ACTIVE - a randomised feasibility trial study protocol of a behavioural intervention to reduce fatigue in women undergoing radiotherapy for early breast cancer: study protocol.

BACKGROUND: Fatigue is rated as the most distressing side effect of radiotherapy treatment for curable breast cancer. About four in ten women treated experience fatigue, which can last for years after treatment. The impact of this debilitating tiredness is loss of independence and impaired physical and mental function. Our study will take a behavioural intervention with demonstrated effect in treating fatigue in a mixed group of chemotherapy patients and adapt it for women undergoing radiotherapy for early breast cancer. The purpose of this trial is to evaluate the feasibility of delivering the intervention in the radiotherapy pathway for patients at a high risk of fatigue and to explore participants' experiences of the trial and intervention. METHODS: A pragmatic single-site non-blinded feasibility trial of a behavioural intervention. Main inclusion criteria are prescription of the UK standard 40 Gy in 15 fractions over 3 weeks of radiotherapy (± tumour bed boost) for early (stage 0-IIIa) breast cancer. The total projected sample size after attrition is 70. A previously developed fatigue risk score tool will be used to predict individual's likelihood of experiencing fatigue. Thirty women predicted to be at a high risk of experiencing significant fatigue will be allocated in the ratio 2:1 to the behavioural intervention or education trial arms, respectively. These feasibility trial participants will be assessed at baseline, after 10 and 15 fractions of radiotherapy and 10 days, 3 weeks and 6 months after radiotherapy. A further 40 women predicted to be at a lower risk of fatigue will join a risk score validation group.Measures to assess feasibility include recruitment, retention and completion rates and variation in implementation of the intervention. Process evaluation with intervention providers and users includes fidelity and adherence checks and qualitative interviews to understand how changes in behaviour are initiated and sustained. DISCUSSION: This feasibility study collates data to both inform the progression to and design of a future definitive trial and to refine the intervention. TRIAL REGISTRATION: ISRCTN 10303368. Registered August 2017 (retrospectively registered); Health and Care Research Wales Clinical Research Portfolio (CRP) registration 31419.

Immunology of experimental and natural human hookworm infection.

Human hookworm infection is one amongst the most prevalent of the neglected tropical diseases. An informative experimental animal model, that is, one that parallels a human infection, is not available for the study of human hookworm infection. Much of our current understanding of the human immune response during hookworm infection relies on the studies from experimental infection of hookworm-naïve individuals or the natural infections from individuals residing in hookworm-endemic areas. The experimental human infections tend to be acute, dose-controlled infections, often with a low larval inoculum so that they are well tolerated by human volunteers. Natural hookworm infections usually occur in areas where hookworm transmission is constant and infection is chronic. In cases where there has been drug administration in an endemic area, re-infection often occurs quickly even amongst those who were treated. Hence, although many of the characteristics of experimental and natural hookworm infection differ, both models have elements in common: mainly an intense Th2 response with the production of total and specific IgE as well as elevated levels of eosinophilia, IL-5, IL-10 and TNF. While hookworm infection affects millions of individuals worldwide, much of the human immunology of this infection still needs to be studied and understood.

"Covering our backs": ambulance crews' attitudes towards clinical documentation when emergency (999) patients are not conveyed to hospital.

BACKGROUND: Up to 30% of people who call for an emergency ambulance are, for various reasons, not conveyed to hospital. Across the UK, the majority of ambulance services have policies and procedures requiring ambulance crews to complete clinical documentation for these patients, as they do for patients who travel to hospital. However, studies have suggested that documentation does not get completed for a large proportion of non-conveyed patients. METHODS: A qualitative study in one large ambulance service trust used focus groups to explore crew members' attitudes towards clinical documentation and non-conveyed patients. RESULTS: Considerable ambiguity was found: crews were aware of the need to "cover their backs" by completing clinical records, but at the same time expressed doubts about the value of this documentation. There appeared to be two main circumstances in which records were not completed. Firstly, there were the cases where crews may have been unable to obtain necessary information from patients who were intoxicated or otherwise uncooperative. Secondly, there were cases where the crews may not have recognised their encounter with a patient as having a clinical dimension, such as older people who had fallen but were apparently uninjured. These circumstances were combined with a lack of monitoring by managers of whether forms were being completed, and a disinclination on the part of some crew members to do what they regarded as unnecessary work. CONCLUSION: The low rates of completion of clinical records for non-conveyed patients appeared to result from crew members not believing they were important in every circumstance, combined with a lack of management focus. Low rates of completion may lead in turn to clinical risk and a risk of litigation if things go wrong.

Mucosal leishmaniasis patients display an activated inflammatory T-cell phenotype associated with a nonbalanced monocyte population.

Leishmania braziliensis is a parasite that can induce at least two clinical forms of leishmaniasis in humans: cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML). In humans, the specific mechanisms that determine which form will develop following infection are not well established. In this study, peripheral blood mononuclear cells from 17 CL and 9 ml patients were compared both ex vivo and after culture with soluble leishmania antigen (SLA). Patients with ML presented a higher frequency of activated T cells as measured by ex vivo frequencies of (CD4+)(CD69+), (CD4+)(CD28-), (CD4+)(CD62L-) and (CD8+)(CD69+) than those with CL. Moreover, after stimulation with SLA, patients with ML presented a higher frequency of TNF-alpha-producing CD4+ and CD14+ cells than CL individuals. While CL patients displayed a positive correlation between the frequency of IL-10 and TNF-alpha-producing monocytes, the ML patients did not. This lack of a positive correlation between IL-10-producing and TNF-alpha-producing monocytes in ML patients could lead to a less controlled inflammatory response in vivo. These results corroborate with a model of an exacerbated, unregulated, immune response in ML patients and point to key immunomodulatory leucocyte populations and cytokine networks that may be involved in the development of immunopathology in ML patients.