Supportive and palliative care needs in advanced non-malignant liver disease: systematic review.

Advanced cirrhosis confers a significant symptom burden and has a 50% 2-year mortality rate in those with decompensated disease. There is increasing demand for supportive and palliative care (SAPC) for these patients, yet no consensus on the best model of delivery. It is necessary to identify the needs of such patients and their carers, and evaluate whether they are being met.A literature search was conducted using key words pertaining to adult patients with liver cirrhosis and their SAPC needs. Study quality was assessed and findings grouped by theme. 51 full texts were selected for inclusion, 8 qualitative studies, 33 quantitative studies, 7 systematic reviews, 2 mixed methods studies and 1 Delphi methods. Key findings were grouped into three main themes: SAPC needs, access to SAPC and models of care.Patients with cirrhosis have significant psychological and physical symptom burden with many unmet needs. These data failed to identify the best service model of care. The impact of specialist palliative care (SPC) referral was limited by small numbers and late referrals. With the majority of studies conducted in the USA, it is unclear how well these findings translate to other healthcare systems. Comparison between hepatology led services and SPC was limited by inconsistent outcome measures and prevented pooling of data sets. These data also had limited evaluation of patient-reported outcome measures. We propose the development of a core outcome set to ensure consistent and meaningful evaluation of the SAPC needs of patients with advanced non-malignant liver cirrhosis.

Risk of Venous Thromboembolism in Patients With Stage III and IV Non-Small-Cell Lung Cancer: Nationwide Descriptive Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) is a common complication in patients starting cancer therapies for non-small-cell lung cancer (NSCLC). We examined the risk and timing of VTE in patients with stage IIIA, IIIB to C, and stage IV NSCLC according to received cancer treatments. MATERIALS AND METHODS: A nationwide registry-based cohort study of patients recorded in the Danish Lung Cancer Registry (2010-2021) followed for 1 year after entry into the registry to assess the incidence of VTE. The Aalen-Johansen estimator was used to calculate the risk of VTE after treatment commencement with chemotherapy, radiotherapy, chemoradiation, immunotherapy, and targeted therapy. RESULTS: Among the 3475 patients with stage IIIA, 4047 with stage IIIB to C, and 18,082 patients with stage IV cancer, the 1-year risk of VTE was highest in the first 6 months and varied markedly by cancer stage and cancer treatment. In stage IIIA, VTE risk was highest with chemotherapy (3.9%) and chemoradiation (4.1%). In stage IIIB to C, risks increased with chemotherapy (5.2%), immunotherapy (9.4%), and targeted therapy (6.0%). Stage IV NSCLC showed high risk with targeted therapy (12.5%) and immunotherapy (12.2%). The risk was consistently higher for pulmonary embolism than deep vein thrombosis. CONCLUSION: VTE risks vary substantially according to cancer treatments and cancer stages. The highest risk was observed in the initial 6 months of therapy initiation. These insights emphasize the need for tailored risk assessment and vigilance in managing VTE complications in patients with NSCLC. Further research is needed to optimize individual thromboprophylaxis strategies for patients with unresectable and metastatic NSCLC.

Risk of bleeding amongst warfarin and direct oral anticoagulant users prescribed immediate antibiotics for respiratory tract infection: Cohort study.

PURPOSE: Incidence of bleeding amongst warfarin and direct oral anticoagulant (DOAC) users is greater following a respiratory tract infection (RTI). It is unclear whether immediate antibiotics modify this association. We estimated the risk of bleeding amongst warfarin and DOAC users with RTI by antibiotic treatment. METHODS: This retrospective cohort study used data from the Clinical Practice Research Datalink (CPRD) GOLD for adults in England prescribed warfarin or a DOAC, who sought primary care for an RTI between 1st January 2011 and 31st December 2019. Outcomes were major bleeding (hospital admission for intracranial or gastrointestinal bleeding), and non-major bleeding (hospital admission or General Practice consult for epistaxis, haemoptysis, or haematuria). Cox models derived hazard ratios (HRs) and 95% confidence intervals (CIs) for each outcome, adjusting for confounders using inverse probability of treatment weighting. RESULTS: Of 14 817 warfarin and DOAC users consulting for an RTI, 8768 (59%) were prescribed immediate antibiotics and 6049 (41%) were not. Approximately 49% were female, and median age was 76 years. Antibiotics were associated with reduced risk of major bleeding (adjusted HR 0.38, 95% CI 0.25 to 0.58). This was consistent across several sensitivity analyses. Antibiotics were also associated with a reduced risk of non-major bleeding (adjusted HR 0.78, 95% CI 0.61 to 0.99). CONCLUSIONS: Immediate antibiotics were associated with reduced risk of bleeding amongst warfarin and DOAC users with an RTI. Further work is needed to understand mechanisms and confirm whether a lower threshold for antibiotic use for RTI in this population may be beneficial.

Cancer-associated venous thrombosis in adults (second edition): A British Society for Haematology Guideline.

A shared decision on the most appropriate agent for the treatment of cancer-associated thrombosis should consider the following factors, which should be reassessed as patients continue along their cancer care pathway: risk of bleeding; tumour site; suitability of oral medications; potential for drug-drug interactions; and patient preference and values regarding choice of drug. Continuing anticoagulation beyond 6 months in patients with cancer-associated venous thromboembolism and active cancer is recommended.

Risk and Timing of Venous Thromboembolism After Surgery for Lung Cancer: A Nationwide Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable serious complication in patients with lung cancer undergoing thoracic operation. We examined the risk and timing of VTE after surgery for primary non-small cell lung cancer (NSCLC). METHODS: All patients undergoing operation for NSCLC in Denmark between 2003 and 2021 were identified in the Danish Lung Cancer Registry. VTE events in the year after operation were assessed by stage, patient characteristics, and surgical procedure. RESULTS: We identified 13,197 patients who underwent operation for NSCLC in 2003 to 2021 (mean age, 67.6 years; 50% female); 10,524 (79.7%) had stage I-II NSCLC, and 2673 (20.3%) had stage III-IV. During 1-year follow-up, there were 335 VTE events, yielding a rate of 2.87 events/100 person-years and an absolute risk of 3.3% (95% CI, 2.3-4.0). VTE risk increased with advancing cancer stage (1.8% for stage I vs 3.9% for stage IV) but varied little by pathologic type, sex, and comorbidity level. Bilobectomy was associated with highest VTE risk (4.8%; 95% CI, 3.2-6.9), followed by pneumonectomy (3.5%; 95% CI, 2.3-5.0). The hazard of VTE was highest during the first 3 months after operation, after which it declined. For stage IV cancer, hazards increased again after 6 months. At 1 year, all-cause death was 12.6% (95% CI, 12.0%-13.1%). CONCLUSIONS: VTE developed in 3.3% of patients undergoing operation for NSCLC, most commonly within 3 months postoperatively. Prolonged thromboprophylaxis could be considered, particularly in those with advanced cancer stage and undergoing extended resections.

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.

Risk of recurrent cancer-associated venous thromboembolism: A Danish nationwide cohort study.

BACKGROUND: Predictive factors for recurrent cancer-associated venous thromboembolism have been inconsistent across previous studies. To provide data for improved risk stratification, we described the risk of recurrent venous thromboembolism overall and across age, sex, calendar period, cancer type, Ottawa risk score, cancer stage, and cancer treatment in a nationwide cohort of patients with active cancer. METHODS: Using Danish administrative registries, we identified a cohort of all adult patients with active cancer and a first-time diagnosis of venous thromboembolism during 2003-2018. We accounted for the competing risk of death and calculated absolute risks of recurrent venous thromboembolism at six months. RESULTS: The population included 34,072 patients with active cancer and venous thromboembolism. Recurrence risks at six months were higher for patients with genitourinary cancer (6.5%), lung cancer (6.1%), gastrointestinal cancer (5.6%), brain cancer (5.2%), and hematological cancer (5.1%) than for patients with gynecological cancer (4.7%), breast cancer (4.1%), and other cancer types (4.8%). Recurrence risks were similar for men (5.2%) and women (4.9%), with and without chemotherapy (5.1%), across Ottawa risk score group (low: 5.0%; high: 5.1%) and across calendar periods but increased with increasing cancer stage. The overall six-month all-cause mortality risk was 26%, and highest for patients with lung cancer (49%) and lowest among breast cancer patients (4.1%). CONCLUSIONS: Six-month recurrence risk after first-time cancer-associated venous thromboembolism was high and varied by cancer type and patient characteristics. Refining risk stratification for recurrence may improve decision-making regarding treatment duration after cancer-associated thromboembolism.

Development of a Core Outcome Set for the research and assessment of inoperable malignant bowel obstruction.

BACKGROUND: Malignant bowel obstruction is experienced by 15% of people with advanced cancer, preventing them from eating and drinking and causing pain, nausea and vomiting. Surgery is not always appropriate. Management options include tube or stent drainage of intestinal contents and symptom control using medication. Published literature describing palliative interventions uses a broad range of outcome measures, few of which are patient-relevant. This hinders evidence synthesis, and fails to consider the perspectives of people undergoing treatment. AIMS: To develop a Core Outcome Set for the assessment of inoperable malignant bowel obstruction with clinician, patient and caregiver involvement, using COMET methodology (Core Outcome Measures in Effectiveness Trials). METHODS: A systematic review of clinical trials and observational studies, a rapid review of the qualitative literature and in-depth patient and clinician interviews were conducted to identify a comprehensive list of outcomes. Outcomes were compared and consolidated by the study Steering Group and Patient and Public Involvement contributors, and presented to an international clinical Expert Panel for review. Outcomes from the finalised list were rated for importance in a three-round international Delphi process: results of two survey rounds were circulated to respondents, and two separate consensus meetings were conducted with clinicians and with patients and caregivers via virtual conferencing, using live polling to reach agreement on a Core Outcome Set. RESULTS: 130 unique outcomes were identified. Following the independent Expert Panel review, 82 outcomes were taken into round 1 of the Delphi survey; 24 outcomes reached criteria for critical importance across all stakeholder groups and none reached criteria for dropping. All outcomes rated critically important were taken forward for re-rating in round 2 and all other outcomes dropped. In round 2, all outcomes were voted critically important by at least one stakeholder group. Round 2 outcomes were presented again at online consensus meetings, categorised as high ranking (n = 9), middle ranking (n = 7) or low ranking (n = 8). Stakeholders reached agreement on 16 core outcomes across four key domains: Symptom control, Life impact, Treatment outcomes, and Communication and patient preferences. CONCLUSION: Use of this Core Outcome Set can help to address current challenges in making sense of the evidence around treatment for inoperable malignant bowel obstruction to date, and underpin a more robust future approach. Clearer communication and an honest understanding between all stakeholders will help to provide a basis for responsible decision-making in this distressing situation in clinical practice.

Challenges to delivering evidence-based palliative medicine.

Established as a medical specialty in 1987, palliative medicine approaches middle age facing existential questions of identity, purpose and vision. Time has weakened strong foundations laid by Dame Cicely Saunders in research, education and clinical excellence. Clinical knowledge gaps are wide, and widening. Palliative medicine research is underfunded and underrepresented in discourse. Despite huge advances in modern medicine, there is still clinical uncertainty about simple interventions, such as whether artificial hydration at the end of life is helpful or harmful. Where good quality data do exist, the pace of change is slow, if change is happening at all. Trial design often fails to assess the holistic impact of interventions, using primary endpoints that are inconsistent with outcomes most valued to the patient. Recent years have seen a rapid expansion in innovation and investment in digital technologies, embraced by many in palliative medicine. Experience shows that caution must be applied where the evidence base is sparse. While as a specialty we must remain forward looking and progressive in our mindset, it cannot be assumed that these new interventions alone will provide the solutions to the old problems that exist in palliative medicine.This review summarises the key points presented in the Palliative Medicine section of the RCP Clinical Medicine Conference, 2022.

Right needle, right patient, right time? A national flash-mob audit of thromboprophylaxis in palliative care.

BACKGROUND: The prevention of hospital associated thrombosis in palliative care remains controversial yet many countries recommend the documented risk assessment and where appropriate pharmacological prophylaxis of inpatients with advanced cancer. AIM: To audit adherence to national guidelines which require hospitalised patients to be risk assessed and receive appropriate thromboprophylaxis. DESIGN: A one day "flash-mob" audit across multiple clinical inpatient sites across the United Kingdom. SETTING/PARTICIPANTS: Inpatients receiving palliative care within hospitals, hospices and specialist palliative care units across the United Kingdom. RESULTS: Data were collected from 1125 patients (514 hospital and 611 hospice/specialist palliative care units). Appropriate thromboprophylaxis was observed in 90 % of hospital and 90 % hospice/specialist palliative care units. Documented risk assessment was only found in 79 % and 71 % of patient notes respectively. Pharmacological thromboprophylaxis was contraindicated in 88 % of hospice/specialist palliative care unit patients due to bleeding risk or receiving end-of-life care. Twenty-four percent of patients in hospital had contraindications due to receiving end of life care, bleeding risk and thrombocytopenia. Patients in hospice/specialist palliative care units were of poorer performance status prior to admission with a history of gradual deterioration. Hospitalised patients were more likely to have been admitted following an acute deterioration of previous good performance status. CONCLUSION: Thromboprophylaxis guidelines were followed correctly for the majority of patients. There were considerable differences in the demographics of patients according to place of admission. Patients admitted to hospice/specialist palliative care units were sicker and had more contraindications to prophylaxis than those admitted to hospital. Thromboprophylaxis focused research data conducted in hospices is unlikely to be applicable to the care of palliative care patients admitted acutely to hospital.

The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review.

BACKGROUND: Malignant bowel obstruction, a complication of certain advanced cancers, causes severe symptoms which profoundly affect quality of life. Clinical management remains complex, and outcome assessment is inconsistent. AIM: To identify outcomes evaluating palliative treatment for inoperable malignant bowel obstruction, as part of a four-phase study developing a core outcome set. DESIGN: The review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); PROSPERO (ID: CRD42019150648). Eligible studies included at least one subgroup with obstruction below the ligament of Treitz undergoing palliative treatment for inoperable malignant bowel obstruction. Study quality was not assessed because the review does not evaluate efficacy. DATA SOURCES: Medline, Embase, the Cochrane Database, CINAHL, PSYCinfo Caresearch, Open Grey and BASE were searched for trials and observational studies in October 2021. RESULTS: A total of 4769 studies were screened, 290 full texts retrieved and 80 (13,898 participants) included in a narrative synthesis; 343 outcomes were extracted verbatim and pooled into 90 unique terms across six domains: physiological, nutrition, life impact, resource use, mortality and survival. Prevalent outcomes included adverse events (78% of studies), survival (54%), symptom control (39%) and mortality (31%). Key individual symptoms assessed were vomiting (41% of studies), nausea (34%) and pain (33%); 19% of studies assessed quality of life. CONCLUSIONS: Assessment focuses on survival, complications and overall symptom control. There is a need for definitions of treatment 'success' that are meaningful to patients, a more consistent approach to symptom assessment, and greater consideration of how to measure wellbeing in this population.

The Khorana score and venous and arterial thrombosis in patients with cancer treated with immune checkpoint inhibitors: A Danish cohort study.

BACKGROUND: Thrombosis is common among patients with cancer. Primary thromboprophylaxis guided by the Khorana score is endorsed by guidelines but recommendations rely mainly on data from patients treated with chemotherapy. OBJECTIVES: To explore if the Khorana score could risk stratify patients with cancer treated with immune checkpoint inhibitors according to risk of venous and arterial thrombosis. PATIENTS/METHODS: The study population and Khorana score were defined using administrative Danish health registries. The primary outcome was 6-month risk of venous thromboembolism after initiation of checkpoint inhibitor treatment. Secondary outcomes were arterial thrombosis and any thromboembolic event. Death was considered a competing risk event. RESULTS: Among 3946 patients with cancer initiating checkpoint inhibitor treatment without other indications for anticoagulation, the overall 6-month incidence of venous thromboembolism was 2.6% (95% confidence interval [CI]: 2.1-3.1). Risks were 2.1% (95% CI: 1.5-3.0), 2.6% (95% CI: 2.0-3.4), and 3.7% (95% CI: 2.1-5.9) in low (score 0), intermediate (score 1-2), and high risk (score ≥3) Khorana categories, respectively. Among patients eligible for primary thromboprophylaxis according to guidelines (Khorana score ≥2), risk of venous thromboembolism was 4.1% (95% CI: 3.1-5.4). Higher Khorana risk category was also associated with higher 6-month risk of both arterial thrombosis and any thromboembolic events. CONCLUSIONS: The Khorana score was able to risk stratify patients with cancer treated with immune checkpoint inhibitors according to 6-month risk of thromboembolic events. Risks of venous thromboembolism were lower than in randomized thromboprophylaxis trials, thus questioning the absolute benefit of routine primary thromboprophylaxis in an unselected population of patients treated with immune checkpoint inhibitors.

Development of an international standard set of outcome measures for patients with venous thromboembolism: an International Consortium for Health Outcomes Measurement consensus recommendation.

The International Consortium for Health Outcomes Measurement assembled an international working group of venous thromboembolism experts and patient representatives to develop a standardised minimum set of outcomes and outcome measurements for integration into clinical practice and potentially research to support clinical decision making and benchmarking of quality of care. 15 core outcomes important to patients and health-care professionals were selected and categorised into four domains: patient-reported outcomes, long term consequences of the disease, disease-specific complications, and treatment-related complications. The outcomes and outcome measures were designed to apply to all patients with venous thromboembolism aged 16 years or older. A measurement tool package was selected for inclusion in the core standard set, with a minimum number of items to be measured at predefined timepoints, which capture all core outcomes. Additional measures can be introduced to the user by a cascade opt-in system that allows for further assessment if required. This set of outcomes and measurement tools will facilitate the implementation of the use of patient-centred outcomes in daily practice.

UK Palliative trainees Research Collaborative (UK-PRC): the first 5 years - 0-100 study sites.

OBJECTIVES: Palliative care research suffers from underfunding and a workforce spread across multiple settings leading to a lack of large-scale studies. To facilitate multisite research and audit we set up the UK Palliative trainees Research Collaborative (UKPRC), the first national trainee-led audit and research collaborative in palliative care. Here, we critically review the progress and potential of the UKPRC since its inception in 2016, identifying key challenges and facilitators. Members of the UKPRC steering committee collaborated to write this reflection, reviewing existing evidence regarding trainee-led research collaboratives. FINDINGS: The UKPRC has representation from 16/19 UK training regions. Projects are run by a core team; local collaborators collect data at each site. The collaborative is supported by academic leads and newly qualified consultants to develop a culture of continuous improvement in practice. We have conducted four national projects to date, including an audit covering 119 sites. Facilitators for our work include a focus on inclusivity and national representation; support from recently qualified consultants to ensure continuity; and taking a pragmatic approach, focusing initially on straightforward projects to build momentum. Challenges include the step from national audit to multisite, patient-facing research and maintaining continuity in a membership with high turnover. CONCLUSIONS: There is potential to change practice through large scale data collection via the trainee-led collaborative model. Collaboration is especially important in a small specialty with limited resources. The UKPRC has demonstrated 'proof of concept' and has the potential to support and sustain a culture where research can flourish within palliative care.

Symptom burden and lived experiences of patients, caregivers and healthcare professionals on the management of malignant bowel obstruction: A qualitative systematic review.

BACKGROUND: Malignant bowel obstruction occurs in up to 50% of people with advanced ovarian and 15% of people with gastrointestinal cancers. Evaluation and comparison of interventions to manage symptoms are hampered by inconsistent evaluations of efficacy and lack of agreed core outcomes. The patient perspective is rarely incorporated. AIM: To synthesise the qualitative data regarding patient, caregiver and healthcare professionals' views and experience of malignant bowel obstruction to inform the development of a core outcome set for the evaluation of malignant bowel obstruction. DESIGN: A qualitative systematic review was conducted, with narrative synthesis. The review protocol was registered prospectively (https://www.crd.york.ac.uk/prospero, CRD42020176393). DATA SOURCES: MEDLINE, EMBASE, CINAHL, PsycINFO and Scopus databases were searched for studies published between 2010 and 2021. Reference lists were screened for further relevant publications, and citation tracking was performed. RESULTS: Nine papers were included, reporting on seven studies which described the views and experiences of malignant bowel obstruction through the perspectives of 75 patients, 13 caregivers and 62 healthcare professionals. Themes across the papers included symptom burden, diverse experiences of interventions, impact on patient quality of life, implications and trajectory of malignant bowel obstruction, mixed experience of communication and the importance of realistic goals of care. CONCLUSION: Some of the most devastating sequelae of malignant bowel obstruction, such as pain and psychological distress, are not included routinely in its clinical or research evaluation. These data will contribute to a wider body of work to ensure the patient and caregiver perspective is recognised in the development of a core outcome set.

Cancer-associated venous thromboembolism.

Cancer-associated thrombosis (including venous thromboembolism (VTE) and arterial events) is highly consequential for patients with cancer and is associated with worsened survival. Despite substantial improvements in cancer treatment, the risk of VTE has increased in recent years; VTE rates additionally depend on the type of cancer (with pancreas, stomach and primary brain tumours having the highest risk) as well as on individual patient's and cancer treatment factors. Multiple cancer-specific mechanisms of VTE have been identified and can be classified as mechanisms in which the tumour expresses proteins that alter host systems, such as levels of platelets and leukocytes, and in which the tumour expresses procoagulant proteins released into the circulation that directly activate the coagulation cascade or platelets, such as tissue factor and podoplanin, respectively. As signs and symptoms of VTE may be non-specific, diagnosis requires clinical assessment, evaluation of pre-test probability, and objective diagnostic testing with ultrasonography or CT. Risk assessment tools have been validated to identify patients at risk of VTE. Primary prevention of VTE (thromboprophylaxis) has long been recommended in the inpatient and post-surgical settings, and is now an option in the outpatient setting for individuals with high-risk cancer. Anticoagulant therapy is the cornerstone of therapy, with low molecular weight heparin or newer options such as direct oral anticoagulants. Personalized treatment incorporating risk of bleeding and patient preferences is essential, especially as a diagnosis of VTE is often considered by patients even more distressing than their cancer diagnosis, and can severely affect the quality of life. Future research should focus on current knowledge gaps including optimizing risk assessment tools, biomarker discovery, next-generation anticoagulant development and implementation science.

Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy.

The Khorana score is recommended for guiding primary venous thromboembolism (VTE) prophylaxis in cancer patients, but its clinical utility overall and across cancer types remains debatable. Also, some previous validation studies have ignored the competing risk of death, hereby potentially overestimating VTE risk. We identified ambulatory cancer patients initiating chemotherapy without other indications for anticoagulation using Danish health registries and estimated 6-month cumulative incidence of VTE stratified by Khorana levels. Analyses were conducted with and without considering death as a competing risk using the Kaplan-Meier method vs the cumulative incidence function. Analyses were performed overall and stratified by cancer types. Of 40 218 patients, 35.4% were categorized by Khorana as low risk (score 0), 53.6% as intermediate risk (score 1 to 2), and 10.9% as high risk (score ≥3). Considering competing risk of death, the corresponding 6-month risks of VTE were 1.5% (95% confidence interval [CI], 1.3-1.7), 2.8% (95% CI, 2.6-3.1), and 4.1% (95% CI, 3.5-4.7), respectively. Among patients recommended anticoagulation by guidelines (Khorana score ≥2), the 6-month risk was 3.6% (95% CI, 3.3-3.9). Kaplan-Meier analysis overestimated incidence up to 23% compared with competing risk analyses. Using the guideline-recommended threshold of ≥2, the Khorana score did not risk-stratify patients with hepatobiliary or pancreatic cancer, lung cancer, and gynecologic cancer. In conclusion, the Khorana score was able to stratify ambulatory cancer patients according to the risk of VTE, but not for all cancer types. Absolute risks varied by methodology but were lower than in key randomized trials. Thus, although certain limitations with outcome identification using administrative registries apply, the absolute benefit of implementing routine primary thromboprophylaxis in an unselected cancer population may be smaller than seen in randomized trials.

Which human factors design issues are influencing system performance in out-of-hours community palliative care? Integration of realist approaches with an established systems analysis framework to develop mid-range programme theory.

OBJECTIVE: To develop mid-range programme theory from perceptions and experiences of out-of-hours community palliative care, accounting for human factors design issues that might be influencing system performance for achieving desirable outcomes through quality improvement. SETTING: Community providers and users of out-of-hours palliative care. PARTICIPANTS: 17 stakeholders participated in a workshop event. DESIGN: In the UK, around 30% of people receiving palliative care have contact with out-of-hours services. Interactions between emotions, cognition, tasks, technology and behaviours must be considered to improve safety. After sharing experiences, participants were presented with analyses of 1072 National Reporting and Learning System incident reports. Discussion was orientated to consider priorities for change. Discussions were audio-recorded and transcribed verbatim by the study team. Event artefacts, for example, sticky notes, flip chart lists and participant notes, were retained for analysis. Two researchers independently identified context-mechanism-outcome configurations using realist approaches before studying the inter-relation of configurations to build a mid-range theory. This was critically appraised using an established human factors framework called Systems Engineering Initiative for Patient Safety (SEIPS). RESULTS: Complex interacting configurations explain relational human-mediated outcomes where cycles of thought and behaviour are refined and replicated according to prior experiences. Five such configurations were identified: (1) prioritisation; (2) emotional labour; (3) complicated/complex systems; (4a) system inadequacies and (4b) differential attention and weighing of risks by organisations; (5) learning. Underpinning all these configurations was a sixth: (6a) trust and access to expertise; and (6b) isolation at night. By developing a mid-range programme theory, we have created a framework with international relevance for guiding quality improvement work in similar modern health systems. CONCLUSIONS: Meta-cognition, emotional intelligence, and informal learning will either overcome system limitations or overwhelm system safeguards. Integration of human-centred co-design principles and informal learning theory into quality improvement may improve results.

Management of venous thromboembolism in far-advanced cancer: current practice.

OBJECTIVES: Venous thromboembolism (VTE) is common in advanced cancer. Guidelines suggest that indefinite anticoagulation be considered for patients with ongoing active cancer. There are no data on the management of cancer-associated thrombosis (CAT) at the end of life or when to stop anticoagulation as death approaches. We reviewed current practice and associated symptoms at the end of life for patients with advanced cancer who had been anticoagulated for VTE. METHODS: Data on patients attending a regional CAT service were cross-referenced with death notifications. Hospital, hospice and community notes were reviewed to evaluate the end-of-life care within the context of VTE management. Data specific to discontinuation of anticoagulation, complications of anticoagulation and symptoms associated with VTE were recorded. RESULTS: 214 patients died over a 2-year period; 98 (46%) home, 59 (27%) hospice, 53 (25%) acute hospital and 4 (2%) community hospital. 108 (50%) continued low-molecular-weight heparin (LMWH) until death, 23 (11%) up to 7 days prior to death, 23 (11%), 1 week to 1 month 29 (13.5%), over 1 month 40 (18%). Clinically relevant non-major bleeding occurred in 9/131 (7%) of the patients who continued LMWH to death or 7 days up to death. No symptoms attributable to VTE were recorded. CONCLUSION: The majority of CAT patients with metastatic disease remain anticoagulated up to or within days of death. Despite the limitations of retrospective data across healthcare settings, it appears that anticoagulation as death approaches confers a significant bleeding risk without additional benefit of preventing VTE symptoms.

'Hospice inpatient deep vein thrombosis detection (HIDDen) in advanced non-malignant diseases': a longitudinal pilot study.

OBJECTIVES: To gain preliminary data regarding the prevalence of proximal deep vein thrombosis (DVT) in those with non-malignant conditions admitted to specialist palliative care units (SPCUs). METHODS: Data were collected as part of a prospective longitudinal observational study in five SPCUs in England, Wales and Northern Ireland (Registration: ISRCTN97567719) to estimate the prevalence of proximal femoral vein DVT in people admitted to SPCUs. The primary outcome for this exploratory substudy was the prevalence of DVT in patients with non-malignant palliative conditions. Consecutive consenting adults underwent bilateral femoral vein ultrasonography within 48 hours of admission. Data were collected on symptoms associated with venous thromboembolism. Patients were ineligible if the estimated prognosis was <5 days. Cross-sectional descriptive analysis was conducted on baseline data and prevalence estimates presented with 95% CIs. RESULTS: 1390 patients were screened, 28 patients had non-malignant disease and all were recruited. The mean age 68·8 (SD 12·0), range 43-86 years; men 61%; survival mean 86 (SD 108.5) range 1-345 days. No patient had a history of venous thromboembolism. Four (14%) were receiving thromboprophylaxis. Of 22 evaluable scans, 8 (36%, 95% CI: 17% to 59%) showed femoral vein DVT. The level of reported relevant symptoms (leg oedema, leg pain, chest pain and breathlessness) was high irrespective of the presence of DVT. CONCLUSIONS: Our exploratory data indicate one in three people admitted to an SPCU with non-malignant disease had a femoral vein DVT. Although definitive conclusions cannot be drawn, these data justify a larger prospective survey.