Carina Hibberd

Management of depression for people with cancer (SMaRT oncology 1): a randomised trial

BACKGROUND Major depressive disorder severely impairs the quality of life of patients with medical disorders such as cancer, but evidence to guide its management is scarce. We aimed to assess the efficacy and cost of a nurse-delivered complex intervention that was designed to treat major depressive disorder in patients who have cancer. METHODS We did a randomised trial in a regional cancer centre in Scotland, UK. 200 outpatients who had cancer with a prognosis of greater than 6 months and major depressive disorder (identified by screening) were eligible and agreed to take part. Their mean age was 56.6 (SD 11.9) years, and 141 (71%) were women. We randomly assigned 99 of these participants to usual care, and 101 to usual care plus the intervention, with minimisation for sex, age, diagnosis, and extent of disease. The intervention was delivered by a cancer nurse at the centre over an average of seven sessions. The primary outcome was the difference in mean score on the self-reported Symptom Checklist-20 depression scale (range 0 to 4) at 3 months after randomisation. Analysis was by intention to treat. This trial is registered as ISRCTN84767225. FINDINGS Primary outcome data were missing for four patients. For 196 patients for whom we had data at 3 months, the adjusted difference in mean Symptom Checklist-20 depression score, between those who received the intervention and those who did not, was 0.34 (95% CI 0.13-0.55). This treatment effect was sustained at 6 and 12 months. The intervention also improved anxiety and fatigue but not pain or physical functioning. It cost an additional pound sterling 5278 (US

Lack of tissue glucocorticoid reactivation in 11 beta-hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments

10 556) per quality-adjusted life-year gained. INTERPRETATION The intervention-Depression Care for People with Cancer-offers a model for the management of major depressive disorder in patients with cancer and other medical disorders who are attending specialist medical services that is feasible, acceptable, and potentially cost effective.

Emotional distress in cancer patients: the Edinburgh Cancer Centre symptom study.

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) intracellularly regenerates active corticosterone from circulating inert 11-dehydrocorticosterone (11-DHC) in specific tissues. The hippocampus is a brain structure particularly vulnerable to glucocorticoid neurotoxicity with aging. In intact hippocampal cells in culture, 11β-HSD-1 acts as a functional 11β-reductase reactivating inert 11-DHC to corticosterone, thereby potentiating kainate neurotoxicity. We examined the functional significance of 11β-HSD-1 in the central nervous system by using knockout mice. Aged wild-type mice developed elevated plasma corticosterone levels that correlated with learning deficits in the watermaze. In contrast, despite elevated plasma corticosterone levels throughout life, this glucocorticoid-associated learning deficit was ameliorated in aged 11β-HSD-1 knockout mice, implicating lower intraneuronal corticosterone levels through lack of 11-DHC reactivation. Indeed, aged knockout mice showed significantly lower hippocampal tissue corticosterone levels than wild-type controls. These findings demonstrate that tissue corticosterone levels do not merely reflect plasma levels and appear to play a more important role in hippocampal functions than circulating blood levels. The data emphasize the crucial importance of local enzymes in determining intracellular glucocorticoid activity. Selective 11β-HSD-1 inhibitors may protect against hippocampal function decline with age.

Enhanced Hippocampal Long-Term Potentiation and Spatial Learning in Aged 11β-Hydroxysteroid Dehydrogenase Type 1 Knock-Out Mice

To: (1) estimate the prevalence of clinically significant emotional distress in patients attending a cancer outpatient department and (2) determine the associations between distress and demographic and clinical variables, we conducted a survey of outpatients attending selected clinics of a regional cancer centre in Edinburgh, UK. Patients completed the Hospital Anxiety and Depression Scale (HADS) on touch-screen computers and the scores were linked to clinical variables on the hospital database. Nearly one quarter of the cancer outpatients 674 out of 3071 (22%; 95% confidence interval (CI) 20–23%) met our criterion for clinically significant emotional distress (total HADS score 15 or more). Univariate analysis identified the following statistically significant associations: age <65, female gender, cancer type and extent of disease. Multivariate analysis indicated that age <65 (odds ratio 1.41; 95% CI 1.18–1.69), female gender (odds ratio 1.58; 95% CI 1.31–1.92) and active disease (odds ratio 1.72; 95% CI 1.43–2.05) but not cancer diagnosis, were the independent predictors of clinically significant emotional distress. Services to treat distress in cancer patients should be organised to target patients by characteristics other than their cancer diagnosis.

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

Glucocorticoids are pivotal in the maintenance of memory and cognitive functions as well as other essential physiological processes including energy metabolism, stress responses, and cell proliferation. Normal aging in both rodents and humans is often characterized by elevated glucocorticoid levels that correlate with hippocampus-dependent memory impairments. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies local intracellular (“intracrine”) glucocorticoid action; in the brain it is highly expressed in the hippocampus. We investigated whether the impact of 11β-HSD1 deficiency in knock-out mice (congenic on C57BL/6J strain) on cognitive function with aging reflects direct CNS or indirect effects of altered peripheral insulin-glucose metabolism. Spatial learning and memory was enhanced in 12 month “middle-aged” and 24 month “aged” 11β-HSD1−/− mice compared with age-matched congenic controls. These effects were not caused by alterations in other cognitive (working memory in a spontaneous alternation task) or affective domains (anxiety-related behaviors), to changes in plasma corticosterone or glucose levels, or to altered age-related pathologies in 11β-HSD1−/− mice. Young 11β-HSD1−/− mice showed significantly increased newborn cell proliferation in the dentate gyrus, but this was not maintained into aging. Long-term potentiation was significantly enhanced in subfield CA1 of hippocampal slices from aged 11β-HSD1−/− mice. These data suggest that 11β-HSD1 deficiency enhances synaptic potentiation in the aged hippocampus and this may underlie the better maintenance of learning and memory with aging, which occurs in the absence of increased neurogenesis.

A qualitative study of primary care professionals' views of case finding for depression in patients with diabetes or coronary heart disease in the UK

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.

Monitoring symptoms at home: what methods would cancer patients be comfortable using?

BackgroundRoutinely conducting case finding (also commonly referred to as screening) in patients with chronic illness for depression in primary care appears to have little impact. We explored the views and experiences of primary care nurses, doctors and managers to understand how the implementation of case finding/screening might impact on its effectiveness.MethodsTwo complementary qualitative focus group studies of primary care professionals including nurses, doctors and managers, in five primary care practices and five Community Health Partnerships, were conducted in Scotland.ResultsWe identified several features of the way case finding/screening was implemented that may lead to systematic under-detection of depression. These included obstacles to incorporating case finding/screening into a clinical review consultation; a perception of replacing individualised care with mechanistic assessment, and a disconnection for nurses between management of physical and mental health. Far from being a standardised process that encouraged detection of depression, participants described case finding/screening as being conducted in a way which biased it towards negative responses, and for nurses, it was an uncomfortable task for which they lacked the necessary skills to provide immediate support to patients at the time of diagnosis.ConclusionThe introduction of case finding/screening for depression into routine chronic illness management is not straightforward. Routinized case finding/screening for depression can be implemented in ways that may be counterproductive to engagement (particularly by nurses), with the mental health needs of patients living with long term conditions. If case finding/screening or engagement with mental health problems is to be promoted, primary care nurses require more training to increase their confidence in raising and dealing with mental health issues and GPs and nurses need to work collectively to develop the relational work required to promote cognitive participation in case finding/screening.

Symptoms 'unexplained by organic disease' in 1144 new neurology out-patients: how often does the diagnosis change at follow-up?

PurposeThis study aimed to determine which methods of remote symptom assessment cancer outpatients would be comfortable using, including those involving information technology, and whether this varied with age and gender.MethodsA questionnaire survey of 477 outpatients attending the Edinburgh Cancer Centre in Edinburgh, UK.ResultsMost patients reported that they would not feel comfortable using methods involving technology such as a secure website, email, mobile phone text message, or a computer voice on the telephone but that they would be more comfortable using more traditional methods such as a paper questionnaire, speaking to a nurse on the telephone, or giving information in person.ConclusionsThe uptake of new, potentially cost-effective technology-based methods of monitoring patients’ symptoms at home might be limited by patients’ initial discomfort with the idea of using them. It will be important to develop methods of addressing this potential barrier (such as detailed explanation and supervised practice) if these methods are to be successfully implemented.