HIDDEN2: Study protocol for the hospital deep vein thrombosis detection study in patients with cancer receiving palliative care.

INTRODUCTION: Medical patients, admitted acutely to hospital, are at risk of venous thromboembolism (VTE). Clinical guidelines advise thromboprophylaxis prophylaxis for those at high risk of VTE. VTE is a common sequela of cancer, but guidelines take little consideration of cancer as an independent risk factor and their utility in palliative care patients is unclear. The hospice inpatient deep vein thrombosis (DVT) detection study (HIDDen) reported a 28% prevalence of asymptomatic iliofemoral DVT in hospice patients of poor performance status (PS) and prognosis, calling into question the utility of thromboprophylaxis in the palliative care setting. However, the majority of cancer inpatients receiving palliative care are admitted to hospital through the acute medical setting, yet their risk factors for VTE may differ from those admitted to hospices. OBJECTIVE: To better understand the prevalence and behaviours of VTE in patients with cancer receiving palliative care who are admitted as an acute medical emergency. DESIGN: Multicentre, observational cohort study. SETTING: Secondary care acute hospitals in South Wales, UK. PATIENTS: We plan to recruit 232 patients≥18 years old with a diagnosis of incurable cancer, and/or receiving palliative or best supportive care who are admitted acutely to hospital. Patients will be followed up for a maximum of 6 months following registration. PRIMARY OUTCOME: Presence of lower extremity DVT. SECONDARY OUTCOMES: Symptom burden attributed to DVT or pulmonary embolism, patient PS, patient demographics and development of new VTE within 90 days of registration. ANALYSIS: The study statistical analysis plan will document analysis, methodology and procedures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee, reference 22/WA/0037 (IRAS 306352)-the main trial results will be analysed as soon as practically possible and the publication shared with investigators and on sponsor website; applications to access trial data will be subject to sponsor review process.

'It is easier to not allow them to see your disability straight away, to see you as a person': An Interpretative Phenomenological Analysis of video gaming from the perspectives of men with Duchenne Muscular Dystrophy.

BACKGROUND: Young men with Duchenne Muscular Dystrophy benefit from palliative care that supports their psychosocial needs. Acknowledging the sub-cultures they engage with can support their wellbeing. Anecdotal reports suggest video gaming is a sub-culture engaged with by young men with Duchenne Muscular Dystrophy. AIM: To explore the lived experience of video gaming from the perspective of young men with Duchenne Muscular Dystrophy. DESIGN: Interpretative Phenomenological Analysis approach involving in-depth interviews using a topic guide that focused on social media broadly, with reference to video gaming. Sequential interviewing was undertaken to support participation regarding fatigue and tiredness, symptoms of Duchenne Muscular Dystrophy. SETTING/PARTICIPANTS: Participants were purposefully recruited from a hospice in the North of England. Twitter was used to support recruitment. Eight young men with Duchenne Muscular Dystrophy were recruited to the study. RESULTS: Five themes were developed; 'gamer as a shared and accepted identity', 'an existential and bodily escapism', 'introspection through video gaming', 'video gaming as a release' and 'when life gives you few choices-video game'. Motivations for engagement with video gaming are diverse and reflective of the situated perspectives of young men with Duchenne Muscular Dystrophy. CONCLUSIONS: An awareness of the popular sub-cultures that young men with Duchenne Muscular Dystrophy engage with is key to building a therapeutic alliance, establishing rapport and recognising personhood in interactions between professionals and persons in palliative care settings. This study highlights the value of video gaming, offering professionals valuable insight into its placement in the daily lives of young men with Duchenne Muscular Dystrophy.

Brief transdiagnostic group intervention for people living with HIV and emotional disorders: feasibility and clinical utility.

Emotional regulation-based transdiagnostic interventions provide positive but limited evidence regarding efficacy with people living with human immunodeficiency virus (HIV). In the present study, 10 participants living with HIV with emotional disorders completed a five-session transdiagnostic group intervention to improve their emotional regulation skills (Unified Protocol). Changes at pre-treatment, post-treatment and three-month follow-up were explored at the population (mean-rank) and the individual level (reliable change index). Compared to pre-treatment, participants improved significantly in anxiety, depression, negative affect and quality of life. Changes were maintained at the three-month follow-up. Emotion regulation, particularly the confusion factor, improved when comparing pre-treatment with the three-month follow-up. At the three-month follow-up, the percentage of normalized scores was the largest in maladjustment (70%), followed by depression, negative affect, and lack of control (50%). All participants indicated high treatment satisfaction and perceived benefits. These promising results suggest that brief emotion regulation interventions might be feasible and effective in the public health settings for people living with HIV suffering emotional disorders.

Arthroscopic hip surgery compared with personalised hip therapy in people over 16 years old with femoroacetabular impingement syndrome: UK FASHIoN RCT.

BACKGROUND: Femoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery or with physiotherapist-led conservative care. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of hip arthroscopy with best conservative care. DESIGN: The UK FASHIoN (full trial of arthroscopic surgery for hip impingement compared with non-operative care) trial was a pragmatic, multicentre, randomised controlled trial that was carried out at 23 NHS hospitals. PARTICIPANTS: Participants were included if they had femoroacetabular impingement, were aged ≥ 16 years old, had hip pain with radiographic features of cam or pincer morphology (but no osteoarthritis) and were believed to be likely to benefit from hip arthroscopy. INTERVENTION: Participants were randomly allocated (1 : 1) to receive hip arthroscopy followed by postoperative physiotherapy, or personalised hip therapy (i.e. an individualised physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre using a central telephone randomisation service. Outcome assessment and analysis were masked. MAIN OUTCOME MEASURE: The primary outcome was hip-related quality of life, measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed by intention to treat. RESULTS: Between July 2012 and July 2016, 648 eligible patients were identified and 348 participants were recruited. In total, 171 participants were allocated to receive hip arthroscopy and 177 participants were allocated to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% (N = 319; hip arthroscopy, n = 157; personalised hip therapy, n = 162). At 12 months, mean International Hip Outcome Tool (iHOT-33) score had improved from 39.2 (standard deviation 20.9) points to 58.8 (standard deviation 27.2) points for participants in the hip arthroscopy group, and from 35.6 (standard deviation 18.2) points to 49.7 (standard deviation 25.5) points for participants in personalised hip therapy group. In the primary analysis, the mean difference in International Hip Outcome Tool scores, adjusted for impingement type, sex, baseline International Hip Outcome Tool score and centre, was 6.8 (95% confidence interval 1.7 to 12.0) points in favour of hip arthroscopy (p = 0.0093). This estimate of treatment effect exceeded the minimum clinically important difference (6.1 points). Five (83%) of six serious adverse events in the hip arthroscopy group were related to treatment and one serious adverse event in the personalised hip therapy group was not. Thirty-eight (24%) personalised hip therapy patients chose to have hip arthroscopy between 1 and 3 years after randomisation. Nineteen (12%) hip arthroscopy patients had a revision arthroscopy. Eleven (7%) personalised hip therapy patients and three (2%) hip arthroscopy patients had a hip replacement within 3 years. LIMITATIONS: Study participants and treating clinicians were not blinded to the intervention arm. Delays were encountered in participants accessing treatment, particularly surgery. Follow-up lasted for 3 years. CONCLUSION: Hip arthroscopy and personalised hip therapy both improved hip-related quality of life for patients with femoroacetabular impingement syndrome. Hip arthroscopy led to a greater improvement in quality of life than personalised hip therapy, and this difference was clinically significant at 12 months. This study does not demonstrate cost-effectiveness of hip arthroscopy compared with personalised hip therapy within the first 12 months. Further follow-up will reveal whether or not the clinical benefits of hip arthroscopy are maintained and whether or not it is cost-effective in the long term. TRIAL REGISTRATION: Current Controlled Trials ISRCTN64081839. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 16. See the NIHR Journals Library website for further project information.

In some people, the ball and the socket of the hip joint develop so that they do not fit together properly. This is called hip impingement, and is an important cause of hip and groin pain in young and middle-aged adults. Treatments include physiotherapy and surgery. Physiotherapy typically involves a programme of 6­10 outpatient consultations that aim to strengthen the muscles around the hip: we called this personalised hip therapy. Surgery can be carried out by a keyhole operation, called a hip arthroscopy, which aims to reshape the hip to prevent impingement. Surgery is normally followed by some physiotherapy. We performed a research study to compare the results of hip arthroscopy and personalised hip therapy in people with hip impingement. A total of 348 people with painful hip impingement in 23 hospitals in the UK agreed to take part. About half were treated with hip arthroscopy and half with personalised hip therapy. We used questionnaires to ask participants about pain in the hip and their ability to do everyday things at 6 months and 1 year after entering the study. At 2 and 3 years, we asked if patients required any additional treatments. We found that both groups improved, but those treated with hip arthroscopy improved a moderate amount more than those treated with personalised hip therapy. However, these improvements were not cost-effective compared with personalised hip therapy at 1 year. We need to see whether or not this difference continues after several years, but the results, so far, suggest that if a person has painful hip impingement, then hip arthroscopy offers greater improvements than personalised hip therapy.

Factors influencing an eruption of teeth associated with a dentigerous cyst: a systematic review and meta-analysis.

BACKGROUND: A dentigerous cyst (DC) is a pathology embracing the crown of an unerupted tooth at risk of malignant transformation. The causal tooth is usually removed together with the cyst. However, if there are orthodontic contraindications for extraction, two questions arise. (1) Which factors favor spontaneous eruption? (2) Which factors imply the necessity of applying orthodontic traction? This systematic review aimed to identify factors conducive/inconducive to the spontaneous eruption of teeth after dentigerous cyst marsupialization. METHODS: In accordance with the PRISMA guidelines, the main research question was defined in the PICO format (P: patients with dentigerous cysts; I: spontaneous tooth eruption after surgical DC treatment; C: lack of a spontaneous tooth eruption after surgical DC treatment; O: determining factors potentially influencing spontaneous tooth eruption). The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for keywords combining dentigerous/odontogenic/follicular cysts with teeth and/or orthodontics, as well as human teeth and eruption patterns/intervals/periods/durations. The following data were extracted from the qualified articles (4 out of 3005 found initially): the rate of tooth eruption after surgical treatment of the cyst, the age and sex of the patients, the perpendicular projection distance between the top of the tooth cusp and the edge of the alveolar process, tooth angulation, the root formation stage, the cyst area, and the eruption space. The articles were subjected to risk of bias and quality analyses with the ROBINS-I protocol and the modified Newcastle-Ottawa QAS, respectively. Meta-analyses were performed with both fixed and random effects models. The GRADE approach was used to evaluate the quality of the evidence. The systematic review was registered in PROSPERO under ID CRD42020189044. RESULTS: Nearly 62% of DC-associated premolars erupted spontaneously after cyst marsupialization/decompression. Young age (mean = 10 years) and root formation not exceeding 1/2 of its fully developed length were the factors likely to favor spontaneous eruption. CONCLUSION: The small number of published studies, as well as their heterogeneity and the critical risk of bias, did not allow the creation of evidence-based protocols for managing teeth with DC after marsupialization. More high-quality research is needed to draw more reliable conclusions.

Social media use in adolescents and young adults with serious illnesses: an integrative review.

OBJECTIVES: Adolescents and young adults with life-limiting or life-threatening conditions are often socially isolated because of the demands of their illness. Although adolescents and young adults have a noticeable online and social media presence, their motivations for using social media remain unclear. This article aims to summarise empirical research undertaken about how and why social media is used by adolescents and young adults with life-limiting or life-threatening conditions. METHODS: An integrative literature review was undertaken. Key healthcare research databases including CINHAL, MEDLINE and PSYCHINFO were searched for empirical studies reporting the use of social media by adolescents and young adults with life-limiting or life-threatening conditions. Fifteen articles met the inclusion criteria; included articles were quality appraised and a thematic synthesis undertaken to identify key themes. RESULTS: The reasons why adolescents and young adults with life-limiting or life-threatening conditions use social media are diverse, with differences relating to age and gender. However, this population in general uses social media to connect with others who have similar lived experiences. CONCLUSION: Social media platforms can be useful adjuncts to the care of adolescents and young adults with life-limiting or life-threatening conditions. However, current evidence is dominated by studies on social media use by adolescents and young adults with cancer. More research is required to gain a holistic understanding of how and why social media is used by this population and its perceived benefits and limitations.

Missed opportunity? Worsening breathlessness as a harbinger of death: a cohort study.

The aim of the study was to explore trajectories of breathlessness intensity by function and life-limiting illness diagnosis in the last 3 weeks of life in palliative care patients.A prospective, consecutive cohort study obtained point-of-care data of patients of Silver Chain Hospice Care Service (Perth, Australia) over the period 2011-2014 (n=6801; 51 494 data-points). Breathlessness intensity (0-10 numerical rating scale) and physical function (Australia-modified Karnofsky Performance Status (AKPS)) were measured at each visit. Time was anchored at death. Breathlessness trajectory was analysed by physical function and diagnosis using mixed effects regression.Mean±sd age was 71.5±15.1 years and 55.2% were male, most with cancer. The last recorded AKPS was >40 for 26.8%. Breathlessness was worst in people with cardiorespiratory disease and AKPS >40, and breathlessness in the last week of life increased most in this group (adjusted mean 2.92 versus all others 1.51; p=0.0001). The only significant interaction was with diagnosis and function in the last week of life (p<0.0001).Breathlessness is more intense and increases more in people with better function and cardiorespiratory disease immediately before death. Whether there are reversible causes for these people should be explored prospectively. Omitting function from previous population estimates may have overestimated breathlessness intensity for many patients in the days preceding death.

Hip arthroscopy versus best conservative care for the treatment of femoroacetabular impingement syndrome (UK FASHIoN): a multicentre randomised controlled trial.

BACKGROUND: Femoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery, including reshaping the hip, or with physiotherapist-led conservative care. We aimed to compare the clinical effectiveness of hip arthroscopy with best conservative care. METHODS: UK FASHIoN is a pragmatic, multicentre, assessor-blinded randomised controlled trial, done at 23 National Health Service hospitals in the UK. We enrolled patients with femoroacetabular impingement syndrome who presented at these hospitals. Eligible patients were at least 16 years old, had hip pain with radiographic features of cam or pincer morphology but no osteoarthritis, and were believed to be likely to benefit from hip arthroscopy. Patients with bilateral femoroacetabular impingement syndrome were eligible; only the most symptomatic hip was randomly assigned to treatment and followed-up. Participants were randomly allocated (1:1) to receive hip arthroscopy or personalised hip therapy (an individualised, supervised, and progressive physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre and was done by research staff at each hospital, using a central telephone randomisation service. Patients and treating clinicians were not masked to treatment allocation, but researchers who collected the outcome assessments and analysed the results were masked. The primary outcome was hip-related quality of life, as measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed in all eligible participants who were allocated to treatment (the intention-to-treat population). This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN64081839, and is closed to recruitment. FINDINGS: Between July 20, 2012, and July 15, 2016, we identified 648 eligible patients and recruited 348 participants: 171 participants were allocated to receive hip arthroscopy and 177 to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% (319 of 348 participants). At 12 months after randomisation, mean iHOT-33 scores had improved from 39·2 (SD 20·9) to 58·8 (27·2) for participants in the hip arthroscopy group, and from 35·6 (18·2) to 49·7 (25·5) in the personalised hip therapy group. In the primary analysis, the mean difference in iHOT-33 scores, adjusted for impingement type, sex, baseline iHOT-33 score, and centre, was 6·8 (95% CI 1·7-12·0) in favour of hip arthroscopy (p=0·0093). This estimate of treatment effect exceeded the minimum clinically important difference (6·1 points). There were 147 patient-reported adverse events (in 100 [72%] of 138 patients) in the hip arthroscopy group) versus 102 events (in 88 [60%] of 146 patients) in the personalised hip therapy group, with muscle soreness being the most common of these (58 [42%] vs 69 [47%]). There were seven serious adverse events reported by participating hospitals. Five (83%) of six serious adverse events in the hip arthroscopy group were related to treatment, and the one in the personalised hip therapy group was not. There were no treatment-related deaths, but one patient in the hip arthroscopy group developed a hip joint infection after surgery. INTERPRETATION: Hip arthroscopy and personalised hip therapy both improved hip-related quality of life for patients with femoroacetabular impingement syndrome. Hip arthroscopy led to a greater improvement than did personalised hip therapy, and this difference was clinically significant. Further follow-up will reveal whether the clinical benefits of hip arthroscopy are maintained and whether it is cost effective in the long term. FUNDING: The Health Technology Assessment Programme of the National Institute of Health Research.

Consult, Negotiate, and Involve: Evaluation of an Advanced Communication Skills Program for Health Care Professionals.

Effective communication is central to children, young people, and their families' experiences of health care. Most patient complaints in developed health care systems result from ineffective communication, including inadequate information provision, not feeling listened to, failure to value patients concerns, and patients not feeling involved in care decisions. Advanced communication skills training is now embedded within cancer care policy in the United Kingdom and now features prominently within cancer education in many countries. Here, we share findings from a research evaluation of an advanced communication skills training program dedicated to health professionals caring for children and young people with cancer. We evaluated participants' (n = 59) perceptions of the program, impact on their skills, knowledge, competence, and confidence. An appreciative inquiry design was adopted; data included interviews, precourse-postcourse evaluations, e-mail blog survey, and 360-degree reflective work records. The framework approach underpinned data analysis and triangulation of data sets. Key findings highlighted good and poor practice in health professionals' engagement with children, young people, and their families; the purpose of communicating effectively was not always consistent with collaborative working. Attending a program helped participants expand their knowledge of communication theories and strategies. Participants valued using simulated scenarios to develop their skills and were keen to use their new skills to enhance care delivery. Our emphasis within this evaluation, however, remained on what was communicated, when and how, rather than to what effect. The impact of programs such as these must now be evaluated in terms of patient benefit.

Reactive oxygen species in BCR-ABL1-expressing cells - relevance to chronic myeloid leukemia.

Chronic myeloid leukemia (CML) results from the t(9;22) reciprocal chromosomal translocation producing the BCR-ABL1 gene, conferring growth and proliferation advantages in the CML cells. CML progresses from chronic, often syndrome-free, to blast phase, fatal if not treated. Although the involvement of BCR-ABL1 in some signaling pathways is considered as the cause of CML, the mechanisms resulting in its progression are not completely known. However, BCR-ABL1 stimulates the production of reactive oxygen species (ROS), which levels increase with CML progression and induce BCR-ABL1 self-mutagenesis. Introducing imatinib and other tyrosine kinase inhibitors (TKIs) to CML therapy radically improved its outcome, but TKIs-resistance became an emerging problem. TKI resistance can be associated with even higher ROS production than in TKI-sensitive cells. Therefore, ROS-induced self-mutagenesis of BCR-ABL1 can be crucial for CML progression and TKI resistance and in this way should be taken into account in therapeutic strategies. As a continuous production of ROS by BCR-ABL1 would lead to its self-destruction and death of CML cells, there must be mechanisms controlling this phenomenon. These can be dependent on DNA repair, which is modulated by BCR-ABL1 and can be different in CML stem and progenitor cells. Altogether, the mechanisms of the involvement of BCR-ABL1 in ROS signaling can be engaged in CML progression and TKI-resistance and warrant further study.

Undertaking safe medicine administration with children part 2: essential numeracy.

This is the second of two articles which aim to provide children's nurses with an opportunity to develop their knowledge and skills of medicines management when caring for children and young people. The first article considered the processes associated with effective medicines management, including the concept of human error. This article addresses essential numeracy and calculation skills that have been identified as an important risk factor associated with medication errors in children. The range of activities throughout the article will help you develop and practise numeracy skills, with the answers for each activity at the end of the article.

Undertaking safe medicine administration with children: part 1.

This is the first of two articles that aim to provide children's nurses with an opportunity to develop their skills and knowledge of medicines management when caring for children and young people. This first article outlines the principles of effective medicines management including the pharmacology language required to accurately read prescriptions, the way children respond to medicines, managing risk, including the concept of human error, and working in partnership with children, young people and families. The second article, to be published in September, will focus on numeracy and calculation skills, identified as an important risk factor associated with medication errors in children.

Positive trends in paediatric renal biopsy service provision in the UK: a national survey and re-audit of paediatric renal biopsy practice.

BACKGROUND: Paediatric renal biopsy standards introduced in the UK in 2010 were intended to reduce variation and improve practice. A concurrent national drive was aimed at building robust paediatric nephrology networks to ensure services cater for the needs of the family and minimise time away from home. We aimed to identify current national practice since these changes on behalf of the British Association for Paediatric Nephrology. METHODS: All UK paediatric nephrology centres were invited to complete a survey of their biopsy practice, including advance preparation. From 1 January to 30 June 2012, a national prospective audit of renal biopsies was undertaken at participating centres comparing practice with the British Association for Paediatric Nephrology (BAPN) standards and audit results from 2005. RESULTS: Survey results from 11 centres demonstrated increased use of pre-procedure information leaflets (63.6 % vs 45.5 %, P = 0.39) and play preparation (90.9 % vs 9.1 %, P = 0.0001). Audit of 331 biopsies showed a move towards day-case procedures (49.5 % vs 32.9 %, P = 0.17) and reduced major complications (4.5 % vs 10.4 %, P = 0.002). Biopsies with 18-gauge needles had significantly higher mean pass rates (3.2 vs 2.3, P = 0.0008) and major complications (15.3 % vs 3.3 %, P = 0.0015) compared with 16-gauge needles. CONCLUSIONS: Percutaneous renal biopsy remains a safe procedure in children, thus improving family-centered service provision in the UK.

Symptom burden of haematological malignancies as death approaches in a community palliative care service: a retrospective cohort study of a consecutive case series.

BACKGROUND: Patients with haematological malignancies are less likely to use palliative care services than are patients with solid tumours. This difference might stem from differing symptom burden, care needs, disease trajectories, or a combination of these factors. We described symptom burden and physical decline over time for people with haematological malignancies compared with people with solid tumours in a consecutive case series. METHODS: We included patients admitted to Silver Chain Hospice Care Service who died between Jan 1, 2011, and Dec 31, 2013, and who completed the eight-item Symptom Assessment Scale (0-10, with 0=no distress and 10=worst distress) at each clinical encounter. Physical function was assessed with the Australia-modified Karnofsky performance scale. Symptom and functional assessments were analysed at 7 days, 30 days, 60 days, and 90 days before death, by descriptive statistics. FINDINGS: We included 4638 participants. For people with haematological malignancies (n=224), the most troublesome symptoms were fatigue (mean score 5·2, SD 2·7) and loss of appetite (2·3, SD 2·9), and both worsened significantly near death (p=0·0035 for fatigue, p=0·016 for appetite). Other symptoms were often absent, and changed little over time. Compared with patients with solid tumours (n=4414), there were no significant differences in individual or cumulative symptom scores, changes over time, or the pattern of functional decline. INTERPRETATION: Community patients with haematological malignancies receiving palliative care have similar symptoms and patterns of physical decline at the end of life to people with solid tumours, suggesting similar care needs. This finding questions present limited palliative care service use by patients with haematological malignancies. FUNDING: None.

A feasibility study to inform the design of a randomised controlled trial to identify the most clinically effective and cost-effective length of Anticoagulation with Low-molecular-weight heparin In the treatment of Cancer-Associated Thrombosis (ALICAT).

BACKGROUND: Venous thromboembolism is common in cancer patients and requires anticoagulation with low-molecular-weight heparin (LMWH). Current data recommend LMWH for anticoagulation as far as 6 months, yet guidelines recommend LMWH beyond 6 months in patients who have ongoing or active cancer. This recommendation, based on expert consensus, has not been evaluated in a clinical study. OBJECTIVES: (1) To identify the most clinically and cost-effective length of anticoagulation with LMWH in the treatment of cancer-associated thrombosis (CAT); (2) to identify practicalities of conducting a full randomised controlled trial (RCT) with regard to recruitment, retention and outcome measurement; and (3) to explore the barriers for progressing to a full RCT. DESIGN: The Anticoagulation with Low-molecular-weight heparin In the treatment of Cancer-Associated Thrombosis (ALICAT) trial is a randomised, multicentre, feasibility mixed-methods study with three components: (1) a RCT comparing ongoing LMWH treatment for CAT with cessation of LMWH at 6 months' treatment (current licensed practice) in patients with locally advanced or metastatic cancer, consulted in three clinical settings (haematology outpatients, oncology outpatients and primary care); (2) a nested qualitative study, including focus groups with clinicians to investigate attitudes for recruiting to the study and identify the challenges of progressing to a full RCT, and semistructured interviews with patients and relatives to explore their attitudes towards participating in the study, and potential barriers and concerns to participation; and (3) a UK-wide survey exercise to develop a classification and enumeration system for the CAT models and pathways of care. SETTING: A haematology outpatients department, an oncology outpatients department and primary care. PARTICIPANTS: Patients with ongoing active or metastatic cancer who have received 6 months of LMWH for CAT. INTERVENTIONS: Ongoing LMWH treatment for CAT versus cessation of LMWH at 6 months' treatment in patients with locally advanced or metastatic cancer. MAIN OUTCOME MEASURES: (i) The number of eligible patients over 12 months; (ii) the number of recruited patients over 12 months (target recruitment rate of 30% of eligible patients); and (iii) the proportion of randomised participants with recurrent venous thromboembolisms (VTEs) during follow-up. RESULTS: Following several delays in setting up the RCT component of the study, 5 out of 32 eligible patients consented to be randomised to the RCT suggesting progression to a full RCT was not feasible. Reasons for non-consenting were primarily based on a fixed preference for continuing or discontinuing treatment after 6 months of anticoagulation, and a fear of randomisation to their non-preferred option. Views were largely influenced by patients' initial experience of CAT. Focus groups with clinicians revealed that they would be reticent to recruit to such a study as they had fixed views of best management despite the lack of evidence. Patient pathway modelling suggested that there is a broad heterogeneity of practice with respect to CAT management and co-ordination, with no consensus on which specialty should best manage such cases. CONCLUSIONS: The results of the RCT reflect recruitment from the oncology site only and provide no recruitment data from haematology centres. However, it is unlikely that these other sites would have access to more eligible patients. The management of cancer-associated thrombosis beyond 6 months will remain a clinical challenge. As it is unlikely that a prospective study will successfully recruit, other strategies to accrue relevant data are necessary. Currently the LONGHEVA (Long-term treatment for cancer patients with deep-venous thrombosis or pulmonary embolism) registry is in development to prospectively evaluate this important and common clinical scenario. STUDY REGISTRATION: This study is registered as clinical trials.gov number NCT01817257 and International Standard Randomised Controlled Trial Number (ISRCTN) 37913976. FUNDING DETAILS: Funding for the ALICAT trial was provided by the Health Technology Assessment programme (10/145/01) in response to a themed funding call. The study was designed in accordance with the initial funding brief and feedback from the review process.

Anatomical curve identification.

Methods for capturing images in three dimensions are now widely available, with stereo-photogrammetry and laser scanning being two common approaches. In anatomical studies, a number of landmarks are usually identified manually from each of these images and these form the basis of subsequent statistical analysis. However, landmarks express only a very small proportion of the information available from the images. Anatomically defined curves have the advantage of providing a much richer expression of shape. This is explored in the context of identifying the boundary of breasts from an image of the female torso and the boundary of the lips from a facial image. The curves of interest are characterised by ridges or valleys. Key issues in estimation are the ability to navigate across the anatomical surface in three-dimensions, the ability to recognise the relevant boundary and the need to assess the evidence for the presence of the surface feature of interest. The first issue is addressed by the use of principal curves, as an extension of principal components, the second by suitable assessment of curvature and the third by change-point detection. P-spline smoothing is used as an integral part of the methods but adaptations are made to the specific anatomical features of interest. After estimation of the boundary curves, the intermediate surfaces of the anatomical feature of interest can be characterised by surface interpolation. This allows shape variation to be explored using standard methods such as principal components. These tools are applied to a collection of images of women where one breast has been reconstructed after mastectomy and where interest lies in shape differences between the reconstructed and unreconstructed breasts. They are also applied to a collection of lip images where possible differences in shape between males and females are of interest.

SUCCINCT: an open-label, single-arm, non-randomised, phase 2 trial of gemcitabine and cisplatin chemotherapy in combination with sunitinib as first-line treatment for patients with advanced urothelial carcinoma.

UNLABELLED: Gemcitabine and cisplatin chemotherapy (GC regimen) represents a standard treatment for advanced urothelial carcinoma. We performed an open-label, single-arm, non-randomised, phase 2 trial evaluating the addition of sunitinib to standard GC chemotherapy (SGC regimen). Overall, 63 treatment-naïve participants were recruited and received up to six 21-d cycles of cisplatin 70 mg/m2 (intravenously [IV], day 1) and gemcitabine 1000 mg/m2 (IV, days 1 and 8) combined with sunitinib 37.5 mg (orally, days 2-15). Following review of toxicity after the first six patients, the sunitinib dose was reduced to 25 mg for all patients. Overall response rate was 64%, with response noted in 37 of 58 patients. At 6 mo, 30 of 58 assessable patients (52%; 90% confidence interval [CI], 40-63%) were progression free. Median overall survival was 12 mo (95% CI, 9-15) and was heavily influenced by Bajorin prognostic group. Grade 3-4 toxicities were predominantly haematologic and limited the deliverability of the triple SGC regimen. The trial did not meet its prespecified primary end point of >60% patients progression free at 6 mo. Cumulative myelosuppression led to treatment delays of gemcitabine and cisplatin and dose reduction and/or withdrawal of sunitinib in the majority of cases. The triple-drug combination was not well tolerated. Phase 3 evaluation of the triple SGC regimen in advanced transitional cell carcinoma is not recommended. PATIENT SUMMARY: The addition of sunitinib to standard cisplatin and gemcitabine chemotherapy was poorly tolerated and did not improve outcomes in advanced urothelial carcinoma. Treatment delivery was limited by myelotoxicity.

A feasibility study to inform the design of a randomized controlled trial to identify the most clinically and cost effective anticoagulation length with low molecular weight heparin in the treatment of cancer associated thrombosis (ALICAT): study protocol for a mixed-methods study.

BACKGROUND: Venous thromboembolism is common in patients with cancer and requires anticoagulation with low molecular weight heparin. Current data informs anticoagulation as far as six months, yet guidelines recommend anticoagulation beyond six months in patients who have locally advanced or metastatic cancer. This recommendation, based on expert consensus, has not been evaluated in a clinical study. ALICAT (Anticoagulation Length in Cancer Associated Thrombosis) is a feasibility study to identify the most clinically and cost effective length of anticoagulation with low molecular weight heparin in the treatment of cancer associated thrombosis. METHODS/DESIGN: ALICAT is a randomized multi-centre phase two mixed-methods study with three components: a randomized controlled trial, embedded qualitative study and a survey investigating pathways of care. The randomized controlled trial will compare ongoing low molecular weight heparin treatment for cancer-associated thrombosis versus cessation of low molecular weight heparin at six months treatment (current licensed practice) in patients with locally advanced or metastatic cancer. The embedded qualitative study will include focus groups with clinicians to investigate attitudes to recruiting to the study, identify the challenges of progressing to a full randomized controlled trial, and also semi-structured interviews with patients and relatives/carers to explore their attitudes towards participating in the study and potential barriers and concerns to participation. Finally, a UK wide survey exercise will be undertaken to develop a classification and enumeration system for the cancer associated thrombosis models and pathways of care. DISCUSSION: There is a lack of evidence determining the length of anticoagulation for patients with cancer associated thrombosis and subsequently treatment length varies. The ALICAT study will consider the feasibility of recruiting patients to a phase three trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN37913976.