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Background: Adults with congenital heart disease (CHD) are exposed to increasing amounts of low-dose ionizing radiation (LDIR) from cardiac procedures. Cancer prevalence in this population is higher than in the general population. This study estimates the association between LDIR exposure from cardiac procedures and incident cancer in adult patients with CHD.Methods: The study population derived from the Quebec Congenital Heart Disease Database. We measured cumulative numbers of LDIR-related cardiac procedures for each patient until 1 year before the time of cancer diagnosis or administrative censoring. To assess the association between LDIR exposure and cancer risk, we conducted a nested case-control study and matched cancer cases with controls on sex, CHD severity, birth year, and age.Results: The study included 24 833 adult patients with CHD aged 18 to 64 years from 1995 to 2009. In >250 791 person-years of follow-up, 602 cancer cases were observed (median age, 55.4 years). The cumulative incidence of cancer estimated up to 64 years of age was 15.3% (95% confidence interval [CI], 14.2-16.5). Cases had more LDIR-related cardiac procedures than controls (1410 versus 921 per 1000 adult patients with CHD, P<0.0001). Cumulative LDIR exposure was independently associated with cancer (odds ratio [OR], 1.08 per procedure; 95% CI, 1.04-1.13). Similar results were obtained by using dose estimates for LDIR exposure (OR, 1.10 per 10 mSv; 95% CI, 1.05-1.15) with a possible dose-related response. The effect measure was in the same direction, and the association was persistent for exposure from ≥6 procedures in all sensitivity analyses: after excluding most smoking-related cancer cases (OR, 1.10 per procedure; 95% CI, 1.05-1.16 and OR when exposure from ≥6 procedures, 3.08; 95% CI, 1.77-5.37), and after applying a 3-year lag period (OR, 1.09 per procedure; 95% CI, 1.03-1.14 and OR when exposure from ≥6 procedures: 2.58; 95% CI, 1.43-4.69).Conclusions: To our knowledge, this is the first large population-based study to analyze and document the association between LDIR-related cardiac procedures and incident cancer in the population of adults with CHD. Confirmations of these findings by prospective studies are needed to reinforce policy recommendations for radiation surveillance in patients with CHD where no regulation currently exists. Physicians ordering and performing cardiac imaging should ensure that exposure is as low as reasonably achievable without sacrificing quality of care. [ABSTRACT FROM AUTHOR]

BACKGROUND: Glycerophosphocholine (GPC) metabolites modulate atherosclerosis and thus risk for cardiovascular disease (CVD). Preclinical CVD may start during adolescence. Here, we used targeted serum lipidomics to identify a new panel of GPCs, and tested whether any of these GPCs are associated, in adolescence, with classical risk factors of CVD, namely excess visceral fat (VF), elevated blood pressure, insulin resistance, and atherogenic dyslipidemia. METHODS: We studied a population-based sample of 990 adolescents (12-18 years, 48% male), as part of the Saguenay Youth Study. Using liquid chromatography-electrospray ionization-mass spectrometry, we identified 69 serum GPCs within the 450 to 680 m/z range. We measured VF with MRI. RESULTS: We identified several novel GPCs that were associated with multiple CVD risk factors. Most significantly, PC16:0/2:0 was negatively associated with VF (P=1.4×10-19), blood pressure (P=7.7×10-5), and fasting triacylglycerols (P=9.0×10-5), and PC14:1/0:0 was positively associated with VF (P=3.0×10-7), fasting insulin (P=5.4×10-32), and triacylglycerols (P=1.4×10-29). The Sobel test of mediation revealed that both GPCs mediated their respective relations between VF (as a potential primary exposure) and CVD risk factors (as outcomes, P values<1.3×10-3). Furthermore, a GPC shown recently to predict incident coronary heart disease in older adults, PC18:2/0:0, was associated with several CVD risk factors in adolescents; these associations were less strong than those with the newly identified GPCs. CONCLUSIONS: We identified novel GPCs strongly associated with multiple CVD risk factors in adolescents. These GPCs may be sensitive indicators of obesity-related risk for CVD outcomes in adults, and may improve biological understanding of CVD risk. [ABSTRACT FROM AUTHOR]

BACKGROUND: Clinical guidelines recommend specialized care for adult congenital heart disease (ACHD) patients. In reality, few patients receive such dedicated care. We sought to examine the impact of specialized care on ACHD patient mortality. METHODS AND RESULTS: We examined referral rates to specialized ACHD centers and ACHD patient mortality rates between 1990 and 2005 in the population-based Quebec Congenital Heart Disease database (n=71 467). This period covers several years before and after the publication of guidelines endorsing specialized care for ACHD patients. A time-series design, based on Joinpoint and Poisson regression analyses, was used to assess the changes in annual referral and patient mortality rates. The association between specialized ACHD care and all-cause mortality was assessed in both case-control and cohort studies. The time-series analysis demonstrated a significant increase in referral rates to specialized ACHD centers in 1997 (rate ratio, +7.4%; 95% confidence interval [CI], +6.6% to +8.2%). In parallel, a significant reduction in expected ACHD patient mortality was observed after year 2000 (rate ratio, -5.0%;95% CI, -10.8% to -0.8%). In exploratory post hoc cohort and case-control analyses, specialized ACHD care was independently associated with reduced mortality (hazard ratio, 0.78; 95% CI, 0.65-0.94) and a reduced odds of death (adjusted odds ratio, 0.82; 95% CI, 0.08-0.97), respectively. This effect was predominantly driven by patients with severe congenital heart disease (hazard ratio, 0.38; 95% CI, 0.22-0.67). CONCLUSIONS: A significant increase in referrals to specialized ACHD centers followed the introduction of the clinical guidelines. Moreover, referral to specialized ACHD care was independently associated with a significant mortality reduction. Our findings support a model of specialized care for all ACHD patients. [ABSTRACT FROM AUTHOR]

Background--Clinical guidelines recommend specialized care for adult congenital heart disease (ACHD) patients. In reality, few patients receive such dedicated care. We sought to examine the impact of specialized care on ACHD patient mortality. Methods and Results--We examined referral rates to specialized ACHD centers and ACHD patient mortality rates between 1990 and 2005 in the population-based Quebec Congenital Heart Disease database (n=71 467). This period covers several years before and after the publication of guidelines endorsing specialized care for ACHD patients. A time-series design, based on Joinpoint and Poisson regression analyses, was used to assess the changes in annual referral and patient mortality rates. The association between specialized ACHD care and all-cause mortality was assessed in both case-control and cohort studies. The time-series analysis demonstrated a significant increase in referral rates to specialized ACHD centers in 1997 (rate ratio, +7.4%; 95% confidence interval [CI], +6.6% to +8.2%). In parallel, a significant reduction in expected ACHD patient mortality was observed after year 2000 (rate ratio, -5.0%;95% CI, -10.8% to -0.8%). In exploratory post hoc cohort and case-control analyses, specialized ACHD care was independently associated with reduced mortality (hazard ratio, 0.78; 95% CI, 0.65-0.94) and a reduced odds of death (adjusted odds ratio, 0.82; 95% CI, 0.08-0.97), respectively. This effect was predominantly driven by patients with severe congenital heart disease (hazard ratio, 0.38; 95% CI, 0.22-0.67). Conclusions--A significant increase in referrals to specialized ACHD centers followed the introduction of the clinical guidelines. Moreover, referral to specialized ACHD care was independently associated with a significant mortality reduction. Our findings support a model of specialized care for all ACHD patients. [ABSTRACT FROM AUTHOR]

Objectives: To investigate mortality of ICU patients over a 3-month period after an initial episode of septic shock and to identify factors associated with mortality. Design: Prospective multicenter observational cohort study. Setting: Fourteen ICUs from 10 French nonacademic and university teaching hospitals. Patients: All consecutive adult patients with septic shock admitted between October 2009 and September 2011 were eligible. Intervention: None. Measurements and Main Results: Multivariable analyses were performed using a Cox proportional hazard model and a flexible extension of the Cox model. In total, 1,495 of 10,941 patients (13.7%) had septic shock and 1,488 patients (99.5%) were included. Median age was 68 years (range, 58-78 yr). The majority of admissions (84%) were medical. Median (interquartile range) Simplified Acute Physiological Score II and Sequential Organ Failure Assessment were, respectively, 56 (45-70) and 11 (9-14). ICU and hospital mortality were, respectively, 39.4% and 48.6%. At 3 months, 776 patients (52.2%) had died. Factors significantly associated with increased risk of death in the multivariable Cox model were older age, male sex, comorbidities (immune deficiency, cirrhosis), Knaus C/D score, and high Sequential Organ Failure Assessment score. Flexible analyses indicated that the impact of Sequential Organ Failure Assessment score was greatest early after septic shock, while the onset of the effect of age, nosocomial infection, and cirrhosis was later. Conclusions: This is the most recent large-scale epidemiological study to investigate medium-term mortality in nonselected patients hospitalized in the ICU for septic shock. Advances in early management have improved survival at the initial phase, but risk of death persists in the medium term. Flexible modeling techniques yield insights into the profile of the risk of death in the first 3 months. [ABSTRACT FROM AUTHOR]

The article presents a maternal mortality score to identify patients at risk of in-hospital death in developing countries such as Senegal and Mali. A prospective observational study in 46 referral hospitals in the two countries were conducted. Generalized estimating equation was used to derive a maternal mortality score on patients included during the first 6 months of the study and validated on those included during the next 6 months.

Background: Few aspects of the occurrence of infections with multiple HPV types have been described. Since the immunity conferred by vaccines is type-specific, the epidemiology of such coinfections needs to be addressed.Goal: The goal of the study was to document the prevalence and incidence of infection with multiple HPV types and the distribution of HPV types in coinfections.Study Design: In a prospective cohort of 2075 Brazilian women, cervical specimens were collected for cytology and HPV detection. Information on potential risk factors was obtained by interview.Results: The prevalence of HPV coinfections was 3% among cytologically normal women, 10% among women with ASCUS, 23% among those with LSIL, and 7% among those with HSIL. The incidence rate of coinfection declined markedly with age (Ptrend<0.001). Some HPV types co-occurred less frequently than expected, namely, HPV 16 and 18 occurring with other oncogenic HPV types and HPV 6/11.Conclusion: We have observed that occurrence of HPV coinfection was dependent both on age and on the presence of cytologic abnormalities. These results may have implications for vaccine development and for public health decisions about vaccination programs. [ABSTRACT FROM AUTHOR]

Introduction: Randomized control trials have described protective cardiovascular effects of new glucose lowering drugs. However, the proportion of women enrolled was low, limiting the studies' generalizability. Hypothesis: Sex-differences may exist in cardiovascular outcomes for new users of sodium-glucose like transport-2 inhibitor (SGLT-2i), dipeptidyl peptidase-4 inhibitor (DPP-4i), glucagon-like peptide 1 agonist (GLP-1a), and sulfonylurea in type 2 diabetes (T2DM) patients not controlled on metformin therapy. Methods: Using the MarketScan database (2011-2015) we selected T2DM individuals with newly dispensed sulfonylureas, SGLT-2i, DPP-4i, or GLP-1a, as second-line therapy, added to metformin. Time to first cardiovascular event (i.e. acute myocardial infarction, unstable angina, hemorrhagic/ischemic stroke, transient ischemic attack, congestive heart failure, and cardiovascular interventions) was compared using Cox regression models adjusted for confounders. To explore whether sex-related differences in effects exist, we tested two-way sex-by-drug interactions. Results: Among 118,774 T2DM metformin users (46% women, mean age: 56), men were at slightly higher cardiovascular risk, and more commonly prescribed anti-hypertensive and statins. A GLP-1a was more likely prescribed to women (60%) while sulfonylurea (56%) or DPP-4i (55%) to men. During a mean 10-month follow-up, 1421 (2.2%) cardiovascular events occurred in men and 863 (1.6%) in women. Compared to sulfonylurea, novel glucose lowering drugs reduced the risk of cardiovascular events in men (aHR: 0.85, 95% CI: 0.76-0.95) and in women (aHR: 0.71, 95% CI: 0.62-0.82). DPP-4i and SGLT-2i reduced the primary outcome in men by 22% and 57% and in women by 35% and 75% respectively, with no significant sex-interaction. Conversely, the reduction of risk in GLP-1a users was larger for women than men (65 vs 40%) (sex-interaction, p=0.04) and largely mediated by reduction of congestive heart failure events in women (aHR: 0.6, 95% CI: 0.66-0.96) compared to men (aHR: 0.83, 95% CI: 0.55-1.2). Conclusions: Diabetic women achieve a greater cardiovascular benefit from GLP-1a whereas the effect of other novel agents was similar between sexes. Greater inclusion of women in clinical trials is warranted to clarify sex differences in drug response towards a personalized T2DM management. [ABSTRACT FROM AUTHOR]

Background: Glycerophosphocholine (GPC) metabolites modulate atherosclerosis and thus risk for cardiovascular disease (CVD). Preclinical CVD may start during adolescence. Here, we used targeted serum lipidomics to identify a new panel of GPCs, and tested whether any of these GPCs are associated, in adolescence, with classical risk factors of CVD, namely excess visceral fat (VF), elevated blood pressure, insulin resistance, and atherogenic dyslipidemia.Methods: We studied a population-based sample of 990 adolescents (12-18 years, 48% male), as part of the Saguenay Youth Study. Using liquid chromatography-electrospray ionization-mass spectrometry, we identified 69 serum GPCs within the 450 to 680 m/z range. We measured VF with MRI.Results: We identified several novel GPCs that were associated with multiple CVD risk factors. Most significantly, PC16:0/2:0 was negatively associated with VF (P=1.4×10-19), blood pressure (P=7.7×10-5), and fasting triacylglycerols (P=9.0×10-5), and PC14:1/0:0 was positively associated with VF (P=3.0×10-7), fasting insulin (P=5.4×10-32), and triacylglycerols (P=1.4×10-29). The Sobel test of mediation revealed that both GPCs mediated their respective relations between VF (as a potential primary exposure) and CVD risk factors (as outcomes, P values<1.3×10-3). Furthermore, a GPC shown recently to predict incident coronary heart disease in older adults, PC18:2/0:0, was associated with several CVD risk factors in adolescents; these associations were less strong than those with the newly identified GPCs.Conclusions: We identified novel GPCs strongly associated with multiple CVD risk factors in adolescents. These GPCs may be sensitive indicators of obesity-related risk for CVD outcomes in adults, and may improve biological understanding of CVD risk. [ABSTRACT FROM AUTHOR]