Palliative care treatment patterns and associated costs of healthcare resource use for specific advanced cancer patients in the UK.

The purpose of this paper is to identify the treatment patterns and corresponding costs of healthcare resource use associated with palliative care for different types of advanced cancer patients, from the time they started strong opioid treatment until death. This was a modelling study performed from the perspective of the UK's National Health Service (NHS). A data set was created comprising 547 patients in the DIN-Link database who had a Read code for malignant neoplasms with a specific tumour-type diagnosis and who received their first strong opioid between 1 January 1998 and 30 September 2000 and died during that period. Palliative care-related resource utilization data were obtained from the DIN-Link database. Unit costs at 2000/2001 prices were applied to the resource use estimates to determine the mean cost of palliative care from the start of treatment until death. There were significant differences in age between patients with different cancer types and in patients' survival from diagnosis, time to the start of palliative care and duration of palliative care. The mean duration from cancer diagnosis to the start of strong opioid treatment ranged from 0.7 to 5.4 years in patients with lung and breast cancer respectively. Moreover, the length of palliative care ranged from 180 to 372 days in patients with these cancer types respectively. There were also statistically significant differences in resource use between patients with different cancer types, but this reflected, in part, the varying durations of palliative care. Nevertheless, there were also differences in the monthly number of primary care visits reflecting the different number of monthly prescriptions. There was no apparent relationship between the length and corresponding cost of palliative care which ranged from 1816 pounds sterling for colon cancer to 4789 pounds sterling for ovarian cancer. Additionally, on average, only a third of all patients also received 4-hourly morphine as part of their initial strong opioid treatment. The total cost of palliative care varied between cancer type and reflects, at least in part, the distinct clinical features associated with different tumours and the varying lengths of survival following the start of strong opioid treatment. Nevertheless, no apparent relationship was found between length of palliative care and corresponding costs. This analysis provides data on palliative care resource use for a variety of cancers and could provide useful input when planning local healthcare strategies and building service commissioning models.

Methadone titration in opioid-resistant cancer pain.

AIM: To assess the use of methadone in patients with cancer pain who fail to respond to increasing doses of other opioids or experience intolerable side-effects from them. METHOD: Inpatients of a specialist palliative care unit were titrated onto oral methadone. The dose was calculated as 10% of the previous morphine equivalent dose, up to maximum of 40 mg, given every 3 h as required for analgesia. When daily requirements were stable it was divided into two regular doses. Pain was assessed on a five-point verbal rating score (VRS): a good response was defined as a fall in VRS of two points or more. Results are expressed as median (range). RESULTS: Thirty-three patients (13 men, 20 women, age 61 (34-91) years), 26 with inadequate analgesia and seven with intolerable opioid related side-effects, were converted to methadone from diamorphine (12), morphine (19) or fentanyl (two). Morphine equivalent dose was 480 (20-1200) mg/day prior to titration. Pain was neuropathic (11), nociceptive (three) or mixed (19). Stabilisation on methadone was complete in 3 (2-18) days in 29 (88%) patients at 80 (20-360) mg/day. Twenty-six (78%) had a good response. Four (12%) patients were withdrawn during titration (three entered terminal phase, one failed to respond). During follow-up 15 (45%) required alteration of methadone dose. Twenty-three (70%) patients were discharged home at 12 (4-26) days. In all cases the stable dose of methadone was less than the previous morphine equivalent, and there was a weak correlation between them. CONCLUSIONS: This method of methadone titration often results in improved pain control in patients with morphine resistance or intolerance. It requires careful titration in a specialist inpatient unit as there is no reliable formula for dose equivalence.

Palliative care needs in a district general hospital: a survey of patients with cancer.

Although sophisticated treatment of cancer requires the resources of specialist cancer treatment centres, most patients with cancer still undergo initial diagnostic investigation and treatment in district general hospitals (DGHs). The DGH frequently remains the principle site of referral for management of symptoms and terminal care. This survey was carried out at a DGH which has no palliative care services. It aimed to demonstrate the need for such services by collecting data on inpatients with cancer and interviewing members of the nursing staff. Of 63 patients studied, 76% were admitted as emergencies, 50% had newly diagnosed cancer and 27% died in hospital. The majority (85%) were cared for on general medical, surgical and care of the elderly wards. Assessment of patients' symptoms suggested that 39 (62%) might have benefited from the services of a palliative care team. Interviews with nursing staff highlighted the need for improved communication between professionals, increased staff education and support, and highlighted the particular difficulties that exist in caring for patients with advanced cancer and their families on busy acute general hospital wards. Imaginative and flexible approaches to the design and delivery of palliative services are essential if patients with cancer in DGHs are to receive the highest standards of care at all stages of their illness.

Use of ketorolac by continuous subcutaneous infusion for the control of cancer-related pain.

Ketorolac tromethamine is a newly available non-steroidal anti-inflammatory drug which is suitable for parenteral administration. We have given it by continuous subcutaneous infusion to 36 patients with pain due to advanced cancer. Improvement in pain control occurred in 29 (80%). A reduction in the dose of concomitant opioid analgesia was possible in 22 (76%) and a reduction in opioid-related adverse effects occurred in 16 (73%) of these. Ketorolac was most effective in patients who had bone or visceral pain. It was mixed safely with diamorphine in a syringe driver at concentrations up to 4 g diamorphine/10 ml and 120 mg ketorolac/10 ml. Infusion was well tolerated for periods of up to 115 days (mean 21 days; median 15 days; range 3-115 days). Four patients experienced gastrointestinal bleeding and one colonic perforation to which treatment with ketorolac may have been a contributory factor. No other clinically significant adverse effects were observed.

Use of exercise Doppler for non-invasive haemodynamic optimization of dose and identification of poor responders to an oral anti-anginal agent. A double-blind dose-finding study of nisoldipine.

Nisoldipine, a new dihydropyridine calcium antagonist, was examined for its dose-related haemodynamic effects using exercise-induced changes in aortic blood flow as measured by Doppler ultrasound. Following a two-week placebo run-in, 24 patients with stable angina pectoris were assigned double-blind to one of three groups receiving doses ranging from 2.5-20 mg/day over 8 weeks, given once or twice daily. Doppler studies identified the low dose group as responding less well at the placebo phase compared to the other two groups. There was an overall improvement in percentage change of peak velocity and stroke distance with exercise at all doses, with a dose of 5 mg/day giving optimal benefit in both variables (P less than 0.05) and no additional benefit being seen on twice-daily dosage. Six patients reporting increased chest pain exhibited a significantly worse rise in peak velocity and a fall in stroke distance to exercise (P less than 0.05) whilst on active drug compared to those who responded favourably. Doppler ultrasound can be of benefit in the haemodynamic assessment of new drugs, the recognition of non-responders and the optimization of therapeutic regimes.

Further characterisation of the 'ileal brake' reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.

Previous studies have shown that ileal infusion of partially digested triglyceride inhibits jejunal motility. The partial digest used in those studies contained a mixture of glycerol, free fatty acid, mono-, di-, and triglycerides. In Part I of the present study we have separately infused emulsions containing either glycerol 3.1 g (n = 6), oleic acid 9.6 g (n = 6), triolein 10 g (n = 12), or medium chain triglycerides 10 g (n = 6) into the ileum and have recorded the effect this has on jejunal motility. Five further subjects received infusions of partial hydrolysates of corn starch 10 g and lactalbumin 7 g. Marked inhibition of jejunal pressure wave activity was seen after all three lipid infusions, per cent activity falling from a control of 37.7 (7.7) to 6.2 (2.1) and 22.4 (8.2)% 30 min after completing the oleic acid and triolein infusions respectively, and from a control value of 39.5 (4.1) to 17.7 (4.7) after MCTs (all p less than 0.05). No significant fall occurred after infusion of glycerol, protein or carbohydrate. All three lipid infusions raised plasma concentrations of neurotensin, enteroglucagon and peptide YY equally effectively, although only the rise in peptide YY correlated significantly with the inhibition of jejunal pressure wave activity (r = 0.80, n = 6, p less than 0.05). In Part II of this study six subjects received a 3 ml/min jejunal infusion of an isotonic carbohydrate saline solution followed after three hours by a similar infusion of a partial digest of lipid. During each infusion flow and transit time was measured by marker and dye dilution. Jejunal infusion of the carbohydrate-saline solution was associated with low jejunal flow, 4.7 (1.0) ml/min and a mean transit time through the 50 cm study segment of 36.5 (7.1) min. By contrast jejunal infusion of partially digested triglyceride was associated with a markedly increased flow, 9.0 (1.2) ml/min, a fall in mean transit time to 20.3 (2.6) min and significant rises in pancreaticobiliary secretions. Jejunal triglyceride also increased the incidence of prolonged high amplitude jejunal pressure waves in four of six subjects. These studies suggest that there are important differences in the jejunal response to ileal versus jejunal lipid. While long and median chain free fatty acids infused into the ileum exert an inhibitory effect on jejunal motility, when infused directly into the jejunum partially digested triglyceride accelerates transit, increases jejunal flow and subtly alters the pattern of jejunal contractions.

Effect of dilatation of peptic esophageal strictures on gastroesophageal reflux, dysphagia, and stricture diameter.

In 10 patients with peptic esophageal stricture the effect of esophageal dilatation on intraesophageal pH, stricture diameter, and dysphagia has been studied. Percentage of time during which intraesophageal pH was less than 4 and the number of reflux episodes per hour did not change significantly. Stricture diameter increased slightly, but consistently, from 7.0 +/- 0.5 mm to 9.1 +/- 0.5 mm (P less than 0.01) four days after dilatation, but was not significantly different from predilatation values after 12 weeks. Improvement in symptoms of dysphagia was striking (P less than 0.01) four days and six weeks after dilatation, but worsened again at 12 weeks (P = NS). It is unlikely that esophageal dilatation adversely affects the intraesophageal environment.

Sigmoid motility in diverticular disease and the irritable bowel syndrome.

Intraluminal pressures were measured with four open ended, water perfused tubes in the fasting state and after a standard liquid meal (400 KCal, 375 ml, protein 15 g, carbohydrate 55 g, lipid 13.4 g) in six patients with sigmoid diverticular disease, 20 with the irritable bowel syndrome and in 13 controls. The pressure sensors were positioned in the true sigmoid colon at colonoscopy at 25, 35, 45, and 55 cm from the anus. Colonic pressures were significantly higher in diverticular disease than in controls before (p less than 0.02) and after the meal (p less than 0.002), some pressure amplitudes exceeding 300 cm H2O. Patients with the irritable bowel syndrome had lower (p less than 0.05) pressures than controls before the meal. Postprandial sigmoid pressures were within the mean +/- 2 SD of controls in 10, above in two and below in eight patients with the irritable bowel. Hypercontractility of the sigmoid colon in the irritable bowel syndrome was not confirmed under the conditions of this study. The association between sigmoid diverticulosis and high intraluminal pressures is confirmed.

Investigation of ranitidine 150 mg bd or 300 mg bd in the treatment of reflux disease.

Twenty patients with symptoms and endoscopic changes of gastro-oesophageal reflux were randomly allocated to treatment with either ranitidine 150 mg bd, or 300 mg bd for 8 weeks. Symptoms, endoscopic appearances, histopathology of oesophageal biopsies and 22-h intra-oesophageal pH profile in ambulant patients on standard diets were recorded before and at the end of the treatment period. Symptoms improved rapidly and markedly on either dose of ranitidine. Both doses produced significant improvement of the endoscopic appearances, but there were no differences in symptomatic and endoscopic improvement related to the dose. Biopsy appearances and the 22-h oesophageal pH profile remained unchanged on either dose of ranitidine.

Bloated irritable bowel syndrome defined by dynamic 99mTc bran scan.

The motility of the ileocaecal region of the gut was studied in 10 women with irritable bowel syndrome (IBS) and bloating and in 8 normal women. Bran labelled with 37 MBq 99mTc was administered after fasting, and a dynamic scan was done after a standard meal 3 h later. Time-activity curves were plotted for the ileum and caecum. In controls, ileal emptying was faster, peak % counts in the caecum were higher, and ileocaecal clearance was greater than in those with IBS. The profound motor dysfunction seen in those with IBS may account for their symptoms, and the "bran scan" could become an important diagnostic aid.

The ileal brake--inhibition of jejunal motility after ileal fat perfusion in man.

The possibility that malabsorbed fat passing through the human ileum exerts an inhibitory feedback control on jejunal motility has been investigated in 24 normal subjects by perfusing the ileum with a fat containing solution designed to produce ileal luminal fat concentrations similar to those in steatorrhoea (30-40 mg/ml). Mean transit times through a 30 cm saline perfused jejunal segment were measured by a dye dilution technique. Thirty minutes after ileal fat perfusion, mean transit times rose markedly to 18.9 +/- 2.5 minutes from a control value of 7.5 +/- 0.9 minutes (n = 5; p less than 0.05). This was associated with an increase in volume of the perfused segment which rose to 175.1 +/- 22.9 ml (control 97.6 +/- 10.3 ml, n = 5; p less than 0.05). Transit times and segmental volumes had returned towards basal values 90 minutes after completing the fat perfusion. Further studies showed that ileal fat perfusion produced a pronounced inhibition of jejunal pressure wave activity, percentage duration of activity falling from a control level of 40.3 +/- 5.0% to 14.9 +/- 2.8% in the hour after ileal perfusion (p less than 0.01). Ileal fat perfusion was associated with marked rises in plasma enteroglucagon and neurotensin, the peak values (218 +/- 37 and 68 +/- 13.1 pmol/l) being comparable with those observed postprandially in coeliac disease. These observations show the existence in man of an inhibitory intestinal control mechanism, whereby ileal fat perfusion inhibits jejunal motility and delays caudal transit of jejunal contents.

Comparison of twice-daily ranitidine with standard cimetidine treatment of duodenal ulcer.

One hundred and three outpatients with endoscopically diagnosed duodenal ulcer were randomly allocated to treatment with either cimetidine 200 mg tds and 400 mg nocte, or ranitidine 150 mg bd for four weeks. The endoscopists were not aware of the treatment and took no part in the clinical management. On completion of treatment ulcers had healed in 43 of 51 (84%) patients given cimetidine and in 40 of 52 (77%) patients given ranitidine. There were no serious unwanted effects in either treatment group. The results show no significant difference between healing rates after four weeks of standard cimetidine therapy or ranitidine 150 mg bd.