Christian Holm Hansen

Integrated collaborative care for comorbid major depression in patients with cancer (SMaRT Oncology-2): a multicentre randomised controlled effectiveness trial

BACKGROUND Medical conditions are often complicated by major depression, with consequent additional impairment of quality of life. We aimed to compare the effectiveness of an integrated treatment programme for major depression in patients with cancer (depression care for people with cancer) with usual care. METHODS SMaRT Oncology-2 is a parallel-group, multicentre, randomised controlled effectiveness trial. We enrolled outpatients with major depression from three cancer centres and their associated clinics in Scotland, UK. Participants were randomly assigned in a 1:1 ratio to the depression care for people with cancer intervention or usual care, with stratification (by trial centre) and minimisation (by age, primary cancer, and sex) with allocation concealment. Depression care for people with cancer is a manualised, multicomponent collaborative care treatment that is delivered systematically by a team of cancer nurses and psychiatrists in collaboration with primary care physicians. Usual care is provided by primary care physicians. Outcome data were collected up until 48 weeks. The primary outcome was treatment response (≥50% reduction in Symptom Checklist Depression Scale [SCL-20] score, range 0-4) at 24 weeks. Trial statisticians and data collection staff were masked to treatment allocation, but participants could not be masked to the allocations. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN40568538. FINDINGS 500 participants were enrolled between May 12, 2008, and May 13, 2011; 253 were randomly allocated to depression care for people with cancer and 247 to usual care. 143 (62%) of 231 participants in the depression care for people with cancer group and 40 (17%) of 231 in the usual care group responded to treatment: absolute difference 45% (95% CI 37-53), adjusted odds ratio 8·5 (95% CI 5·5-13·4), p<0·0001. Compared with patients in the usual care group, participants allocated to the depression care for people with cancer programme also had less depression, anxiety, pain, and fatigue; and better functioning, health, quality of life, and perceived quality of depression care at all timepoints (all p<0·05). During the study, 34 cancer-related deaths occurred (19 in the depression care for people with cancer group, 15 in the usual care group), one patient in the depression care for people with cancer group was admitted to a psychiatric ward, and one patient in this group attempted suicide. None of these events were judged to be related to the trial treatments or procedures. INTERPRETATION Our findings suggest that depression care for people with cancer is an effective treatment for major depression in patients with cancer. It offers a model for the treatment of depression comorbid with other medical conditions. FUNDING Cancer Research UK and Chief Scientist Office of the Scottish Government.

Prevalence, associations, and adequacy of treatment of major depression in patients with cancer: a cross-sectional analysis of routinely collected clinical data

BACKGROUND Major depression is an important complication of cancer. However, reliable data are lacking for the prevalence of depression in patients with cancer in different primary sites, the association of depression with demographic and clinical variables within cancer groupings, and the proportion of depressed patients with cancer receiving potentially effective treatment for depression. We investigated these questions with data from a large representative clinical sample. METHODS We analysed data from patients with breast, lung, colorectal, genitourinary, or gynaecological cancer who had participated in routine screening for depression in cancer clinics in Scotland, UK between May 12, 2008, and Aug 24, 2011. Depression screening was done in two stages (first, Hospital Anxiety and Depression Scale; then, major depression section of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition). Data for depression status were linked with demographic and clinical data obtained from the Scottish National Cancer Registry. FINDINGS We analysed data for 21 151 patients. The prevalence of major depression was highest in patients with lung cancer (13·1%, 95% CI 11·9-14·2%), followed by gynaecological cancer (10·9%, 9·8-12·1), breast cancer (9·3%, 8·7-10·0), colorectal cancer (7·0%, 6·1-8·0), and genitourinary cancer (5·6%, 4·5-6·7). Within these cancer groupings, a diagnosis of major depression was more likely in patients who were younger, had worse social deprivation scores, and, for lung cancer and colorectal cancer, female patients. 1130 (73%) of 1538 patients with depression and complete patient-reported treatment data were not receiving potentially effective treatment. INTERPRETATION Major depression is common in patients attending cancer clinics and most goes untreated. A pressing need exists to improve the management of major depression for patients attending specialist cancer services. FUNDING Cancer Research UK and Chief Scientist Office of the Scottish Government.

Disability, distress and unemployment in neurology outpatients with symptoms ‘unexplained by organic disease’

Objectives To determine the disability, distress and employment status of new neurology outpatients with physical symptoms unexplained by organic disease and to compare them with patients with symptoms explained by organic disease. Methods As part of a cohort study (the Scottish Neurological Symptoms Study) neurologists rated the extent to which each new patients symptoms were explained by organic disease. Patients whose symptoms were rated as ‘not at all’ or only ‘somewhat’ explained by disease were considered cases, and those whose symptoms were ‘largely’ or ‘completely’ explained by disease were considered controls. All patients completed self-ratings of disability, health status (Medical Outcomes Study Short Form 12-Item Scale (SF-12)) and emotional distress (Hospital Anxiety and Depression Scale) and also reported their employment and state financial benefit status. Results 3781 patients were recruited: 1144 (30%) cases and 2637 (70%) controls. Cases had worse physical health status (SF-12 score 42 vs 44; difference in means 1.7 (95% CI –2.5 to 0.9)) and worse mental health status (SF-12 score 43 vs 47; difference in means –3.5 (95% CI –4.3 to to 2.7)). Unemployment was similar in cases and controls (50% vs 50%) but cases were more likely not to be working for health reasons (54% vs 37% of the 50% not working; OR 2.0 (95% CI 1.6 to 2.4)) and also more likely to be receiving disability-related state financial benefits (27% vs 22%; (OR 1.3, 95% CI 1.1 to 1.6)). Conclusions New neurology patients with symptoms unexplained by organic disease have more disability-, distress- and disability-related state financial benefits than patients with symptoms explained by disease.

Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT Oncology-3): a multicentre randomised controlled trial in patients with lung cancer

BACKGROUND The management of depression in patients with poor prognosis cancers, such as lung cancer, creates specific challenges. We aimed to assess the efficacy of an integrated treatment programme for major depression in patients with lung cancer compared with usual care. METHODS Symptom Management Research Trials (SMaRT) Oncology-3 is a parallel-group, multicentre, randomised controlled trial. We enrolled patients with lung cancer and major depression from three cancer centres and their associated clinics in Scotland, UK. Participants were randomly assigned in a 1:1 ratio to the depression care for people with lung cancer treatment programme or usual care by a database software algorithm that used stratification (by trial centre) and minimisation (by age, sex, and cancer type) with allocation concealment. Depression care for people with lung cancer is a manualised, multicomponent collaborative care treatment that is systematically delivered by a team of cancer nurses and psychiatrists in collaboration with primary care physicians. Usual care is provided by primary care physicians. The primary outcome was depression severity (on the Symptom Checklist Depression Scale [SCL-20], range 0-4) averaged over the patients time in the trial (up to a maximum of 32 weeks). Trial statisticians and data collection staff were masked to treatment allocation, but patients and clinicians could not be masked to the allocations. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN75905964. FINDINGS 142 participants were recruited between Jan 5, 2009, and Sept 9, 2011; 68 were randomly allocated to depression care for people with lung cancer and 74 to usual care. 43 (30%) of 142 patients had died by 32 weeks, all of which were cancer-related deaths. No intervention-related serious adverse events occurred. 131 (92%) of 142 patients provided outcome data (59 in the depression care for people with lung cancer group and 72 in the usual care group) and were included in the intention-to-treat primary analysis. Average depression severity was significantly lower in patients allocated to depression care for people with lung cancer (mean score on the SCL-20 1·24 [SD 0·64]) than in those allocated to usual care (mean score 1·61 [SD 0·58]); difference -0·38 (95% CI -0·58 to -0·18); standardised mean difference -0·62 (95% CI -0·94 to -0·29). Self-rated depression improvement, anxiety, quality of life, role functioning, perceived quality of care, and proportion of patients achieving a 12-week treatment response were also significantly better in the depression care for people with lung cancer group than in the usual care group. INTERPRETATION Our findings suggest that major depression can be treated effectively in patients with a poor prognosis cancer; integrated depression care for people with lung cancer was substantially more efficacious than was usual care. Larger trials are now needed to estimate the effectiveness and cost-effectiveness of this care programme in this patient population, and further adaptation of the treatment will be necessary to address the unmet needs of patients with major depression and even shorter life expectancy. FUNDING Cancer Research UK and Chief Scientist Office of the Scottish Government.

Screening for suicidality in cancer patients using Item 9 of the nine-item patient health questionnaire; does the item score predict who requires further assessment?

OBJECTIVE To determine whether a higher score on Item 9 of the Patient Health Questionnaire-9 (range zero to three) was more likely to indicate suicidality as determined at subsequent clinical interview in cancer outpatients. METHOD Analysis of anonymized data (with ethical approval) obtained from the routine clinical administration of self-report questionnaires and telephone interviews to patients attending a cancer centre in the UK. RESULTS Complete data were available on 330 patients. Those with higher scores on the item were more likely to be suicidal at interview. However, a substantial number of those (54/235; 23%) who scored only one on the item were also found to be suicidal. CONCLUSIONS A higher score on Item 9 of the PHQ-9 indicates a greater likelihood that the patient is suicidal. However, even patients who score only 1 may be suicidal and consequently also require further assessment.

Treatment of depression in adults with cancer: a systematic review of randomized controlled trials

BACKGROUND Depression is a leading cause of disease burden worldwide and is especially problematic in people with chronic diseases, including cancer. Although depression can be effectively treated in the general population using antidepressant medication and psychological treatments, these treatments may have different benefits and harms in cancer patients. Previous reviews have not adequately addressed this topic. We therefore aimed to determine which, if any, treatments are effective for patients with diagnoses of both cancer and depression. METHOD We conducted a systematic review of relevant randomized controlled trials identified through searches of Medline, EMBASE, PsycINFO and The Cochrane Central Register of Controlled Trials (CENTRAL). RESULTS Seven relatively small trials met the selection criteria. These provided some evidence that antidepressant medication, given alone or in combination with a psychological treatment, may be effective. We found no good evidence for psychological treatments given alone or for any other forms of treatment. CONCLUSIONS There is very limited evidence from clinical trials to guide the treatment of cancer patients with a diagnosis of depression, especially for psychological treatments. High quality trials of treatments for depression in patients with cancer are urgently needed.

Treatment of depression in people with lung cancer: a systematic review.

Lung cancer commonly occurs in older adults who live in deprived areas and have multiple medical comorbidities. As well as suffering severe physical deterioration they are aware of their poor prognosis. It is therefore unsurprising that people with lung cancer have a high rate of depression. Whilst there are effective treatments for depression in people who do not have cancer, it is uncertain which treatments, if any, are effective in depressed cancer patients; the special characteristics of the condition only increase that uncertainty for people with lung cancer. We therefore conducted a systematic review of relevant randomised controlled trials to determine which, if any, treatments have been found to be effective for depression in patients with lung cancer. Surprisingly, we found no completed trials of treatments in patients selected for having depression and no trials that had evaluated treatments known to be effective for depression in the general population. We did, however, find six trials of interventions intended to improve quality of life in unselected patients with lung cancer. These suggested that enhanced care is more effective in reducing depressive symptoms than standard care. Whilst it may be reasonable to treat depression in individuals with lung cancer with standard treatments until more specific evidence is available, clinicians should be aware that the effectiveness and potential adverse effects of these treatments remain unknown in this patient group. Evidence from randomised trials is urgently required.

Somatic symptom count scores do not identify patients with symptoms unexplained by disease: a prospective cohort study of neurology outpatients

Objective Somatic symptoms unexplained by disease are common in all medical settings. The process of identifying such patients requires a clinical assessment often supported by clinical tests. Such assessments are time-consuming and expensive. Consequently the observation that such patients tend to report a greater number of symptom has led to the use of self-rated somatic symptom counts as a simpler and cheaper diagnostic aid and proxy measure for epidemiological surveys. However, despite their increasing popularity there is little evidence to support their validity. Methods We tested the score on a commonly used self-rated symptom questionnaire- the Patient Health Questionnaire (PHQ 15) (plus enhanced iterations including an additional 10 items on specific neurological symptoms and an additional 5 items on mental state) for diagnostic sensitivity and specificity against a medical assessment (with 18 months follow-up) in a prospective cohort study of 3781 newly attending patients at neurology clinics in Scotland, UK. Results We found 1144/3781 new outpatients had symptoms that were unexplained by disease. The patients with symptoms unexplained by disease reported higher symptoms count scores (PHQ 15: 5.6 (95% CI 5.4 to 5.8) vs 4.2 (4.1 to 4.4) p<0.0001). However, the PHQ15 performed little better than chance in its ability to identify patients with symptoms unexplained by disease. The findings with the enhanced scales were similar. Conclusions Self-rated symptom count scores should not be used to identify patients with symptoms unexplained by disease.

Low-dose dexamethasone as a treatment for women with heavy menstrual bleeding: protocol for response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM)

Introduction Heavy menstrual bleeding (HMB) diminishes individual quality-of-life and poses substantial societal burden. In HMB endometrium, inactivation of cortisol (by enzyme 11β hydroxysteroid dehydrogenase type 2 (11βHSD2)), may cause local endometrial glucocorticoid deficiency and hence increased angiogenesis and impaired vasoconstriction. We propose that ‘rescue’ of luteal phase endometrial glucocorticoid deficiency could reduce menstrual bleeding. Methods and analysis DexFEM is a double-blind response-adaptive parallel-group placebo-controlled trial in women with HMB (108 to be randomised), with active treatment the potent oral synthetic glucocorticoid dexamethasone, which is relatively resistant to 11βHSD2 inactivation. Participants will be aged over 18 years, with mean measured menstrual blood loss (MBL) for two screening cycles ≥50 mL. The primary outcome is reduction in MBL from screening. Secondary end points are questionnaire assessments of treatment effect and acceptability. Treatment will be for 5 days in the mid-luteal phases of three treatment menstrual cycles. Six doses of low-dose dexamethasone (ranging from 0.2 to 0.9 mg twice daily) will be compared with placebo, to ascertain optimal dose, and whether this has advantage over placebo. Statistical efficiency is maximised by allowing randomisation probabilities to ‘adapt’ at five points during enrolment phase, based on the response data available so far, to favour doses expected to provide greatest additional information on the dose–response. Bayesian Normal Dynamic Linear Modelling, with baseline MBL included as covariate, will determine optimal dose (re reduction in MBL). Secondary end points will be analysed using generalised dynamic linear models. For each dose for all end points, a 95% credible interval will be calculated for effect versus placebo. Ethics and dissemination Dexamethasone is widely used and hence well-characterised safety-wise. Ethical approval has been obtained from Scotland A Research Ethics Committee (12/SS/0147). Trial findings will be disseminated via open-access peer-reviewed publications, conferences, clinical networks, public lectures, and our websites. Trial registration number ClinicalTrials.gov NCT01769820; EudractCT 2012-003405-98.

Hypertension Control and Its Correlates Among Adults Attending a Hypertension Clinic in Tanzania.

Hypertension control rates are low in sub‐Saharan Africa. Population‐specific determinants of blood pressure (BP) control have not been adequately described. The authors measured BP and conducted interviews to determine factors associated with BP control among adults attending a hypertension clinic in Tanzania. Three hundred adults were enrolled. BP was controlled in 47.7% of patients at the study visit but only 28.3% over three consecutive visits. Demographic and socioeconomic factors were not associated with control. Obesity and higher medication cost were associated with decreased control. Their effect was mediated through adherence. Good knowledge of (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.0–6.1; P=.047), attitudes towards (OR, 2.7; 95% CI, 1.0–7.1; P=.04), and practices concerning (OR, 5.4; 95% CI, 2.3–13.0; P<.001) hypertension were independently associated with increased control, even after adjusting for mediation through adherence. Good adherence had the strongest association with control (OR, 14.6; 95% CI, 5.8–37.0; P<.001). Strategies to reduce hypertension‐related morbidity and mortality in sub‐Saharan Africa should target these factors. Interventional studies of such strategies are needed.