The Role of Neoadjuvant Chemotherapy in Locally Advanced Colon Cancer.

Neoadjuvant systemic therapy has many potential advantages over up-front surgery, including tumor downstaging, early treatment of micrometastatic disease, and providing an in vivo test of tumor biology. Due to these advantages, neoadjuvant therapy is becoming the standard of care for an increasing number of tumor types. Currently, colon cancer patients are still routinely treated with up-front surgery, and neoadjuvant systemic therapy is not yet standard. Limitations to widespread use of neoadjuvant therapy have included inaccurate radiological staging, concerns about tumor progression while undergoing preoperative treatment rendering a patient incurable, and a lack of randomized data demonstrating benefit. However, there is great interest in neoadjuvant chemotherapy, and a number of trials are under way. Early follow up of the first phase III trial of neoadjuvant chemotherapy for colon cancer demonstrated tumor downstaging and suggested an improvement in disease-free survival with neoadjuvant chemotherapy, and it is hoped that this will translate into longer-term overall survival benefit. Clinicians should closely watch this developing field, consider the option of neoadjuvant chemotherapy for colon cancer patients, and actively seek out opportunities for their patients to participate in ongoing clinical trials to further inform this field in future.

Refractory Metastatic Colorectal Cancer: Current Challenges and Future Prospects.

Despite advances, patients with metastatic colorectal cancer (mCRC) still have poor long-term survival. Identification of molecular subtypes is important to guide therapy through standard treatment pathways and holds promise for the development of new treatments. Following standard first- and second-line chemotherapy plus targeted agents, many patients retain a reasonable performance status, and thus are seeking further effective treatment to extend life and maintain symptom control. The challenge lies in selecting the most appropriate therapy in the third- and fourth-line settings, from a range of options including the relatively new oral agents TAS-102 and regorafenib, or rechallenge with previous chemotherapy or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (mAB). Beyond this, therapy consists of trials involving novel agents and new combinations of treatments with theoretical synergy and/or non-overlapping toxicity. There is a great focus on enhancing immunogenicity in mCRC, to reflect the impressive results of immunotherapy drugs in the small cohort with mismatch repair deficient (dMMR) mCRC. Rare molecular subtypes of mCRC are increasingly being identified, including Her2-positive disease, NTRK fusions and others. Clinical trials exploring the efficacy of immunomodulatory and precision agents are plentiful and will hopefully yield clinically meaningful results that can be rapidly translated into routine care.

Evaluation of community-level interventions to increase early initiation of antenatal care in pregnancy: protocol for the Community REACH study, a cluster randomised controlled trial with integrated process and economic evaluations.

BACKGROUND: The provision of high-quality maternity services is a priority for reducing inequalities in health outcomes for mothers and infants. Best practice includes women having their initial antenatal appointment within the first trimester of pregnancy in order to provide screening and support for healthy lifestyles, well-being and self-care in pregnancy. Previous research has identified inequalities in access to antenatal care, yet there is little evidence on interventions to improve early initiation of antenatal care. The Community REACH trial will assess the effectiveness and cost-effectiveness of engaging communities in the co-production and delivery of an intervention that addresses this issue. METHODS/DESIGN: The study design is a matched cluster randomised controlled trial with integrated process and economic evaluations. The unit of randomisation is electoral ward. The intervention will be delivered in 10 wards; 10 comparator wards will have normal practice. The primary outcome is the proportion of pregnant women attending their antenatal booking appointment by the 12th completed week of pregnancy. This and a number of secondary outcomes will be assessed for cohorts of women (n = approximately 1450 per arm) who give birth 2-7 and 8-13 months after intervention delivery completion in the included wards, using routinely collected maternity data. Eight hospitals commissioned to provide maternity services in six NHS trusts in north and east London and Essex have been recruited to the study. These trusts will provide anonymised routine data for randomisation and outcomes analysis. The process evaluation will examine intervention implementation, acceptability, reach and possible causal pathways. The economic evaluation will use a cost-consequences analysis and decision model to evaluate the intervention. Targeted community engagement in the research process was a priority. DISCUSSION: Community REACH aims to increase early initiation of antenatal care using an intervention that is co-produced and delivered by local communities. This pragmatic cluster randomised controlled trial, with integrated process and economic evaluation, aims to rigorously assess the effectiveness of this public health intervention, which is particularly complex due to the required combination of standardisation with local flexibility. It will also answer questions about scalability and generalisability. TRIAL REGISTRATION: ISRCTN registry: registration number 63066975 . Registered on 18 August 2015.

The prevalence, impact and management of musculoskeletal disorders in older people living in care homes: a systematic review.

The aim was to systematically review the literature describing the prevalence, impact and current management of musculoskeletal pain in older people living in care homes. Published literature (AMED, CINAHL, EMBASE, psycINFO, MEDLINE, Cochrane Library) and unpublished literature (OpenGrey, the WHO International Clinical Trials Registry Platform, Current Controlled Trials, UK National Research Register Archive) were searched on 1 March 2015. All studies assessing the prevalence, impact and management of musculoskeletal disorders in older people living in care homes were included. Literature was appraised using the CASP cohort and qualitative critical appraisal tools. Data were analysed using descriptive statistical approaches, meta-analysis and meta-ethnography techniques. Twenty-four papers reporting the results of 263,775 care home residents in 12 countries were identified. The evidence base was moderate in quality. Prevalence of musculoskeletal pain for people in care homes was 30.2 % (95 % confidence intervals 29.9-30.5 %; n = 105,463). Care home residents reported that musculoskeletal pain had a significant impact on their perceived independence and overall ability to participate in everyday activities of daily living. Three papers which presented data on interventions demonstrated that whilst multi-component assessment and management packages did not significantly change clinical outcomes, these empowered care home staff to feel more confident in managing these patients. Musculoskeletal pain is a common problem in care homes worldwide, and residents report significant impact on their lives. However, there is uncertainty regarding how to assess and manage such pain. PROSPERO Registration Number: CRD42014009824.

Patients' perceptions of physical activity before and after joint replacement: a systematic review with meta-ethnographic analysis.

BACKGROUND: It has been perceived that people following total hip arthroplasty (THA) or total knee arthroplasty (TKA) have the capability, with reduced pain, to increase their levels of physical activity. OBJECTIVES: To determine the attitudes and perceptions of people awaiting or having undergone THA or TKA to physical activity post-arthroplasty and to identify potential facilitators or barriers to engage in active living and physical activity pursuits. METHODS: Systematic review of published and unpublished databases was undertaken from their inception to November 2014. Studies exploring the attitudes and perceptions of people awaiting or having undergone THA or TKA to physical activity post-arthroplasty were included. Data were analysed through a meta-ethnography approach. RESULTS: From 528 citations, 13 papers were eligible, sampling 282 people post-THA or TKA. The literature was judged moderate to high quality. Following THA and TKA, people either wished to return to their pre-pathology level of physical activity or simply be able to engage in less physically demanding activities that are meaningful to them and their lifestyles. Barriers to engaging in higher levels of physical activity were largely related to limited information, which culminated in fear surrounding 'doing the right thing' both for individual's recovery and the longevity of the joint replacement. CONCLUSIONS: While many people post-THA or TKA wish to return to pre-pathological physical activity status, there is limited interest in actually undertaking greater levels of physical activity post-arthroplasty either for pleasure or health gains. Improvement in education and awareness of this may be key drivers to improve habitualisation of physical activity post-arthroplasty. TRIAL REGISTRATION NUMBER: CRD42014014995.