Mammography screening reduces rates of advanced and fatal breast cancers: Results in 549,091 women.

BACKGROUND: It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death. METHODS: Among 549,091 women, covering approximately 30% of the Swedish screening-eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression. RESULTS: Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51-0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66-0.84 [P < .001]). CONCLUSIONS: Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.

Early detection of breast cancer rectifies inequality of breast cancer outcomes.

OBJECTIVES: To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer-specific survival as an outcome. METHODS: We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan-Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression. RESULTS: All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46-55%) to 81% (95% confidence interval 74-85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40-65%) to 74% (95% confidence interval 72-77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77-84%) to 86% (95% confidence interval 83-88%), a considerably narrower range. CONCLUSIONS: Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.

Prevalence of upper and lower airway symptoms: the Skövde population-based study.

CONCLUSION: This study was able to present representative data from Sweden as a whole and illuminates the epidemiological background of symptoms of the upper and lower airways. Current regular smokers, compared with non-smokers, had more problems with nasal blockage, cough and asthma. The relationship between the upper and lower airways was confirmed as regards airway symptoms. BACKGROUND: Epidemiology of common respiratory symptoms is basic information in health care. This study has focused on the prevalence of upper and lower airway symptoms. PATIENTS AND METHODS: A random sample of 1900 age- and gender-stratified adults was recruited from a general population for this study, which included a structured interview about symptoms of nasal secretions and blockage, cough and asthma, and a clinical examination with nasal endoscopy, and peak nasal-inspiratory flow (PNIF). Smoking habits were evaluated by a questionnaire for current and previous smoking. RESULTS: A response rate of 73% was achieved. The prevalence of various symptoms varied between age strata and gender. There was a statistically significant relationship between subjectively experienced nasal blockage and objectively observed nasal congestion. PNIF was negatively related to age and height and was increased in male gender. Smoking was most common among females and related to nasal blockage, cough and asthma, but not to nasal secretions. Significant relationships between the upper and lower airways were found.

Clinical trial design, nasal allergen challenge models, and considerations of relevance to pediatrics, nasal polyposis, and different classes of medication.

Clinical trials in allergic rhinitis present several specific difficulties. In seasonal pollen-related disease, there are variations between subjects in the extent of pollen sensitization, individual variations in exposure to pollen even within a set area because of lifestyle differences, and variations between different areas in pollen counts and weather patterns. Thus, large patient numbers are needed in multicenter trials to account for such variations when the standard endpoint is symptom reporting. Furthermore, a pollen season may be relatively short (eg, lasting 6-8 weeks), and the pollen count is inconsistent during this period. Crossover study designs are thus inappropriate, and trials are usually conducted with a parallel-group design. This further increases the trial sample size as it reduces statistical power. These large patient numbers must be recruited over a very short period. Perennial house dust mite-sensitive allergic rhinitis presents other problems. Although there is less disease variation, it is appreciated that symptoms may be induced by nonallergic as well as allergic mechanisms because of the nasal hyperresponsiveness. The nonallergic symptoms may not be modified by treatments based on allergic disease mechanisms. Thus, symptom outcomes--although relevant to the patient--may not adequately reflect the pharmacologic efficacy of the specific intervention. To control variability and focus on allergic disease mechanisms, nasal allergen challenge has been used in drug development. Single-dose challenges in the laboratory or in a pollen chamber, which allow many volunteers to be studied at the same time, have proven useful in the evaluation of drugs that afford acute symptom relief. However, such challenges incompletely model naturally occurring disease, in which the repeated daily exposure to allergen modifies the mucosal inflammatory cell profile and in particular promotes the epithelial accumulation of effector cells. This alters the response to allergen exposure. To model this, repeated low-dose daily allergen exposure has been used to generate these mucosal changes artificially, and early studies suggest that this may be a more valid model for the evaluation of anti-inflammatory therapy. However, little has been published with this model. Different disease groups are associated with their own specific issues in clinical trials. The pediatric population, in which allergic rhinitis is common, has different requirements for education, quality of life evaluation, and adverse-event monitoring; nasal polyposis, because of the nature of the disease, requires additional means of assessment, such as nasal endoscopy and imaging (eg, computerized tomography scanning), as well as attention to additional outcome measures (eg, the measurement of sense of smell). Within clinical trial design, there are important questions to be considered in relationship to the therapeutic intervention. Should this be given topically or systemically? What are the appropriate timing and frequency of medication? Does the disease itself modify the treatment efficacy, and does combination therapy afford better clinical outcome than single-modality therapy? These issues are discussed, and the influences of current therapies on objective outcome measures in allergic rhinitis are reviewed.

Prevalence of nasal polyps in adults: the Skövde population-based study.

Patients with nasal polyps present repeatedly in otorhinolaryngology practices, but the prevalence of nasal polyps in the general population is not known. Our objective was to investigate the prevalence of nasal polyps in an adult Swedish population in relation to age, gender, asthma, and aspirin intolerance. A random sample of 1,900 inhabitants over the age of 20 years, stratified for age and gender, was drawn from the municipal population register in Skövde, Sweden, in December 2000. The subjects were called to clinical visits that included questions about rhinitis, asthma, and aspirin intolerance and examination by nasal endoscopy. In total, 1,387 volunteers (73% of the sample) were investigated. The sample size was adequate, with a good fit to the whole population. The prevalence of nasal polyps was 2.7% (95% confidence interval, 1.9-3.5), and polyps were more frequent in men (2.2 to 1), the elderly (5% at > or = 60 years of age), and asthmatics. Subjective symptoms of aspirin intolerance were not found to correlate with polyps. Nasal polyps were more common in adults than was stated by the a priori estimate. The Skövde population-based study is considered representative for the Swedish population.

Prevalence of nasal septal perforation: the Skövde population-based study.

BACKGROUND: Patients with nasal septal perforation appear from time to time in Ear, Nose, and Throat (ENT) practices, but the prevalence in a general population is not known. OBJECTIVE: The objective was to investigate the prevalence of nasal septal perforation in an adult Swedish population, and to relate septal perforation to possible risk factors, such as age, gender, diabetes mellitus, nasal polyps, and smoking. METHODS: A random sample of 1,900 inhabitants over the age of 20, stratified for age and gender, was drawn from the municipal population register in Skövde, Sweden, in December 2000. Subjects were called to clinical visits that included questions about diabetes and smoking habits. Nasal endoscopy was performed and, when a perforation was observed, the size was measured. RESULTS: In total, 1,387 volunteers (73% of the sample) were investigated. The sample size was adequate, with a good fit to the whole population. The prevalence of nasal septal perforation was 0.9% [95% CI 0.5-1.6%]. Nasal polyps was a possible risk factor, odds ratio of 11.5 [95% CI 3.0-43.5], but not age, gender, diabetes, or smoking. CONCLUSION: The prevalence of nasal septal perforation was found to be less than 1% in an adult population.

Efficacy and tolerability of budesonide aqueous nasal spray in chronic rhinosinusitis patients.

This study evaluated the efficacy and tolerability of budesonide in an aqueous nasal spray (BANS) in patients with chronic rhinosinusitis. In this double-blind, placebo-controlled, multicentre, parallel-group study, patients (n = 167) with persistent rhinosinusitis symptoms despite 2-weeks' antibiotic treatment were randomised to receive BANS 128 micrograms b.i.d. or placebo for 20 weeks. Morning combined symptom scores (CSS) in patients receiving BANS decreased by a mean of -1.85 (95% CI -2.27, -1.43), versus -1.02 (-1.43, -0.61) in the placebo group (p = 0.005); corresponding values for evening CSS were -1.78 (-2.22, -1.35) and -1.02 (-1.45, -0.60), respectively (p = 0.012). BANS produced significant reductions in nasal congestion and discharge scores, and improved patients' sense of smell (morning only), versus placebo. Peak nasal inspiratory flow (PNIF) increased significantly during BANS treatment. In allergic patients, BANS significantly (p < 0.001) reduced both morning -1.40 (-2.18, -0.62) and evening -1.37 (-2.15, -0.58) CSS from baseline versus placebo, but changes in non-allergic patients (morning: -0.04 [-0.95, 0.87]; evening: 0.14 [-0.81, 1.09]) were not significant. PNIF was significantly (p < 0.01) increased in both allergic and non-allergic patients from baseline versus placebo. BANS is an effective and well-tolerated treatment for chronic rhinosinusitis.

Establishing a model of seasonal allergic rhinitis and demonstrating dose-response to a topical glucocorticosteroid.

BACKGROUND: Symptoms of seasonal allergic rhinitis may vary greatly. Hence, for research purposes, there is a need for disease-like models of allergic rhinitis. In a preliminary study, involving 7 days' challenge with allergen, promising symptom consistency was obtained and dose-response to a glucocorticosteroid could, in part, be demonstrated. OBJECTIVE: To establish this model of seasonal allergic rhinitis and test the hypothesis that mometasone furoate is more potent than budesonide as an antirhinitis drug. METHODS: Thirty-eight patients with seasonal allergic rhinitis received treatment with spray-formulations of placebo, budesonide 64 microg, budesonide 256 microg, and mometasone furoate 200 microg in a double-blind, crossover design. After 3 days' treatment, individualized nasal allergen-challenges were administered daily for 7 days while the treatment continued. Nasal symptoms and peak inspiratory flow (PIF) were recorded. RESULTS: During the last 3 days of allergen challenge without active treatment, consistent around-the-clock symptoms were recorded and recordings during these days were used in the analysis. With few exceptions the active treatments reduced nasal symptoms and improved nasal PIF (P values <0.001 to 0.05). Budesonide caused dose-dependent improvements in evening symptoms, morning nasal PIF, and nasal PIF recorded 10 minutes after allergen-challenge (P values <0.05). Budesonide 256 microg produced greater improvement than mometasone furoate 200 microg for nasal PIF 10 minutes after allergen-challenge (P < 0.05). CONCLUSION: The present allergen challenge method, producing consistent symptoms and nasal PIF data, emerges as a model of seasonal allergic rhinitis well suited for exploring potency and efficacy of drug intervention. The present data do not support the view that mometasone furoate is a more potent antirhinitis drug than budesonide.

The impact of organized mammography service screening on breast carcinoma mortality in seven Swedish counties.

BACKGROUND: The evaluation of organized mammographic service screening programs is a major challenge in public health. In particular, there is a need to evaluate the effect of the screening program on the mortality of breast carcinoma, uncontaminated in the screening epoch by mortality from 1) cases diagnosed in the prescreening period and 2) cases diagnosed among unscreened women (i.e., nonattenders) after the initiation of organized screening. METHODS: In the current study, the authors ascertained breast carcinoma deaths in the prescreening and screening epochs in 7 Swedish counties from tumors diagnosed in these epochs and in the age group 40-69 years in 6 counties and 50-69 years in 1 county. Data regarding deaths were obtained from the Uppsala Regional Oncologic Center in conjunction with the National Cause of Death Register. The total number of women in the eligible age range living in each county was obtained from the annual population data of Statistics Sweden. Detailed screening data were provided by the screening centers in the seven counties, including the number of invited, the number attended, and whether each individual breast carcinoma case was exposed (screen-detected and interval cases combined) or unexposed (not-invited or nonattenders) to mammographic screening. There were 2044 breast carcinoma deaths from 14,092 incident tumors diagnosed in the prescreening and screening epochs, and the total number of person-years was 7.5 million. Data were analyzed using Poisson regression with corrections for self-selection bias and lead-time bias when appropriate. RESULTS: The mortality reduction for breast carcinoma in all 7 counties combined for women actually exposed to screening compared with the prescreening period was 44% (relative risk [RR] = 0.56; 95% confidence interval [95% CI], 0.50-0.62). When all incident tumors were considered, both those exposed and those unexposed to screening combined, counties with > 10 years of screening were found to demonstrate a significant 32% mortality reduction (RR = 0.68; 95% CI, 0.60-0.77) and counties with < or = 10 years of screening showed a significant 18% reduction in breast carcinoma mortality (RR = 0.82; 95% CI, 0.72-0.94) for the screening epoch compared with the prescreening epoch. Within the screening epoch, after adjustment for self-selection bias, a 39% mortality reduction (RR = 0.61; 95%CI, 0.55-0.68) was observed in association with invitation to screening. CONCLUSIONS: Organized service screening in 7 Swedish counties, covering approximately 33% of the population of Sweden, resulted in a 40-45% reduction in breast carcinoma mortality among women actually screened. The policy of offering screening is associated with a mortality reduction in breast carcinoma of 30% in the invited population, exposed and unexposed combined. The results of the current study indicate that the majority of the breast carcinoma mortality reduction is indeed due to the screening.