Differences in coronary risk factors, procedural characteristics, mortality and stent thrombosis between two all-comers percutaneous coronary intervention registries from Europe and Japan: a patient-level data analysis of the Bern-Rotterdam and j-Cypher registries

Aims: The reported rate of stent thrombosis (ST) after drug-eluting stent (DES) implantation varies among registries. To investigate differences in baseline characteristics and clinical outcome in European and Japanese all-comers registries, we performed a pooled analysis of patient-level data. Methods and results: The j-Cypher registry (JC) is a multicentre observational study conducted in Japan, including 12,824 patients undergoing SES implantation. From the Bern-Rotterdam registry (BR) enrolled at two academic hospitals in Switzerland and the Netherlands, 3,823 patients with SES were included in the current analysis. Patients in BR were younger, more frequently smokers and presented more frequently with ST-elevation myocardial infarction (MI). Conversely, JC patients more frequently had diabetes and hypertension. At five years, the definite ST rate was significantly lower in JC than BR (JC 1.6% vs. BR 3.3%, p<0.001), while the unadjusted mortality tended to be lower in BR than in JC (BR 13.2% vs. JC 14.4%, log-rank p=0.052). After adjustment, the j-Cypher registry was associated with a significantly lower risk of all-cause mortality (HR 0.56, 95% CI: 0.49-0.64) as well as definite stent thrombosis (HR 0.46, 95% CI: 0.35-0.61). Conclusions: The baseline characteristics of the two large registries were different. After statistical adjustment, JC was associated with lower mortality and ST.

Predicting 3-year mortality after percutaneous coronary intervention: updated logistic clinical SYNTAX score based on patient-level data from 7 contemporary stent trials

OBJECTIVES This study aimed to update the Logistic Clinical SYNTAX score to predict 3-year survival after percutaneous coronary intervention (PCI) and compare the performance with the SYNTAX score alone. BACKGROUND The SYNTAX score is a well-established angiographic tool to predict long-term outcomes after PCI. The Logistic Clinical SYNTAX score, developed by combining clinical variables with the anatomic SYNTAX score, has been shown to perform better than the SYNTAX score alone in predicting 1-year outcomes after PCI. However, the ability of this score to predict long-term survival is unknown. METHODS Patient-level data (N = 6,304, 399 deaths within 3 years) from 7 contemporary PCI trials were analyzed. We revised the overall risk and the predictor effects in the core model (SYNTAX score, age, creatinine clearance, and left ventricular ejection fraction) using Cox regression analysis to predict mortality at 3 years. We also updated the extended model by combining the core model with additional independent predictors of 3-year mortality (i.e., diabetes mellitus, peripheral vascular disease, and body mass index). RESULTS The revised Logistic Clinical SYNTAX models showed better discriminative ability than the anatomic SYNTAX score for the prediction of 3-year mortality after PCI (c-index: SYNTAX score, 0.61; core model, 0.71; and extended model, 0.73 in a cross-validation procedure). The extended model in particular performed better in differentiating low- and intermediate-risk groups. CONCLUSIONS Risk scores combining clinical characteristics with the anatomic SYNTAX score substantially better predict 3-year mortality than the SYNTAX score alone and should be used for long-term risk stratification of patients undergoing PCI.

A Swiss paradox? Higher income inequality of municipalities is associated with lower mortality in Switzerland.

It has long been surmised that income inequality within a society negatively affects public health. However, more recent studies suggest there is no association, especially when analyzing small areas. This study aimed to evaluate the effect of income inequality on mortality in Switzerland using the Gini index on municipality level. The study population included all individuals >30 years at the 2000 Swiss census (N = 4,689,545) living in 2,740 municipalities with 35.5 million person-years of follow-up and 456,211 deaths over follow-up. Cox proportional hazard regression models were adjusted for age, gender, marital status, nationality, urbanization, and language region. Results were reported as hazard ratios (HR) with 95 % confidence intervals. The mean Gini index across all municipalities was 0.377 (standard deviation 0.062, range 0.202-0.785). Larger cities, high-income municipalities and tourist areas had higher Gini indices. Higher income inequality was consistently associated with lower mortality risk, except for death from external causes. Adjusting for sex, marital status, nationality, urbanization and language region only slightly attenuated effects. In fully adjusted models, hazards of all-cause mortality by increasing Gini index quintile were HR = 0.99 (0.98-1.00), HR = 0.98 (0.97-0.99), HR = 0.95 (0.94-0.96), HR = 0.91 (0.90-0.92) compared to the lowest quintile. The relationship of income inequality with mortality in Switzerland is contradictory to what has been found in other developed high-income countries. Our results challenge current beliefs about the effect of income inequality on mortality on small area level. Further investigation is required to expose the underlying relationship between income inequality and population health.

The impact of prolonged lower limb ischemia on amputation, mortality, and functional status: the FRIENDS registry.

BACKGROUND Peripheral artery disease (PAD) is a major cause of cardiovascular ischemic events and amputation. Knowledge gaps exist in defining and measuring key factors that predict these events. The objective of this study was to assess whether duration of limb ischemia would serve as a major predictor of limb and patient survival. METHODS The FReedom from Ischemic Events: New Dimensions for Survival (FRIENDS) registry enrolled consecutive patients with limb-threatening peripheral artery disease at a single tertiary care hospital. Demographic information, key clinical care time segments, functional status and use of revascularization, and pharmacotherapy data were collected at baseline, and vascular ischemic events, cardiovascular mortality, and all-cause mortality were recorded at 30 days and 1 year. RESULTS A total of 200 patients with median (interquartile range) age of 76 years (65-84 years) were enrolled in the registry. Median duration of limb ischemia was 0.75 days for acute limb ischemia (ALI) and 61 days for chronic critical limb ischemia (CLI). Duration of limb ischemia of <12, 12 to 24, and >24 hours in patients with ALI was associated with much higher rates of first amputation (P = .0002) and worse amputation-free survival (P = .037). No such associations were observed in patients with CLI. CONCLUSIONS For individuals with ischemic symptoms <14 days, prolonged limb ischemia is associated with higher 30-day and 1-year amputation, systemic ischemic event rates, and worse amputation-free survival. No such associations are evident for individuals with chronic CLI. These data imply that prompt diagnosis and revascularization might improve outcomes for patients with ALI.

Evolving biomarkers improve prediction of long-term mortality in patients with stable coronary artery disease: the BIO-VILCAD score.

OBJECTIVE Algorithms to predict the future long-term risk of patients with stable coronary artery disease (CAD) are rare. The VIenna and Ludwigshafen CAD (VILCAD) risk score was one of the first scores specifically tailored for this clinically important patient population. The aim of this study was to refine risk prediction in stable CAD creating a new prediction model encompassing various pathophysiological pathways. Therefore, we assessed the predictive power of 135 novel biomarkers for long-term mortality in patients with stable CAD. DESIGN, SETTING AND SUBJECTS We included 1275 patients with stable CAD from the LUdwigshafen RIsk and Cardiovascular health study with a median follow-up of 9.8 years to investigate whether the predictive power of the VILCAD score could be improved by the addition of novel biomarkers. Additional biomarkers were selected in a bootstrapping procedure based on Cox regression to determine the most informative predictors of mortality. RESULTS The final multivariable model encompassed nine clinical and biochemical markers: age, sex, left ventricular ejection fraction (LVEF), heart rate, N-terminal pro-brain natriuretic peptide, cystatin C, renin, 25OH-vitamin D3 and haemoglobin A1c. The extended VILCAD biomarker score achieved a significantly improved C-statistic (0.78 vs. 0.73; P = 0.035) and net reclassification index (14.9%; P < 0.001) compared to the original VILCAD score. Omitting LVEF, which might not be readily measureable in clinical practice, slightly reduced the accuracy of the new BIO-VILCAD score but still significantly improved risk classification (net reclassification improvement 12.5%; P < 0.001). CONCLUSION The VILCAD biomarker score based on routine parameters complemented by novel biomarkers outperforms previous risk algorithms and allows more accurate classification of patients with stable CAD, enabling physicians to choose more personalized treatment regimens for their patients.

Electrolyte disorders and in-hospital mortality during prolonged heat periods: a cross-sectional analysis

BACKGROUND Heat periods during recent years were associated with excess hospitalization and mortality rates, especially in the elderly. We intended to study whether prolonged warmth/heat periods are associated with an increased prevalence of disorders of serum sodium and potassium and an increased hospital mortality. METHODS In this cross-sectional analysis all patients admitted to the Department of Emergency Medicine of a large tertiary care facility between January 2009 and December 2010 with measurements of serum sodium were included. Demographic data along with detailed data on diuretic medication, length of hospital stay and hospital mortality were obtained for all patients. Data on daily temperatures (maximum, mean, minimum) and humidity were retrieved by Meteo Swiss. RESULTS A total of 22.239 patients were included in the study. 5 periods with a temperature exceeding 25 °C for 3 to 5 days were noticed and 2 periods with temperatures exceeding 25 °C for more than 5 days were noted. Additionally, 2 periods with 3 to 5 days with daily temperatures exceeding 30 °C were noted during the study period. We found a significantly increased prevalence of hyponatremia during heat periods. However, in the Cox regression analysis, prolonged heat was not associated with the prevalence of disorders of serum sodium or potassium. Admission during a heat period was an independent predictor for hospital mortality. CONCLUSIONS Although we found an increased prevalence of hyponatremia during heat periods, no convincing connection could be found for hypernatremia or disorders of serum potassium.

The ADO index as a predictor of two-year mortality in general practice-based chronic obstructive pulmonary disease cohorts.

BACKGROUND Existing prediction models for mortality in chronic obstructive pulmonary disease (COPD) patients have not yet been validated in primary care, which is where the majority of patients receive care. OBJECTIVES Our aim was to validate the ADO (age, dyspnoea, airflow obstruction) index as a predictor of 2-year mortality in 2 general practice-based COPD cohorts. METHODS Six hundred and forty-six patients with COPD with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV were enrolled by their general practitioners and followed for 2 years. The ADO regression equation was used to predict a 2-year risk of all-cause mortality in each patient and this risk was compared with the observed 2-year mortality. Discrimination and calibration were assessed as well as the strength of association between the 15-point ADO score and the observed 2-year all-cause mortality. RESULTS Fifty-two (8.1%) patients died during the 2-year follow-up period. Discrimination with the ADO index was excellent with an area under the curve of 0.78 [95% confidence interval (CI) 0.71-0.84]. Overall, the predicted and observed risks matched well and visual inspection revealed no important differences between them across 10 risk classes (p = 0.68). The odds ratio for death per point increase according to the ADO index was 1.50 (95% CI 1.31-1.71). CONCLUSIONS The ADO index showed excellent prediction properties in an out-of-population validation carried out in COPD patients from primary care settings.

Increased mortality after a first myocardial infarction in human immunodeficiency virus-infected patients; a nested cohort study.

AIMS HIV infection may be associated with an increased recurrence rate of myocardial infarction. Our aim was to determine whether HIV infection is a risk factor for worse outcomes in patients with coronaray artery disease. METHODS We compared data aggregated from two ongoing cohorts: (i) the Acute Myocardial Infarction in Switzerland (AMIS) registry, which includes patients with acute myocardial infarction (AMI), and (ii) the Swiss HIV Cohort Study (SHCS), a prospective registry of HIV-positive (HIV+) patients. We included all patients who survived an incident AMI occurring on or after 1st January 2005. Our primary outcome measure was all-cause mortality at one year; secondary outcomes included AMI recurrence and cardiovascular-related hospitalisations. Comparisons used Cox and logistic regression analyses, respectively. RESULTS There were 133 HIV+, (SHCS) and 5,328 HIV-negative [HIV-] (AMIS) individuals with incident AMI. In the SHCS and AMIS registries, patients were predominantly male (72% and 85% male, respectively), with a median age of 51 years (interquartile range [IQR] 46-57) and 64 years (IQR 55-74), respectively. Nearly all (90%) of HIV+ individuals were on successful antiretroviral therapy. During the first year of follow-up, 5 (3.6%) HIV+ and 135 (2.5%) HIV- individuals died. At one year, HIV+ status after adjustment for age, sex, calendar year of AMI, smoking status, hypertension and diabetes was associated with a higher risk of death (HR 4.42, 95% CI 1.73-11.27). There were no significant differences in recurrent AMIs (4 [3.0%] HIV+ and 146 [3.0%] HIV- individuals, OR 1.16, 95% CI 0.41-3.27) or in hospitalization rates (OR 0.68 [95% CI 0.42-1.11]). CONCLUSIONS HIV infection was associated with a significantly increased risk of all-cause mortality one year after incident AMI.

An Unscathed Past in the Face of Death: Mortality Salience Reduces Individuals’ Regrets

Folk wisdom and popular literature hold that, in the face of death, individuals tend to regret things in their lives that they have done or failed to do. Terror Management Theory (TMT), in contrast, allows for the prediction that individuals who are confronted with death try to minimize the experience of regret in order to retain a positive self-esteem. Three experiments put these competing perspectives to test. Drawing on TMT, we hypothesized and found that participants primed with their own death regret fewer things than control-group participants. This pattern of results cannot be attributed to differing types of regrets (Study 1). Furthermore, we provide evidence suggesting that the effect is not purely a product of cognitive mechanisms such as differing levels of construal (Study 2), cognitive contrast, or deficits (Study 3). Rather, the reported results are best explained in terms of a motivational coping mechanism: When death is salient, individuals strive to bolster as well as protect their self-esteem and accordingly try to minimize the experience of regret. The results add to our conceptual understanding of regret and TMT, and suggest that a multitude of lifestyle guidebooks need updating.

Mortality in patients with HIV-1 infection starting antiretroviral therapy in South Africa, Europe, or North America: a collaborative analysis of prospective studies.

BACKGROUND High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. METHODS AND FINDINGS Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. CONCLUSIONS After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary.

Injury severity and mortality of adult zebra crosswalk and non-zebra crosswalk road crossing accidents: a cross-sectional analysis

PRINCIPALS Over a million people worldwide die each year from road traffic injuries and more than 10 million sustain permanent disabilities. Many of these victims are pedestrians. The present retrospective study analyzes the severity and mortality of injuries suffered by adult pedestrians, depending on whether they used a zebra crosswalk. METHODS Our retrospective data analysis covered adult patients admitted to our emergency department (ED) between 1 January 2000 and 31 December 2012 after being hit by a vehicle while crossing the road as a pedestrian. Patients were identified by using a string term. Medical, police and ambulance records were reviewed for data extraction. RESULTS A total of 347 patients were eligible for study inclusion. Two hundred and three (203; 58.5%) patients were on a zebra crosswalk and 144 (41.5%) were not. The mean ISS (injury Severity Score) was 12.1 (SD 14.7, range 1-75). The vehicles were faster in non-zebra crosswalk accidents (47.7 km/n, versus 41.4 km/h, p<0.027). The mean ISS score was higher in patients with non-zebra crosswalk accidents; 14.4 (SD 16.5, range 1-75) versus 10.5 (SD13.14, range 1-75) (p<0.019). Zebra crosswalk accidents were associated with less risk of severe injury (OR 0.61, 95% CI 0.38-0.98, p<0.042). Accidents involving a truck were associated with increased risk of severe injury (OR 3.53, 95%CI 1.21-10.26, p<0.02). CONCLUSION Accidents on zebra crosswalks are more common than those not on zebra crosswalks. The injury severity of non-zebra crosswalk accidents is significantly higher than in patients with zebra crosswalk accidents. Accidents involving large vehicles are associated with increased risk of severe injury. Further prospective studies are needed, with detailed assessment of motor vehicle types and speed.

Retrocrural space involvement on computed tomography as a predictor of mortality and disease severity in acute pancreatitis

BACKGROUND Because computed tomography (CT) has advantages for visualizing the manifestation of necrosis and local complications, a series of scoring systems based on CT manifestations have been developed for assessing the clinical outcomes of acute pancreatitis (AP), including the CT severity index (CTSI), modified CTSI, etc. Despite the internationally accepted CTSI having been successfully used to predict the overall mortality and disease severity of AP, recent literature has revealed the limitations of the CTSI. Using the Delphi method, we establish a new scoring system based on retrocrural space involvement (RCSI), and compared its effectiveness at evaluating the mortality and severity of AP with that of the CTSI. METHODS We reviewed CT images of 257 patients with AP taken within 3-5 days of admission in 2012. The RCSI scoring system, which includes assessment of infectious conditions involving the retrocrural space and the adjacent pleural cavity, was established using the Delphi method. Two radiologists independently assessed the RCSI and CTSI scores. The predictive points of the RCSI and CTSI scoring systems in evaluating the mortality and severity of AP were estimated using receiver operating characteristic (ROC) curves. PRINCIPAL FINDINGS The RCSI score can accurately predict the mortality and disease severity. The area under the ROC curve for the RCSI versus CTSI score was 0.962±0.011 versus 0.900±0.021 for predicting the mortality, and 0.888±0.025 versus 0.904±0.020 for predicting the severity of AP. Applying ROC analysis to our data showed that a RCSI score of 4 was the best cutoff value, above which mortality could be identified. CONCLUSION The Delphi method was innovatively adopted to establish a scoring system to predict the clinical outcome of AP. The RCSI scoring system can predict the mortality of AP better than the CTSI system, and the severity of AP equally as well.

All-Cause Mortality and Liver-Related Outcomes Following Successful Antiviral Treatment for Chronic Hepatitis C

BACKGROUND: Antiviral therapy for the hepatitis C virus (HCV) reduces all-cause and liver-related morbidity and mortality. Few studies are available from populations with multiple medical and psychiatric comorbidities where the impact of successful antiviral therapy might be limited. AIM: The purpose of this study was to determine the effect of sustained virologic response (SVR) on all-cause and liver-related mortality in a cohort of HCV patients treated in an integrated hepatitis/mental health clinic. METHODS: This was a retrospective review of all patients who initiated antiviral treatment for chronic HCV between January 1, 1997 and December 31, 2009. Cox regression analysis was used to determine factors involved in all-cause mortality, liver-related events and hepatocellular carcinoma. RESULTS: A total of 536 patients were included in the analysis. Median follow-up was 7.5 years. Liver and non-liver-related mortality occurred in 2.7 and 5.0 % of patients with SVR and in 17.8 and 6.4 % of patients without SVR. In a multivariate analysis, SVR was the only factor associated with reduced all-cause mortality (HR 0.47; 95 % CI 0.26-0.85; p = 0.012) and reduced liver-related events (HR 0.23; 95 % CI 0.08-0.66, p = 0.007). Having stage 4 liver fibrosis increased all-cause mortality (HR 2.50; 95 % CI 1.23-5.08; p = 0.011). Thrombocytopenia at baseline (HR 2.66; 95 % CI 1.22-5.79; p = 0.014) and stage 4 liver fibrosis (HR 4.87; 95 % CI 1.62-14.53; p = 0.005) increased liver-related events. CONCLUSIONS: Despite significant medical and psychiatric comorbidities, SVR markedly reduced liver-related outcomes without a significant change in non-liver-related mortality after a median follow-up of 7.5 years.

Body composition and all-cause mortality in subjects older than 65 y.

BACKGROUND A low or high body mass index (BMI) has been associated with increased mortality risk in older subjects without taking fat mass index (FMI) and fat-free mass index (FFMI) into account. This information is essential because FMI is modulated through different healthcare strategies than is FFMI. OBJECTIVE We aimed to determine the relation between body composition and mortality in older subjects. DESIGN We included all adults ≥65 y old who were living in Switzerland and had a body-composition measurement by bioelectrical impedance analysis at the Geneva University Hospitals between 1990 and 2011. FMI and FFMI were divided into sex-specific quartiles. Quartile 1 (i.e., the reference category) corresponded to the lowest FMI or FFMI quartile. Mortality data were retrieved from the hospital database, the Geneva death register, and the Swiss National Cohort until December 2012. Comorbidities were assessed by using the Cumulative Illness Rating Scale. RESULTS Of 3181 subjects included, 766 women and 1007 men died at a mean age of 82.8 and 78.5 y, respectively. Sex-specific Cox regression models, which were used to adjust for age, BMI, smoking, ambulatory or hospitalized state, and calendar time, showed that body composition did not predict mortality in women irrespective of whether comorbidities were taken into account. In men, risk of mortality was lower with FFMI in quartiles 3 and 4 [HR: 0.78 (95% CI: 0.62, 0.98) and 0.64 (95% CI: 0.49, 0.85), respectively] but was not affected by FMI. When comorbidities were adjusted for, FFMI in quartile 4 (>19.5 kg/m(2)) still predicted a lower risk of mortality (HR: 0.72; 95% CI: 0.54, 0.96). CONCLUSIONS Low FFMI is a stronger predictor of mortality than is BMI in older men but not older women. FMI had no impact on mortality. These results suggest potential benefits of preventive interventions with the aim of maintaining muscle mass in older men. This trial was registered at clinicaltrials.gov as NCT01472679.

High Hepatic and Extrahepatic Mortality and Low Treatment Uptake in HCV-coinfected Persons in the Swiss HIV Cohort Study between 2001 and 2013

BACKGROUND & AIMS The landscape of HCV treatments is changing dramatically. At the beginning of this new era, we highlight the challenges for HCV-therapy by assessing the long-term epidemiological trends in treatment uptake, efficacy and mortality among HIV/HCV-coinfected people since the availability of HCV therapy. METHODS We included all SHCS participants with detectable HCV RNA between 2001 and 2013. To identify predictors for treatment uptake uni- and multivariable Poisson regression models were applied. We further used survival analyses with Kaplan-Meier curves and Cox regression with drop-out as competing risk. RESULTS Of 12,401 participants 2107 (17%) were HCV RNA positive. Of those, 636 (30%) started treatment with an incidence of 5.8/100 person years (PY) (95% CI 5.3-6.2). Sustained virological response (SVR) with pegylated interferon/ribavirin was achieved in 50% of treated patients, representing 15% of all participants with replicating HCV infection. 344 of 2107 (16%) HCV RNA positive persons died, 59% from extrahepatic causes. Mortality/100 PY was 2.9 (95% CI 2.6-3.2) in untreated patients, 1.3 (1.0-1.8) in those treated with failure, and 0.6 (0.4-1.0) in patients with SVR. In 2013, 869/2107 (41%) participants remained HCV RNA positive. CONCLUSIONS Over the last 13 years HCV treatment uptake was low and by the end of 2013, a large number of persons remain to be treated. Mortality was high, particularly in untreated patients, and mainly due to non-liver related causes. Accordingly, in HIV/HCV-coinfected patients, integrative care including the diagnosis and therapy of somatic and psychiatric disorders is important to achieve mortality rates similar to HIV-monoinfected patients.