Powerful Predictor Of Mortality Research Articles

Global Performance of Executive Function Is Predictor of Risk of Frailty and Disability in Older Adults.

The executive function is a complex set of skills affected during the aging process and translate into subclinical cerebrovascular disease. Postural instability or motor slowness are some clinical manifestations, being consubstantial with the frailty phenotype, genuine expression of aging. Executive dysfunction is also considered a predictor of adverse health events in the elderly. To study whether the executive dysfunction can be used as an early marker for frailty and the viability of use as a predictor of mortality, hospitalization and/or disability in a Mediterranean population. A population-based cohort study using data from the Toledo Study for Healthy Aging (TSHA). 1690 Spanish elders aged ≥65 years underwent a neuropsychological evaluation in order to measure executive function. To assess whether the accumulation of dysfunctions (in severity and amplitude) could increase the predictive value of adverse health events in relation to each dimension separately an executive dysfunction cumulative index was constructed. Cox proportional hazards model was used to examine mortality and hospitalization over 5.02 and 3.1 years of follow-up, respectively. Executive dysfunction is a powerful predictor of mortality, frailty and disability. Cumulative differences in executive function are associated with high risk of frailty and disability, thus, for each one point increment in the executive function index, the risk of death increased by 7 %, frailty by 13% and disability by 11% (P<0.05). Moreover, the executive impairment exhibits a strong positive tendency with age, comorbidity and mortality. Cumulative differences in four executive dimensions widely used in clinical practice improves the ability to predict frailty and disability compared to each dimension separately.

Predictive significance of low maternal serum cholesterol concentrations in early pregnancy on low birth weight in term neonates

Background: Low- birthweight (LBW) is the single most powerful predictor of mortality in the first few months of life, especially in most developing countries. The physiologic hypercholesterolemia of later pregnancy suggests an adaptive function for pregnancy maintenance or fetal growth. Decreased levels of maternal total cholesterol have been reported in association with intrauterine growth restriction. Aim: The aim of this study is to assess the association between low maternal serum cholesterol during early pregnancy and LBW in term neonates. Patients and Methods: This was a prospective cohort study in which eligible participants were enrolled at the gestational age of 14–20 weeks over a period of 12 months. Blood samples were taken to measure the total serum cholesterol concentrations, and the sera were then analyzed enzymatically by the cholesterol oxidase: p-aminophenazone method. Association between low maternal serum cholesterol and LBW was tested by using Chi-square. All significances are reported at P

Central line-associated blood stream infections: characteristics and risk factors for mortality over a 5.5-year period.

Central line-associated bloodstream infections (CLABSIs) are associated with substantial morbidity and mortality and the infection rates vary in a wide range1397645907(high: 62.5%; low: 20%) in developing countries. We aimed to investigate the characteristics and the risk factors for mortality in patients with CLABSIs in intensive care units (ICUs) and provide the relevant data. The electronic medical records database and file records obtained through active surveillance by an infection control committee of a hospital were screened to identify patients with CLABSIs hospitalized from January 2008 through July 2013. A total of 166 CLABSI episodes in 158 patients out of 17,553 on 38,562 catheter and 94,512 hospitalization days were evaluated. The infection developed in catheterized patients at a median of 14 days (range 2-88), and the highest infection rate with 13.4% (n = 20) was the femoral region among the places where the catheter was inserted. Of the patients catheterized, 54.4% survived whereas 45.6% died. In patients having Candida infection, the mortality was significantly higher. High APACHE II scores and Candida infections were found to be significant risk factors associated with mortality. APACHE II scores and bloodstream infection with Candida species were the most powerful predictors of mortality. In ICU practice, health-care givers must consider the emerging role of Candida for both invasiveness and mortality.

Associations between Soluble Receptor for Advanced Glycation End Products (sRAGE) and S100A12 (EN-RAGE) with Mortality in Long-term Hemodialysis Patients.

Hemodialysis (HD) patients experience vascular calcification, ultimately leading to high mortality rates. Previously, we reported associations between soluble receptor for advanced glycation end products (sRAGEs) and extracellular newly identified RAGE-binding protein S100A12 (EN-RAGE) and vascular calcification. Here, we extended our observations, investigating whether these biomarkers may be useful for predicting cardiovascular morbidity and mortality in these subjects. Thus, we evaluated the relationship between sRAGE and S100A12 and mortality in long-term HD patients. This was a prospective observational cohort study in 199 HD patients from an extended analysis of our previous study. Plasma sRAGE, S100A12, comorbidities, and other traditional risk factors were investigated. The cumulative incidences for death using Cox proportional hazards regression were evaluated in multivariable analyses. The observation period was 44 months. During the observation period, 27 (13.6%) patients died. Univariate analysis demonstrated that S100A12 was correlated with diabetes (P = 0.040) and high-sensitivity C-reactive protein (hsCRP) (P = 0.006). In multivariable analyses, plasma sRAGE (hazard ratio [HR] = 1.155; 95% confidence interval [CI] = 0.612–2.183; P = 0.656) and S100A12 (HR = 0.960; 95% CI = 0.566–1.630; P = 0.881) were not associated with mortality in HD patients, although traditional predictors of mortality, including age, history of cardiovascular diseases (CVDs), and serum levels of albumin and hsCRP were related to mortality. Powerful predictors of mortality were age, CVD, and albumin levels. Plasma sRAGE and S100A12 may be weak surrogate markers for predicting all-cause mortality in patients undergoing HD, although S100A12 was partly related to diabetes and inflammation.

Blunted cyclic variation of heart rate predicts mortality risk in post-myocardial infarction, end-stage renal disease, and chronic heart failure patients.

AimsCyclic variation of heart rate (CVHR) associated with sleep-disordered breathing is thought to reflect cardiac autonomic responses to apnoeic/hypoxic stress. We examined whether blunted CVHR observed in ambulatory ECG could predict the mortality risk.Methods and resultsCVHR in night-time Holter ECG was detected by an automated algorithm, and the prognostic relationships of the frequency (FCV) and amplitude (ACV) of CVHR were examined in 717 patients after myocardial infarction (post-MI 1, 6% mortality, median follow-up 25 months). The predictive power was prospectively validated in three independent cohorts: a second group of 220 post-MI patients (post-MI 2, 25.5% mortality, follow-up 45 months); 299 patients with end-stage renal disease on chronic haemodialysis (ESRD, 28.1% mortality, follow-up 85 months); and 100 patients with chronic heart failure (CHF, 35% mortality, follow-up 38 months). Although CVHR was observed in ≥96% of the patients in all cohorts, FCV did not predict mortality in any cohort. In contrast, decreased ACV was a powerful predictor of mortality in the post-MI 1 cohort (hazard ratio [95% CI] per 1 ln [ms] decrement, 2.9 [2.2–3.7], P < 0.001). This prognostic relationship was validated in the post-MI 2 (1.8 [1.4–2.2], P < 0.001), ESRD (1.5 [1.3–1.8], P < 0.001), and CHF (1.4 [1.1–1.8], P = 0.02) cohorts. The prognostic value of ACV was independent of age, gender, diabetes, β-blocker therapy, left ventricular ejection fraction, sleep-time mean R-R interval, and FCV.ConclusionBlunted CVHR detected by decreased ACV in a night-time Holter ECG predicts increased mortality risk in post-MI, ESRD, and CHF patients.

Changes in Red Cell Distribution Width During Hospitalization for Community-Acquired Pneumonia: Clinical Characteristics and Prognostic Significance.

We investigated outcomes of patients hospitalized with community-acquired pneumonia (CAP) according to the changes in red cell distribution width (RDW). For 980 adults, clinical characteristics, outcomes during hospitalization for CAP (transfer to the intensive care unit, treatment with mechanical ventilation, prolonged hospital stay, and death), and all-cause mortality following discharge were compared: according to RDW changes versus stable RDW during hospitalization, and according to normal (≤14.7%) versus high (>14.7%) RDW values on admission/discharge. RDW changes (n=386) during hospitalization were associated with more severe clinical and laboratory characteristics than stable RDW (n=594). Changes in RDW strongly predicted poor in-hospital outcomes (p<0.001). The respective 30, 90-day, and total (median follow-up 54months) mortality rates were significantly higher (9.8, 16.0 and 43.5%) among patients with RDW changes, compared to 4.0, 7.6 and 30.5% among those with stable RDW (p<0.001 for all comparisons). RDW changes, as well as high RDW (each 1% increment) on admission and discharge, were powerful predictors of mortality (the respective relative risks 1.41, 1.13, and 1.15, and 95% confidence intervals 1.13-1.74, 1.08-1.19, and 1.10-1.21). RDW changes during hospitalization for CAP are common and associated with a severe clinical profile. Time-dependent RDW changes strongly predict poor in-hospital outcomes and increased short- and long-term mortality. Repeated RDW determinations during hospitalization for CAP may provide useful prognostic information.

Grip Strength Decline and Its Determinants in the Very Old: Longitudinal Findings from the Newcastle 85+ Study.

BackgroundWeak grip strength (GS) is a key component of sarcopenia and frailty and a powerful predictor of mortality, morbidity and disability. Despite increasing interest in understanding GS across the lifespan, little is known about GS decline in the very old (aged ≥85). We examined trajectories of GS in very old adults and identified the determinants.MethodsGS (kg) was measured four times over 5 years in 319 men and 526 women participating in the Newcastle 85+ Study. A weak GS sub-cohort was identified as having strength of ≤27 kg (men), and ≤16 kg (women) at baseline and follow-up. Mixed models were used to establish trajectories of GS and associated factors in all participants, men and women, and in those with weak GS.ResultsMen’s mean grip strength was 24.42 (SD = 6.77) kg, and women’s 13.23 (4.42) kg (p<0.001) at baseline, with mean absolute change of -5.27 (4.90) kg and -3.14 (3.41), respectively (p<0.001) by 5-year follow-up. In the time-only mixed model, men experienced linear annual decline in GS of -1.13 (0.8) kg (β (SE), p<0.001), whilst women’s decline although slower, accelerated by -0.06 (0.02) kg (p = 0.01) over time. In the saturated model, higher baseline physical activity, height, fat-free mass, better self-rated health, and not having arthritis in hand(s) were associated with stronger GS initially in both sexes. Annual GS decline in men and participants with weak GS who were highly physically active was slower by 0.95 and 0.52 kg, respectively compared with inactive counterparts.ConclusionGrip strength decline in the very old followed linear (men) and curvilinear (women) trends. High levels of physical activity were protective of GS loss in men (but not in women) and in those with weak GS. Thus maintaining muscle strength in later life is important to reduce the morbidity and mortality in the very old.

Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide.

A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted.

Is cystatin C an evaluative marker for right heart functions in systemic sclerosis?

Background/objectivesSystemic sclerosis (SSc) is a progressive autoimmune disorder with multi-organ involvement. Patients who have SSc are at risk of developing pulmonary arterial hypertension (PAH) and right heart failure. Impaired right heart hemodynamic function is the most powerful predictor of mortality in these patients. We assessed the interactions between levels of NT-proBNP, cystatin C, and right ventricular functions in SSc patients without significant PAH. MethodsFifty SSc patients without significant PAH (37 women and 13 men, mean age 47.2±10.3), and 44 healthy participants as a control group (29 women and 15 men, mean age 47.9±10.4) were included in the study. ResultsCystatin C and NT-proBNP levels were significantly higher in patients with SSc. Both cystatin C and NT-proBNP levels possitively correlate with age, interventricular septum thickness, left ventricular posterior wall thickness, systolic pulmonary artery pressure, the peak late diastolic filling velocity, tricuspid regurgitation velocity, and negatively correlate with pulmonary artery acceleration time in the patients. ConclusionsOur results showed that elevated cystatin-C and NT-proBNP levels may be a clue for diastolic impairment in right ventricular functions in SSc.

Association of Serum Albumin Level and Mortality in Premature Infants.

Hypoalbuminemia has been proven to be a powerful predictor of mortality in adult patients. However, prognostic value of serum albumin in neonates is not clear. To assess the relationship between serum albumin level within the first day of life and outcome in preterm infants born before 32 weeks of gestation. The study was conducted prospectively in Baskent University Hospital between October 2008 and November 2009. Patients were divided by gestational age into two groups as below or of 28 weeks and above 28 weeks. Then serum albumin percentile groups were established within each gestational age group and were defined as <25, 25-75, and >75 percentile groups by combining percentile groups between the two gestational age groups. Three serum albumin percentile groups were compared regarding neonatal outcomes. A total of 199 infants with mean birth weight of 1,272 ± 390 g and mean gestational age of 29.2 ± 2.2 weeks were admitted to the study. The mean serum albumin level was 30.6 ± 4.7 g/l for all patients. The mean serum albumin levels were 25.5 ± 3.8, 30.1 ± 2.7, and 35.3 ± 3.7 g/l for <25, 25-75, and >75 percentile groups, respectively. Prevalence of infants with respiratory distress syndrome and prevalence of infants with sepsis and mortality were significantly higher in <25 percentile group. Logistic regression analysis showed that serum albumin <25 percentile and birth weight were independent predictive variables of mortality. Albumin concentrations lower than 27.2 g/l was associated with mortality, with a sensitivity of 71% and a specificity of 86%. Low serum albumin level within the first day of life is an independent predictor of mortality in preterm infants.

Predicting Survival from Telomere Length versus Conventional Predictors: A Multinational Population-Based Cohort Study.

Telomere length has generated substantial interest as a potential predictor of aging-related diseases and mortality. Some studies have reported significant associations, but few have tested its ability to discriminate between decedents and survivors compared with a broad range of well-established predictors that include both biomarkers and commonly collected self-reported data. Our aim here was to quantify the prognostic value of leukocyte telomere length relative to age, sex, and 19 other variables for predicting five-year mortality among older persons in three countries. We used data from nationally representative surveys in Costa Rica (N = 923, aged 61+), Taiwan (N = 976, aged 54+), and the U.S. (N = 2672, aged 60+). Our study used a prospective cohort design with all-cause mortality during five years post-exam as the outcome. We fit Cox hazards models separately by country, and assessed the discriminatory ability of each predictor. Age was, by far, the single best predictor of all-cause mortality, whereas leukocyte telomere length was only somewhat better than random chance in terms of discriminating between decedents and survivors. After adjustment for age and sex, telomere length ranked between 15th and 17th (out of 20), and its incremental contribution was small; nine self-reported variables (e.g., mobility, global self-assessed health status, limitations with activities of daily living, smoking status), a cognitive assessment, and three biological markers (C-reactive protein, serum creatinine, and glycosylated hemoglobin) were more powerful predictors of mortality in all three countries. Results were similar for cause-specific models (i.e., mortality from cardiovascular disease, cancer, and all other causes combined). Leukocyte telomere length had a statistically discernible, but weak, association with mortality, but it did not predict survival as well as age or many other self-reported variables. Although telomere length may eventually help scientists understand aging, more powerful and more easily obtained tools are available for predicting survival.

Dietary inflammatory index is associated with serum C-reactive protein and protein energy wasting in hemodialysis patients: A cross-sectional study.

BACKGROUND/OBJECTIVEMalnutrition and inflammation are reported as the most powerful predictors of mortality and morbidity in hemodialysis (HD) patients. Diet has a key role in modulating inflammation and dietary inflammatory index (DII) is a new tool for assessment of inflammatory potential of diet. The aim of this study was to evaluate the application of DII on dietary intake of HD patients and examine the associations between DII and malnutrition-inflammation markers.SUBJECTS/METHODSA total of 105 subjects were recruited for this cross-sectional study. Anthropometric measurements, 3-day dietary recall, and pre-dialysis biochemical parameters were recorded for each subject. Subjective global assessment (SGA), which was previously validated for HD patients, and malnutrition inflammation score (MIS) were used for the diagnosis of protein energy wasting. DII was calculated according to average of 3-day dietary recall data.RESULTSDII showed significant correlation with reliable malnutrition and inflammation indicators including SGA (r = 0.28, P < 0.01), MIS (r = 0.28, P < 0.01), and serum C-reactive protein (CRP) (r = 0.35, P < 0.001) in HD patients. When the study population was divided into three subgroups according to their DII score, significant increasing trends across the tertiles of DII were observed for SGA score (P = 0.035), serum CRP (P = 0.001), dietary energy (P < 0.001), total fat (P < 0.001), saturated fatty acids (P < 0.001), polyunsaturated fatty acids (P = 0.006), and omega-6 fatty acids (P = 0.01) intakes.CONCLUSIONThis study shows that DII is a good tool for assessing the overall inflammatory potential of diet in HD patients.

Abstract 16347: The Association of Depressive Symptoms and the Intermountain Mortality Risk Score to All-cause Mortality

Introduction: The patient health questionnaire (PHQ)-9 is widely used for the diagnosis and assessment of depression severity, but further study is needed regarding whether it provides prognostic information for major events such as mortality. The sex-specific Intermountain Mortality Risk Score (IMRS©) is a widely-validated risk stratification tool that utilizes the complete blood count (CBC), basic metabolic profile (BMP), and age to predict all-cause mortality. Hypothesis: IMRS is associated with all-cause mortality among subgroups defined by depressive symptoms. Methods: Patients who completed a PHQ-9, were ≥40 years, and had a CBC and BMP tested as part of their clinical care were studied. Prior validated sex-specific IMRS weightings and risk stratifications of low, moderate, and high were used. Patients were stratified by depressive symptoms of none (PHQ-9 score &lt;10), mild (PHQ-9 score 10-14), and moderate to severe (PHQ-9 score ≥15). Multivariable Cox hazard regression was performed among all patients and within strata defined by depressive symptoms to determine associations of IMRS and depressive symptoms with all-cause mortality. Results: A total of 11,583 females (age: 58.7±12.7 years) and 7,814 males (age: 59.9±12.5 years) were evaluated. Both PHQ-9 and IMRS stratifications were associated with all-cause mortality in a step-wise manner, which persisted despite multivariable adjustment (Table). In categories defined by depressive symptoms, IMRS markedly stratified risk of mortality (Table). Conclusion: IMRS and severity of depression were independent predictors of mortality risk among patients screened for depression. Further, IMRS was a powerful predictor of mortality within each level of depressive symptoms. This study suggests a need to evaluate IMRS as a tool for informing clinical risk stratification among patients with symptoms of depression and directing additional resources to those at highest risk of major adverse events.

Self-rated health and chronic conditions are associated with blood concentrations of persistent organic pollutants in the general population of Catalonia, Spain

BackgroundSelf-rated health (SRH) is a powerful predictor of mortality, morbidity, and need for health services. SRH generally increases with educational level, and decreases with age, number of chronic conditions, and body mass index (BMI). Because human concentrations of most persistent organic pollutants (POPs) also vary by age, education, and BMI, and because of the physiological and clinical effects of POPs, we hypothesized that body concentrations of POPs are inversely associated with SRH. ObjectivesTo analyze the relation between serum concentrations of POPs and SRH in the general population of Catalonia, Spain, taking into account sociodemographic factors and BMI, as well as chronic health conditions and mental disorders, measured by the General Health Questionnaire-12 (GHQ-12). MethodsPOP serum concentrations were measured by gas chromatography with electron-capture detection in 919 participants of the Catalan Health Interview Survey. ResultsIndividuals with higher concentrations of POPs had significantly poorer SRH; e.g., the median concentration of HCB in subjects with poor SRH was twice as high as in subjects with excellent SRH (366ng/g vs. 169ng/g, respectively; p-value<0.001). In crude models and in models adjusted for sex and BMI, the POPs-SRH association was often dose-dependent, and the likelihood of poor or regular SRH was 2 to 4-times higher in subjects with POP concentrations in the top quartile. In models adjusted for age or for chronic conditions virtually all ORs were near unity. No associations were found between POP levels and GHQ-12. ConclusionsIndividuals with higher concentrations of POPs had significantly poorer SRH, an association likely due to age and chronic conditions, but not to sex, education, social class, BMI, or mental disorders.

17β-Estradiol Attenuates Conduit Pulmonary Artery Mechanical Property Changes With Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Because proximal pulmonary arterial (PA) stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to right ventricular function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia. Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of smooth muscle cell activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P<0.05). 17β-Estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via right ventricular catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH.

Cellular Senescence and Inflammatory Burden as Determinants of Mortality in Elderly People Until the Extreme old age

Human aging is accompanied by a chronic low-grade inflammation, called “inflammaging”, a phenomenon associated with frailty, morbidity, and mortality in elderly people (Franceschi and Campisi, 2014). This condition is related to the accumulation of senescent cells in aged tissues through the senescence-associated secretory phenotype (SASP), which includes pro-inflammatory cytokines among its key constituents (Franceschi and Campisi, 2014). A well-known trigger of cellular senescence, closely related to inflammaging, is telomere length shortening. However, while considerable evidence shows that circulating inflammatory markers are predictors of mortality in community-living elderly individuals (Giovannini et al., 2011, Varadhan et al., 2014), there are conflicting results on the role of telomere length (Deelen et al., 2014, Bendix et al., 2014). Arai et al. (2015) in this issue of EbioMedicine demonstrate with a cross-sectional approach that telomere length, measured in the DNA extracted from whole blood of centenarian offspring, centenarians and (semi-)supercentenarians displays a superior maintenance compared to the one measured in community-living elderly subjects. Indeed, telomere length of centenarian offspring is maintained for more than 20 years at a length corresponding to 60 years of age in the general population. Interestingly, the authors observed that while long telomeres might be a prerequisite for exceptional lifespan in humans, they did not predict mortality. Conversely, Arai et al. confirmed that a multibiomarker score of systemic inflammation, which included anti-cytomegalovirus IgG, IL-6, TNF-α and C-reactive protein levels, was associated with an increased risk of mortality, loss of cognitive function and physical function decline, in normal aging and at extreme old age (up to 110 years). These data demonstrate that a multiple biomarker index may represent a more powerful predictor of mortality in older adults than a single inflammatory mediator, as also recently shown through a combined measure of interleukin 6 (IL-6) and soluble TNF receptor 1 (sTNFR1) (Varadhan et al., 2014). Therefore, the development of reliable measures of inflammatory status is of great interest in clinical practice both as risk assessment tools of age-related chronic diseases, and to monitor clinical progression or as a powerful surrogate biomarker in the research of new anti-inflammatory therapeutics. Hence, given that inflammation is a consolidated predictor of mortality, it is also important to investigate the sources of this phenomenon and their relative contribution. While it is known that cell senescence and inflammation can drive each other thus causing accelerated aging, the results of Arai and co-workers suggest that blood telomere length might not reflect the phenomenon of accumulation of senescent cells in various tissues and organs. This could be particularly true if accumulating senescent cells will be confirmed as a major source of circulating inflammatory markers in aging. The finding regarding the clearance of p16Ink4a-positive senescent cells which delay aging-associated disorders in genetically engineered mice (Baker et al., 2011) opens interesting future perspectives regarding therapeutic approaches aimed at the removal of senescent cells to prevent or delay tissue dysfunction and extend healthspan. However, senescent cells may also exert a physiological role as demonstrated for wound healing (Demaria et al., 2014) and their clearance could have adverse outcomes, especially in young organisms. For these reasons it is necessary to intensify the research effort in order to clarify the effects of the selective elimination of senescent damaged cells in aged animal models. In this context, the development of strategies to remove senescent cells could represent an emerging tool for the suppression of chronic inflammation and to ameliorate human healthy lifespan. A feasible and suggestive approach may be the employment of senolytic compounds (Zhu et al., 2015), in particular natural bioactive compounds, such as quercetin, which might be easily used in clinical trials, while minimizing the risk of adverse events (Malavolta et al., 2015).

International Normalized Ratio Variability: A Measure of Anticoagulation Quality or a Powerful Mortality Predictor

As atrial fibrillation (AF) carries twice the mortality hazard when compared with a similar population without diagnosed AF, the importance of risk stratifying is obvious. Several variables are related to outcome: age, comorbidities, and use of several medications, particularly oral anticoagulants. The CHA2DS2VASc score is an extremely useful tool to predict thromboembolic events and also mortality. The international normalized ratio (INR) variability is a treatment efficacy variable also associated with morbidity in patients receiving warfarin. The objective of the study is to compare the prognostic value of the CHA2DS2VASc versus the INR variability or its combination to predict mortality. In this observational study, we analyzed 589 patients from our Atrial Fibrillation Cohort, all on warfarin for more than 1 year and had more than 5 INRs performed in the last 2 years. The CHA2DS2VASc, HAS-BLED, and SAMe-TT2R2 scores were calculated as well as the INR variability using the time-in-therapeutic-range (TTR), the percentage of INRs (%INRs) within range, and the standard deviation of the INRs (SDINRs). Kaplan-Meier survival curves were plotted via different cutoff points. The mean TTR was 53 ± 23%; 34.6% of the patients had a TTR above 64%. The mean %INRs in range was 50.2 ± 20.2; 17.3% of the population had %INRs in range above 70%. The mean SDINRs was .84 ± .54, and 38.4% had SDINRs below .79. Of 598, 139 (22%) discontinued warfarin treatment. Death was responsible for almost 50% of treatment discontinuation. Of 598, 68 patients died during the study period (11.5 %); the most frequent causes of death were heart failure (30%), bleeding (17%), and ischemic stroke (15%). Patient survival had a correlation with TTR, %INRs in range, SDINRs, left ventricular ejection fraction, CHA2DS2VASc, and the combination of CHA2DS2VASc + SDINRs (cutoff >1 and >.79, respectively). INR variability is an extremely useful tool to assess anticoagulation quality. Calculation of both CHA2DS2VASc and INR variability appears to be extremely useful to predict mortality in patients with AF receiving warfarin. The SDINRs emerges as a strong mortality predictor compared to the other INR variability indexes.

Traumatic atlantooccipital dislocation: comprehensive assessment of mortality, neurologic improvement, and patient-reported outcomes at a Level 1 trauma center over 15 years

Background contextOnly Level 3 evidence exists for the diagnosis and treatment of atlantooccipital dislocation (AOD) with few studies examining mortality, neurologic improvement, and patient-reported outcomes (PROs). PurposeFirst, the aim was to determine: the incidence of AOD, 90-day surgical morbidity and mortality after AOD, patient factors that may be associated with delayed or missed diagnosis, and factors that were associated with mortality and neurologic improvement after AOD. Secondly, the aim was to quantify the pain, disability, and quality of life experienced by patients surviving AOD. Study design/settingThis was a retrospective cohort study. Patient sampleA total of 5,337 consecutive spine computed tomography traumagrams from 1997 to 2012 were included. Outcome measuresMortality, neurologic improvement, complications, EuroQol five dimensions (EQ-5D), Neck Disability Index (NDI), Numeric Rating Scale (NRS)-neck, NRS-arm, and return-to-work were the outcome measures. MethodsPatients were considered to have AOD if they met one of the following radiographic criteria: basion-dens interval greater than 10 mm; basion-axial interval: anterior displacement greater than 12 mm or posterior displacement greater than 4 mm between the basion and posterior C2 line; and condyle to C1 interval greater than 1.4 mm. Linear regression analysis was performed to identify factors associated with 90-day mortality, neurologic improvement, and missed diagnosis. Patient-reported outcomes were assessed via phone interview. ResultsThirty-one patients met radiographic criteria for AOD; an incidence of 0.6% over 15 years. Twenty-one (68%) patients were treated with occipital cervical fusion. At 90 days postoperatively, there were no new neurologic deficits or reoperations. Eight (26%) patients died within 90 days. All patients who died had no documented AOD diagnosis and were not treated surgically. Missed AOD diagnosis was the strongest predictor of mortality. Younger age, lower Glasgow Coma Score, lower Injury Severity Score (ISS) score, and worse initial American Spinal Injury Association (ASIA) score were significantly associated with greater neurologic improvement. Higher ISS score and better ASIA score were significantly associated with missed AOD diagnosis. The average PROs metrics at time of telephone follow-up were as follows: EQ-5D=0.73±0.19, NDI=30.89±18.57, NRS-neck=2.33±2.21, NRS-arm=2.00±2.54. Of the patients with follow-up data, four were employed full-time, and five were receiving disability. ConclusionsOur work suggests that failure to diagnose AOD is a powerful predictor of mortality. Higher ISS scores and better neurologic presentation were significantly associated with missed diagnosis. Craniocervical arthrodesis preserved neurologic function with low complication rate and unexpectedly high PROs and return-to-work. These results must be carefully interpreted because it is unclear whether missed AOD diagnosis accompanies another death-causing injury (eg, traumatic brain injury) or if failure to treat AOD contributes to mortality in a multifactorial manner.

Wealth, health and frailty in industrial-era London

Background: Socioeconomic status is a powerful predictor of mortality in living populations, as status affects exposure or access to a variety of factors that impact health and survival, such as diet, healthcare, infectious disease and pollution.Aim: This study examines the effect of socioeconomic status on mortality and survival in London during a period spanning the early 18th through mid-19th centuries. During this period, London experienced rapid industrialization and heightened class distinctions. This study examines whether low-socioeconomic status was associated with reduced survival at a time when the distinctions between social strata were peaking.Subjects and methods: The samples for this study are drawn from three skeletal assemblages in London that represent lower and higher social strata. The upper socioeconomic status sample (n = 394) is from Chelsea Old Church and St Bride’s Fleet Street (crypt assemblage). The low socioeconomic status sample (n = 474) is from St. Bride’s Lower Churchyard (also known as St Bride’s Farringdon Street). The effect of status on mortality and survival is assessed using hazard analysis and Kaplan–Meier analysis.Results: The results reveal elevated mortality and reduced survival for lower socioeconomic status children, but no strong effect of status on adult mortality or survival.Conclusion: These results might indicate strong selective mortality operating during childhood or the effects of migration in the industrial-era population of London.

Estimation of cardiorespiratory fitness in the clinical setting.

e20631 Background: Cardiorespiratory fitness (CRF) is a powerful predictor of mortality in general population and in cancer survivors. There is emerging evidence that treatments for cancer negative...