The association between inhaled fenoterol and death from asthma has been investigated further by studying 112 asthma deaths (cases) during 1981-7 in patients aged 5-45 years who had been admitted to a major hospital for asthma during the 12 months before death. Two age matched control groups were chosen.Control group A comprised 427 patients who had been admitted to hospital for asthma during the calendar year that the corresponding death occurred and who had also had a previous admission for asthma in the previous 12 months. Control group B comprised 448 patients admitted to hospital for asthma during the calendar year in which the admission of the corresponding case occurred. The inhaled fenoterol odds ratio was 2X 11 (95% confidence interval (CI) 1P37-3-23, p < 001) when group A was used as the control (the approach used in previous studies), and 2-66 (95% tI 1-744-06, p < 001) with group B as the control (the approach recommended by critics of previous studies). Markers of chronic asthma severity were associated with asthma death when control group B was used, but not when control group A was used (which indicates that these markers were indirectly matched for when control group A was used). Information was also collected on various markers of acute asthma severity and prescription of psychotropic drugs, but it was found that these were not important confounders. These findings address the major criticisms of previous case-control studies of this issue, and add support to the hypothesis that inhaled fenoterol increases the risk of death in patients with severe asthma.

A previous New Zealand case-control study of asthma deaths in the 5-45 year age group during 1981-3 found that prescription of fenoterol (by metered dose inhaler) was associated with an increased risk of death in patients with severe asthma. One major criticism of this study was that drug data for the cases and controls came from different sources. A new case-control design has been used to evaluate the same hypothesis, with a different set of asthma deaths, the same source for drug information being used for both cases and controls. This depended on identifying deaths from asthma during 1977-81 from national mortality records, and ascertaining which patients from those who died had been admitted to a major hospital for asthma during the 12 months before death. The study was confined to this subgroup, which accounted for about 20% of all asthma deaths in the areas served by a major hospital. For each of the eligible patients who died four age matched controls were selected from patients admitted to hospital for asthma during the year that the death occurred who had also had an admission for asthma in the previous 12 months. For the 58 cases and 227 control subjects information on prescribed drugs was collected from the hospital records relating to the previous admission. The odds ratio of asthma death in patients prescribed inhaled fenoterol was 1-99 (95% confidence interval 112-3-55, p = 0 02). As in the previous study, subgroups defined by markers of chronic asthma severity were also considered. The inhaled fenoterol odds ratio was 2-98 (95% CI 1-15-7 70, p = 0 02) in patients prescribed three or more categories of asthma drugs, 3-91 (95% CI 179-8 54, p < 0-01) in patients with a previous admission for asthma in the past 12 months, and 5 83 (95% CI 1-62-21-0, p = 0-01) in patients prescribed oral corticosteroids at the time of admission. In patients with the most severe asthma (defined by a previous admission for asthma during the past 12 months and prescribed oral corticosteroids at time of admission) the inhaled fenoterol odds ratio was 9-82 (95% CI 2-23-43 4, p < 0 01). These findings add further support to the hypothesis that inhaled fenoterol increases the risk of death in patients with severe asthma.

To assess the efficacy and tolerability of lamotrigine in pain associated with diabetic neuropathy, two replicate randomized, double-blind, placebo-controlled studies were conducted. Patients (n=360 per study) with painful diabetic neuropathy were randomized to receive lamotrigine 200, 300, or 400 mg daily or placebo during the 19-week treatment phase, including a 7-week dose-escalation phase and a 12-week, fixed-dose maintenance phase. The mean reduction in pain-intensity score from baseline to week 19 (primary endpoint) was greater (p< or = 0.05) in patients receiving lamotrigine 400 mg than placebo in Study 2 (observed scores, -2.7 versus -1.6 on a 0- to 10-point scale). This finding was not replicated in Study 1. Lamotrigine 200 and 300 mg did not significantly differ from placebo at week 19 in either study. Lamotrigine 300 and 400 mg were only occasionally more effective than placebo for secondary efficacy endpoints. The 200-mg dose did not separate from placebo. In a post hoc analysis of pooled data including only patients who reached their target dose, lamotrigine 400 mg conferred greater (p0.05) mean reduction in pain-intensity score from baseline to week 19 than placebo (-2.5 for 300 mg and -2.7 for 400mg versus -2.0 for placebo). Adverse events were reported in 71-82% of lamotrigine-treated patients compared with 63-70% of placebo-treated patients. The most common adverse events with lamotrigine were headache and rash. Compared with placebo, lamotrigine (300 and 400 mg daily) was inconsistently effective for pain associated with diabetic neuropathy but was generally safe and well tolerated.

Background: Tonsillectomy is one of the most commonly performed procedures in otolaryngology. Pain is a significant aspect of post-operative patient morbidity. The use of local anaesthetic, by infiltration or topical application, has been advocated as a way of reducing post-operative pain. Objectives: To review the current evidence for the use of local anaesthetic as a means of reducing post-tonsillectomy pain and reducing supplemental analgesic requirements. Type of review: A systematic review of the literature pertaining to the use of local anaesthetic agents for post-tonsillectomy pain and meta-analysis of randomised control trials assessing pain scores. Search strategy: Systematic literature searches of MEDLINE (1952MEDLINE ( -2008, EMBASE (1974EMBASE ( -2008 and the Cochrane Central Register of Controlled Trials. Evaluation method: Review of all randomised controlled trials by two authors and grading of articles for quality.