Treatment of migraine with triptans is highly effective, although cost considerations may prompt a change in therapy. This retrospective database analysis of 3196 patients with migraine, established on sumatriptan therapy, found that 54% of the 292 experiencing a triptan switch returned to sumatriptan within 15 months, suggesting that the alternative was less acceptable. Excluding patients with unusually high use of triptans (> or = 208 tablets/year), switching therapy resulted in a significant increase of pounds sterling 53/patient in total costs, compared with patients continuing on sumatriptan (p = 0.014). Cost savings (pounds sterling 17/patient over 15 months) were observed only among the 41% of patients in whom the initial switch was successful and did not result in a further switch or return to sumatriptan. Among patients who were relatively low cost initially, switching resulted in increased costs, irrespective of the outcome. This study suggests that there is no economic justification for switching from sumatriptan to another triptan.

Objectives To determine whether preoperative dexamethasone reduces postoperative vomiting in patients undergoing elective bowel surgery and whether it is associated with other measurable benefits during recovery from surgery, including quicker return to oral diet and reduced length of stay. Design Pragmatic two arm parallel group randomised trial with blinded postoperative care and outcome assessment. Setting 45 UK hospitals. Participants 1350 patients aged 18 or over undergoing elective open or laparoscopic bowel surgery for malignant or benign pathology. Interventions Addition of a single dose of 8 mg intravenous dexamethasone at induction of anaesthesia compared with standard care. Main outcome measures Primary outcome: reported vomiting within 24 hours reported by patient or clinician. Secondary outcomes: vomiting with 72 and 120 hours reported by patient or clinician; use of antiemetics and postoperative nausea and vomiting at 24, 72, and 120 hours rated by patient; fatigue and quality of life at 120 hours or discharge and at 30 days; time to return to fluid and food intake; length of hospital stay; adverse events. Results 1350 participants were recruited and randomly allocated to additional dexamethasone (n=674) or standard care (n=676) at induction of anaesthesia. Vomiting within 24 hours of surgery occurred in 172 (25.5%) participants in the dexamethasone arm and 223 (33.0%) allocated standard care (number needed to treat (NNT) 13, 95% confidence interval 5 to 22; P=0.003). Additional postoperative antiemetics were given (on demand) to 265 (39.3%) participants allocated dexamethasone and 351 (51.9%) allocated standard care (NNT 8, 5 to 11; P<0.001). Reduction in on demand antiemetics remained up to 72 hours. There was no increase in complications. Conclusions Addition of a single dose of 8 mg intravenous dexamethasone at induction of anaesthesia significantly reduces both the incidence of postoperative nausea and vomiting at 24 hours and the need for rescue antiemetics for up to 72 hours in patients undergoing large and small bowel surgery, with no increase in adverse events. Trial registration EudraCT (2010-022894-32) and ISRCTN (ISRCTN21973627).

This study was designed to determine whether the benefit of adding salmeterol was superior to doubling the dose of fluticasone propionate (FP) over 6 months, compared to a control group who remained on a lower dose of FP. The multi-centre, double-blind, parallel group study involved 496 symptomatic asthmatic patients with a history of exacerbations on 500-800 micrograms (microg) inhaled corticosteroids (ICS) twice daily (b.d.) in a broadly representative group of 100 hospitals and general practices in six countries. Two doses of FP--250 microg b.d. (FP250) or 500 microg b.d. (FP500)--were compared with the lower dose of FP plus a long-acting beta2-agonist, salmeterol 50 microg b.d. (SM/FP250). Patients symptomatic on the run-in dose of FP250 alone formed the control group in the treatment period. Over 6 months, SM/FP250 significantly improved mean morning peak expiratory flow rates (amPEF) by 42.1 l/min, more than twice the improvement achieved with either dose of FP alone. SM/FP250 also resulted in more symptom-free days and nights (P < 0.002) and days and nights with no relief medication (P < 0.001). The number of severe exacerbations was low: 3, 6 and 8% in the SM/FP250, low- and high-dose FP groups, respectively. This study confirms that adding salmeterol to low-dose inhaled FP offers greater improvements than either maintaining or doubling the dose of FP. Significant benefit was gained from adding salmeterol in a group of patients who appeared to have been at the top of their steroid dose-response curve receiving FP250. There was no evidence of tolerance and a low incidence of exacerbations in all treatment groups.

When compared against capecitabine alone, the addition of lapatinib has a cost-effectiveness ratio exceeding the threshold normally used by NICE. Compared with T+C, L+C is dominant in the base case and approximately equally likely to be cost-effective in probabilistic sensitivity analyses over a wide range of threshold values.

SUMMARY Renal resistance vessels of the mature spontaneously hypertensive rat (SHR) exhibit an increased reactivity to exogenous norepinephrine, but a normal response to renal nerve stimulation. This difference could be due either to depression of the exocytotic process or to accelerated disposition of the released transmitter. We compared the overflow of norepinephrine in isolated perfused kidneys from adult SHR and normotensive rats. After previous incubation with *H-norepinephrine, renal nerve stimulation caused smaller increases in the overflow of intact tritlated transmitter and its metabolites in kidneys from SHR than in those from normotensive controls. A similar difference was found when the amounts of endogenous norepinephrine were measured radioenzyraatlcally. The tissue content of norepinephrine was comparable in kidneys from both hypertensive and normotensive animals. The uptake of * H-norepinephrine was similar in the kidneys from SHR and normotensive controls; cocaine caused a comparable depression of the 'H-uptake in both groups. These data indicate that in the adult SHR the exocytotic release of norepinephrine is depressed, which then explains the normal vasoconstrictor response to renal nerve stimulation despite the increased responsiveness of the vascular smooth muscle cells to norepinephrine. IN the isolated Tyrode-perfused kidney of the young spontaneously hypertensive rat (SHR), the vasoconstrictor response to periarterial nerve stimulation is larger than that observed in kidneys from normotensive control animals, at a time when the responsiveness to exogenous norepinephrine is comparable in both groups; the greater response to nerve stimulation is paralleled by a greater than normal overflow of endogenous norepinephrine. "' These observations demonstrate that at the early stages of hypertension, the adrenergic nerve endings release more transmitter in the SHR than in normotensive rats. Isolated Perfused Kidney PreparationRats were anesthetized with pentobarbitone-sodium (50 mg/kg, i.p.) and the abdomen opened by midline incision. The right renal artery, the left spermatic artery, and the left suprarenal artery were ligated. A cannula was inserted into the aorta rostral to the renal arteries and positioned with its tip adjacent to the left renal artery. The cannula was secured by a ligature, and the aorta caudal to the left renal artery was tied off and cut. The left kidney and cannulated segment of the aorta were removed from the animal and placed in a chamber containing Tyrode's solution at 37°C. This procedure interrupted the blood supply to the kidney for 15 to 30 seconds while the cannula was inserted, and before perfusion with Tyrode's solution was commenced.The isolated kidney was perfused with Tyrode's solution (37°C), using a constant flow roller pump (Gilson, Minipuls II, Middleton, Wisconsin). The perfusion rate was set at 6.2 ml/min; earlier work has shown that this rate ensures optimal perfusion conditions for the kidney of both normotensive and hypertensive rats.*-7 ' 10 Ren...