ObjectivesTo conduct an up-to-date systematic review of all randomised controlled trials assessing efficacy of advance care planning (ACP) in improving patient outcomes, healthcare use/costs and documentation.DesignNarrative synthesis conducted for randomised controlled trials. We searched electronic databases (MEDLINE/PubMed, Embase and Cochrane databases) for English-language randomised or cluster randomised controlled trials on 11 May 2020 and updated it on 12 May 2021 using the same search strategy. Two reviewers independently extracted data and assessed methodological quality. Disagreements were resolved by consensus or a third reviewer.ResultsWe reviewed 132 eligible trials published between 1992 and May 2021; 64% were high-quality. We categorised study outcomes as patient (distal and proximal), healthcare use and process outcomes. There was mixed evidence that ACP interventions improved distal patient outcomes including end-of-life care consistent with preferences (25%; 3/12 with improvement), quality of life (0/14 studies), mental health (21%; 4/19) and home deaths (25%; 1/4), or that it reduced healthcare use/costs (18%; 4/22 studies). However, we found more consistent evidence that ACP interventions improve proximal patient outcomes including quality of patient–physician communication (68%; 13/19), preference for comfort care (70%; 16/23), decisional conflict (64%; 9/14) and patient-caregiver congruence in preference (82%; 18/22) and that it improved ACP documentation (a process outcome; 63%; 34/54).ConclusionThis review provides the most comprehensive evidence to date regarding the efficacy of ACP on key patient outcomes and healthcare use/costs. Findings suggest a need to rethink the main purpose and outcomes of ACP.PROSPERO registration numberCRD42020184080.

Objective: To delineate the trajectories of physical symptoms and psychological distress among patients with a solid metastatic cancer during the last year of life. Methods:We used data of 345 decedents from a prospective cohort of 600 patients with a Stage IV solid cancer. Using group-based trajectory modelling, we assessed (a) demographic (age, gender, education, cancer site) predictors of trajectory membership, (b) shift in trajectories associated with planned and unplanned hospitalizations, emergency room visits and chemotherapy, and (c) the association between trajectory membership and place of death. Results:We identified three trajectories of physical symptoms-"persistent mild" (56%), "progressive moderate" (36%), and "progressive severe" (8%), and two for psychological distress-"persistent mild" (72%) and "progressive distress" (28%). Females (β = 1.40 [SE = 0.55], p-value = 0.01) and highly educated patients (β = 1.46 [SE = 0.62], p-value = 0.02) were more likely to experience progressive severe symptoms compared to persistent mild symptoms. Older patients were less likely (β = −1.01 [SE = 0.33], p-value = 0.003), while those with gynecological cancers (β = 1.51 [SE = 0.65], p-value = 0.02) were more likely to experience progressive distress compared to persistent mild distress. Planned and unplanned hospitalizations, emergency room visits, and chemotherapy were associated with a worsening in trajectories. Patients with higher distress were more likely to die in a hospice compared to a hospital. Conclusions: Interventions to improve physical symptoms and distress can focus on patients at risk of being in worse trajectories and at critical time points in the last year of life-hospitalizations, emergency room visits, and chemotherapy.

ContextCaregivers make difficult end-of-life (EOL) decisions for patients, often adversely affecting their own psychological health. Understanding whether advance care planning (ACP) interventions benefit caregivers can enable healthcare systems to use these approaches to better support them.ObjectiveWe conducted a systematic review and meta-analysis to identify and quantify the impacts of ACP interventions on caregiver outcomes.MethodsWe searched MEDLINE, Embase and Cochrane databases for English-language randomised or cluster randomised controlled trials (RCTs) published until May 2021. Two reviewers independently assessed methodological quality using the Physiotherapy Evidence-Based Database Scale. We conducted a narrative synthesis for each outcome. Difference between arms with a p value of <0.05 was considered statistically significant.ResultsOf the 3487 titles reviewed, 35 RCTs met eligibility; 68.6% were rated high quality. Included RCTs were heterogeneous in intervention characteristics, setting and disease. Meta-analysis of 17 RCTs showed that ACP had large and significant improvement in congruence in EOL care preferences between caregivers and patients (standardised mean difference 0.73, 95% CI 0.42 to 1.05). The effect of ACP on this outcome, however, declined over time. We also found some evidence that ACP improved bereavement outcomes (three of four RCTs), satisfaction with care quality/communication (four of the six RCTs), reduced decisional conflict (two of the two RCTs) and burden (one RCT). No study showed that mental health of caregivers were adversely affected.ConclusionThe review provides most comprehensive evidence about the efficacy of ACP on caregiver outcomes. Findings suggest some evidence of benefit of ACP on caregiver outcomes.

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Background Patients with advanced cancer prioritise health-related quality of life (HrQoL) in end-of-life care, however an understanding of pre-death HrQoL trajectories is lacking. We aimed to delineate and describe the trajectories of physical, social, emotional and functional HrQoL during last year of life among advanced cancer patients. We assessed associations between these trajectories and patient socio-demographic characteristics, healthcare use and place of death. Methods We used data from 345 decedents from a prospective cohort study of 600 patients with a solid advanced cancer receiving secondary care at public hospitals in Singapore. Patients were surveyed every three months until death and HrQoL was assessed using the Functional Assessment of Cancer Therapy – General (FACT-G) questionnaire. Interviews were conducted between July 2016 and December 2019. Group-based multi-trajectory modelling was used to assess potential heterogeneity in the four HrQoL dimensions during patients’ last year of life. Results We identified four distinct trajectories of HrQoL − (1) overall high HrQoL (47% of sample), (2) progressively decreasing HrQoL (32%), (3) asymmetric decline in HrQoL (13%), (4) overall low HrQoL (8%). Compared to patients with secondary or above education, those with primary education or less (β = 1.39, SE = 0.55, p-value = 0.012) were more likely to have “progressively decreasing HrQoL” or “overall low HrQoL” in contrast to “overall high HrQoL”. Compared to patients with ‘overall high HrQoL’, those with ‘overall low HrQoL’ had longer length of hospital stay during the last year of life (β = 0.47, SE = 0.21, p-value = 0.026) and were more likely to die in a hospice/care home (β = 1.86, SE = 0.66, p-value = 0.005). Conclusion Our results showed heterogeneity in deterioration of HrQoL among patients with advanced cancer in the last year of life. Systematic monitoring of HrQoL, early identification and referral of high-risk patients to palliative care may provide timely relief and mitigate the steep decline in their HrQoL. Trial Registration : NCT02850640.

The authors have withdrawn this preprint due to author disagreement.

Background Various cardiovascular biomarkers are used to assess and compare the risk of cardiovascular diseases across populations. However, artefactual variations due to the use of different laboratories may make these comparisons invalid. This work describes the inter-laboratory variations in a multi-country cohort, LIFECARE, and the use of recalibration to a reference laboratory to minimise this variability. Methods LIFECARE is a cohort of 10,479 participants recruited from Indonesia, Malaysia, Philippines and Thailand between 2008 and 2011, with blood samples analysed at country-specific laboratories(n=4). Thailand was the designated reference laboratory. The measurements from each laboratory were compared against the reference laboratory using a common set of samples analysed at all laboratories, using the MethComp package in R. Laboratory values for cohort participants were recalibrated using the equation generated by the package, if large, statistically significant differences were observed during the comparison. Results Glucose, total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride measurements were reported for all four countries. Cholesterol and HDL from all laboratories required recalibration while glucose did not. Recalibration altered the proportions of the population at risk substantially, with prevalence of high cholesterol changing from 56.3% to 75.0% in Malaysia, 52.1% to 37.5% in Indonesia and 31.3% to 22.7% in Philippines. Prevalence of low HDL was similarly altered. Conclusion There was significant variation in serum lipid levels measured by different laboratories, leading to variations in estimates of population at risk. Recalibration to a reference laboratory can overcome this variability and facilitate meaningful comparisons of laboratory data across countries.

Background Despite medical advancements, pain is a major source of suffering at the end of life for patients with a solid metastatic cancer. We aimed to assess the trajectory of pain prevalence, severity, interference, and inadequacy of analgesia during the last year of life. Methods We analysed data from the last year of life of 345 decedents from a prospective cohort study of 600 patients with a solid metastatic cancer in Singapore. Patients were surveyed every 3 months and their pain outcomes (prevalence, severity, and interference) and inadequacy of analgesia were analysed. We used mixed-effects regressions to assess the association of pain outcomes with patients’ time from death, demographics, and planned or unplanned hospitalisations. Results Prevalence of pain was higher in the last 2 months (65%) compared to 11 to 12 months (41%) before death. Pain severity and interference scores (mean ± SD) were also higher in the last month (severity: 2.5±2.6; interference: 2.6±3.0) compared to 12 months before death (severity: 1.4±2.0; interference: 1.4±2.0). At any time during the last year of life, 38% of the patients were prescribed non-steroidal anti-inflammatory drugs, 11% were prescribed weak-opioids and 29% were prescribed strong opioids. These analgesics were prescribed through either oral, topical or injectable route. Pain outcomes were significantly worse (p-value<0.05) for younger patients, those with higher education, and more financial difficulties, while interference was higher after an unplanned hospitalisation in the last month. Females reported higher pain severity score during their last year of life compared to males. For patients reporting moderate to severe pain, inadequacy of analgesia was lower in the last 2 months (43%) compared to 11 to 12 months before death (83%). Conclusion Findings highlight the need for greater attention in monitoring and treatment of pain even earlier in the disease trajectory, and increased attention to patients discharged from an unplanned hospitalisation.