A feasibility study testing four hypotheses with phase II outcomes in advanced colorectal cancer (MRC FOCUS3): a model for randomised controlled trials in the era of personalised medicine?

Background: Molecular characteristics of cancer vary between individuals. In future, most trials will require assessment of biomarkers to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in the planning of such studies.

Patients and methods: Patients with advanced colorectal cancer were registered from 24 centres between February 2010 and April 2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular strata; within each strata patients were randomised to one of two hypothesis-driven experimental therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of patient information sheets (PISs) was developed to avoid patient overload.

Results: A total of 332 patients were registered, 244 randomised. Among randomised patients, biomarker results were provided within 10 working days (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100% concordant between two laboratories. Over 90% of participants reported excellent understanding of all aspects of the trial. In this randomised phase II setting, omission of irinotecan in the low topo-1 group was associated with increased response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was associated with longer progression-free survival.

Conclusions: Patient samples can be collected and analysed within workable time frames and with reproducible mutation results. Complex multi-arm designs are acceptable to patients with good PIS. Randomisation within each cohort provides outcome data that can inform clinical practice.

Expert opinion on the cough hypersensitivity syndrome in respiratory medicine

In 2011, a European Respiratory Society Task Force embarked on a process to determine the position and clinical relevance of the cough hypersensitivity syndrome, a disorder characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure, in the management of patients with chronic cough. A 21-component questionnaire was developed by an iterative process supported by a literature review. 44 key opinion leaders in respiratory medicine were selected and interviewed as to their opinions. There was a high degree of unanimity in the responses obtained, with all opinion leaders supporting the concept of cough hypersensitivity as a clinically useful paradigm. The classic stratification of cough into asthmatic, rhinitic and reflux-related phenotypes was supported. Significant disparity of opinion was seen in the response to two questions concerning the therapy of chronic cough. First, the role of acid suppression in reflux cough was questioned. Secondly, the opinion leaders were split as to whether a trial of oral steroids was indicated to establish a diagnosis of eosinophilic cough. The cough hypersensitivity syndrome was clearly endorsed by the opinion leaders as a valid and useful concept. They considered that support of patients with chronic cough was inadequate and the Task Force recommends that further work is urgently required in this neglected area.

An official American thoracic society research statement: Comparative effectiveness research in pulmonary, critical care, and sleep medicine

Background: Comparative effectiveness research (CER) is intended to inform decision making in clinical practice, and is central to patientcentered outcomes research (PCOR). Purpose: To summarize key aspects of CER definitions and provide examples highlighting the complementary nature of efficacy and CER studies in pulmonary, critical care, and sleep medicine. Methods: An ad hoc working group of the American Thoracic Society with experience in clinical trials, health services research, quality improvement, and behavioral sciences in pulmonary, critical care, and sleepmedicinewas convened. The group used an iterative consensus process, including a reviewbyAmerican Thoracic Society committees and assemblies. Results: The traditional efficacy paradigm relies on clinical trials with high internal validity to evaluate interventions in narrowly defined populations and in research settings. Efficacy studies address the question, "Can it work in optimal conditions?" The CER paradigm employs a wide range of study designs to understand the effects of interventions in clinical settings. CER studies address the question, "Does it work in practice?" The results of efficacy and CER studies may or may not agree. CER incorporates many attributes of outcomes research and health services research, while placing greater emphasis on meeting the expressed needs of nonresearcher stakeholders (e.g., patients, clinicians, and others). Conclusions: CER complements traditional efficacy research by placing greater emphasis on the effects of interventions in practice, and developing evidence to address the needs of the many stakeholders involved in health care decisions. Stakeholder engagement is an important component of CER. Copyright © 2013 by the American Thoracic Society.

Musculoskeletal (MSK) and Sport and Exercise Medicine (SEM) in General Practice (GP): A Novel GP-based MSK and SEM Clinic for Managing Musculoskeletal symptoms in a GP

Musculoskeletal (MSK) complaints are common within primary care (1) (2) (3) but some General Practitioners (GPs)/family physicians do not feel comfortable managing these symptoms (3), preferring to refer onto hospital specialists or Integrated Clinical Assessment and Treatment Services (ICATs). Long waiting times for hospital outpatient reviews are a major cause of patient inconvenience and complaints (4). We therefore aimed to establish a GP-ran MSK and sport and exercise medicine (SEM) clinic based within a Belfast GP surgery that would contribute to a sustainable improvement in managing these common conditions within primary care as well as reducing waiting times for patients with these conditions to see a specialist. This shift from hospital-based to community-based management is in-keeping with recent policy changes within the UK health-system, including Transforming Your Care within Northern Ireland (NI) (5). The GP-ran MSK and SEM clinic was held monthly within a Belfast GP practice, staffed by one GP with a specialist interest in MSK and SEM conditions and its performance was reviewed over a three month period. Parameters audited included cases seen, orthopaedic and x-ray referral rates and secondary care referrals comparing the GP practice’s performance to the same time period in the previous year as well as patient satisfaction questionnaires.

How should teaching on whole person medicine, including spiritual issues, be delivered in the undergraduate medical curriculum in the United Kingdom?

Background

Although the General Medical Council recommends that United Kingdom medical students are taught ‘whole person medicine’, spiritual care is variably recognised within the curriculum. Data on teaching delivery and attainment of learning outcomes is lacking. This study ascertained views of Faculty and students about spiritual care and how to teach and assess competence in delivering such care.

A questionnaire comprising 28 questions exploring attitudes to whole person medicine, spirituality and illness, and training of healthcare staff in providing spiritual care was designed using a five-point Likert scale. Free text comments were studied by thematic analysis. The questionnaire was distributed to 1300 students and 106 Faculty at Queen’s University Belfast Medical School.

351 responses (54 staff, 287 students; 25 %) were obtained. >90 % agreed that whole person medicine included physical, psychological and social components; 60 % supported inclusion of a spiritual component within the definition. Most supported availability of spiritual interventions for patients, including access to chaplains (71 %), counsellors (62 %), or members of the patient’s faith community (59 %). 90 % felt that personal faith/spirituality was important to some patients and 60 % agreed that this influenced health. However 80 % felt that doctors should never/rarely share their own spiritual beliefs with patients and 67 % felt they should only do so when specifically invited. Most supported including training on provision of spiritual care within the curriculum; 40-50 % felt this should be optional and 40 % mandatory. Small group teaching was the favoured delivery method. 64 % felt that teaching should not be assessed, but among assessment methods, reflective portfolios were most favoured (30 %). Students tended to hold more polarised viewpoints but generally were more favourably disposed towards spiritual care than Faculty. Respecting patients’ values and beliefs and the need for guidance in provision of spiritual care were identified in the free-text comments.

Students and Faculty generally recognise a spiritual dimension to health and support provision of spiritual care to appropriate patients. There is lack of consensus whether this should be delivered by doctors or left to others. Spiritual issues impacting patient management should be included in the curriculum; agreement is lacking about how to deliver and assess.

A systematic review investigating the effectiveness of Complementary and Alternative Medicine (CAM) for the management of low back and/or pelvic pain (LBPP) in pregnancy

Aim: To evaluate and summarize the current evidence on the effectiveness of complementary and alternative medicine for the management of low back pain and/or pelvic pain in pregnancy.

Background: International research demonstrates that 25-30% of women use complementary and alternative medicine to manage low back and pelvic pain in pregnancy without robust evidence demonstrating its effectiveness.

Design: A systematic review of randomized controlled trials to determine the effectiveness of complementary and alternative medicine for low back and/or pelvic pain in pregnancy.

Data Sources: Cochrane library (1898-2013), PubMed (1996-2013), MEDLINE (1946-2013), AMED (1985-2013), Embase (1974-2013), Cinahl (1937-2013), Index to Thesis (1716-2013) and Ethos (1914-2013).

Review Methods: Selected studies were written in English, randomized controlled trials, a group 1 or 2 therapy and reported pain reduction as an outcome measure. Study quality was reviewed using Risk of Bias and evidence strength the Cochrane Grading of Recommendations and Development Evaluation Tool.

Results: Eight studies were selected for full review. Two acupuncture studies with low risk of bias showed both clinically important changes and statistically significant results. There was evidence of effectiveness for osteopathy and chiropractic. However, osteopathy and chiropractic studies scored high for risk of bias. Strength of the evidence across studies was very low.

Conclusion: There is limited evidence supporting the use of general CAM for managing pregnancy-related low back and/or pelvic pain. However, the restricted availability of high-quality studies, combined with the very low evidence strength, makes it impossible to make evidence-based recommendations for practice.