Kathleen Bennett

Beta Blockers and Breast Cancer Mortality: A Population- Based Study

PURPOSE Preclinical studies have demonstrated that antagonism of β₂-adrenergic signaling inhibits several pathways necessary for breast tumor progression and metastasis. A series of population-based observational studies were conducted to examine associations between beta blocker use and breast tumor characteristics at diagnosis or breast cancer-specific mortality. PATIENTS AND METHODS Linked national cancer registry and prescription dispensing data were used to identify women with a diagnosis of stage I to IV invasive breast cancer between January 1, 2001, and December 31, 2006. Women taking propranolol (β₁/β₂ antagonist; n = 70) or atenolol (β₁ antagonist; n = 525), in the year before breast cancer diagnosis were matched (1:2) to women not taking a beta blocker (n = 4,738). Associations between use of propranolol or atenolol and risk of local tumor invasion at diagnosis (T4 tumor), nodal or metastatic involvement at diagnosis (N2/N3/M1 tumor), and time to breast cancer-specific mortality were assessed. RESULTS Propranolol users were significantly less likely to present with a T4 (odds ratio [OR], 0.24, 95% CI, 0.07 to 0.85) or N2/N3/M1 (OR, 0.20; 95% CI, 0.04 to 0.88) tumor compared with matched nonusers. The cumulative probability of breast cancer-specific mortality was significantly lower for propranolol users compared with matched nonusers (hazard ratio, 0.19; 95% CI, 0.06 to 0.60). There was no difference in T4 or N2/N3/M1 tumor incidence or breast cancer-specific mortality between atenolol users and matched nonusers. CONCLUSION The results provide evidence in humans to support preclinical observations suggesting that inhibiting the β₂-adrenergic signaling pathway can reduce breast cancer progression and mortality.

Early discontinuation of tamoxifen: a lesson for oncologists.

Five years of treatment provides the optimum duration of tamoxifen therapy for the prevention of breast cancer recurrence and mortality. Durations of adjuvant tamoxifen therapy less than 5 years are associated with poorer outcomes for breast cancer patients. The purpose of the study was to assess rates of tamoxifen nonpersistence (early discontinuation) in women aged 35 years or older using prescription refill data from a national prescribing database.

Modelling the decreasing coronary heart disease mortality in Sweden between 1986 and 2002.

AIMS Coronary heart disease (CHD) mortality rates have been falling in Sweden since the 1980s. We used the previously validated IMPACT CHD model to examine how much of the mortality decrease in Sweden between 1986 and 2002 could be attributed to medical and surgical treatments, and how much to changes in cardiovascular risk factors. METHODS AND RESULTS The IMPACT mortality model was used to combine and analyse data on uptake and effectiveness of cardiological treatments and risk factor trends in Sweden. The main data sources were official statistics, national quality of care registers, published trials and meta-analyses, and national population surveys. Between 1986 and 2002, CHD mortality rates in Sweden decreased by 53.4% in men and 52.0% in women aged 25-84 years. This resulted in 13 180 fewer deaths in 2002. Approximately 36% of this decrease was attributed to treatments in individuals and 55% to population risk factor reductions. Adverse trends were seen for diabetes and overweight. CONCLUSION More than half of the substantial CHD mortality decrease in Sweden between 1986 and 2002 was attributable to reductions in major risk factors, mainly a large decrease in total serum cholesterol. These findings emphasize the value of a comprehensive strategy that promotes primary prevention and evidence-based medical treatments, especially secondary prevention.

Relationship between the intensity of physical activity, inactivity, cardiorespiratory fitness and body composition in 7–10-year-old Dublin children

Objective: To investigate the relationships between the time spent in specific intensities of activity and inactivity, cardiorespiratory fitness and body composition in children. Methods: A cross-sectional study was conducted in a random sample of schools. Height, weight and waist circumference were measured in 224 children aged 7–10 years. Cardiorespiratory fitness was estimated by the 20 m multistage running test, and physical activity was measured over 4 days by the RT3 (a triaxial accelerometer). Time each day spent in moderate and vigorous intensities of activity was calculated. Results: Twelve schools agreed to participate in the study. Body composition and fitness data were obtained for 224 children and activity data for 152 children. Boys were found to take part in about twice as much vigorous and hard activity as girls (mean (95% confidence interval) 64.3 (53.2 to 75.4) min in boys compared with 37 (33.1 to 40.9) min in girls; p<0.001). In boys there was significant difference between those defined as normal, overweight and obese in the time spent in vigorous activity (p<0.05), but no such difference was found in girls. A significant negative correlation between waist circumference and time spent in vigorous activity (r = –0.31, p<0.05) was found in boys but not in girls. Time spent sedentary was positively correlated with waist circumference in boys (r = 0.33, p<0.01) but not in girls. In both boys and girls there were significant negative correlations between fitness and both body mass index (r = –0.274, p<0.001) and waist circumference (boys: r = –0.503, p<0.01; girls: r = –0.286, p<0.01). Conclusion: In boys, body composition was inversely related to fitness and to vigorous activity and was positively related to inactivity. In girls, body composition was related to fitness but not to specific components of physical activity.

Assessment of arterial stiffness in hypertension: comparison of oscillometric (Arteriograph), piezoelectronic (Complior) and tonometric (SphygmoCor) techniques.

Background Arterial stiffness, measured as aortic pulse wave velocity (PWV), and wave reflection, measured as augmentation index (AIx), are independent predictors for total and cardiovascular morbidity and mortality. The aim of this study was to compare a new device, based on oscillometric pressure curves (Arteriograph), which simultaneously measures PWV and AIx, with standard techniques for measuring PWV (Complior) and AIx (SphygmoCor) in untreated hypertensive patients. Methods We compared PWV and AIx measured using the Arteriograph with corresponding Complior and SphygmoCor measurements in 254 untreated hypertensive patients, age 48 ± 14 years (mean ± SD, range 17–85 years). Results Arteriograph PWV and AIx were closely related with Complior (r = 0.60, P < 0.001) and SphygmoCor (r = 0.89, P < 0.001), respectively. Using stepwise regression analysis, the independent determinants of Arteriograph PWV were age, mean arterial pressure, heart rate and sex (r2 = 0.44, P < 0.0001) and for AIx were age, weight, mean arterial pressure, heart rate and sex (r2 = 0.65, P < 0.0001). The bias between the different techniques was determined by age and sex for PWV and age, body weight, sex, heart rate and mean arterial pressure for AIx. Bland–Altman plots showed that although the techniques were closely related, the limits of agreement were wide. Conclusion Although Arteriograph values and the determinants of PWV and AIx are in close agreement with corresponding parameters obtained by Complior and SphygmoCor, respectively, the techniques are not interchangeable.

Explaining the recent decrease in coronary heart disease mortality rates in Ireland, 1985–2000

Study objectives: To examine the proportion of the recent decline in coronary heart disease (CHD) deaths in Ireland attributable to (a) “evidence based” medical and surgical treatments, and (b) changes in major cardiovascular risk factors. Design setting: IMPACT, a previously validated model, was used to combine and analyse data on the use and effectiveness of specific cardiology treatments and risk factor trends, stratified by age and sex. The main data sources were published trials and meta-analyses, official statistics, clinical audits, and observational studies. Results: Between 1985 and 2000, CHD mortality rates in Ireland fell by 47% in those aged 25–84. Some 43.6% of the observed decrease in mortality was attributed to treatment effects and 48.1% to favourable population risk factor trends; specifically declining smoking prevalence (25.6%), mean cholesterol concentrations (30.2%), and blood pressure levels (6.0%), but offset by increases in adverse population trends related to obesity, diabetes, and inactivity (−13.8%). Conclusions: The results emphasise the importance of a comprehensive strategy that maximises population coverage of effective treatments, and that actively promotes primary prevention, particularly tobacco control and a cardioprotective diet.

Sputum Candida albicans Presages FEV1 Decline and Hospital-Treated Exacerbations in Cystic Fibrosis

BACKGROUND The role of Candida albicans in the cystic fibrosis (CF) airway is underexplored. Considered a colonizer, few question its pathogenic potential despite high isolation frequencies from sputum culture. We evaluated the frequency and identified the strongest predictors of C albicans colonization in CF. Independent associations of colonization with clinical outcomes were determined, and the longitudinal effects of C albicans acquisition on BMI and FEV₁ were evaluated. METHODS A prospective observational study of 89 patients with CF was performed (3,916 sputum samples over 11 years). Frequency of C albicans growth in sputum allowed classification of the cohort into colonizers and noncolonizers. BMI, FEV₁, hospital-treated exacerbations, and other clinical parameters were followed throughout the study to determine association with colonization status. Multivariate regression determined the strongest predictors of colonization and for clinical effects after adjustment for confounders. Repeated-measures analysis of variance assessed the longitudinal effect of colonization on BMI and FEV₁. RESULTS Colonization with C albicans was frequent (49.4%) and best predicted by pancreatic insufficiency (P = .014), osteopenia (P = .03), and cocolonization with Pseudomonas species (P = .002). C albicans colonization significantly predicted hospital-treated exacerbations (P = .004) after adjustment for confounders. Exacerbation rate significantly increased in patients with chronic or intermittent colonizations following first acquisition of C albicans. Colonization accelerated rates of decline for BMI (P < .0001) and FEV₁ (P < .001). CONCLUSION Airway colonization with C albicans presaged a greater rate of FEV₁ decline and hospital-treated exacerbations in CF.

Decline in mortality from coronary heart disease in Poland after socioeconomic transformation: modelling study.

Objectives To examine how much of the observed rapid decrease in mortality from coronary heart disease in Poland after the political, social, and economic transformation in the early 1990s could be explained by the use of medical and surgical treatments and how much by changes in cardiovascular risk factors. Design A modelling study. Setting Sources of data included controlled trials and meta-analyses, national surveys, and official statistics. Participants Population of adults aged 25-74 in Poland in 1991-2005. Main outcome measures Number of deaths prevented or postponed in 2005 attributable to specific treatments for coronary heart disease and changes in risk factors. A previously validated epidemiological model for coronary heart disease was used to combine and analyse data on the uptake and effectiveness of specific cardiac treatments and changes in risk factors. The observed fall in deaths from coronary heart disease from 1991 to 2005 was then partitioned among specific treatments and risk factor changes. Results From 1991 to 2005, the death rate from coronary heart disease in Poland halved, resulting in 26 200 fewer coronary deaths in 2005 in people aged 25-74. About 37% (minimum estimate 13%, maximum estimate 77%) of this decrease was attributable to treatments, including treatments for heart failure (12%), initial treatments for acute coronary syndrome (9%), secondary prevention treatments after myocardial infarction or revascularisation (7%), chronic angina treatments (3%), and other treatments (6%). About 54% of the fall was attributed to changes in risk factors (minimum estimate 41%, maximum estimate 65%), mainly reductions in total cholesterol concentration (39%) and an increase in leisuretime physical activity (10%); however, these were partially offset by increases in body mass index (−4%) and prevalence of diabetes (−2%). Blood pressure fell in women, explaining about 29% of their decrease in mortality, but rose in men generating a negative influence (−8%). About 15% of the observed decrease in mortality was attributable to reduced smoking in men but was negligible in women. Conclusions Over half of the recent fall in mortality from coronary heart disease in Poland can be attributed to reductions in major risk factors and about one third to evidence based medical treatments.

An improved medical admissions risk system using multivariable fractional polynomial logistic regression modelling

AIM To develop and validate an in-hospital mortality risk prediction tool for unselected acutely ill medical patients using routinely collected physiological and laboratory data. DESIGN Analysis of all emergency medical patients admitted to St Jamess Hospital (SJH), Dublin, between 1 January 2002 and 31 December 2007. Validation using a dataset of acute medical admissions from Nenagh Hospital 2000-04. METHODS Using routinely collected vital signs and laboratory findings, a composite 5-day in-hospital mortality risk score, designated medical admissions risk system (MARS), was developed using an iterative approach involving logistic regression and multivariable fractional polynomials. Results are presented as area under receiver operating characteristics curves (AUROC) as well as Hosmer and Lemeshow goodness-of-fit statistics. RESULTS A total of 10 712 and 3597 unique patients were admitted to SJH and Nenagh Hospital, respectively. The final score included nine variables [age, heart rate, mean arterial pressure, respiratory rate, temperature, urea, potassium (K), haematocrit and white cell count]. The AUROC for 5-day in-hospital mortality was 0.93 [95% confidence interval (CI) 0.92-0.94] for the SJH cohort (Hosmer and Lemeshow test, P = 0.32) and 0.92 (95% CI 0.90-0.94) for the external Nenagh hospital validation cohort (Hosmer and Lemeshow test, P = 0.28). CONCLUSION In-hospital mortality estimation using only routinely collected emergency department admission data is possible in unselected acute medical patients using the MARS system. Such a score applied to acute medical patients at the time of admission, could assist senior clinical decision makers in promptly and accurately focusing limited clinical resources. Further studies validating the impact of this model on clinical outcomes are warranted.

Explaining the Decrease in Coronary Heart Disease Mortality in Italy Between 1980 and 2000

OBJECTIVES We examined the extent to which the decrease in coronary heart disease (CHD) mortality rates in Italy could be explained by changes in cardiovascular risk factors versus the use of medical and surgical treatments. METHODS We used a validated model to combine data on changes in risk factors and uptake and effectiveness of cardiac treatments among adult men and women in Italy between 1980 and 2000. Data sources included results of published trials, meta-analyses, official statistics, longitudinal studies, and national surveys. The difference between observed and expected CHD deaths in 2000 was partitioned among treatments and risk factors. RESULTS From 1980 to 2000, the age-adjusted CHD mortality rate in Italy fell among persons aged 25 to 84 years, resulting in 42 930 fewer CHD deaths in 2000. Approximately 40% of this decrease was attributed to treatments and 55% to changes in risk factors. CONCLUSIONS Over half of the CHD mortality fall in Italy between 1980 and 2000 was attributable to reductions in major risk factors, mainly cholesterol and blood pressure, and less than half to evidence-based medical therapies. These results are becoming increasingly important, both for understanding past trends and for planning future prevention and treatment strategies.