Effects of immediate-release opioid on memory functioning: a randomized-controlled study in patients receiving sustained-release opioids.

BACKGROUND: The effects of opioid medication on cognitive functioning in patients with cancer and non-cancer pain remain unclear. METHOD: In this mechanistic randomized, double-blind, placebo-controlled, cross-over study of patients (n = 20) receiving sustained-release and immediate-release opioid medication as part of their palliative care, we examine memory effects of an additional dose of participants' immediate-release medication (oxycodone or morphine) or placebo. Immediate prose recall and recall of related and unrelated word pairs was assessed pre-and post-drug (placebo or immediate-release opioid). Memory for these stimuli was also tested after a delay on each testing occasion. Finally, performance on an 'interference' word pair task was assessed on the two testing occasions since proactive interference has been posited as a mechanism for acute opioid-induced memory impairment. RESULT: Unlike previous work, we found no evidence of memory impairment for material presented before or after individually tailored, 'breakthrough' doses of immediate-release opioid. Furthermore, immediate-release opioid did not result in increased memory interference. On the other hand, we found enhanced performance on the interference word pair task after immediate-release opioid, possibly indicating lower levels of interference. CONCLUSION: These results suggest that carefully titrated immediate-release doses of opioid drugs may not cause extensive memory impairment as previously reported, and in fact, may improve memory in certain circumstances. Importantly, our findings contrast strikingly with those of a study using the same robust design that showed significant memory impairment. We propose that factors, such as depressive symptoms, education level and sustained-release opioid levels may influence whether impairment is observed following immediate-release opioid treatment.

Prospective cohort study of adverse events in older people admitted to the acute general hospital: risk factors and the impact of dementia.

BACKGROUND: Reported adverse events (RAEs) are relatively common in the acute hospital and are associated with significant mortality and morbidity. Dementia is increasing in hospital in-patients, however there have been few studies exploring risk factors for RAEs, in particular cognitive impairment and dementia. Our objective was to identify the prevalence of RAEs in older acute medical inpatients and associated demographic, clinical or cognitive risk factors. METHOD: A longitudinal cohort study set on acute medical wards in a large general hospital. We recruited 710 people aged over 70 years undergoing emergency medical admission. Dementia was diagnosed using operationalised DSM-IV criteria. Patients were assessed using standardised tools including the Confusion Assessment Method, mini-mental state examination, the Functional Assessment Staging scale, the APACHE scale and Charlson co-morbidity index. Data on adverse events was supplied independently by the hospital clinical risk department. RESULTS: 8.6% (95% CI 6.4-10.6) of patients experienced an RAE; 5.9% (95% CI 4.2-7.6) were patient-related and 2.7% (95% CI 1.5-3.8) system-related (incidence rate for all RAEs was 2.1 (95% CI 1.7-2.8)) per person year of hospital admission. Median length of admission was 8 days (inter-quartile range 4-17 days). Patient-related RAEs were associated with male gender, delirium, mild/moderate cognitive impairment and a FAST score of 2-6. Overall, 11.1% died during the admission-this was not associated with experiencing an RAE. Staff comments on incident forms indicated an apparent lack of understanding of the impact of cognitive impairment. CONCLUSIONS: RAEs were common and associated with risk factors identifiable at admission.

Attitudes and barriers to employment in HIV-positive patients.

BACKGROUND: Unemployment in the human immunodeficiency virus (HIV) population remains a major issue. Recent changes in the benefits system have triggered concerns about (re)integration into work for adults with HIV. AIMS: To examine attitudes and barriers to employment in HIV patients. METHODS: We undertook a cross-sectional study in the Royal Free HIV outpatient department from December 2008 to February 2009. The questionnaire collected data on demographics, date of HIV diagnosis, combination antiretroviral therapy, CD4 count, employment status, attitudes to work, psychological health and perception of barriers to employment. Logistic regression analyses were used to assess factors associated with not working. RESULTS: Five hundred and forty-five HIV patients took part. Overall, 26% were not working and of these, half (53%) had been unemployed for >5 years. Associations with not working were having been diagnosed with HIV >10 years before, poor psychological health and poor attitudes to employment. There was no association between objective measures of health (CD4 count) and employment status. Those not working were less likely to agree with that 'work is good for physical and mental health' (90 versus 97%: P < 0.01) and more likely to agree that 'should only work if 100% fit and well' (76 versus 51%: P < 0.001) compared to workers. Those currently not working had negative perceptions of their abilities to gain employment and to remain in work. CONCLUSIONS: There are opportunities for HIV services to provide psychological support around attitudes associated with unemployment and to help HIV-positive men in particular obtain and remain in work.

Development and pilot evaluation of a complex intervention to improve experienced continuity of care in patients with cancer.

High experienced continuity of care in patients with cancer is associated with lower needs for care, better quality of life and better psychological outcomes. We developed and evaluated an intervention to improve experienced continuity. The intervention, consisted of (1) a 17-item patient-completed continuity assessment; (2) feedback to clinical nurse specialists and action to address the needs identified. Multidisciplinary team meetings and oncology outpatient clinics were observed, and patients and staff were interviewed. After qualitative work and reliability testing, the intervention was evaluated in a feasibility trial. Sixty-one patients provided data for analysis. No statistically significant differences were found in patients' experienced continuity between the trial arms, but important trends were seen in measures of needs for care in favour of those receiving the intervention. Feeding back findings from the continuity assessment to clinicians reduced patients' needs for care. Our results indicate that an intervention to target patients' experiences of continuity can reduce their subsequent needs for care. However, overcoming barriers to organisational change and addressing some patients' hesitation to report their continuity difficulties must be considered when implementing such an intervention. A phase III trial targeting patients with inadequate experienced continuity of care is recommended.

Perceived concepts of continuity of care in people with colorectal and breast cancer--a qualitative case study analysis.

We aimed to develop ideas on continuity of cancer care. In-depth qualitative interviews were conducted with 28 people. Seven had cancer. Each person with cancer nominated a close person and a primary and secondary health care professional. We examined from four perspectives: experiences of the initial diagnosis; subsequent treatment; views on continuity of care; information given about the illness; psychological/physical impact of cancer and communication with professionals, family and friends. Perceived continuity of care was influenced by the actions of patients', involvement of close contacts and engagement in shared decision making. Additionally communication between primary and secondary care, the role of various health professionals and hospital administrative systems strongly influenced continuity of care. Informational, management and relational continuity have been previously described. Our data uncovered the effect of patients' actions and the involvement of close friends and families on continuity of cancer care. People with cancer should be enabled to influence continuity of their care. Full recognition of the role of health professionals, different approaches to sharing information with patients and tightening of hospital administrative systems should also be considered.

Fatigue in patients with advanced cancer: a pilot study of an intervention with infliximab.

GOALS OF WORK: The objective of this study was to determine the effect of infliximab, an antitumor necrosis factor alpha (TNFalpha) antibody, on fatigue in patients with advanced cancer. MATERIALS AND METHODS: This was a pilot study undertaken in a specialist palliative care unit. Seventeen eligible outpatients were enrolled in this study. Infliximab 5 mg/kg was administered intravenously at baseline and if there was observable clinical benefit, every 4 weeks thereafter until clinical benefit was lost. The primary outcome measure assessing subjective functional improvement was the change in fatigue severity scale (FSS) score at 4 weeks following an infliximab infusion. Secondary outcome measures of subjective functional improvement that were assessed 4 weeks after each infliximab infusion included changes in Karnofsky performance status (KPS), hospital anxiety and depression scale (HADS) score, anxiety and depression subscores, and appetite visual analogue scale. Clinical laboratory assessments were C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), TNFalpha, interleukin-6, and leptin concentrations. MAIN RESULTS: At week 4, 9 of 14 patients improved in FSS, 3 of 15 improved in KPS, 7 of 15 improved in total HADS and the majority had modest improvements in serum CRP, ESR, or leptin concentrations. Case studies of six patients with overall improvement are described in detail. Five serious adverse events occurred; two were serious infections possibly related to treatment. CONCLUSIONS: A subgroup of patients in this small pilot study demonstrated uniform subjective/clinical benefit. We were not able to identify any predictors of this response; a larger, controlled study may reveal more information.

Psychostimulants for depression.

BACKGROUND: Depression is common, disabling, costly and under-treated. There are problems in the current first-line drug treatment, antidepressants, for moderate or severe depression. There is a body of research that has evaluated the effect of psychostimulants (PS) in the treatment of depression. This has not been reviewed systematically. OBJECTIVES: To determine the effectiveness of PS in the treatment of depression and to assess adverse events associated with PS. SEARCH STRATEGY: Databases CCDANCTR-Studies and CCDANCTR-References were searched on 21/6/2006. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycInfo, AMED, CINAHL, Dissertation Abstracts and the National Health Service Research Register were searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing the effectiveness of PS were included. The trial population comprised adults of either sex with a diagnosis of depression. DATA COLLECTION AND ANALYSIS: Two review authors extracted the data independently and assessed trial quality. Meta-analysis was considered for trials with comparable key characteristics. The primary outcome was depression symptoms, based on a continuous outcome, using the standardised mean difference (SMD), or a dichotomous measure of clinical response, using odds ratios (OR), with 95% confidence intervals (CI). MAIN RESULTS: Twenty-four RCTs were identified. The overall quality of the trials was low. Five drugs were evaluated; dexamphetamine, methylphenidate, methylamphetamine, pemoline and modafinil. Modafinil was evaluated separately as its pharmacology is different to that of the other PS. PS were administered as a monotherapy, adjunct therapy, in oral or intravenous preparation and in comparison with a placebo or an active therapy. Most effects were measured in the short term (up to four weeks). Thirteen trials had some usable data for meta-analyses. Three trials (62 participants) demonstrated that oral PS, as a monotherapy, significantly reduced short term depressive symptoms in comparison with placebo (SMD -0.87, 95% CI -1.40, -0.33, with non-significant heterogeneity. A similar effect was found for fatigue. In the short term PS were acceptable and well tolerated. Tolerance and dependence were under evaluated. No statistically significant difference in depression symptoms was found between modafinil and placebo. AUTHORS' CONCLUSIONS: There is some evidence that in the short-term, PS reduce symptoms of depression. Whilst this reduction is statistically significant, the clinical significance is less clear. Larger high quality trials with longer follow-up and evaluation of tolerance and dependence are needed to test the robustness of these findings and, furthermore, to explore which PS may be more beneficial and in which clinical situations they are optimal.

The relationship between patients' experiences of continuity of cancer care and health outcomes: a mixed methods study.

It is difficult to define continuity of care or study its impact on health outcomes. This study took place in three stages. In stage I we conducted qualitative research with patients, their close relatives and friends, and their key health professionals from which we derived a number of self completion statements about experienced continuity that were tested for reliability and internal consistency. A valid and reliable 18-item measure of experienced continuity was developed in stage II. In stage III we interviewed 199 patients with cancer up to five times over 12 months to ascertain whether their experiences of continuity were associated with their health needs, psychological status, quality of life, and satisfaction with care. The qualitative data revealed that experienced continuity involved receiving consistent time and attention, knowing what to expect in the future, coping between service contacts, managing family consequences, and believing nothing has been overlooked. Transitions between phases of treatment were not associated with changes in experienced continuity. However, higher experienced continuity predicted lower needs for care, after adjustment for other potential explanatory factors (standardised regression coefficients ranging from -0.12 (95% CI -0.20, -0.05) to -0.32 (95% CI -0.41, -0.23)). Higher experienced continuity may be linked to lower health care needs in the future.

Screening for distress in cancer patients: is the distress thermometer a valid measure in the UK and does it measure change over time? A prospective validation study.

A prospective validation study was conducted in 171 consenting patients from oncology and palliative care outpatient clinics to validate the Distress Thermometer (DT) against the Hospital Anxiety and Depression Scale (HADS), General Health Questionnaire-12 (GHQ-12) and Brief Symptom Inventory-18 (BSI-18) at baseline, four weeks and eight weeks. Receiver Operating Characteristic analysis was used to examine the sensitivity and specificity of the DT scores against the clinically significant cut-off scores of the criterion measures reporting 95% confidence intervals. Standardised response means were used to compare DT scores with criterion measures over time. For a cut-off of 4 vs 5, sensitivity against HADS was 79%, specificity 81%; against GHQ-12, sensitivity was 63%, specificity 83%; and against BSI-18, sensitivity was 88%, specificity 74%. At both four and eight weeks, DT scores tended to change significantly in the same direction as the criterion measures. Ninety-five percent of patients found completing the DT acceptable. The DT is valid and acceptable for use as a rapid screening instrument for patients in the UK with cancer. Our results indicate that it can be used to monitor change in psychological distress over time, but further work is needed to confirm this.

Interventions for sexual dysfunction following treatments for cancer.

BACKGROUND: The proportion of people living with and surviving cancer is growing. This has led to increased awareness of the importance of quality of life including sexual function in people with cancer. Sexual dysfunction (SD) is a potential long-term complication of cancer treatments. OBJECTIVES: Evaluate effectiveness of interventions for SD following treatments for cancer and their adverse effects. SEARCH STRATEGY: The Cochrane Pain, Palliative & Supportive Care Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycInfo, AMED, CINAHL, Dissertation Abstracts and NHS Research Register were searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) were included that assessed the effectiveness of a treatment for SD. The trial population comprised of adults of either sex who at trial entry had developed SD as a consequence of cancer treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data and assessed trial quality. Meta-analysis was considered for trials with comparable key characteristics. MAIN RESULTS: Eleven RCTs with a total of 1743 participants were identified. The quality of the trials was poor. Ten trials explored interventions for SD in men following treatments for non-metastatic prostate cancer. One trial explored effectiveness in women of a lubricating vaginal cream following radiotherapy for cervical cancer. The strongest evidence (from four trials) was on oral phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction (ED) following radiotherapy of the prostate or radical prostatectomy. The results using validated measures in all trials significantly favoured those in the PDE5 inhibitor group(s). The combined results of two trials indicated a significantly greater improvement in ED in the PDE5 inhibitor groups (odds ratio (OR) 10.09 95% confidence interval (CI) 6.20 to 16.43). Negative effects were few and usually mild to moderate headaches or flushing. One trial reported more clinically serious events including six events of tachycardia and six of chest pain. Following prostate cancer treatments there was some evidence that PDE5 inhibitors are more effective in combination with acetyl-L-carnitine and propionyl-L-carnitine and that sexual counselling improves self-administration of prostaglandin intra-cavernous injection for SD. There was some evidence following treatment for prostate cancer that transurethral alprostadil and vacuum constriction devices reduce SD, although in both trials negative effects were fairly common. There is some evidence that vaginal lubricating creams reduce SD. AUTHORS' CONCLUSIONS: PDE5 inhibitors are an effective treatment for SD secondary to treatments for prostate cancer. Other interventions identified need to be tested in further RCTs. The SD interventions in this review are not representative of the range available for men and women. Further evaluations are needed for these interventions for SD following cancer treatments.

A case series of inferior vena cava stenting for lower limb oedema in palliative care.

Inferior vena caval obstruction (IVCO) is an occasional cause of lower limb oedema in palliative care patients with metastatic malignancy. We present five cases who underwent IVC stenting for symptomatic relief. Four of the five cases had significant reduction in their oedema but three of these four patients died within two weeks of the procedure. The procedure itself is described and the appropriateness of this intervention in patients with end-stage disease is discussed.

Rehabilitation and specialist palliative care.

Enabling individuals to achieve their maximum potential and quality of life following a diagnosis of advanced cancer, has long been a stated aim of palliative care. Increased life expectancy and the introduction of specialist palliative care to patients at an earlier stage of their illness presents professionals in the specialty with new challenges in meeting the need for rehabilitative care. This article examines some of the recent developments affecting the provision of rehabilitative care and describes one specialist palliative care unit's response to the challenge, highlighting the role of a nurse-led clinic within the service framework.

The use of phenobarbitone in the management of agitation and seizures at the end of life.

This study investigated the role of phenobarbitone at the end of life by retrospective analysis of case notes. During a 3-year period, of the 748 patients who died in a 32-bed palliative care unit, 60 received phenobarbitone during the last week of life. Fifty-nine patients had advanced cancer, 16 of whom had cerebral involvement. Phenobarbitone was used to control agitation and seizures. It was administered via subcutaneous infusion at a dose of 600-2400 mg/day. The mean time from starting phenobarbitone to death was 34.1 hours. Phenobarbitone was well tolerated and effective, controlling physical and psychological agitation. No further seizures occurred. This study suggests that phenobarbitone has a useful role in the management of distressing symptoms in the last few days of life.

Fatigue in advanced cancer: a prospective controlled cross-sectional study.

Uncontrolled studies have reported that fatigue is a common symptom among patients with advanced cancer. It is also a frequent complaint among the general population. Simply asking cancer patients whether or not they feel fatigued does not distinguish between the 'background' level of this symptom in the community and any 'excess' arising as a result of illness. The aim of this study was to determine the prevalence of fatigue among palliative care inpatients in comparison with a control group of age and sex-matched volunteers without cancer. In addition, the correlates of fatigue were investigated. The prevalence of 'severe subjective fatigue' (defined as fatigue greater than that experienced by 95% of the control group) was found to be 75%. Patients were malnourished, had diminished muscle function and were suffering from a number of physical and mental symptoms. The severity of fatigue was unrelated to age, sex, diagnosis, presence or site of metastases, anaemia, dose of opioid or steroid, any of the haematological or biochemical indices (except urea), nutritional status, voluntary muscle function, or mood. A multivariate analysis found that fatigue severity was significantly associated with pain and dypnoea scores in the patients, and with the symptoms of anxiety and depression in the controls. The authors conclude that subjective fatigue is both prevalent and severe among patients with advanced cancer. The causes of this symptom remain obscure. Further work is required in order to determine if the associations reported between fatigue and pain and between fatigue and dyspnoea are causal or coincidental.

Specialist palliative care and patients with noncancer diagnoses: the experience of a service.

This retrospective review was undertaken to identify the pattern of noncancer referrals to a specialist palliative care service, comprising a teaching hospital support team, home care, outpatients and inpatient hospice, over a 1-year period. Of 287 hospital ward referrals, 83 patients had a noncancer diagnosis (29%); they were referred predominantly for symptom control (92%), particularly of pain (84%). Of 130 outpatient referrals, 30 had a noncancer diagnosis (23%) and were also referred mainly for the management of pain (85%). Of 196 home care referrals, 18 had a noncancer diagnosis (9%); they tended to be referred for multiprofessional care of endstage disease. Of 421 hospice inpatient admissions, 17 were for patients with a noncancer diagnosis (4%) and were predominantly for respite care. These admissions accounted for 2% of occupied bed days. It is concluded that specialist palliative care skills are perceived to be transferable to patients with noncancer diagnoses. Resource implications focus on hospital and outpatient services, where shared care with medical teams is usual practice. Defining management goals at the outset is particularly important.

Development of an instrument to measure terminal restlessness.

Terminal restlessness is a clinical phenomenon that is frequently observed but poorly defined. Its management is important in providing good quality palliative care. We present the development of an objective observer-rated instrument to measure terminal restlessness.

Morphine: yesterday's drug or yardstick for the future?

The correct use of opioids has had a major impact on the management of pain in patients with advanced disease, but pain is still badly managed by many doctors. Unfounded fears about the use of strong opioids, ignorance of the way in which opioids should be prescribed and an inability to recognize pain that is morphine resistant all contribute to this problem.

Ketamine injection used orally.

Ketamine has been used parenterally for pain unresponsive to opioids, including neuropathic pain, and has also been used as an alternative analgesic agent after surgery. Although oral administration of ketamine has been used for some time as a single dose, it has not been given by this route on a regular basis. The use of ketamine administered orally is described for two patients with severe neuropathic pain who were intolerant of, or whose pain was unrelieved by, more commonly used agents. Pain relief was achieved without significant side effects.