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.

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.

Prevalence, symptom burden, and natural history of deep vein thrombosis in people with advanced cancer in specialist palliative care units (HIDDen): a prospective longitudinal observational study.

BACKGROUND: The prevalence of deep venous thrombosis in patients with advanced cancer is unconfirmed and it is unknown whether current international thromboprophylaxis guidance is applicable to this population. We aimed to determine prevalence and predictors of femoral deep vein thrombosis in patients admitted to specialist palliative care units (SPCUs). METHODS: We did this prospective longitudinal observational study in five SPCUs in England, Wales, and Northern Ireland (four hospices and one palliative care unit). Consecutive adults with cancer underwent bilateral femoral vein ultrasonography on admission and weekly until death or discharge for a maximum of 3 weeks. Data were collected on performance status, attributable symptoms, and variables known to be associated with venous thromboembolism. Patients with a short estimated prognosis (<5 days) were ineligible. The primary endpoint of the study was the prevalence of femoral deep vein thrombosis within 48 h of SPCU admission, analysed by intention to treat. This study is registered with the ISRCTN registry, number ISRCTN97567719. FINDINGS: Between June 20, 2016, and Oct 16, 2017, 343 participants were enrolled (mean age 68·2 years [SD 12·8; range 25-102]; 179 [52%] male; mean Australian-modified Karnofsky performance status 49 [SD 16·6; range 20-90]). Of 273 patients with evaluable scans, 92 (34%, 95% CI 28-40) had femoral deep vein thrombosis. Four participants with a scan showing no deep vein thrombosis on admission developed a deep vein thrombosis on repeat scanning over 21 days. Previous venous thromboembolism (p=0·014), being bedbound in the past 12 weeks for any reason (p=0·003), and lower limb oedema (p=0·009) independently predicted deep vein thrombosis. Serum albumin concentration (p=0·43), thromboprophylaxis (p=0·17), and survival (p=0·45) were unrelated to deep vein thrombosis. INTERPRETATION: About a third of patients with advanced cancer admitted to SPCUs had a femoral deep vein thrombosis. Deep vein thrombosis was not associated with thromboprophylaxis, survival, or symptoms other than leg oedema. These findings are consistent with venous thromboembolism being a manifestation of advanced disease rather than a cause of premature death. Thromboprophylaxis for SPCU inpatients with poor performance status seems to be of little benefit. FUNDING: National Institute for Health Research (Research for Patient Benefit programme).

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.

Primary thromboprophylaxis in hospices: the association between risk of venous thromboembolism and development of symptoms.

CONTEXT: Venous thromboembolism (VTE) risk assessment for adults admitted to hospital is commonplace, but the utility of assessment tools in patients admitted to hospices or palliative care units and prediction of symptomatic VTE is unknown. OBJECTIVES: To investigate the relationship between risk of VTE and development of symptoms. METHODS: Retrospective consecutive admission, case-note data from seven U.K. hospices were collected during an evaluation of a VTE risk assessment protocol using the Pan Birmingham Cancer Network palliative-modified Thromboembolic Risk Factors (THRIFT) Consensus Group criteria and presence/absence of a temporary elevated risk (TER) of VTE. Symptoms/signs during admission consistent with possible VTE were documented. RESULTS: A total of 1164 case-notes were analyzed (age range 23-99; men 627). THRIFT risk was high in 13%, medium in 83%, and low in 4%; a TER was identified in 24%. In the "clinically relevant group" (no contraindication, not anticoagulated), where primary thromboprophylaxis could have been prescribed (n = 528), TER and symptoms were associated (21% symptoms with TER vs. 9% symptoms without TER: Chi-squared, P < 0.001). A high/moderate THRIFT score had a sensitivity of 98.4% (95% CI 91.3%-99.9%) and specificity of 5.8% (95% CI 3.9%-8.3%). The TER assessment had a more evenly balanced sensitivity (41.9%; 95% CI 29.5%-55.2%) and specificity (79%; 95% CI 75.0%-82.6%). CONCLUSION: Hospice inpatients are at risk for VTE. TER alone is simpler to use and may be more useful in this population than the THRIFT but still has limitations regarding ability to predict symptoms.

Nurses' views of the coping and support mechanisms experienced in managing terminal haemorrhage.

INTRODUCTION: Although palliative care is a rewarding specialty, it presents emotive personal challenges for the health professionals working within it. Terminal haemorrhage is arguably the most feared and distressing event in the palliative care setting, both for the patient and for the health professionals looking after them. The aim of this study was to explore and reflect on the coping and support mechanisms that have helped nurses to manage these events. METHOD: Purposive sampling was used to recruit nurses from palliative care and oncology who had personal experience of managing terminal haemorrhage. Semi-structured interviews were used to collect qualitative data that were then analysed using interpretative phenomenological analysis. Saturation of data was reached after 11 participants had been interviewed. RESULTS: The participants had a combined experience of managing 37 patients with a terminal haemorrhage. The key themes that emerged were the role of the 'autopilot', having a plan, education and training, the value of debriefing and peer support, and the importance of supporting the whole team. Education and training specifically about terminal haemorrhage and structured debriefing after such events were both identified by the participants as currently unmet needs. CONCLUSION: Professionals working in areas in which patients are at particular risk of terminal haemorrhage require adequate training and education prior to these events and a structure for formal debriefing and peer support afterwards.

What challenges good palliative care provision out-of-hours? A qualitative interview study of out-of-hours general practitioners.

BACKGROUND: Not much is known about how general practitioners (GPs) who work regular out-of-hours shifts in the community feel about prescribing medication for symptom control in end-of-life care patients, how they gain palliative care experience and what they perceive as benefits and hindrances within service delivery to this vulnerable patient and carer group. OBJECTIVES: To determine, by interviewing GPs who provide out-of-hours care, aspects of care provision that augmented or challenged palliative care delivery. METHODS: Semistructured interviews were conducted with GPs who worked out-of-hours shifts regularly. All interviews were analysed using interpretative phenomenological analysis. RESULTS: Out-of-hours doctors were not confident about their palliative care knowledge and expressed a wish for more education. Lack of familiarity with patients requiring acute palliative care, compared with the closer bonds formed within the in-hours general practice setting, was perceived as troublesome and problematic, and lack of follow-up was felt to be a major factor. There was a clearly expressed fear of killing or harming patients with the strong drugs used in palliative care. Opiophobia, especially when faced with patients who were seen only once, affected prescribing decisions. CONCLUSIONS: This study provides further evidence of the needs of a specific subgroup of GPs. In-depth interview analysis of their experiences with palliative care provides a framework for which aspects are perceived as a hindrance in providing good palliative care, and can inform out-of-hours policy and teaching.

Management of terminal hemorrhage in patients with advanced cancer: a systematic literature review.

Although terminal hemorrhage is an infrequent occurrence in advanced cancer patients, it is extremely distressing for patients, their families, and health care professionals when it does occur. By definition, there is a very short time period to support and comfort the patient, and it is vital that the management approach follows the best available evidence base. A systematic literature search was carried out to retrieve relevant publications relating to the management of terminal hemorrhage in patients with advanced cancer in whom invasive or interventional procedures are no longer appropriate. From 3,564 initial citations, 18 were appropriate to include in the final review, many of which focused on patients with head and neck tumors. The reported incidence of significant bleeding in patients with advanced cancer is 6%-14% and incidence of terminal hemorrhage 3%-12%. Key areas arising from the literature were 1) identifying patients at risk, 2) general supportive measures to use, and 3) use of sedative medication. General supportive measures included use of dark towels to camouflage blood loss, use of suction, and applying external pressure. There was variation in the recommended sedative medication (drug, dose, and route). Drugs recommended included diazepam, midazolam, diamorphine, and ketamine at varying doses and routes of administration. Current guidelines are based completely on isolated case reports and expert opinion. Clinical research is needed in this area but is difficult because of practical and ethical limitations.

Management of venous thromboembolism in patients with advanced cancer: a systematic review and meta-analysis.

Venous thromboembolism is common in patients with cancer. However, no management guidelines exist for venous thromboembolism specific to patients with advanced progressive cancer. To help develop recommendations for practice, we have done a comprehensive review of anticoagulation treatment in patients with cancer, with particular focus on studies that included patients with advanced disease. Data from 19 publications, including randomised, prospective, and retrospective studies suggest that: long-term full-dose low-molecular-weight heparin (LMWH) is more effective than warfarin in the secondary prophylaxis of venous thromboembolism in patients with cancer of any stage, performance status, or prognosis; warfarin should not be used in patients with advancing progressive disease; and in patients at high risk of bleeding, full-dose LMWH for 7 days followed by a long-term decreased fixed dose long term can be considered. The optimum treatment duration is unclear, but because the prothrombotic tendency will persist in patients with advanced cancer, indefinite treatment is generally recommended. For patients with contraindications to anticoagulation, inferior-vena-caval filters can be considered, but their use needs careful patient selection. Ultimately, the decision to initiate, continue, and stop anticoagulation will need to be made on an individual basis, guided by the available evidence, the patient's circumstances, and their informed preferences.

The evidence base of palliative medicine: is inpatient palliative medicine evidence-based?

BACKGROUND: In 2001, Good and Stafford published a study attempting to show that inpatient palliative medicine is evidence-based. AIM: To critically examine the papers cited in support of the claim that palliative medicine is evidence-based. METHOD: All the papers cited were re-examined by at least two reviewers. The papers were graded using a tool used in the production of 22 evidence-based national clinical guidelines over the past three years. Differences of opinion about quality were resolved by discussion or independent arbitration. RESULTS: The 41 papers cited by Good and Stafford included 25 randomized controlled trials (RCT), six other controlled studies and 10 uncontrolled studies. Sample size. Mean sample size was 160 (range 9-1404). The median sample size was 56; 19/41(46%) had <50 subjects; 30/41 (73%) had <100. Power calculations. 16/25 (64%) of RCTs, had no power calculations, making it difficult to draw conclusions about true differences between groups. Quality rating and grade of evidence: Of the RCTs 15/25 (60%) had a high risk of bias; of the other controlled studies 5/6 (83%) had a high risk of bias. Applicability. The studies were generally applicable to a population with advanced disease: 30/41 (73%) related with populations with advanced disease. CONCLUSIONS: This study demonstrates that studies cited in support of palliative medicine as an evidence-based specialty are of variable, and at times poor quality. This study seems to show that the claim that inpatient palliative medicine is evidence-based is at best tenuous and at worst misleading. Palliative Medicine 2007; 21 : 623-627.

Have palliative care teams' attitudes toward venous thromboembolism changed? A survey of thromboprophylaxis practice across British specialist palliative care units in the years 2000 and 2005.

Palliative care patients are highly prothrombotic, yet there are no national guidelines for the prevention of venous thromboembolism (VTE). A survey was undertaken to explore thromboprophylaxis practice within British palliative care inpatient units and whether it changed over 5 years in keeping with emerging evidence. A descriptive semistructured telephone survey was conducted in April, 2000 and March, 2005 to explore current thromboprophylaxis practice. Seventy-four percent of units participated in 2000 and 91% participated in 2005. Units surveyed in 2000 revealed that 2% had thromboprophylaxis guidelines and up to 75% would stop ongoing low molecular weight heparin (LMWH) in a highly prothrombotic, good prognosis inpatient. The survey in 2005 indicated that thromboprophylaxis guidelines were being developed in 19% of units and only 18% of units surveyed would stop LMWH in a patient already receiving thromboprophylaxis (P < 0.001). There appears to be a growing awareness of the problem of VTE in British palliative care inpatients, as evidenced by changes in attitudes and practice. Reasons for this are discussed.

Is long-term low-molecular-weight heparin acceptable to palliative care patients in the treatment of cancer related venous thromboembolism? A qualitative study.

Venous thromboembolism (VTE) is common in patients with terminal cancer. Current treatment practice with warfarin has a high incidence of complications, including bleeding, poor control and recurrent VTE. Long-term low-molecular-weight heparin (LMWH) therapy is safer and more efficacious in this patient group, but there are concerns that daily therapy may have a negative impact on quality of life. A qualitative study was carried out to determine whether LMWH was acceptable in palliative care patients, both in the community and in-patient units. Forty palliative care patients receiving LMWH for VTE were interviewed. Participants found LMWH to be an acceptable intervention, allowing them freedom from blood tests and optimism regarding their care. It was considered a preferable therapy to warfarin, which had a negative impact on participant's quality of life. The findings of this study support the use of LMWH, first line in the treatment of established VTE in the palliative care setting.