Jamilla Hussain

Comparison of survival analysis and palliative care involvement in patients aged over 70 years choosing conservative management or renal replacement therapy in advanced chronic kidney disease

Background: There are limited data on the outcomes of elderly patients with chronic kidney disease undergoing renal replacement therapy or conservative management. Aims: We aimed to compare survival, hospital admissions and palliative care access of patients aged over 70 years with chronic kidney disease stage 5 according to whether they chose renal replacement therapy or conservative management. Design: Retrospective observational study. Setting/participants: Patients aged over 70 years attending pre-dialysis clinic. Results: In total, 172 patients chose conservative management and 269 chose renal replacement therapy. The renal replacement therapy group survived for longer when survival was taken from the time estimated glomerular filtration rate <20 mL/min (p < 0.0001), <15 mL/min (p < 0.0001) and <12 mL/min (p = 0.002). When factors influencing survival were stratified for both groups independently, renal replacement therapy failed to show a survival advantage over conservative management, in patients older than 80 years or with a World Health Organization performance score of 3 or more. There was also a significant reduction in the effect of renal replacement therapy on survival in patients with high Charlson’s Comorbidity Index scores. The relative risk of an acute hospital admission (renal replacement therapy vs conservative management) was 1.6 (p < 0.05; 95% confidence interval = 1.14–2.13). A total of 47% of conservative management patients died in hospital, compared to 69% undergoing renal replacement therapy (Renal Registry data). Seventy-six percent of the conservative management group accessed community palliative care services compared to 0% of renal replacement therapy patients. Conclusions: For patients aged over 80 years, with a poor performance status or high co-morbidity scores, the survival advantage of renal replacement therapy over conservative management was lost at all levels of disease severity. Those accessing a conservative management pathway had greater access to palliative care services and were less likely to be admitted to or die in hospital.

Triggers in advanced neurological conditions: prediction and management of the terminal phase

Context The challenge to provide a palliative care service for individuals with advanced neurological conditions is compounded by variability in disease trajectories and symptom profiles. The National End of Life Care Programme (2010) recommended seven ‘triggers’ for a palliative approach to care for patients with advanced neurological conditions. Objectives To establish the frequency of triggers in the palliative phase, and if they could be reduced to fewer components. Management of the terminal phase also was evaluated. Method Retrospective study of 62 consecutive patients under the care of a specialist palliative neurology service, who had died. Principle component analysis (PCA) was performed to establish the interrelationship between triggers. Results Frequency of triggers increased as each patient approached death. PCA found that four symptom components explained 76.8% of the variance. These represented: rapid physical decline; significant complex symptoms, including pain; infection in combination with cognitive impairment; and risk of aspiration. Median follow-up under the palliative care service was 336 days. In 56.5% of patients, the cause of death was pneumonia. The terminal phase was recognised in 72.6%. The duration of the terminal phase was 8.8 days on average, and the Liverpool Care of the dying Pathway was commenced in 33.9%. All carers were offered bereavement support. Conclusions Referral criteria based on the triggers can facilitate appropriate and timely patient access to palliative care. The components deduced through PCA have face validity; however larger studies prospectively validating the triggers are required. Closer scrutiny of the terminal phase is necessary to optimise management.

One evidence base; three stories: do opioids relieve chronic breathlessness?

The efficacy of low-dose systemic opioids for chronic breathlessness was questioned by the recent Cochrane review by Barnes et al. We examined the reasons for this conflicting finding and re-evaluated the efficacy of systemic opioids. Compared with previous meta-analyses, Barnes et al reported a smaller effect and lower precision, but did not account for matched data of crossover trials (11/12 included trials) and added a risk-of-bias criterion (sample size). When re-analysed to account for crossover data, opioids decreased breathlessness (standardised mean differences −0.32; −0.18 to −0.47; I2=44.8%) representing a clinically meaningful reduction of 0.8 points (0–10 numerical rating scale), consistent across meta-analyses.

Missing data in randomized controlled trials testing palliative interventions pose a significant risk of bias and loss of power: a systematic review and meta-analyses.

Objectives To assess the risk posed by missing data (MD) to the power and validity of trials evaluating palliative interventions. Study Design and Setting A systematic review of MD in published randomized controlled trials (RCTs) of palliative interventions in participants with life-limiting illnesses was conducted, and random-effects meta-analyses and metaregression were performed. CENTRAL, MEDLINE, and EMBASE (2009–2014) were searched with no language restrictions. Results One hundred and eight RCTs representing 15,560 patients were included. The weighted estimate for MD at the primary endpoint was 23.1% (95% confidence interval [CI] 19.3, 27.4). Larger MD proportions were associated with increasing numbers of questions/tests requested (odds ratio [OR], 1.19; 95% CI 1.05, 1.35) and with longer study duration (OR, 1.09; 95% CI 1.02, 1.17). Meta-analysis found evidence of differential rates of MD between trial arms, which varied in direction (OR, 1.04; 95% CI 0.90, 1.20; I2 35.9, P = 0.001). Despite randomization, MD in the intervention arms (vs. control) were more likely to be attributed to disease progression unrelated to the intervention (OR, 1.31; 95% CI 1.02, 1.69). This was not the case for MD due to death (OR, 0.92; 95% CI 0.78, 1.08). Conclusion The overall proportion and differential rates and reasons for MD reduce the power and potentially introduce bias to palliative care trials.

Palliative care triggers in progressive neurodegenerative conditions: An evaluation using a multi-centre retrospective case record review and principal component analysis:

Background: The use of specific triggers has been suggested to help identify patients with progressive neurological disease who would benefit from palliative care. Aim: This study aimed to improve the evidence base for the use of triggers for patients with progressive neurological disease. Design: An evaluation of palliative care services was undertaken using a retrospective case note review of the timing and presence of triggers in the last 2 years of life. Setting/participants: A total of 12 specialist palliative care units across the United Kingdom provided data from 300 patients: mean patient age 70 years, 50% male, diagnoses included motor neurone disease 58%, Parkinson’s disease 17% and Parkinson’s Plus syndromes 12%. Results: There was a high burden of triggers – 17 in the last 2 years of life and 10 in the last 6 months of life. The most frequent triggers were deteriorating physical function, complex symptoms and dysphagia. Four factors were found to explain 64% of the total variance: Factor 1 – Deterioration in physical function, dysphagia, significant complex symptoms and pain; Factor 2 – Weight loss and respiratory symptoms; Factor 3 – Recurrent infections and cognitive decline; Factor 4 – Aspiration pneumonia. Cox regression analyses found different triggers were associated with survival from diagnosis versus survival from referral to palliative care. Different triggers were also associated with survival for different neurological conditions. Conclusion: This study demonstrates that there is a high burden of triggers in the last months and years of life and that these could potentially be reduced to fewer components. Prospective studies assessing which triggers are useful for different conditions are now required.

Quality of missing data reporting and handling in palliative care trials demonstrates that further development of the CONSORT statement is required : a systematic review

Objectives Assess (i) the quality of reporting and handling of missing data (MD) in palliative care trials, (ii) whether there are differences in the reporting of criteria specified by the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement compared with those not specified, and (iii) the association of the reporting of MD with journal impact factor and CONSORT endorsement status. Study Design and Setting Systematic review of palliative care randomized controlled trials. CENTRAL, MEDLINE, and EMBASE (2009–2014) were searched. Results One hundred and eight trials (15,560 participants) were included. MD was incompletely reported and not handled in accordance with current guidance. Reporting criteria specified by the CONSORT statement were better reported than those not specified (participant flow, 69%; number of participants not included in the primary outcome analysis, 94%; and the reason for MD, 71%). However, MD in items contributing to scale summaries (10%) and secondary outcomes (9%) were poorly reported, so the proportion of MD stated is likely to be an underestimate. The reason for MD provided was unclear for 54% of participants and only 16% of trials with MD reported a MD sensitivity analysis. The odds of reporting most of the MD and other risk of bias reporting criteria were increased as the journal impact factor increased and in journals that endorsed the CONSORT statement. Conclusion Further development of the CONSORT MD reporting guidance is likely to improve the quality of reporting. Reporting recommendations are provided.

Analysing data in palliative care trials

We commend Colantuoni and colleagues for their review on methods to compare functional outcomes in trials with high mortality.1 This is important in people with advanced, life limiting illnesses requiring palliative care.2 We have previously found that 18% of participants in palliative care trials have truncated data—for example, on quality of life—due to death.3 A survivors analysis …

Missing data in randomised controlled trials evaluating palliative interventions: a systematic review and meta-analysis

Abstract Background Missing data reduce the power and precision of the results of a randomised controlled trial (RCT). Sample size inflation will avoid this problem, but will not avoid the threat to internal validity introduced by differential rates and reasons for missing data. In palliative care trials, data missing because of death and disease progression are expected, but have not been quantified. This study assessed the risk that missing data pose to the power and validity of trials testing palliative interventions in patients with terminal disease. Methods We systematically searched CENTRAL, Medline, and EMBASE with no language restrictions for RCTs published between Jan 1, 2009, and April 30, 2014, of palliative interventions in participants with life-limiting disease. Random-effects meta-analysis was performed. The primary outcomes were proportion of missing data at the primary endpoint of the trial, covariates associated with missing data (meta-regression analysis), and differential rates and reasons for missing data between the intervention and control arms. Findings 108 RCTs representing 15 560 patients were included (mean age 64 years [SD 8·4], ECOG performance status 2). The weighted estimate for missing data at the primary endpoint was 23·1% (95% CI 19·3–27·4). Larger proportions of missing data were associated with increasing numbers of questions asked or tests requested (odds ratio [OR] per doubling of questions or tests requested 1·19, 95% CI 1·05–1·35) and with longer study duration (OR per days doubling 1·09, 1·02–1·17). Meta-analysis showed evidence of differential rates of missing data between trial arms, which varied in direction (OR 1·04 [95% CI 0·90–1·20], I 2 =35·9; p=0·001). Despite randomisation, missing data in the intervention arms were more likely than in the control arms to be attributed to disease-progression unrelated to the intervention (OR 1·31, 95% CI 1·02–1·69), but not for data missing because of death (0·92, 95% CI 0·78–1·08). Interpretation This review of international RCTs testing a range of palliative interventions found that the overall weighted proportion of missing data is at a level that poses a substantial risk to the validity of trial results. Trial burden and duration need consideration when adjusting sample-size calculations for missing data. Differential reasons and rates of missing data at trial-level also present a risk of bias. Our review only included published trials, so it probably represents an overoptimistic picture. Funding National Institute for Health Research.

END OF LIFE CARE IN NEURODEGENERATIVE CONDITIONS: EVALUATION OF A SPECIALIST NEUROLOGY PALLIATIVE CARE SERVICE

Background The last year of life for people with advanced neurodegenerative conditions (ANC) is often unsatisfactory, characterised by multiple unplanned hospital admissions. Despite this few patients with ANC access palliative care services, with limited evidence of effective service models and when such individuals should be referred to palliative care. Aims 1. To evaluate the Scarborough Palliative Neurology Service (PNS) model, led by specialist palliative neurology nurses, against the National End of Life Care Programme (NEoLCP) ANC recommendations. 2. To evaluate the validity of the seven NEOLCP triggers for palliative care referral. Method Retrospective observational study of 62 consecutive patients under a PNS. Principle component analysis (PCA) was performed to examine the relationship between triggers and survival. Results All patients had a key-worker who coordinated care. Capacity was assessed in 95% of cases, for who advance care planning and best interest decisions were documented in 95%. The terminal-phase was recognised in 72.6% and 100% of carers were offered bereavement support. The median follow-up under the PNS was 336 days. The mean number of hospital admissions was 0.9 in the last year of life (compared to 3.5 nationally across diagnoses). Pneumonia was the cause of death in 56.5%. Thirty-one percent of patients died at home (nationally 14% of ANC patients die at home), 26% in hospital (46% nationally) and 24% in hospices (0.03% nationally). Frequency of triggers increased as patients approached death. PCA found 4 components in combination explained 76.8% of the variance in survival. These represented rapid physical decline; significant complex symptoms-including pain; infection with cognitive impairment; and risk of aspiration. Conclusion A model of service provision investing in specialist palliative neurology nurses is an effective model in delivering palliative care to this vulnerable patient group. The triggers for referral require further validation, although the derived PCA components do have face-validity.