastroenterologists and IBD specialist nurses, and patients). Participants received feedback from their panel (in the second round) and all participants (in the third round) to allow refinement of their scores. Results A total of 295 outcomes were identified from systematic reviews and interviews that were categorised into 92 domains. 187 stakeholders (response rate 78.5%) prioritised 49 outcomes through a three-round Delphi study. The final consensus meeting of 41 experts and patients generated agreement on an eight domain COS. The COS comprised three patient-reported outcome domains (quality of life, incontinence and a combined score of patient priorities) and five clinician-reported outcome domains (perianal disease activity, development of new perianal abscess/sepsis, new/recurrent fistula, unplanned surgery and faecal diversion). Conclusion A fistulising pCD COS has been produced by all key stakeholders. Application of the COS will reduce heterogeneity in outcome reporting, thereby facilitating more meaningful comparisons between treatments, data synthesis and ultimately benefit patient care