Major Depression and Survival in People With Cancer.

OBJECTIVE: The question of whether depression is associated with worse survival in people with cancer remains unanswered because of methodological criticism of the published research on the topic. We aimed to study the association in a large methodologically robust study. METHODS: We analyzed data on 20,582 patients with breast, colorectal, gynecological, lung, and prostate cancers who had attended cancer outpatient clinics in Scotland, United Kingdom. Patients had completed two-stage screening for major depression as part of their cancer care. These data on depression status were linked to demographic, cancer, and subsequent mortality data from national databases. We estimated the association of major depression with survival for each cancer using Cox regression. We adjusted for potential confounders and interactions between potentially time-varying confounders and the interval between cancer diagnosis and depression screening, and used multiple imputation for missing depression and confounder data. We pooled the cancer-specific results using fixed-effects meta-analysis. RESULTS: Major depression was associated with worse survival for all cancers, with similar adjusted hazard ratios (HRs): breast cancer (HR = 1.42, 95% confidence interval [CI] = 1.15-1.75), colorectal cancer (HR = 1.47, 95% CI = 1.11-1.94), gynecological cancer (HR = 1.36, 95% CI = 1.08-1.71), lung cancer (HR = 1.39, 95% CI = 1.24-1.56), and prostate cancer (HR = 1.76, 95% CI = 1.08-2.85). The pooled HR was 1.41 (95% CI = 1.29-1.54, p < .001, I2 = 0%). These findings were not materially different when we only considered the deaths (90%) that were attributed to cancer. CONCLUSIONS: Major depression is associated with worse survival in patients with common cancers. The mechanisms of this association and the clinical implications require further study.

The prevalence of depression in general hospital inpatients: a systematic review and meta-analysis of interview-based studies.

BACKGROUND: Comorbid depression in the medically ill is clinically important. Admission to a general hospital offers an opportunity to identify and initiate treatment for depression. However, we first need to know how common depression is in general hospital inpatients. We aimed to address this question by systematically reviewing the relevant literature. METHODS: We reviewed published prevalence studies in any language which had used diagnostic interviews of general hospital inpatients and met basic methodological quality criteria. We focussed on interview-based studies in order to estimate the proportion of patients with a diagnosis of depressive illness. RESULTS: Of 158 relevant articles, 65 (41%) describing 60 separate studies met our inclusion criteria. The 31 studies that focussed on general medical and surgical inpatients reported prevalence estimates ranging from 5% to 34%. There was substantial, highly statistically significant, heterogeneity between studies which was not materially explained by the covariates we were able to consider. The average of the reported prevalences was 12% (95% CI 10-15), with a 95% prediction interval of 4-32%. The remaining 29 studies, of a variety of specific clinical populations, are described. CONCLUSIONS: The available evidence suggests a likely prevalence high enough to make it worthwhile screening hospital inpatients for depression and initiating treatment where appropriate. Further, higher quality, research is needed to clarify the prevalence of depression in specific settings and to further explore the reasons for the observed heterogeneity in estimates.

Screening Medical Patients for Depression: Lessons From a National Program in Cancer Clinics.

BACKGROUND: Screening has been recommended to improve the identification of depression in medical patients. There is, therefore, a need for useful practical information on how to successfully implement large-scale depression screening in medical clinics. OBJECTIVE: To describe the practical lessons learned from our experience of implementing a large-scale depression screening program in cancer clinics throughout Scotland, UK. METHOD: Reflective review based on the experience of the screening team and records of the iterative development of the program. FINDINGS: Systematic screening for depression in patients with medical illnesses can be delivered in clinics as long as the program is well designed. Design issues include ensuring the engagement of staff and patients, implementing efficient 2-stage screening processes and effectively managing workflow and quality assurance. DISCUSSION: Screening has the potential to offer a solution to the well-documented problem of missed depression and other psychiatric diagnoses, thereby improving patient care if closely linked to treatment provision.

Why do patients with cancer die?

Cancer is a major cause of global mortality, both in affluent countries and increasingly in developing nations. Many patients with cancer experience reduced life expectancy and have metastatic disease at the time of death. However, the more precise causes of mortality and patient deterioration before death remain poorly understood. This scarcity of information, particularly the lack of mechanistic insights, presents a challenge for the development of novel treatment strategies to improve the quality of, and potentially extend, life for patients with late-stage cancer. In addition, earlier deployment of existing strategies to prolong quality of life is highly desirable. In this Roadmap, we review the proximal causes of mortality in patients with cancer and discuss current knowledge about the interconnections between mechanisms that contribute to mortality, before finally proposing new and improved avenues for data collection, research and the development of treatment strategies that may improve quality of life for patients.

Do not attempt cardiopulmonary resuscitation (DNACPR) decisions for older medical inpatients: a cohort study.

OBJECTIVES: A decision not to attempt cardiopulmonary resuscitation in the event of cardiorespiratory arrest requires a discussion between the doctor and the patient and/or their relatives. We aimed to determine how many older patients admitted to acute medical wards had a pre-existing 'do not attempt cardiopulmonary resuscitation' (DNACPR) decision, how many had one recorded on the ward and how many of those who died had a DNACPR decision in place. METHODS: A prospective cohort study, using data from medical records, of 481 consecutive patients aged ≥65 years admitted to the six acute medical wards of the John Radcliffe Hospital, Oxford. RESULTS: 105/481 (22%) had a DNACPR decision at ward admission, 30 of which had been made in the emergency unit. A further 45 decisions were recorded on the ward, mostly after discussion with relatives. Of the 37 patients who died, 36 had a DNACPR decision. For the 20 deceased patients whose DNACPR decision was recorded during their admission, the median time from documentation to death was 4 days with 7/20 (35%) recorded the day before death. CONCLUSIONS: Older patients with multimorbidity need the opportunity to discuss the role of CPR earlier in their care and preferably before acute hospital admission.

'Do not attempt cardiopulmonary resuscitation' (DNACPR)-difficulty in discussions with older medical inpatients and their families: a survey of hospital doctors.

OBJECTIVES: To determine, for doctors looking after older medical inpatients: (1) how difficult they find discussions about 'do not attempt cardiopulmonary resuscitation' (DNACPR); (2) whether difficulty is associated with doctors' personal and professional characteristics; (3) how frequently DNACPR discussions are made more difficult by practical issues and by doctors' uncertainties. METHODS: Survey of hospital doctors working on the acute medical wards of a UK NHS teaching hospital. RESULTS: 171/200 (86%) of eligible doctors participated. 165 had experience of DNACPR discussions with older inpatients and/or their families and were included in our analysis. 'Difficulty' (defined as finding discussions 'fairly difficult' or 'difficult') was experienced by 52/165 (32%) for discussions with patients and 60/165 (36%) for discussions with families. Doctors with specific training in DNACPR discussions were less likely to have difficulty in discussions with patients. Older, more experienced doctors were less likely to have difficulty in discussions with families. Lack of time and place, and uncertainty about prognosis were the most frequently reported causes of difficulty. CONCLUSIONS: Many doctors have difficulty in DNACPR discussions. Training needs to include managing discussions with families, as well as with patients, and doctors need time and space to deliver this important part of their job.

Different independent associations of depression and anxiety with survival in patients with cancer.

OBJECTIVE: Depression and anxiety have both been reported to predict worse subsequent survival in people with cancer. However, depression and anxiety are mutually associated and we lack understanding of their independent associations with survival. We therefore aimed to investigate these in a large sample of patients with common cancers. METHODS: We analysed data on 19,966 patients with common cancers (breast, colorectal, gynaecological, lung and prostate) who had attended specialist NHS outpatient clinics in Scotland, UK. Hospital Anxiety and Depression Scale (HADS) data were linked with demographic, cancer and mortality data. We estimated the independent associations of depression (HADS depression score) and anxiety (HADS anxiety score) with survival by fitting (separately for each cancer) Cox proportional hazards models which incorporated cubic splines to allow for non-linear associations. We also adjusted for potential confounders. RESULTS: The median time from HADS completion to death or censoring was 1.9 years. Greater depression was found to be strongly associated with worse survival from all cancers. When adjusted for anxiety, this association remained in males and increased in females. Greater anxiety was also associated with worse survival in nearly all cancers. However, when adjusted for depression, the association of anxiety with worse survival was lost. In females the association reversed direction so that greater anxiety was associated with better survival. CONCLUSION: Although often considered together as aspects of 'emotional distress', depression and anxiety have different independent associations with survival in patients with cancer and should therefore be considered separately.

The HOME Study: Statistical and economic analysis plan for a randomised controlled trial comparing the addition of Proactive Psychological Medicine to usual care, with usual care alone, on the time spent in hospital by older acute hospital inpatients.

BACKGROUND: Prolonged acute hospital stays are a problem for older people and for health services. Failure to effectively manage the psychological and social aspects of illness is an important cause of prolonged hospital stay. Proactive Psychological Medicine (PPM) is a new way of providing psychiatry services to medical wards which is proactive, focussed, intensive and integrated with medical care. The primary aim of PPM is to reduce the time older people spend in hospital because of unmanaged psychological and social problems. The HOME Study will test the effectiveness and cost-effectiveness of PPM. METHODS/DESIGN: The study is a two-arm, parallel-group, randomised, controlled superiority trial with linked health economic analysis and an embedded process evaluation. The target population is people aged 65 years and older admitted to acute hospitals. Participants will be randomly allocated to either usual care plus PPM or usual care alone. The primary outcome is the number of days spent as an inpatient in a general hospital in the month following randomisation. Secondary outcomes include quality of life, cognitive function, independent functioning, symptoms of anxiety and depression, and experience of hospital stay. The cost-effectiveness of usual care plus PPM compared with usual care alone will be assessed using quality-adjusted life-years as an outcome as well as costs from the NHS perspective. DISCUSSION: This update to the published trial protocol gives a detailed plan of the statistical and economic analysis of The HOME Study. TRIAL REGISTRATION: ISRCTN registry, ISRCTN86120296. Registered on 3 January 2018.

Is improvement in comorbid major depression associated with longer survival in people with cancer? A long-term follow-up of participants in the SMaRT Oncology-2 and 3 trials.

OBJECTIVE: There is evidence that patients with cancer have worse survival if they have comorbid major depression, but uncertainty whether a reduction in depression severity improves survival. We aimed to address this question. METHODS: We did a secondary analysis of data from participants in the SMaRT Oncology-2 and 3 trials of depression treatment in patients with cancer and comorbid major depression (total n = 642). Participants' data were analysed as cohorts, defined by treatment (usual care or Depression Care for People with Cancer, an intensive treatment programme, in both trials) and cancer prognosis (good or poor, in SMaRT Oncology-2 and 3 respectively). We measured change in depression severity from randomisation to 12 weeks using Symptom Checklist Depression Scale (SCL-20) scores and assessed survival by linked mortality data. We used Cox regression to estimate the effect of a one-unit decrease in SCL-20 score on survival, controlling for measured confounders. RESULTS: We found no evidence for an association between improvement in depression and survival in any of the four cohorts, after adjusting for age, sex, primary cancer, baseline cancer severity and baseline depression severity. Pooling the cohorts in a fixed-effects meta-analysis yielded an estimated 7% reduction in the hazard of death per one-unit decrease in SCL-20 score. This finding was not statistically significant; the 95% confidence interval extended from a 26% decrease to an 18% increase in hazard of death. CONCLUSION: We found no evidence that reduction in severity of comorbid major depression is associated with longer survival in patients with cancer.

The HOME Study: study protocol for a randomised controlled trial comparing the addition of Proactive Psychological Medicine to usual care, with usual care alone, on the time spent in hospital by older acute hospital inpatients.

BACKGROUND: Prolonged acute hospital stays are a major problem for older people and for health services. Failure to effectively manage the psychological and social aspects of illness is an important cause of prolonged hospital stays. Proactive Psychological Medicine (PPM) is a new way of providing psychiatry services to medical wards. PPM is proactive, focussed, intensive and integrated with medical care. A major aim of PPM is to reduce the time older people spend in hospital because of unmanaged psychological and social problems. The HOME Study will test the effectiveness and cost-effectiveness of PPM. METHODS/DESIGN: A two-arm parallel-group randomised controlled superiority trial, with a linked health economic analysis and an embedded process evaluation, will be conducted at three sites. A total of 3588 participants will be recruited and randomised to usual care or usual care plus PPM. The primary outcome is the number of days spent as an inpatient in a general hospital in the month (30 days) post-randomisation. Secondary outcomes for each participant (measured at 1 and 3 months) include quality of life, independent functioning, symptoms of anxiety and depression, cognitive function, and their experience of the hospital stay. DISCUSSION: The trial has been designed to produce findings that are generalisable to all older medical inpatients (including those with cognitive impairment). It will provide information on the effectiveness and cost-effectiveness of PPM, which we hope will be of value to patients, clinicians, managers and service planners. TRIAL REGISTRATION: ISRCTN86120296 . Registered on 3 January 2018.

Does depression treatment improve the survival of depressed patients with cancer? A long-term follow-up of participants in the SMaRT Oncology-2 and 3 trials.

BACKGROUND: Comorbid major depression has been associated with worse survival in patients with cancer. However, we do not know if treating depression improves survival. In the SMaRT Oncology-2 (good prognosis cancers) and SMaRT Oncology-3 (lung cancer, a poor prognosis cancer) trials, we found that a depression treatment programme, Depression Care for People with Cancer (DCPC), was effective in reducing comorbid major depression. In this analysis, we aimed to identify whether DCPC also had an effect on survival. METHODS: The trials were conducted in three cancer centres and their associated clinics in Scotland, UK. In SMaRT Oncology-2, outpatients with good prognosis cancers and major depression were randomly assigned in a 1:1 ratio to DCPC or usual care, with stratification (by trial centre) and minimisation (by age, primary cancer, and sex) with allocation concealment. In SMaRT Oncology-3, outpatients with lung cancer and major depression were randomly assigned (1:1 ratio) to DCPC or usual care with stratification (by trial centre) and minimisation (by age, sex, and cancer type) with allocation concealment. For this analysis, we obtained long-term data on deaths (all causes) in the SMaRT Oncology-2 and 3 trial participants, censored at July 31, 2015, and analysed survival as a trial outcome. We estimated unadjusted hazard ratios (HRs) for each trial using Cox regression, and pooled the log HRs in a fixed-effects meta-analysis. FINDINGS: We recruited 642 participants; between May 12, 2008, and May 13, 2011, 500 participants were recruited to the SMaRT Oncology-2 trial and between Jan 5, 2009, and Sept 9, 2011, 142 participants were recruited to the SMaRT Oncology-3 trial. We followed up SMaRT Oncology-2 and SMaRT Oncology-3 participants for a median of 5 years and 1 year, respectively. 135 (27%) of 500 SMaRT Oncology-2 participants and 114 (80%) of 142 SMaRT Oncology-3 participants died within this period. We found no significant effect of DCPC on survival in the total follow-up period for either SMaRT Oncology 2 (HR 1·02, 95% CI 0·72-1·42, p=0·93) or SMaRT Oncology-3 (HR 0·82, 95% CI 0·56-1·18, p=0·28; pooled HR 0·92, 95% CI 0·72-1·18, p=0·51). INTERPRETATION: DCPC is highly effective in improving depression and quality of life in depressed patients with cancer, but there was no evidence for a significant effect on survival. Despite the absence of an effect on length of life, the management of depression remains important for its beneficial effect on quality of life. FUNDING: NIHR CLAHRC Oxford, Cancer Research UK, and the Chief Scientist Office of the Scottish Government.

Linked symptom monitoring and depression treatment programmes for specialist cancer services: protocol for a mixed-methods implementation study.

INTRODUCTION: There is growing awareness that cancer services need to address patients' well-being as well as treating their cancer. We developed systematic approaches to (1) monitoring patients' symptoms including depression using a 'Symptom Monitoring Service' and (2) providing treatment for those with major depression using a programme called 'Depression Care for People with Cancer'. Used together, these two programmes were found to be highly effective and cost-effective in clinical trials. The overall aims of this project are to: (1) study the process of introducing these programmes into routine clinical care in a large cancer service, (2) identify the challenges associated with implementation and how these are overcome, (3) determine their effectiveness in a routine non-research setting and (4) describe patients' and clinicians' experience of the programmes. METHODS AND ANALYSIS: This is a mixed-methods longitudinal implementation study. We will study the process of implementation in three phases (April 2016-December 2018): 'Pre-implementation' (setting up of the new programmes), 'Early Implementation' (implementation of the programmes in a small number of clinics) and 'Implementation and Maintenance' (implementation in the majority of clinics). We will use the following methods of data collection: (1) contemporaneous logs of the implementation process, (2) interviews with healthcare professionals and managers, (3) interviews with patients and (4) routinely collected clinical data. ETHICS AND DISSEMINATION: The study has been reviewed by a joint committee of Oxford University Hospitals National Health Service Foundation Trust Research and Development Department and the University of Oxford's Clinical Trials and Research Governance Department and judged to be service evaluation, not requiring ethics committee approval. The findings of this study will guide the scaling up implementation of the programmes across the UK and will enable us to construct an implementation toolkit. We will disseminate our findings in publications and at relevant national and international conferences.