Incidence of cancer in the general population and in patients with or without atopic dermatitis in the U.K.

BACKGROUND: Atopic dermatitis (AD) affects approximately 20% of children and 1-3% of adults in developed countries. OBJECTIVE: To study the incidence of cancer in patients with AD in the U.K. general population. METHODS: We conducted a follow-up study in the U.K. using The Health Improvement Network (THIN) database. We calculated the incidence rate (IR) of the first occurrence of overall cancer, lymphoma, melanoma and nonmelanoma skin cancer (NMSC) in the general population, in patients with AD and in individuals without AD. In addition we calculated the IR ratio (IRR) of overall cancer and subtypes of cancer in patients with AD vs. those without. RESULTS: The study population included 4,518,131 patients [2,336,230 (51·7%) female]. There were 129,972 subjects [68,688 (52·8%) female] with a diagnosis of cancer (excluding NMSC). The IR (per 10,000 person-years) of cancer (excluding NMSC) was 42·41 [95% confidence interval (CI) 42·18-42·64]; of lymphoma 1·70 (95% CI 1·65-1·74); of skin melanoma 1·71 (95% CI 1·67-1·76) and of NMSC 11·76 (95% CI 11·64-11·88). The age- and sex-adjusted IRR for cancer (excluding NMSC) was 1·49 (95% CI 1·39-1·61); for lymphoma 2·21 (95% CI 1·65-2·98); for melanoma 1·74 (95% CI 1·25-2·41); and for NMSC 1·46 (95% CI 1·27-1·69). CONCLUSIONS: Our results indicate an increased incidence of cancer overall as well as of specific cancer subtypes, including lymphoma, in patients with AD. Further studies are needed to disentangle the effects of treatment for AD from AD itself.

A metaregression analysis of the dose-response effect of aspirin on stroke.

BACKGROUND: We evaluated whether the risk of stroke depends on aspirin dose in patients with a previous transient ischemic attack or stroke. METHODS: We conducted a metaregression analysis of stroke by using published randomized, placebo-controlled trials. We analyzed studies of patients who had recently had a transient ischemic attack or stroke (ie, secondary prevention). We abstracted data on the treatment regimen and stroke. To evaluate the dose-response relationship, we conducted a metaregression analysis of study-specific risk ratios by means of weighted linear regression. RESULTS: Eleven randomized, placebo-controlled trials contributed a total of 5228 patients randomized to aspirin only and 4401 patients randomized to placebo only. The slope of the dose-response curve was virtually flat across a wide range of aspirin doses from 50 to 1500 mg/d (P = .49 for test of slope not =0). Summarizing across studies, aspirin decreases the risk of stroke by about 15% (risk ratio, 0.85;95% confidence interval, 0.77-0.94). CONCLUSIONS: Aspirin reduces the risk of stroke by approximately 15%, and this effect is uniform across aspirin doses from 50 to 1500 mg/d. The lowest effective aspirin dose has not yet been identified, but it could be lower than 50 mg/d.

The effect of adding ipratropium bromide to salbutamol in the treatment of acute asthma: a pooled analysis of three trials.

OBJECTIVE: To assess the effect on FEV1 and clinical outcomes of adding ipratropium bromide to salbutamol in the treatment of acute asthma. METHODS: We conducted a pooled analysis of three randomized double-blinded clinical trials conducted in the United States, Canada, and New Zealand. The studies enrolled 1,064 patients aged 18 to 55 years who presented at the emergency department with acute asthma. Patients were randomized to treatment with a combination of nebulized 2.5 mg salbutamol plus 0.5 mg ipratropium bromide, or 2.5 mg salbutamol alone. Medications were administered at baseline and, in the US study, at 45 min. FEV1 was measured at baseline, 45 min, and 90 min. Patients were followed up for 48 h after hospital discharge for occurrence of asthma exacerbation and hospitalization. RESULTS: Treatment groups were comparable at baseline. Of the 1,064 patients randomized, 1,015 patients (95%) remained in the study for measurement at 45 min, and 961 patients (90%) completed the final measurement at 90 min. Comparison of overall improvement in FEV1 at 45 min indicated a better response for patients receiving combination therapy (mean difference=43 mL, 95% confidence interval [CI]=-20, 107). The distribution of change in FEV1 was skewed by a small number of patients with extreme values (38 of 1,064=3.6%) that may have been due to unreliable lung function testing. Removing these outliers produced a larger and more precise estimate of effect (mean difference=55 mL, 95% CI=2,107). Because the distribution was skewed, we performed nonparametric analyses that showed evidence of a beneficial effect of combination therapy. The difference between median values at 45 min is 40 mL (Wilcoxon p value=0.03). In addition, 4.9% (95% CI=-1%, 11%) more patients in the combination group achieved at least 20% of their potential improvement, as measured by the difference between their baseline FEV1 and their predicted FEV1. Patients receiving combination therapy had lower risk for each of three clinical outcomes: the need for additional treatment (relative risk [RR]=0.92, 95% CI=0.84, 1.0), risk of asthma exacerbation (RR=0.84, 95% CI=0.67, 1.04), and risk of hospitalization (RR=0.80, 95% CI=0.61, 1.06). CONCLUSION: Adding ipratropium bromide to salbutamol in the treatment of acute asthma produces a small improvement in lung function, and reduces the risk of the need for additional treatment, subsequent asthma exacerbations, and hospitalizations. These apparent benefits of adding ipratropium bromide were independent of the amount of beta-agonist that had been used earlier in the attack, and possibly related to a recent upper respiratory tract infection. Confirmatory studies are needed, especially for clinical outcomes.

Risk of emergency care, hospitalization, and ICU stays for acute asthma among recipients of salmeterol.

We used automated health insurance claims records of a New England insurer to assess the relation between salmeterol and severe nonfatal asthma. We identified 61,712 members who received a beta-agonist from January 1, 1993 to August 31, 1995, including 2, 708 recipients of salmeterol. Compared with recipients of other beta-agonists, future salmeterol recipients had higher rates of asthma hospitalization and dispensings of asthma medications during the year before they received salmeterol. We selected as a comparison group 3,825 recipients of sustained-release theophylline. We defined a baseline period as the year before the start of the follow-up period, and we characterized patients according to age, sex, calendar period, presence of baseline hospitalizations for asthma, presence of chronic obstructive pulmonary disease (COPD), and baseline dispensings of asthma medications. After adjusting for baseline factors, incidence rates of severe asthma in the salmeterol group were not elevated for emergency care (rate ratio estimate [RR] = 0.69, 95% confidence intervals [CI] = 0.42, 1.11), hospitalization (RR = 1.09, 95% CI = 0.60, 1.98), or intensive care unit (ICU) stays (RR = 0.81, 95% CI = 0.25, 2.62). We conclude that salmeterol was prescribed preferentially to high-risk patients and, after adjusting for baseline risk, salmeterol recipients did not have a greater risk than theophylline recipients of severe nonfatal asthma.