Vincent Crosby

The Safety and Efficacy of a Single Dose (500 mg or 1 g) of Intravenous Magnesium Sulfate in Neuropathic Pain Poorly Responsive to Strong Opioid Analgesics in Patients with Cancer

Neuropathic pain may respond poorly to morphine and is often difficult to relieve. Recent attention has been drawn to the role of the N-methyl-D-aspartate (NMDA) receptor in the potentiation of neuropathic pain. Magnesium is known to block the NMDA receptor. It reduces the neuropathic pain response in animals, and attenuates postoperative pain and migraine in humans. We have examined the safety, tolerability, and efficacy of two intravenous doses of magnesium sulfate in 12 patients with neuropathic pain due to malignant infiltration of the brachial or lumbosacral plexus. The first six patients received 500 mg, the remainder 1 g. Apart from a mild feeling of warmth at the time of the injection, both doses were well tolerated. After receiving 500 mg, three patients experienced complete pain relief and two experienced partial pain relief for up to 4 hours duration; pain was unchanged in one patient. After receiving 1 g, one patient experienced complete relief and four experienced partial pain relief of similar duration; pain was unchanged in one patient. Intravenous magnesium sulfate in these doses appears to be safe and well tolerated. A useful analgesic effect may be obtained in some patients and further evaluation is warranted.

Descriptors of Breathlessness in Patients With Cancer and Other Cardiorespiratory Diseases

The objective of this study was to examine the relationship between descriptors of breathlessness and its underlying cause in patients with lung cancer and cardiopulmonary diseases to see whether descriptors might be used to help determine the cause of breathlessness, particularly in patients with lung cancer. We studied 131 patients with primary or secondary lung cancer, whose breathlessness was attributed to tumor mass, pleural effusion, lung collapse, metastases, pleural thickening or lymphangitis carcinomatosis, and 130 patients with breathlessness attributed to asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease or cardiac failure. Patients selected statements (descriptors) that described the quality of their breathlessness from a 15-item questionnaire and the relationship between the descriptors and the attributed cause of breathlessness was evaluated by cluster analysis. All patient groups were characterized by more than one cluster and several clusters were shared between groups. Specific sets of clusters were associated with breathlessness due to asthma, COPD and cardiac failure, and to cancer causing collapse, metastases or pleural thickening. The association of different sets of clusters with the different diagnostic groups suggests that patients are describing qualitatively different experiences of breathlessness, but the relationship does not appear to be sufficiently robust for the questionnaire to aid differential diagnosis.

Repeatability of breathlessness measurements in cancer patients

Visual analogue scales (VAS) and numerical rating scales are commonly used to assess breathlessness in patients with cancer.1-3 Their repeatability in this situation has not, however, been assessed in a way that allows calculation of the sample size required to design studies with sufficient power to detect a change in breathlessness. We asked 31 patients with breathlessness due to cancer to complete …

How integrated are neurology and palliative care services?: Results of a multicentre mapping exercise

BackgroundPatients affected by progressive long-term neurological conditions might benefit from specialist palliative care involvement. However, little is known on how neurology and specialist palliative care services interact. This study aimed to map the current level of connections and integration between these services.MethodsThe mapping exercise was conducted in eight centres with neurology and palliative care services in the United Kingdom. The data were provided by the respective neurology and specialist palliative care teams. Questions focused on: i) catchment and population served; ii) service provision and staffing; iii) integration and relationships.ResultsCentres varied in size of catchment areas (39-5,840 square miles) and population served (142,000-3,500,000). Neurology and specialist palliative care were often not co-terminus. Service provisions for neurology and specialist palliative care were also varied. For example, neurology services varied in the number and type of provided clinics and palliative care services in the settings they work in. Integration was most developed in Motor Neuron Disease (MND), e.g., joint meetings were often held, followed by Parkinsonism (made up of Parkinson’s Disease (PD), Multiple-System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP), with integration being more developed for MSA and PSP) and least in Multiple Sclerosis (MS), e.g., most sites had no formal links. The number of neurology patients per annum receiving specialist palliative care reflected these differences in integration (range: 9–88 MND, 3–25 Parkinsonism, and 0–5 MS).ConclusionsThis mapping exercise showed heterogeneity in service provision and integration between neurology and specialist palliative care services, which varied not only between sites but also between diseases. This highlights the need and opportunities for improved models of integration, which should be rigorously tested for effectiveness.

Prolongation of the QT interval in palliative care patients

Prolonged QT interval on the electrocardiogram (ECG) is associated with an increased risk of cardiac arrhythmia and sudden death. Many drugs used in palliative medicine increase the QT interval and several have had their licenses withdrawn or severely restricted. The relative importance of prolonged QT interval will increase for palliative medicine physicians when dealing with patients with longer prognoses and especially cardiac disease. Given these safety concerns, the aim of this study was to determine the prevalence of a prolonged QT interval in palliative care patients who were not in the terminal stage and were referred to a specialist service. Of 300 patients, 47 (16%) had prolonged QTc but only two had QT >500ms. The presence of coexistent cardiac disease or high levels of serum alkaline phosphatase appear to be the clinical features most robustly associated with a prolonged QTc. Although prolonged QTc is relatively common in patients referred to a specialist palliative care service, severely prolonged QT is rare.

Lung cancer diagnosed following an emergency admission: Mixed methods study of the management, outcomes and needs and experiences of patients and carers

BACKGROUND In the UK, although 40% of patients with lung cancer are diagnosed following an emergency admission (EA), data is limited on their needs and experiences as they progress through diagnostic and treatment pathways. METHODS Prospective data collection using medical records, questionnaires and in-depth interviews. Multivariate logistic regression explored associations between diagnosis following EA and aspects of interest. Questionnaire responses with 95% confidence intervals were compared with local and national datasets. A grounded theory approach identified patient and carer themes. RESULTS Of 401 patients, 154 (38%) were diagnosed following EA; 37 patients and six carers completed questionnaires and 13 patients and 10 carers were interviewed. Compared to those diagnosed electively, EA patients adjusted results found no difference in treatment recommendation, treatment intent or place of death. Time to diagnosis, review, or treatment was 7-14 days quicker but fewer EA patients had a lung cancer nurse present at diagnosis (37% vs. 62%). Palliative care needs were high (median [IQR] 21 [13-25] distressing or bothersome symptoms/issues) and various information and support needs unmet. Interviews highlighted in particular, perceived delays in obtaining investigations/specialist referral and factors influencing success or failure of the cough campaign. CONCLUSIONS Presentation as an EA does not appear to confer any inherent disadvantage regarding progress through lung cancer diagnostic and treatment pathways. However, given the frequent combination of advanced disease, poor performance status and prognosis, together with the high level of need and reported short-fall in care, we suggest that a specialist palliative care assessment is routinely offered.

Integrating palliative care into neurology services: what do the professionals say?

Objectives Evaluations of new services for palliative care in non-cancer conditions are few. OPTCARE Neuro is a multicentre trial evaluating the effectiveness of short-term integrated palliative care (SIPC) for progressive long-term neurological conditions. Here, we present survey results describing the current levels of collaboration between neurology and palliative care services and exploring the views of professionals towards the new SIPC service. Methods Neurology and palliative care teams from six UK trial sites (London, Nottingham, Liverpool, Cardiff, Brighton and Chertsey) were approached via email to complete an online survey. The survey was launched in July 2015 and consisted of multiple choice or open comment questions with responses collected using online forms. Results 33 neurology and 26 palliative care professionals responded. Collaborations between the two specialties were reported as being ‘good/excellent’ by 36% of neurology and by 58% of palliative care professionals. However, nearly half (45%) of neurology compared with only 12% of palliative care professionals rated current levels as being ‘poor/none’. Both professional groups felt that the new SIPC service would influence future collaborations for the better. However, they identified a number of barriers for the new SIPC service such as resources and clinician awareness. Conclusions Our results demonstrate the opportunity to increase collaboration between neurology and palliative care services for people with progressive neurological conditions, and the acceptability of SIPC as a model to support this. Trial registration number ISRCTN18337380; Pre-results.

Psychometric properties of a generic, patient-centred palliative care outcome measure of symptom burden for people with progressive long term neurological conditions

Background There is no standard palliative care outcome measure for people with progressive long term neurological conditions (LTNC). This study aims to determine the psychometric properties of a new 8-item palliative care outcome scale of symptom burden (IPOS Neuro-S8) in this population. Data and Methods Data were merged from a Phase II palliative care intervention study in multiple sclerosis (MS) and a longitudinal observational study in idiopathic Parkinson’s disease (IPD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). The IPOS Neuro-S8 was assessed for its data quality, score distribution, ceiling and floor effects, reliability, factor structure, convergent and discriminant validity, concurrent validity with generic (Palliative care Outcome Scale) and condition specific measures (Multiple Sclerosis Impact Scale; Non-motor Symptoms Questionnaire; Parkinson’s Disease Questionnaire), responsiveness and minimally clinically important difference. Results Of the 134 participants, MS patients had a mean Extended Disability Status Scale score 7.8 (SD = 1.0), patients with an IPD, MSA or PSP were in Hoehn & Yahr stage 3–5. The IPOS Neuro-S8 had high data quality (2% missing), mean score 8 (SD = 5; range 0–32), no ceiling effects, borderline floor effects, good internal consistency (Cronbach’s α = 0.7) and moderate test-retest reliability (intraclass coefficient = 0.6). The results supported a moderately correlated two-factor structure (Pearson’s r = 0.5). It was moderately correlated with generic and condition specific measures (Pearson’s r: 0.5–0.6). There was some evidence for discriminant validity in IPD, MSA and PSP (p = 0.020), and for good responsiveness and longitudinal construct validity. Conclusions IPOS Neuro-S8 shows acceptable to promising psychometric properties in common forms of progressive LTNCs. Future work needs to confirm these findings with larger samples and its usefulness in wider disease groups.

The importance of low magnesium in palliative care

We agree with Brogan et al. that magnesium deficiency can be important in palliative care, is probably underdiagnosed and so undertreated.1 Measurement of serum magnesium, however, is not always diagnostic, and we have found the magnesium loading test to be necessary if chronic magnesium deficiency is to be reliably diagnosed in palliative care patients. Both of the patients described by Brogan et al. had received platinum-based chemotherapy, which can quickly result in marked and sometimes protracted renal wasting of magnesium sufficient to cause symptomatic hypomagnesaemia. When magnesium deficiency develops more insidiously, serum magnesium, being under tight homeostatic control, is maintained whilst tissue stores are depleted. Indeed, in our survey of patients attending a palliative care unit, with multiple risk factors for deficiency, the incidence of hypomagnesaemia was low at only 3%.2 In the magnesium loading test an intravenous dose of magnesium sulphate is administered (based on the weight of the patient) followed by a 24 h urine collection to calculate the dose of magnesium retained by the patient. Probable magnesium deficiency is suggested by retention of more than 20% and definite magnesium deficiency by retention of more than 50% of the dose.3 Of the seven patients we have examined to date all have been shown to be definitely deficient (mean retention 76%, range 62–98%), despite serum magnesium levels within or above the normal range (mean 0.9 mmol/l, range 0.7–1.4 mmol/l). Thus, for many patients within a palliative care setting, serum magnesium is not the most reliable way of identifying chronic magnesium deficiency.4,5 Along with the magnesium loading test we are measuring serum ionized magnesium, urinary, red cell and white cell magnesium in order to find a simple, reliable and more readily available method of assessing chronic magnesium deficiency in palliative care patients.

Is clarithromycin a potential treatment for cachexia in people with lung cancer? A feasibility study

Clarithromycin may improve cachexia and survival in non-small cell lung cancer (NSCLC), but adequately controlled data are lacking. This study was undertaken primarily to inform the feasibility and scale of a phase III trial. Eligible consenting patients with stage IV NSCLC and cachexia were to be randomized to receive either clarithromycin 250mg twice daily or placebo for eight weeks. Aspects of trial feasibility recorded included numbers eligible, approached and recruited, together with adherence and completion of treatment and assessments. Over 6 months, none of 125 patients identified fulfilled the entry criteria. The commonest reasons for ineligibility were the use of an excluded concurrent drug (45, 36%), brain metastases (22, 18%), poor performance status (21, 17%) and current chemotherapy (15, 12%). A phase III trial of clarithromycin using these entry criteria is not feasible in this setting. Other macrolides that have a lower risk of a drug-drug interaction may be more practical to pursue.