Inverse association between circulating vitamin D and mortality-dependent on sex and cause of death?

BACKGROUND AND AIMS: In various populations, vitamin D deficiency is associated with chronic diseases and mortality. We examined the association between concentration of circulating 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and all-cause as well as cause-specific mortality. METHODS AND RESULTS: The study included 3404 participants of the general adult Swiss population, who were recruited between November 1988 and June 1989 and followed-up until the end of 2008. Circulating 25(OH)D was measured by protein-bound assay. Cox proportional hazards regression was used to examine the association between 25(OH)D concentration and all-cause and cause-specific mortality adjusting for sex, age, season, diet, nationality, blood pressure, and smoking status. Per 10 ng/mL increase in 25(OH)D concentration, all-cause mortality decreased by 20% (HR = 0.83; 95% CI 0.74-0.92). 25(OH)D concentration was inversely associated with cardiovascular mortality in women (HR = 0.68, 95% CI 0.46-1.00 per 10 ng/mL increase), but not in men (HR = 0.97; 95% CI 0.77-1.23). In contrast, 25(OH)D concentration was inversely associated with cancer mortality in men (HR = 0.72, 95% CI 0.57-0.91 per 10 ng/mL increase), but not in women (HR = 1.14, 95% CI 0.93-1.39). Multivariate adjustment only slightly modified the 25(OH)D-mortality association. CONCLUSION: 25(OH)D was similarly inversely related to all-cause mortality in men and women. However, we observed opposite effects in women and men with respect to cardiovascular and cancer mortality.

Thyroid cancer mortality and incidence: a global overview.

In most areas of the world, thyroid cancer incidence has been appreciably increasing over the last few decades, whereas mortality has steadily declined. We updated global trends in thyroid cancer mortality and incidence using official mortality data from the World Health Organization (1970-2012) and incidence data from the Cancer Incidence in Five Continents (1960-2007). Male mortality declined in all the major countries considered, with annual percent changes around -2/-3% over the last decades. Only in the United States mortality declined up to the mid 1980s and increased thereafter. Similarly, in women mortality declined in most countries considered, with APCs around -2/-5% over the last decades, with the exception of the UK, the United States and Australia, where mortality has been declining up to the late 1980s/late 1990s to level off (or increase) thereafter. In 2008-2012, most countries had mortality rates (age-standardized, world population) between 0.20 and 0.40/100,000 men and 0.20 and 0.60/100,000 women, the highest rates being in Latvia, Hungary, the Republic of Moldova and Israel (over 0.40/100,000) for men and in Ecuador, Colombia and Israel (over 0.60/100,000) for women. In most countries, a steady increase in the incidence of thyroid cancer (mainly papillary carcinomas) was observed in both sexes. The declines in thyroid cancer mortality reflect both variations in risk factor exposure and changes in the diagnosis and treatment of the disease, while the increases in the incidence are likely due to the increase in the detection of this neoplasm over the last few decades.

Myocardial infarct size and mortality depend on the time of day-a large multicenter study.

BACKGROUND: Different studies have shown circadian variation of ischemic burden among patients with ST-Elevation Myocardial Infarction (STEMI), but with controversial results. The aim of this study was to analyze circadian variation of myocardial infarction size and in-hospital mortality in a large multicenter registry. METHODS: This retrospective, registry-based study was based on data from AMIS Plus, a large multicenter Swiss registry of patients who suffered myocardial infarction between 1999 and 2013. Peak creatine kinase (CK) was used as a proxy measure for myocardial infarction size. Associations between peak CK, in-hospital mortality, and the time of day at symptom onset were modelled using polynomial-harmonic regression methods. RESULTS: 6,223 STEMI patients were admitted to 82 acute-care hospitals in Switzerland and treated with primary angioplasty within six hours of symptom onset. Only the 24-hour harmonic was significantly associated with peak CK (p = 0.0001). The maximum average peak CK value (2,315 U/L) was for patients with symptom onset at 23:00, whereas the minimum average (2,017 U/L) was for onset at 11:00. The amplitude of variation was 298 U/L. In addition, no correlation was observed between ischemic time and circadian peak CK variation. Of the 6,223 patients, 223 (3.58%) died during index hospitalization. Remarkably, only the 24-hour harmonic was significantly associated with in-hospital mortality. The risk of death from STEMI was highest for patients with symptom onset at 00:00 and lowest for those with onset at 12:00. DISCUSSION: As a part of this first large study of STEMI patients treated with primary angioplasty in Swiss hospitals, investigations confirmed a circadian pattern to both peak CK and in-hospital mortality which were independent of total ischemic time. Accordingly, this study proposes that symptom onset time be incorporated as a prognosis factor in patients with myocardial infarction.

Growth arrest-specific gene 6 » (Gas6) as an intra-hospital mortality predictor for patients in septic shock

Aim: Gas6 is known to be elevated in sepsis, correlating with the severity of infection and¦organ failure. We aimed to investigate the performance of Gas6 plasma levels at¦admission to predict the risk of mortality in a cohort of septic patients.¦Methods: We used prospectively collected data and plasma samples from the "Sepsis¦Cohorte Romande". Gas6 level was measured by ELISA at admission and expressed in¦percentage relative to its level in a pool of normal plasma.¦Results: Non-survivors (n=21) presented higher Gas6 levels than survivors (n=73) (median¦258% vs 164%, IQR 194 and 117 respectively) (p=0.0027). Gas6 correlated positively with¦different cytokines and was the best mortality predictor, as shown by the ROC curves area.¦In patients with septic shock (n=66), using 249% as a cut-off value, Gas6 measurement¦had a specificity of 67% and a sensitivity of 81% for predicting mortality. ROC curve area¦was 0.75. Positive and negative predictive values were 57% and 87%, respectively.¦Conclusion: Thus, Gas6 plasma level at admission might be a useful tool to predict¦mortality in patients with septic shock. Although Gas6 hold promise as an early sepsis¦marker, its precise implication in sepsis remains to be elucidated. Our observation should¦be further investigated in larger prospective clinical trials.

Aortobronchial and aortoesophageal fistulae as risk factors in surgery of descending thoracic aortic aneurysms.

OBJECTIVE: Assess outcome of patients with descending thoracic aortic aneurysms complicated by aortobronchial and aortoesophageal fistulae in comparison to patients undergoing repair of aortic aneurysms without fistulae. METHODS: In a consecutive series of 145 patients (age 60 +/- 12 years) with repair of descending thoracic and thoracoabdominal aortic aneurysms, 11 patients (8%; age 63 +/- 9; NS) primarily presented for hematemesis and/or hemoptysis. In 8/11 patients (73%) an aortobronchial fistula was identified, and 3/11 patients (27%) suffered from an aortoesophageal fistula. Five of 11 patients (45%) had undergone previous aortic surgery in the same region. RESULTS: Extent of aortic segments (range 1-8) replaced was 3.1 +/- 1.4 for all versus 2.6 +/- 0.9 for fistulae (NS). Aortic cross clamp time was 38 +/- 22 min for all versus 45 +/- 15 min for fistulae (NS). Mortality at 30 days was 18/145 (12%) for all versus 16/134 (12%) without fistulae versus 2/11 (18%) with fistulae (NS). Paraparesis and or paraplegia was observed in 11/145 (8%) for all versus 10/134 (7%) without fistulae versus 1/11 (9%) for cases with fistulae (NS). Nine additional patients died after hospital discharge, seven without fistulae and two with fistulae (days 80, and 120) bringing the 1-year mortality up to 23/134 (17%) without fistulae versus 4/11 (36%) with fistulae (NS). Further analysis shows that the 1-year mortality accounts for 1/8 patients (13%) with aorto-bronchial fistulae versus to 3/3 patients (100%) with aorto-esophageal fistulae (esophageal versus bronchial fistula: P = 0.018; esophageal versus no fistula: P = 0.006). CONCLUSIONS: Outcome of patients suffering from descending thoracic aortic aneurysms complicated by aorto-bronchial fistulae can be similar to that without fistulae, whereas for cases complicated by aorto-esophageal fistulae the prognosis seems to remain poor even after successful hospital discharge.

Association of socioeconomic position with health behaviors and mortality

CONTEXT: Previous studies may have underestimated the contribution of health behaviors to social inequalities in mortality because health behaviors were assessed only at the baseline of the study. OBJECTIVE: To examine the role of health behaviors in the association between socioeconomic position and mortality and compare whether their contribution differs when assessed at only 1 point in time with that assessed longitudinally through the follow-up period. DESIGN, SETTING, AND PARTICIPANTS: Established in 1985, the British Whitehall II longitudinal cohort study includes 10 308 civil servants, aged 35 to 55 years, living in London, England. Analyses are based on 9590 men and women followed up for mortality until April 30, 2009. Socioeconomic position was derived from civil service employment grade (high, intermediate, and low) at baseline. Smoking, alcohol consumption, diet, and physical activity were assessed 4 times during the follow-up period. MAIN OUTCOME MEASURES: All-cause and cause-specific mortality. RESULTS: A total of 654 participants died during the follow-up period. In the analyses adjusted for sex and year of birth, those with the lowest socioeconomic position had 1.60 times higher risk of death from all causes than those with the highest socioeconomic position (a rate difference of 1.94/1000 person-years). This association was attenuated by 42% (95% confidence interval [CI], 21%-94%) when health behaviors assessed at baseline were entered into the model and by 72% (95% CI, 42%-154%) when they were entered as time-dependent covariates. The corresponding attenuations were 29% (95% CI, 11%-54%) and 45% (95% CI, 24%-79%) for cardiovascular mortality and 61% (95% CI, 16%-425%) and 94% (95% CI, 35%-595%) for noncancer and noncardiovascular mortality. The difference between the baseline only and repeated assessments of health behaviors was mostly due to an increased explanatory power of diet (from 7% to 17% for all-cause mortality, respectively), physical activity (from 5% to 21% for all-cause mortality), and alcohol consumption (from 3% to 12% for all-cause mortality). The role of smoking, the strongest mediator in these analyses, did not change when using baseline or repeat assessments (from 32% to 35% for all-cause mortality). CONCLUSION: In a civil service population in London, England, there was an association between socioeconomic position and mortality that was substantially accounted for by adjustment for health behaviors, particularly when the behaviors were assessed repeatedly.

Traitements des facteurs de risque cardiovasculaire et dépistage de la maladie coronarienne dans le diabète de type 2 [Treatments for cardiovascular risk factors and screening for coronary artery disease in type 2 diabetes mellitus]

The recent ACCORD and DIAD studies revealed results which could modify treatments and the screening of diabetes vascular complications. Indeed, ACCORD shows no benefit on the prevention of diabetes vascular complications by aggressive treatment of hypertension or the combined treatment of the dyslipidemia. The intensive treatment of the blood glucose, if associated with severe hypoglycemias, increases mortality. DIAD revealed 20% of silent myocardial ischaemia in diabetic patients but no beneficial effect on the cardiovascular mortality. A careful reading of these studies in the light of long term studies such as UKPDS and STENO reveals that these negative results are generated by a too short follow-up and too aggressive objectives. The long term studies reveal that more realistic objectives remain beneficial.

Who is at low risk for cardiovascular disease? An assessment of different definitions

Purpose: To assess the prevalence and trends of low cardiovascular risk factor (RF) profile in the Swiss population according to different definitions. Methods: Population-based cross-sectional study of 6170 subjects (3241 women) aged 35-75 years living in Lausanne, Switzerland. Trends were assessed using data from the Swiss MONICA population surveys conducted in 1984-6 (N=3300), 1988-9 (N=3331) and 1992-3 (N=3133) and restricted to the same age group. Seven different definitions of low RF profile were used. Results: Prevalence of low RF profile varied between 6.5% (95% confidence interval: 5.9-7.1) and 9.7% (9.0-10.5) depending on the definition used. The prevalence was inversely related to the number of criteria used and higher than in other countries. Irrespective of the definition used, the prevalence of low RF profile was higher in women and in physically active participants, and decreased with increasing age or in the presence of a family history of cardiovascular disease (table). The prevalence of low RF profile increased from 3.8% (3.1-4.5) in 1984-6 to 6.7% (6.1-7.3) in 2003-6; using another definition, the results were 5.9% (5.1-6.8) and 9.7% (9.0-10.5), respectively. Conclusion: The prevalence of low RF profile varies according to the criteria used; this prevalence is relatively high and increasing in the Swiss population, which might partly explain the low and decreasing trend in cardiovascular mortality rates.

Test of four colon cancer risk-scores in formalin fixed paraffin embedded microarray gene expression data.

BACKGROUND: Prognosis prediction for resected primary colon cancer is based on the T-stage Node Metastasis (TNM) staging system. We investigated if four well-documented gene expression risk scores can improve patient stratification. METHODS: Microarray-based versions of risk-scores were applied to a large independent cohort of 688 stage II/III tumors from the PETACC-3 trial. Prognostic value for relapse-free survival (RFS), survival after relapse (SAR), and overall survival (OS) was assessed by regression analysis. To assess improvement over a reference, prognostic model was assessed with the area under curve (AUC) of receiver operating characteristic (ROC) curves. All statistical tests were two-sided, except the AUC increase. RESULTS: All four risk scores (RSs) showed a statistically significant association (single-test, P < .0167) with OS or RFS in univariate models, but with HRs below 1.38 per interquartile range. Three scores were predictors of shorter RFS, one of shorter SAR. Each RS could only marginally improve an RFS or OS model with the known factors T-stage, N-stage, and microsatellite instability (MSI) status (AUC gains < 0.025 units). The pairwise interscore discordance was never high (maximal Spearman correlation = 0.563) A combined score showed a trend to higher prognostic value and higher AUC increase for OS (HR = 1.74, 95% confidence interval [CI] = 1.44 to 2.10, P < .001, AUC from 0.6918 to 0.7321) and RFS (HR = 1.56, 95% CI = 1.33 to 1.84, P < .001, AUC from 0.6723 to 0.6945) than any single score. CONCLUSIONS: The four tested gene expression-based risk scores provide prognostic information but contribute only marginally to improving models based on established risk factors. A combination of the risk scores might provide more robust information. Predictors of RFS and SAR might need to be different.

Validation of a clinical algorithm to identify low-risk patients with pulmonary embolism.

Summary Background: We previously derived a clinical prognostic algorithm to identify patients with pulmonary embolism (PE) who are at low-risk of short-term mortality who could be safely discharged early or treated entirely in an outpatient setting. Objectives: To externally validate the clinical prognostic algorithm in an independent patient sample. Methods: We validated the algorithm in 983 consecutive patients prospectively diagnosed with PE at an emergency department of a university hospital. Patients with none of the algorithm's 10 prognostic variables (age >/= 70 years, cancer, heart failure, chronic lung disease, chronic renal disease, cerebrovascular disease, pulse >/= 110/min., systolic blood pressure < 100 mm Hg, oxygen saturation < 90%, and altered mental status) at baseline were defined as low-risk. We compared 30-day overall mortality among low-risk patients based on the algorithm between the validation and the original derivation sample. We also assessed the rate of PE-related and bleeding-related mortality among low-risk patients. Results: Overall, the algorithm classified 16.3% of patients with PE as low-risk. Mortality at 30 days was 1.9% among low-risk patients and did not differ between the validation and the original derivation sample. Among low-risk patients, only 0.6% died from definite or possible PE, and 0% died from bleeding. Conclusions: This study validates an easy-to-use, clinical prognostic algorithm for PE that accurately identifies patients with PE who are at low-risk of short-term mortality. Low-risk patients based on our algorithm are potential candidates for less costly outpatient treatment.

Mortality associated with diabetes mellitus in comparison with history of cardiovascular disease in older women.

BACKGROUND: Women with diabetes mellitus have an increased risk of cardiovascular disease (CVD) mortality and current treatment guidelines consider diabetes to be equivalent to existing CVD, but few data exist about the relative importance of these risk factors for total and cause-specific mortality in older women. METHODS: We studied 9704 women aged ≥65 years enrolled in a prospective cohort study (Study of Osteoporotic Fractures) during a mean follow-up of 13 years and compared all-cause, CVD and coronary heart disease (CHD) mortality among non-diabetic women without and with a prior history of CVD at baseline and diabetic women without and with a prior history of CVD. Diabetes mellitus and prior CVD (history of angina, myocardial infarction or stroke) were defined as self-report of physician diagnoses. Cause of death was adjudicated from death certificates and medical records when available (>95% deaths confirmed). Ascertainment of vital status was 99% complete. Log-rank tests for the rates of death and multivariate Cox hazard models adjusted for age, smoking, physical activity, systolic blood pressure, waist girth and education were used to compare mortality among the four groups with non-diabetic women without CVD as the referent group. Results are reported as adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: At baseline mean age was 71.7±5.3 years, 7.0% reported diabetes mellitus and 14.5% reported prior CVD. 4257 women died during follow-up, 36.6% were attributed to CVD. The incidence of CVD death per 1000 person-years was 9.9 and 21.6 among non-diabetic women without and with CVD, respectively, and 23.8 and 33.3 among diabetic women without and with CVD, respectively. Compared to nondiabetic women without prior CVD, the risk of CVD mortality was elevated among both non-diabetic women with CVD (HR=1.82, CI: 1.60-2.07, P<0.001) and diabetic women without prior CVD (HR=2.24, CI: 1.87-2.69, P<0.001). CVD mortality was highest among diabetic women with CVD (HR=3.41, CI: 2.61-4.45, P<0.001). Compared to non-diabetic women with CVD, diabetic women without prior CVD had a significantly higher adjusted HR for total and CVD mortality (P<0.001 and P<0.05 respectively). CHD mortality did not differ significantly between non-diabetic women with CVD and diabetic women without prior CVD. CONCLUSION: Older diabetic women without prior CVD have a higher risk of all-cause and CVD mortality and a similar risk of CHD mortality compared to non-diabetic women with pre-existing CVD. For older women, these data support the equivalence of prior CVD and diabetes mellitus in current guidelines for the prevention of CVD.

Mortality among 24,865 workers exposed to polychlorinated biphenyls (PCBs) in three electrical capacitor manufacturing plants: a ten-year update.

The objective of this analysis was to evaluate mortality among a cohort of 24,865 capacitor-manufacturing workers exposed to polychlorinated biphenyls (PCBs) at plants in Indiana, Massachusetts, and New York and followed for mortality through 2008. Cumulative PCB exposure was estimated using plant-specific job-exposure matrices. External comparisons to US and state-specific populations used standardized mortality ratios, adjusted for gender, race, age and calendar year. Among long-term workers employed 3 months or longer, within-cohort comparisons used standardized rate ratios and multivariable Poisson regression modeling. Through 2008, more than one million person-years at risk and 8749 deaths were accrued. Among long-term employees, all-cause and all-cancer mortality were not elevated; of the a priori outcomes assessed only melanoma mortality was elevated. Mortality was elevated for some outcomes of a priori interest among subgroups of long-term workers: all cancer, intestinal cancer and amyotrophic lateral sclerosis (women); melanoma (men); melanoma and brain and nervous system cancer (Indiana plant); and melanoma and multiple myeloma (New York plant). Standardized rates of stomach and uterine cancer and multiple myeloma mortality increased with estimated cumulative PCB exposure. Poisson regression modeling showed significant associations with estimated cumulative PCB exposure for prostate and stomach cancer mortality. For other outcomes of a priori interest--rectal, liver, ovarian, breast, and thyroid cancer, non-Hodgkin lymphoma, Alzheimer disease, and Parkinson disease--neither elevated mortality nor positive associations with PCB exposure were observed. Associations between estimated cumulative PCB exposure and stomach, uterine, and prostate cancer and myeloma mortality confirmed our previous positive findings.

Modifiable and nonmodifiable risk factors for postoperative delirium after cardiac surgery with cardiopulmonary bypass.

Postoperative delirium after cardiac surgery is associated with increased morbidity and mortality as well as prolonged stay in both the intensive care unit and the hospital. The authors sought to identify modifiable risk factors associated with the development of postoperative delirium in elderly patients after elective cardiac surgery in order to be able to design follow-up studies aimed at the prevention of delirium by optimizing perioperative management. A post hoc analysis of data from patients enrolled in a randomized controlled trial was performed. A single university hospital. One hundred thirteen patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. None. MEASUREMENTS AND MAINS RESULTS: Screening for delirium was performed using the Confusion Assessment Method (CAM) on the first 6 postoperative days. A multivariable logistic regression model was developed to identify significant risk factors and to control for confounders. Delirium developed in 35 of 113 patients (30%). The multivariable model showed the maximum value of C-reactive protein measured postoperatively, the dose of fentanyl per kilogram of body weight administered intraoperatively, and the duration of mechanical ventilation to be independently associated with delirium. In this post hoc analysis, larger doses of fentanyl administered intraoperatively and longer duration of mechanical ventilation were associated with postoperative delirium in the elderly after cardiac surgery. Prospective randomized trials should be performed to test the hypotheses that a reduced dose of fentanyl administered intraoperatively, the use of a different opioid, or weaning protocols aimed at early extubation prevent delirium in these patients.

Pre-hospital risk factors for inpatient death from severe febrile illness in malian children.

BACKGROUND: Inpatient case fatality from severe malaria remains high in much of sub-Saharan Africa. The majority of these deaths occur within 24 hours of admission, suggesting that pre-hospital management may have an impact on the risk of case fatality. METHODS: Prospective cohort study, including questionnaire about pre-hospital treatment, of all 437 patients admitted with severe febrile illness (presumed to be severe malaria) to the paediatric ward in Sikasso Regional Hospital, Mali, in a two-month period. FINDINGS: The case fatality rate was 17.4%. Coma, hypoglycaemia and respiratory distress at admission were associated with significantly higher mortality. In multiple logistic regression models and in a survival analysis to examine pre-admission risk factors for case fatality, the only consistent and significant risk factor was sex. Girls were twice as likely to die as boys (AOR 2.00, 95% CI 1.08-3.70). There was a wide variety of pre-hospital treatments used, both modern and traditional. None had a consistent impact on the risk of death across different analyses. Reported use of traditional treatments was not associated with post-admission outcome. INTERPRETATION: Aside from well-recognised markers of severity, the main risk factor for death in this study was female sex, but this study cannot determine the reason why. Differences in pre-hospital treatments were not associated with case fatality.