197 research outputs found

    The volume of liver irradiated during modern free-breathing breast radiotherapy: implications for theory and practice

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    Introduction Incidental liver irradiation during breast radiotherapy can increase the risk of second primary malignancy and induce adverse inflammatory states. This study establishes the volume of liver irradiated during free-breathing breast radiotherapy. Novel associations between liver dose-volume data and systemic interleukin-6 soluble receptor and blood counts are evaluated. Methods The volume of liver within the 10%, 50% and 90% isodose was determined for 100 women with stage 0 to II breast carcinoma undergoing 40Gy in 15 fractions over three weeks tangential irradiation. Blood counts and interleukin 6 soluble receptor concentration were recorded before, during and four weeks after radiotherapy. Dose-volume data for right-sided treatments was associated with longitudinal measures at bivariate and multivariable levels. Results A maximum of 226cm3 (19%), 92 cm3 (8%) and 62 cm3 (5%) of the liver was irradiated within the 10%, 50% and 90% isodose. Liver irradiation was almost exclusively a feature of the 52 right-sided treatments and was strongly correlated with breast volume (ρ = 0.7, p < 0.0001). Liver V10% was significantly associated with interleukin-6 soluble receptor concentration four weeks post-radiotherapy (beta = 0.38, p = 0.01) after controlling for theoretical confounding variables. Conclusion Up to 8% of the liver is irradiated within the primary beam during local right-sided breast radiotherapy. Select use of a deep inspiration breath hold technique would reduce this volume, and minimise the risk of radiation-induced malignancy and acute systemic elevation of inflammatory interleukin 6 soluble receptor

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

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    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

    Perspectives on the Social, Physical and Emotional Impact of Living with Perthes’ Disease in Children and their Family: a Mixed Methods Study.

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    Aim: To determine the social, physical and emotional impact of living with Perthes’ disease on affected children and their family (caregivers). Patients and Methods: Through a mixed methods approach, we interviewed 18 parents and explored the perspectives of 12 children affected by Perthes’ disease (mean 7.1 years, SD±4.1 years) using a survey tool. Thematic analysis of parents’ interviews provided an insight into disease-specific factors influencing patients and family’s daily life activities. Using the childhood survey tool, good and bad day scores were analyzed using MANOVA. Results: Thematic analysis of the parent interviews (main themes n=4) identified a marked effect of the disease on many facets of the child’s life, particularly pain and the impact on sleep, play and school attendance. In addition, the interviews identified a negative effect on the family life of the parents and siblings. Children indicated that activities of daily living were affected even during ‘good days’ (p<0.05) but pain was the key limiting factor. Conclusion: Perthes’ disease negatively affects the social, physical and emotional well-being of children and their family. These findings provide outcome domains that are important to measure in day-to-day care and add in-depth insight into the challenges caused by this disease for health care professionals involved in clinical management

    The outcomes of Perthes' disease.

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    AIMS: To identify a suite of the key physical, emotional, and social outcomes to be employed in clinical practice and research concerning Perthes' disease in children. METHODS: The study follows the guidelines of the COMET-Initiative (Core Outcome Measures in Effectiveness Trials). A systematic review of the literature was performed to identify a list of outcomes reported in previous studies, which was supplemented by a qualitative study exploring the experiences of families affected by Perthes' disease. Collectively, these outcomes formed the basis of a Delphi survey (two rounds), where 18 patients with Perthes' disease, 46 parents, and 36 orthopaedic surgeons rated each outcome for importance. The International Perthes Study Group (IPSG) (Dallas, Texas, USA (October 2018)) discussed outcomes that failed to reach any consensus (either 'in' or 'out') before a final consensus meeting with representatives of surgeons, patients, and parents. RESULTS: In total, 23 different outcome domains were identified from the systematic review, and a further ten from qualitative interviews. After round one of the Delphi survey, participants suggested five further outcome domains. A total of 38 outcomes were scored in round two of the Delphi. Among these, 16 outcomes were scored over the prespecified 70% threshold for importance (divided into six main categories: adverse events; life impact; resource use; pathophysiological manifestations; death; and technical considerations). Following the final consensus meeting, 14 outcomes were included in the final Core Outcome Set (COS). CONCLUSION: Core Outcome Sets (COSs) are important to improve standardization of outcomes in clinical research and to aid communication between patients, clinicians, and funding bodies. The results of this study should be a catalyst to develop high-quality clinical research in order to determine the optimal treatments for children with Perthes' disease. Cite this article: Bone Joint J 2020;102-B(5):611-617

    Managing lifestyle change to reduce coronary risk: a synthesis of qualitative research on peoples’ experiences

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    Background Coronary heart disease is an incurable condition. The only approach known to slow its progression is healthy lifestyle change and concordance with cardio-protective medicines. Few people fully succeed in these daily activities so potential health improvements are not fully realised. Little is known about peoples’ experiences of managing lifestyle change. The aim of this study was to synthesise qualitative research to explain how participants make lifestyle change after a cardiac event and explore this within the wider illness experience. Methods A qualitative synthesis was conducted drawing upon the principles of meta-ethnography. Qualitative studies were identified through a systematic search of 7 databases using explicit criteria. Key concepts were identified and translated across studies. Findings were discussed and diagrammed during a series of audiotaped meetings. Results The final synthesis is grounded in findings from 27 studies, with over 500 participants (56% male) across 8 countries. All participants experienced a change in their self-identity from what was ‘familiar’ to ‘unfamiliar’. The transition process involved ‘finding new limits and a life worth living’ , ‘finding support for self’ and ‘finding a new normal’. Analyses of these concepts led to the generation of a third order construct, namely an ongoing process of ‘reassessing past, present and future lives’ as participants considered their changed identity. Participants experienced a strong urge to get back to ‘normal’. Support from family and friends could enable or constrain life change and lifestyle changes. Lifestyle change was but one small part of a wider ‘life’ change that occurred. Conclusions The final synthesis presents an interpretation, not evident in the primary studies, of a person-centred model to explain how lifestyle change is situated within ‘wider’ life changes. The magnitude of individual responses to a changed health status varied. Participants experienced distress as their notion of self identity shifted and emotions that reflected the various stages of the grief process were evident in participants’ accounts. The process of self-managing lifestyle took place through experiential learning; the level of engagement with lifestyle change reflected an individual’s unique view of the balance needed to manage ‘realistic change’ whilst leading to a life that was perceived as ‘worth living’. Findings highlight the importance of providing person centred care that aligns with both psychological and physical dimensions of recovery which are inextricably linked

    Multimode fibre:Light-sheet microscopy at the tip of a needle

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    We also thank the UK Engineering and Physics Sciences Research Council for funding under grant EP/J01771X/1. Finally, we would like to thank EXCELLENT TEAMS (CZ.1.07/2.3.00/30.0005) from European Social Fund and CEITEC - Central European Institute of Technology (CZ.1.05/1.1.00/02.0068) from European Regional Development Fund for support.Light-sheet fluorescence microscopy has emerged as a powerful platform for 3-D volumetric imaging in the life sciences. Here, we introduce an important step towards its use deep inside biological tissue. Our new technique, based on digital holography, enables delivery of the light-sheet through a multimode optical fibre - an optical element with extremely small footprint, yet permitting complex control of light transport processes within. We show that this approach supports some of the most advanced methods in light-sheet microscopy: by taking advantage of the cylindrical symmetry of the fibre, we facilitate the wavefront engineering methods for generation of both Bessel and structured Bessel beam plane illumination. Finally, we assess the quality of imaging on a sample of fluorescent beads fixed in agarose gel and we conclude with a proof-of-principle imaging of a biological sample, namely the regenerating operculum prongs of Spirobranchus lamarcki.Publisher PDFPeer reviewe

    Role of potassium and calcium channels in sevoflurane-mediated vasodilation in the foeto-placental circulation

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    <p>Abstract</p> <p>Background</p> <p>Sevoflurane has been demonstrated to vasodilate the foeto-placental vasculature. We aimed to determine the contribution of modulation of potassium and calcium channel function to the vasodilatory effect of sevoflurane in isolated human chorionic plate arterial rings.</p> <p>Methods</p> <p>Quadruplicate <it>ex vivo </it>human chorionic plate arterial rings were used in all studies. <b><it>Series 1 and 2 </it></b>examined the role of the K<sup>+ </sup>channel in sevoflurane-mediated vasodilation. Separate experiments examined whether tetraethylammonium, which blocks large conductance calcium activated K<sup>+ </sup>(K<sub>Ca++</sub>) channels (<b><it>Series 1A+B</it></b>) or glibenclamide, which blocks the ATP sensitive K<sup>+ </sup>(K<sub>ATP</sub>) channel (<b><it>Series 2</it></b>), modulated sevoflurane-mediated vasodilation. <b><it>Series 3 – 5 </it></b>examined the role of the Ca<sup>++ </sup>channel in sevoflurane induced vasodilation. Separate experiments examined whether verapamil, which blocks the sarcolemmal voltage-operated Ca<sup>++ </sup>channel (<b><it>Series 3</it></b>), SK&F 96365 an inhibitor of sarcolemmal voltage-independent Ca<sup>++ </sup>channels (<b><it>Series 4A+B</it></b>), or ryanodine an inhibitor of the sarcoplasmic reticulum Ca<sup>++ </sup>channel (<b><it>Series 5A+B</it></b>), modulated sevoflurane-mediated vasodilation.</p> <p>Results</p> <p>Sevoflurane produced dose dependent vasodilatation of chorionic plate arterial rings in all studies. Prior blockade of the K<sub>Ca++ </sub>and K<sub>ATP </sub>channels augmented the vasodilator effects of sevoflurane. Furthermore, exposure of rings to sevoflurane in advance of TEA occluded the effects of TEA. Taken together, these findings suggest that sevoflurane blocks K<sup>+ </sup>channels. Blockade of the voltage-operated Ca<sup>++</sup>channels inhibited the vasodilator effects of sevoflurane. In contrast, blockade of the voltage-independent and sarcoplasmic reticulum Ca<sup>++</sup>channels did not alter sevoflurane vasodilation.</p> <p>Conclusion</p> <p>Sevoflurane appears to block chorionic arterial K<sub>Ca++ </sub>and K<sub>ATP </sub>channels. Sevoflurane also blocks voltage-operated calcium channels, and exerts a net vasodilatory effect in the <it>in vitro </it>foeto-placental circulation.</p
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