Modelling the lifetime cost-effectiveness of radical prostatectomy, radiotherapy and active monitoring for men with clinically localised prostate cancer from median 10-year outcomes in the ProtecT randomised trial.

BACKGROUND: Optimal management strategies for clinically localised prostate cancer are debated. Using median 10-year data from the largest randomised controlled trial to date (ProtecT), the lifetime cost-effectiveness of three major treatments (radical radiotherapy, radical prostatectomy and active monitoring) was explored according to age and risk subgroups. METHODS: A decision-analytic (Markov) model was developed and informed by clinical input. The economic evaluation adopted a UK NHS perspective and the outcome was cost per Quality-Adjusted Life Year (QALY) gained (reported in UK£), estimated using EQ-5D-3L. RESULTS: Costs and QALYs extrapolated over the lifetime were mostly similar between the three randomised strategies and their subgroups, but with some important differences. Across all analyses, active monitoring was associated with higher costs, probably associated with higher rates of metastatic disease and changes to radical treatments. When comparing the value of the strategies (QALY gains and costs) in monetary terms, for both low-risk prostate cancer subgroups, radiotherapy generated the greatest net monetary benefit (£293,446 [95% CI £282,811 to £299,451] by D'Amico and £292,736 [95% CI £284,074 to £297,719] by Grade group 1). However, the sensitivity analysis highlighted uncertainty in the finding when stratified by Grade group, as radiotherapy had 53% probability of cost-effectiveness and prostatectomy had 43%. In intermediate/high risk groups, using D'Amico and Grade group > = 2, prostatectomy generated the greatest net monetary benefit (£275,977 [95% CI £258,630 to £285,474] by D'Amico and £271,933 [95% CI £237,864 to £287,784] by Grade group). This finding was supported by the sensitivity analysis. Prostatectomy had the greatest net benefit (£290,487 [95% CI £280,781 to £296,281]) for men younger than 65 and radical radiotherapy (£201,311 [95% CI £195,161 to £205,049]) for men older than 65, but sensitivity analysis showed considerable uncertainty in both findings. CONCLUSION: Over the lifetime, extrapolating from the ProtecT trial, radical radiotherapy and prostatectomy appeared to be cost-effective for low risk prostate cancer, and radical prostatectomy for intermediate/high risk prostate cancer, but there was uncertainty in some estimates. Longer ProtecT trial follow-up is required to reduce uncertainty in the model. TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Dose response to intrathecal diamorphine for elective caesarean section and compliance with a national audit standard.

BACKGROUND: This double-blind randomised controlled trial investigated the most appropriate dose of intrathecal diamorphine to use with high-dose diclofenac as part of a multimodal analgesic regimen for caesarean section under subarachnoid block. We also wished to establish whether it was possible to satisfy the Royal College of Anaesthetists postoperative pain audit recommendation for this patient group. METHODS: One hundred and twenty patients presenting for elective caesarean section under subarachnoid block were recruited and divided into four groups. Treatment was standard except that patients were given either placebo or one of three different doses of intrathecal diamorphine (100 microg, 200 microg or 300 microg). All patients were given regular paracetamol, high-dose diclofenac and an hourly subcutaneous diamorphine regimen for breakthrough pain. RESULTS: There was a dose-dependent improvement in analgesia with intrathecal diamorphine. Only 37.9% of patients given 300 microg of intrathecal diamorphine had a visual analogue pain score of 3/10 or less throughout the study. There was a dose-dependent increase in the incidence of itching with intrathecal diamorphine although the incidence of nausea and vomiting was similar between groups. CONCLUSIONS: We found that for elective caesarean section under subarachnoid block with high dose diclofenac, analgesia was optimal with 300 microg of intrathecal diamorphine. Even the highest dose of intrathecal diamorphine did not achieve the Royal College of Anaesthetists postoperative audit target that 90% of patients should have a pain score of no more than 3/10. We believe that this target is too arduous.

Arm and ankle blood pressure during caesarean section.

BACKGROUND: We have previously reported that measurement of non-invasive blood pressure during caesarean section under spinal anaesthesia fails in over 50% of cases. We felt that errors would be less likely if blood pressure could be measured at the ankle as it is immobile during caesarean section. The purpose of our study was to determine whether blood pressure measurement at the ankle was equivalent to the arm. METHOD: Following ethical approval, informed consent was obtained from 30 women scheduled for elective caesarean section. Two non-invasive blood pressure cuffs, one on the upper arm and one on the ankle, were used to measure blood pressures at three timed intervals: before spinal insertion, before surgery and after delivery of the neonate. RESULTS: Using the method of Bland and Altman we found that there was only marginal agreement between the two methods. On eight out of 15 occasions where there was a greater than 20% fall in arm systolic blood pressure, this was not detected at the ankle. CONCLUSION: We cannot recommend the use of the ankle to measure blood pressure during caesarean section.

The formation of polymeric model biomembranes from diacetylenic fatty acids and phospholipids.

Diacetylenic fatty acid monolayers at the air/water interface and multilayers on suitable supports polymerise when exposed to ultraviolet radiation. It has been found that polymerisation still occurs when monolayers are diluted with cholesterol or gramicidin. The rigid, crystalline nature of the films formed makes them useful biomembrane models. Phospholipids made from the fatty acids were less reactive. Multilayers deposited on hydrophobic supports would polymerise but not monolayers on water.

Phospholipid polymers--synthesis and spectral characteristics.

A new approach has been developed for the study of model and natural biomembranes. This involves the cross-linking of diacetylene groups after ultraviolet irradiation. For the study of model biomembranes, pure phospholipids (phosphatidylcholines) have been synthesized containing diacetylene groups in each acyl chain. The physical properties of these lipids have been examined and the conditions under which they polymerise have been determined. Polymerisation occurs when the lipid is in a crystalline phase, either compressed in KBr, dispersed in water (liposomes) or deposited on a suitable support (multilayers). The resultant polymer contains a conjugated backbone and is coloured. The visible spectrum of the phospholipid polymer is sensitive to its environment. Preliminary experiments show that similar polymerisation can be induced in Acholeplasma laidlawii cells grown on diacetylenic fatty acid.

Double-blind comparison of amlodipine and nifedipine retard in the treatment of mild to moderate hypertension.

The efficacy and safety profiles of amlodipine (5-10 mg once daily) and nifedipine retard (20-40 mg twice daily) were compared in 111 hypertensive patients (sitting DBP in 95-115 mmHg) during eight weeks of treatment in a randomised double-blind parallel group study. BP was measured 22-24 hours after the daily dose of amlodipine and 10-12 hours after a dose of nifedipine retard. Baseline sitting BPs of 175/105 mmHg and 168/104 mmHg were significantly reduced (P < 0.05) to 157/93 mmHg and 151/92 mmHg at the end of treatment in response to mean daily doses of amlodipine 7.3 mg and nifedipine retard 58.9 mg. There were no clinically significant changes in heart rate with either treatment. Three patients in the amlodipine group and five patients in the nifedipine retard group could not be considered in analysis. The total numbers of adverse events (considered related or possibly related to treatment) (42 vs. 36) as well as the numbers of patients experiencing such events (22 vs. 22) were similar in the amlodipine and nifedipine retard treated groups, respectively, but with a greater incidence of headaches in response to nifedipine retard and of oedema in response to amlodipine. Five patients in each treatment group discontinued therapy due to such events. Overall the results showed once daily amlodipine as equivalent to twice daily nifedipine retard in the management of mild to moderate hypertension.

Buccal nitroglycerin in congestive cardiac failure: a multicentre study.

One-hundred-and-ninety-two elderly patients with symptoms of congestive cardiac failure, despite therapy with diuretics and inotropic agents, received buccal nitroglycerin as additional medication. They were assessed for up to 6 months. Improvements in symptoms and functional classification were apparent within 14 days, and were maintained for the duration of the study.

Postoperative pain following primary lower limb arthroplasty and enhanced recovery pathway.

INTRODUCTION: Enhanced recovery is a concept that has become increasingly popular for arthroplasty surgery over the last ten years. This study was designed to assess the analgesia requirements, pain levels and time to discharge for patients having primary arthroplasty in the enhanced recovery pathway. METHODS: A multidisciplinary prospective cohort study was carried out between January 2012 and March 2012. Data were collected for patients undergoing primary arthroplasty in one hospital during this time. Details of anaesthesia, local infiltration, additional medications and analgesia were recorded. A visual analogue scale pain score was obtained from each patient at time of mobilisation on days 0, 1, 2 and 3 postoperatively. RESULTS: Ninety-six patients were included in the study. Of these, 34 underwent total hip arthroplasty and 62 total knee arthroplasty (TKA). Pain was the greatest contributor for delayed discharge in TKA patients. The patients who had TKA and did not receive non-steroidal anti-inflammatory drugs (NSAIDs) had significantly higher pain scores (day 0, p<0.01; day 1, p<0.001; day 2, p<0.01) and significantly increased opiate demands compared with those patients who did receive NSAIDs. CONCLUSIONS: There are unacceptably high pain scores in patients undergoing TKA without the use of NSAIDs. There should be focused intervention with this group of patients to improve their pain scores and reduce their length of stay.

Cardiovascular effects of fibrescope-guided nasotracheal intubation.

The cardiovascular effects of fibrescope-guided nasotracheal intubation were compared to those of a control group of patients who were intubated using the Macintosh laryngoscope. The 60 patients studied received a standard anaesthetic technique which included a muscle relaxant and were allocated randomly to one of two groups immediately before tracheal intubation. Systolic and diastolic arterial pressures in the fibreoptic group were significantly lower than in the control group during the first minute after intubation. The maximum increase in diastolic pressure was significantly lower in the fibreoptic group. The heart rate in the fibreoptic group was significantly higher than in the control group during all five minutes after intubation. The maximum increase in heart rate was significantly higher in the fibreoptic group. The cardiovascular responses to fibreoptic nasotracheal intubation under general anaesthesia should not cause undue concern in fit patients, but appropriate measures should be taken to prevent excessive tachycardia in compromised patients.

Analgesia mediated by spinal kappa-opioid receptors.

The results from 44 experiments performed on 13 rats with chronically implanted lumbar subarachnoid catheters are reported. ICI 197 067 produced dose-dependent segmental analgesic effects when measurement of electrical current threshold for pain was used as the nociceptive test. Ten microliters of intrathecal ICI 197 067 (0.06 mg ml-1; 1.5 nmol) caused a significant rise in the current threshold for pain in the tail of 1.56 +/- 0.04 x control (mean +/- SEM) but no significant change in pain threshold in the neck (1.03 +/- 0.03 x control). By contrast, simultaneous measurements of tail-flick latency in these animals revealed no significant rise in pain thresholds using this nociceptive test. Intraperitoneally administered naloxone produced a dose-dependent suppression of the spinally mediated analgesic effect produced by ICI 197 067; the ED50 for this effect was 0.79 mumol kg-1, a value very close to the ED50 for naloxone antagonism of ketocyclazocine spinally mediated analgesia. We conclude that ICI 197 067 produces spinally mediated analgesia by binding to spinal-cord kappa-opioid receptors.