Somatic Mosaic Chromosomal Alterations and Death of Cardiovascular Disease Causes among Cancer Survivors.

BACKGROUND: Cancer survivors are at an increased risk of cardiovascular disease (CVD) compared with the general population. We sought to evaluate the impact of mosaic chromosomal alterations (mCA) on death of CVD causes, coronary artery disease (CAD) causes, and of any cause in patients with a cancer diagnosis. METHODS: The study was a prospective cohort analysis of 48,919 UK Biobank participants with a cancer diagnosis. mCAs were characterized using DNA genotyping array intensity data and long-range chromosomal phase inference. Multivariable Cox regression models were used to ascertain the associations of mCAs. Exploratory endpoints included various incident cardiovascular phenotypes. RESULTS: Overall, 10,070 individuals (20.6%) carried ≥ 1 mCA clone. In adjusted analyses, mCA was associated with an increased risk of death of CAD causes [HR, 1.37; 95% confidence interval (CI), 1.09-1.71; P = 0.006]. In sub-analyses, we found that carriers of mCAs diagnosed with kidney cancer had an increased risk of death of CVD causes (HR, 2.03; 95% CI, 1.11-3.72; P = 0.022) and CAD causes (HR, 3.57; 95% CI, 1.44-8.84; P = 0.006). Women diagnosed with breast cancer who carried a mCA also had a higher risk of death of CAD causes (HR, 2.46; 95% CI, 1.23-4.92; P = 0.011). CONCLUSIONS: Among cancer survivors, carriers of any mCA are at an increased risk of CAD death compared with noncarriers. Mechanistic studies should be considered to better ascertain the biological mechanisms underneath the observed associations between mCAs and cardiovascular events for specific cancer types. IMPACT: There may be clinical relevance in considering mCAs in patients diagnosed with cancer and undergoing treatment.

Psychological distress, social support, and use of outpatient care among adult men and women with coronary artery disease or other non-cardiovascular chronic disease.

OBJECTIVES: Psychological distress, as defined by elevations in symptoms of depression, anxiety, and/or perceived stress, is frequent in patients with chronic diseases, such as coronary artery disease (CAD). While psychological distress is known to impact disease outcomes, less is known about its influence on health care utilization, or on the factors that may modify these relationships. This prospective study examined whether 1) psychological distress predicts greater use of outpatient care services over a period of up to eight years in middle-aged to older individuals with CAD or other non-cardiovascular chronic diseases; 2) this relationship differs according to sex, presence of CAD, and/or social support. METHODS: Men and women (N = 1236; aged 60.85 ± 6.95 years) with and without CAD completed validated questionnaires on symptoms of depression, anxiety, perceived stress, and social support. Number of medical outpatient visits was obtained from the Régie de l'assurance maladie du Québec. Analyses included bivariate correlations, hierarchical regressions, and moderation analyses, controlling for sociodemographic and lifestyle variables. RESULTS: Psychological distress, social support, and yearly outpatient visits were significantly correlated (ps < 0.05). In regression analyses, only depressive symptoms were associated with significantly greater use of outpatient care (b = 0.048, p = .004), particularly among CAD patients (b = 0.085, p < .001). Neither sex nor social support moderated this relation. CONCLUSION: Depression predicted greater outpatient visits in patients with chronic disease, especially CAD patients. More research is needed to determine whether psychosocial interventions may have an impact on health care utilization.

Comparison of the adherence and persistence to inhaled corticosteroids among adult patients with public and private drug insurance plans.

BACKGROUND: Despite important differences in reimbursement procedures between private and public drug insurance plans in Quebec (Canada), no study has evaluated the impact of the type of drug insurance on the use of essential medications such as inhaled corticosteroids (ICS). The lack of data might be attributable, at least in part, to the absence of a provincial medication database for patients with private drug insurance. OBJECTIVES: To compare patient's adherence and persistence to ICS between Quebec residents (Canada) with private and public drug insurance. METHODS: A matched cohort design with patients selected from the database of the Régie de l'assurance maladie du Québec (RAMQ) and from reMed, a database that we have put in place for Quebec residents covered by a private drug insurance, was used. ICS users with private drug insurance were selected from reMed between 2008 and 2010 and matched to ICS users with public drug insurance selected from the RAMQ database. Patient's adherence, measured with the proportion of prescribed days covered (PPDC) and persistence over one year, was compared between patients privately and publicly insured using linear regression and Cox regression models. RESULTS: This study included 330 and 1,109 ICS users with private and public drug insurance, respectively. Patients privately insured were significantly less adherent than patients publicly insured (adjusted mean difference of PPDC: -9.7%; 95% CI: -13.2% to -6.5%). Moreover, patients privately insured were found to be 52% more likely to stop ICS during the first year than patients publicly insured (adjusted HR=1.5; 95% CI: 1.2 to 2.0). CONCLUSIONS: Although adherence and persistence were rather low in both groups, patients with public drug insurance appeared to have greater adherence and persistence to ICS than patients with private drug insurance. Differences in reimbursement policies might explain the observed differences.

Effects of inhaled corticosteroids in monotherapy or combined with long-acting {beta}2-agonists on mortality among patients with chronic obstructive pulmonary disease.

BACKGROUND: The benefits of inhaled corticosteroids (ICS) in reducing the mortality related to chronic obstructive pulmonary disease (COPD) are controversial. OBJECTIVE: To estimate whether ICS in monotherapy or in combination with long-acting beta(2)-agonists (LABA) reduces the mortality rate among COPD patients compared to those treated with LABA monotherapy. METHODS: Using data from the Canadian province of Quebec's health administrative databases, a nested case-control study was conducted. A cohort of COPD patients aged 50 years and over between 1996 and 2000 was initially formed. Patients were included if they filled at least 6 prescriptions of an inhaled bronchodilator, received at least 1 medical service for COPD, and did not receive any diagnosis of asthma over a 12-month period. For each case of death identified in the cohort, up to 37 controls were time matched. For cases and controls, the exposure to ICS and LABA was assessed within the 3 months prior to the date of death for cases and date of selection for controls. Adjusted mortality rate ratios were estimated by conditional logistic regression comparing patients using ICS monotherapy or ICS/LABA combination therapy with patients using LABA monotherapy. RESULTS: This study included 5996 cases of death and 54,750 controls. The mortality rates were found to be lower among users of ICS monotherapy than users of LABA monotherapy (OR 0.69; 95% CI 0.53 to 0.88) and lower among users of an ICS/LABA combination than users of LABA monotherapy (OR 0.73; 95% CI 0.56 to 0.96). No significant differences were observed between users of ICS/LABA combination therapy and users of ICS monotherapy (OR 1.07; 95% CI 0.93 to 1.23). CONCLUSIONS: ICS were found to be associated with a reduction in mortality rate when compared to LABA among patients with COPD. However, the ICS/LABA combination therapy did not provide any additional benefit on mortality when compared to ICS monotherapy.

Effect of theophylline on the rate of moderate to severe exacerbations among patients with chronic obstructive pulmonary disease.

AIM: To determine the effectiveness of theophyllines in real clinical practice on moderate to severe exacerbations. METHODS: A cohort of 36,492 chronic obstructive pulmonary disease (COPD) patients aged > or =50 years was reconstructed from the health administrative databases of the province of Quebec, Canada, between 1 January 1995 and 31 December 2002 to compare users of theophyllines with users of inhaled corticosteroids (ICS) and users of long-acting beta(2)-agonists (LABA) on their rate of moderate to severe COPD exacerbations. RESULTS: Users of theophyllines were found to be less likely than users of LABA [crude rates 84 vs. 91 per 100 patient-years, adjusted rate ratio (RR) 0.89, 95% confidence interval (CI) 0.84, 0.95] and users of theophyllines plus ICS were found to be less likely than users of LABA plus ICS (crude rates 114 vs. 112 per 100 patient-years, adjusted RR 0.89, 95% CI 0.87, 0.92) to have moderate to severe COPD exacerbations. Users of theophyllines were found to be more likely than users of ICS to have a COPD exacerbation (crude rates 84 vs. 77 per 100 patient-years, adjusted RR 1.07, 95% CI 1.04, 1.10), and this association was even stronger among patients who had at least three exacerbations in the year prior to cohort entry (crude rates 273 vs. 213 per 100 patient-years, adjusted RR 1.28, 95% CI 1.19, 1.38). CONCLUSION: The use of theophyllines was found to be associated with a reduction in the rate of COPD exacerbations among all COPD patients, but to be less effective than ICS among patients with frequent exacerbations.

Continuity of care in the ambulatory treatment of adolescents with asthma.

PURPOSE: To estimate the level of continuity of care, an important component in the management of asthma, using a general index based on medical visits and a disease-specific index based on prescribed medications, and to compare how the indexes predict the use of health care services among adolescents with asthma. METHODS: A cohort of 5586 adolescents with asthma was selected from the administrative database of the province of Québec, Canada between 1997 and 1999. Patients were followed for at least 1 year to a maximum of 3.5 years. The main exposure variables were an index of continuity of care based on the number of physicians prescribing a medication for asthma (RxICC) and an index of continuity of care based on the number of unreferred physicians (COC). RESULTS: The average RxICC was .42 +/- .29 and the average COC was .26 +/- .22. The adjusted rate ratios for RxICC as a predictor of hospitalizations and emergency department (ED) visits for asthma were, respectively, .83 (95% confidence interval [CI] .80-.87) and .81 (95% CI .80-.83). No significant association was found between COC, hospitalizations, and ED visits for asthma. CONCLUSION: Continuity of care is low among adolescents with asthma in Québec. The RxICC was, on average, higher than the COC, because patients were more likely to visit the same physician to treat their asthma than they would for other types of care. Only the RxICC was associated with the risk of hospitalization and ED visits for asthma.