Assessing the independent contribution to quality of life from anxiety and depression in patients with advanced cancer.

BACKGROUND: The aim of palliative care services is to ensure the best quality of life for patients and their carers. Depression is common amongst palliative care patients and has been shown to adversely affect quality of life. This study aimed to examine the independent contribution of depression to quality of life. OBJECTIVE: To investigate the hypothesis that a) illness severity, pain, anxiety and depression are all associated with impaired health-related quality of life and b) once the effects of illness severity have been adjusted for, there is further independent contribution to quality of life from anxiety and depression. METHOD: Consecutive patients with advanced cancer under the care of palliative care services were screened. Sixty-eight patients were evaluated for levels of anxiety and depression, severity of illness, pain severity and health-related quality of life. RESULTS: Thirty-three males and 35 females were recruited and had an age range of 41-93 years (median 71). Seventeen (25%) of patients were anxious [anxiety score > or = 11 on the Hospital Anxiety and Depression Scale (HADS)], 15 (22%) were depressed (HADS depression score > or = 11). After controlling for the effects of pain and illness severity, anxiety and depression were independently associated with global health status, emotional and cognitive functioning, and fatigue. Anxiety further contributed significantly towards social functioning, nausea and vomiting. CONCLUSIONS: This study has confirmed that pain, anxiety and depression were associated with impaired quality of life. Anxiety and depression contributed independently towards various dimensions of quality of life. Longitudinal studies are required to examine the direction of the causal association between pain and depression in patients receiving palliative care.

The concerns of patients under palliative care and a heart failure clinic are not being met.

Patients with a terminal illness, identified by palliative care teams working in Manchester, and patients attending a heart failure clinic, were asked to participate in a prospective survey to determine their main concerns. Data were collected from 213 palliative care (PC) patients (mostly with cancer) and 66 patients with heart failure (HF). The median ages of the two patient groups were similar, but the HF patients were more likely to be male and living with a partner; 13% of PC and 7% of HF patients reported that they had no carer. The PC patients had more district nurse, hospice, social work and physiotherapy input. The most frequently reported troublesome problems for PC patients were pain (49%), loss of independence (30%) and difficulty walking (27%). HF patients reported dyspnoea (55%), angina (32%) and tiredness (27%) as the most troublesome problems. From a checklist of symptoms, the frequency of tiredness (PC = 77%, HF = 82%) and difficulty getting about (PC = 71%, HF = 65%) were high in each group. Psychological problems were reported by 61% of PC and 41% of HF patients. Cardiac patients reported more breathlessness and cough than PC patients (83% vs 49% and 44% vs 26%, respectively). Reduced libido was more common in cardiac patients (42% vs 21%). Patient disclosure of troublesome problems to professional carers was high (>87% in both PC and HF patients). Documented action was greater for physical than social or psychological problems. For PC patients, documented action was recorded for 83% physical, 43% social/functional and 52% psychological problems. For HF patients documented action was recorded for 74% cardiac, 60% physical - non-cardiac, 30% social/functional and 28% psychological problems. Clearly many patients' troublesome problems were not being addressed. As a result of this study, specific action by health care professionals was taken in 50% of PC patients and 71% of HF patients. We plan to target specific educational events on the treatment of physical problems, psychological assessment and social service provision.

Serum neuron-specific enolase (S-NSE) and the prognosis in small-cell lung cancer (SCLC): a combined multivariable analysis on data from nine centres.

The influence of pretreatment serum neuron-specific enolase (S-NSE) in addition to more conventional prognostic factors on survival duration in small-cell lung cancer (SCLC) was investigated in 770 patients from nine centres in six countries. The other variables included stage of disease, performance status (PS), age, sex, serum lactate dehydrogenase (S-LDH), serum alkaline phosphatase (S-AP), and serum carcinoembryonic antigen (S-CEA). Increased values of S-NSE (> 12.5 micrograms-1 l) were observed in 81% of the patients, whereas S-LDH, S-AP and S-CEA were elevated in only half of the patients or less. Multivariable analysis by Cox's proportional hazard model disclosed S-NSE as the most powerful prognostic factor followed by poor PS and extensive stage disease. If PS was ignored, S-LDH came up as a significant prognostic factor. S-AP, S-CEA, age and sex had no significant influence on the prognosis. The three prognostic factors, S-NSE, PS and stage of disease, enabled establishment of a prognostic index (PI) based on a simple algorithm PI = zNSE + z(stage) + 2zPS. This segregated the patients into four groups with clearly different prognosis. The median survival and 95% confidence intervals of the four groups were: 468 days (540-408), 362 days (405-328), 256 days (270-241) and 125 days (179-58). Based on the present results we recommend S-NSE and PS, in addition to stage, for prognostic stratification in treatment trials on SCLC.

The management of cryptogenic fibrosing alveolitis in three regions of the United Kingdom.

The case notes of 200 patients with cryptogenic fibrosing alveolitis, from three regions in the United Kingdom, were reviewed, in order to determine how physicians manage this uncommon condition. In the majority of cases (119), the diagnosis was based solely on clinical grounds, with no attempt at histological confirmation of the diagnosis. Transbronchial biopsy was attempted in 66 patients, but was unhelpful in confirming a diagnosis of pulmonary fibrosis in 30% of these patients. Thirty five patients underwent bronchoalveolar lavage, and 15 had an open lung biopsy. Of the 132 patients treated, 110 received prednisolone alone, and the rest a combination of other immunosuppressive agents. The doses and duration of therapy varied considerably. These results suggest that, in the late 1980s, there were wide variations of practice in the management of cryptogenic fibrosing alveolitis in the United Kingdom. This is likely to reflect a paucity of information on the optimum management of this uncommon condition.

High dose combination chemotherapy with ifosfamide, cyclophosphamide or cisplatin, mitomycin C and mustine with autologous bone marrow support in advanced non-small cell lung cancer. A phase I/II study.

Twenty-three patients with advanced NSCLC were treated with high dose chemotherapy using four agents and autologous bone marrow reinfusion. Ten patients received two bolus doses of cyclophosphamide (maximum tolerated total dose 10 G m-2), ifosfamide as a 24 h infusion (11 G m-2) followed by mitomycin C (70 mg m-2) as a subsequent 24 h infusion and mustine as two boluses (total dose 30 mg m-2). Another 13 patients received the same agents except cisplatin was substituted for cyclophosphamide, two doses (total dose 100 mg m-2) being given in a 24 h period. The median time of recovery to greater than or equal to 20,000 platelets was 21 days and of neutropaenia greater than or equal to 500 was 12-15 days. Unusual non-haematological toxicity e.g. cardiomyopathy, colitis, veno occlusive disease was not noted, all patients being given regular selenium and other trace elements. Three patients died in the first 2 weeks. There were five complete responses (22%) and 12 partial responses (52%) with four patients (2CR, 2PR) still alive at 27, 48, 73 and 82 weeks. The patient's Karnofsky performance in the cisplatin regimen improved over pretreatment values when compared a month after the end of treatment. The high dose regimen was associated with a high (74%) response rate, but with an overall median survival of only 6 months. The regimen has no advantage over conventional doses with the same agents in patients with metastatic NSCLC.

A clinicopathological study of the paraneoplastic neuromuscular syndromes associated with lung cancer.

The highest incidence of remote neuromuscular disorders in cancer has previously been reported in lung carcinoma. The clinical incidence of neuromuscular disorder was estimated and correlated with muscle histology and the histological type of lung tumour in 100 patients with lung carcinoma who were studied prospectively. Thirty-five patients had small cell carcinoma and 65 patients non-small cell lung cancer. Clinically, 33 patients had a polymyopathy, of whom 18 had a cachectic myopathy and 15 had a proximal myopathy (two patients had Lambert-Eaton myasthenic syndrome, one presented with dermatomyositis and one had evidence of ectopic ACTH production). Cachexia was more common in non-small cell cancer; proximal myopathy was more common in small cell cancer. Ninety-nine patients had abnormal muscle histology; 74 had type II atrophy, 12 had type I and II atrophy, one had type I atrophy and 12 had necrosis. The majority of patients were affected sub-clinically and the clinical entities of cachectic and proximal myopathy did not correspond to previous pathological classifications. Atrophy was not related to the duration of tumour symptoms, ageing, clinical type of myopathy or histological type of lung tumour, and was statistically different from that seen in controls. Qualitatively, the presence of weight loss, muscle wasting and metastatic disease were not factors in the development of atrophy. Similarly, necrosis was not related to the type of lung tumour, the presence of metastases, ageing, weight loss, muscle wasting, duration of tumour symptoms or the clinical form of myopathy. This study demonstrates that lung carcinoma has a direct effect on the motor unit, including atrophy, a necrobiotic myopathy and Lambert-Eaton myasthenic syndrome. Clinical assessment does not accurately assess the 'remote' neuromuscular effects of cancer on the motor unit.

The value of tumour markers in lung cancer.

The pre-treatment serum levels of neuron-specific enolase (NSE), phosphohexose isomerase (PHI) and circulating immune complexes (CC) as tumour markers were compared to measurements of standard haematology and biochemical indices in 73 patients with lung cancer, as an aid to differentiation of tumour type, estimating disease extent, predicting response to therapy and prognosis. Elevated NSE greater than or equal to 12.5 ng ml-1, PHI greater than or equal to 55 mgl-1 levels were observed in 55% of cases for NSE, 90% for PHI and 49% for CC. NSE was significantly elevated in 61% (25/41) of patients with SCLC (P less than 0.005) compared to 41% (13/32) with NSCLC. CC levels were significantly raised in 72% (23/32) of patients with NSCLC (P less than 0.05) compared to 32% with SCLC. The levels of NSE and PHI were not related to tumour stage but CC was significantly raised in limited compared to extensive disease in SCLC (P less than 0.05). Serum albumin was significantly lower in NSCLC compared to SCLC, and median values of alkaline phosphatase, gamma-glutamyltranspeptidase and aminoaspartate transferase were significantly higher in patients with extensive disease. The pre-treatment serum values of NSE, PHI, and CC did not predict the response to therapy or prognosis in the 73 patients with lung cancer. The most important prognostic factor was the number of abnormal routine laboratory parameters (greater than 4) in this group of patients.

An unusual presentation of sarcoidosis--spontaneous haemopneumothorax.

Pneumothorax is a very rare complication of early stage sarcoidosis. A young man is reported with a left sided spontaneous haemopneumothorax and a right apical pneumothorax in association with early sarcoidosis.

Dose-response comparison of ipratropium bromide from a metered-dose inhaler and by jet nebulisation.

The dose-response relationships of the anticholinergic bronchodilator drug ipratropium bromide were studied. Cumulative doses totalling 288 micrograms ipratropium were given by inhalation of a liquid aerosol from a Wright nebuliser to each of 10 patients with stable, moderately severe airflow obstruction. Up to 80% of the maximum achievable bronchodilator response, as assessed by a rise in the patients' mean forced expiratory volume in one second (FEV1), was obtained with a cumulative total dose of 72 micrograms; with additional doses beyond 72 micrograms there was no significant further improvement. In the same patients the effects of administration of cumulative doses of ipratropium to a total of 72 micrograms from a Wright nebuliser were compared with those achieved with a metered-dose inhaler. Bronchodilatation was assessed by measurement of peak expiratory flow rate, FEV1, forced vital capacity, thoracic gas volume and specific airways conductance (sGaw). No significant difference was observed in the response at any dose level between the wet and the dry aerosols. By fitting a curve to the mean values of FEV1 and sGaw an estimate was made of the dose of ipratropium bromide required to produce 99% of the achievable bronchodilator response. For FEV1 this dose was 78 micrograms when ipratropium was inhaled as a nebulised solution from the Wright nebuliser and 82 micrograms when it was inhaled from the metered-dose inhaler; for sGaw the respective values were 54 and 58 micrograms. In these patients with stable airflow obstruction there was no therapeutic advantage in the use of ipratropium bromide as a wet aerosol.

Comparison of nebulized salbutamol with nebulized ipratropium bromide in acute asthma.

Twelve patients admitted to hospital with an acute attack of bronchial asthma were studied. Six were treated initially with nebulized salbutamol solution by inhalation and 1 hour later by ipratropium bromide given in the same way; the other six were treated first with ipratropium bromide and 1 hour later by salbutamol. Ipratropium bromide was shown to be as effective as salbutamol when used as the initial bronchodilator but salbutamol produced significant further improvement when given 1 hour after ipratropium.

Effect of an extension tube on the bronchodilator efficacy of terbutaline delivered from a metered dose inhaler.

A double-blind within-patient investigation was performed to determine whether the interposition of an extension tube (10 cm length X 3.2 cm diameter) between a metered dose inhaler and the mouth alters the bronchodilator efficacy of terbutaline sulphate. On two consecutive study days 14 adult patients with stable reversible airways obstruction inhaled a cumulative dose of 500 micrograms of terbutaline which was delivered from a metered dose inhaler with or without the extension tube attached and received placebo in a similar manner. The drug was inhaled in doses of 125, 125, and 250 micrograms at 20 minutes intervals. The following measurements were made: forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), thoracic gas volume (TGV), and specific airways conductance (sGaw). These were done immediately before and at five and 15 minute intervals after each dose, and were repeated 90, 120, 180, 240, and 300 minutes after the first inhalation of terbutaline. Administration of terbutaline with and without an extension tube achieved significant bronchodilation at all dose levels in all respiratory variables (p < 0.001). There was no statistically significant difference in FEV1, FVC, PEFR, and sGaw values at any time or dose level with either method of administration. The use of the extension tube did not impair the efficacy or duration of action of inhaled terbutaline.