Matched-pair analysis of endovascular versus open surgical repair of abdominal aortic aneurysms in young patients at low risk

PURPOSE: To compare clinical outcomes of endovascular and open aortic repair of abdominal aortic aneurysms (AAAs) in young patients at low risk. It was hypothesized that endovascular aneurysm repair (EVAR) compares favorably with open aneurysm repair (OAR) in these patients. MATERIALS AND METHODS: Twenty-five patients aged 65 years or younger with a low perioperative surgical risk profile underwent EVAR at a single institution between April 1994 and May 2007 (23 men; mean age, 62 years+/-2.8). A sex- and risk-matched control group of 25 consecutive patients aged 65 years or younger who underwent OAR was used as a control group (23 men; mean age, 59 years+/-3.9). Patient outcomes and complications were classified according to Society of Vascular Surgery/International Society for Cardiovascular Surgery reporting standards. RESULTS: Mean follow-up times were 7.1 years+/-3.2 after EVAR and 5.9 years+/-1.8 after OAR (P=.1020). Total complication rates were 20% after EVAR and 52% after OAR (P=.0378), and all complications were mild or moderate. Mean intensive care unit times were 0.2 days+/-0.4 after EVAR and 1.1 days+/-0.4 after OAR (P<.0001) and mean lengths of hospital stay were 2.3 days+/-1.0 after EVAR and 5.0 days+/-2.1 after OAR (P<.0001). Cumulative rates of long-term patient survival did not differ between EVAR and OAR (P=.144). No AAA-related deaths or aortoiliac ruptures occurred during follow-up for EVAR and OAR. In addition, no surgical conversions were necessary in EVAR recipients. Cumulative rates of freedom from secondary procedures were not significantly different between the EVAR and OAR groups (P=.418). Within a multivariable Cox proportional-hazards analysis adjusted for patient age, maximum AAA diameter, and cardiac risk score, all-cause mortality rates (odds ratio [OR], 0.125; 95% CI, 0.010-1.493; P=.100) and need for secondary procedures (OR, 5.014; 95% CI, 0.325-77.410; P=.537) were not different between EVAR and OAR. CONCLUSIONS: Results from this observational study indicate that EVAR offers a favorable alternative to OAR in young patients at low risk.

[Is resting heart rate a cardiovascular risk factor?]

During recent years, resting heart rate was not considered as a cardiovascular risk factor. However, new evidences have showed that resting heart rate is an important prognostic factor for sudden cardiac death and heart failure in the general population, and especially among patients with known cardiac disease. Interestingly, resting heart rate not only predicts cardiac mortality but also all-cause mortality. The most common pathophysiological explanation is related to the fact that increased heart rate increases myocardial oxygen consumption and in parallel reduces coronary blood flow (reduction in the diastolic duration).

Residence near power lines and mortality from neurodegenerative diseases: longitudinal study of the Swiss population

The relation between residential magnetic field exposure from power lines and mortality from neurodegenerative conditions was analyzed among 4.7 million persons of the Swiss National Cohort (linking mortality and census data), covering the period 2000-2005. Cox proportional hazard models were used to analyze the relation of living in the proximity of 220-380 kV power lines and the risk of death from neurodegenerative diseases, with adjustment for a range of potential confounders. Overall, the adjusted hazard ratio for Alzheimer's disease in persons living within 50 m of a 220-380 kV power line was 1.24 (95% confidence interval (CI): 0.80, 1.92) compared with persons who lived at a distance of 600 m or more. There was a dose-response relation with respect to years of residence in the immediate vicinity of power lines and Alzheimer's disease: Persons living at least 5 years within 50 m had an adjusted hazard ratio of 1.51 (95% CI: 0.91, 2.51), increasing to 1.78 (95% CI: 1.07, 2.96) with at least 10 years and to 2.00 (95% CI: 1.21, 3.33) with at least 15 years. The pattern was similar for senile dementia. There was little evidence for an increased risk of amyotrophic lateral sclerosis, Parkinson's disease, or multiple sclerosis.

Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials

BACKGROUND: Erythropoiesis-stimulating agents reduce anaemia in patients with cancer and could improve their quality of life, but these drugs might increase mortality. We therefore did a meta-analysis of randomised controlled trials in which these drugs plus red blood cell transfusions were compared with transfusion alone for prophylaxis or treatment of anaemia in patients with cancer. METHODS: Data for patients treated with epoetin alfa, epoetin beta, or darbepoetin alfa were obtained and analysed by independent statisticians using fixed-effects and random-effects meta-analysis. Analyses were by intention to treat. Primary endpoints were mortality during the active study period and overall survival during the longest available follow-up, irrespective of anticancer treatment, and in patients given chemotherapy. Tests for interactions were used to identify differences in effects of erythropoiesis-stimulating agents on mortality across prespecified subgroups. FINDINGS: Data from a total of 13 933 patients with cancer in 53 trials were analysed. 1530 patients died during the active study period and 4993 overall. Erythropoiesis-stimulating agents increased mortality during the active study period (combined hazard ratio [cHR] 1.17, 95% CI 1.06-1.30) and worsened overall survival (1.06, 1.00-1.12), with little heterogeneity between trials (I(2) 0%, p=0.87 for mortality during the active study period, and I(2) 7.1%, p=0.33 for overall survival). 10 441 patients on chemotherapy were enrolled in 38 trials. The cHR for mortality during the active study period was 1.10 (0.98-1.24), and 1.04 (0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients given different anticancer treatments (p for interaction=0.42). INTERPRETATION: Treatment with erythropoiesis-stimulating agents in patients with cancer increased mortality during active study periods and worsened overall survival. The increased risk of death associated with treatment with these drugs should be balanced against their benefits. FUNDING: German Federal Ministry of Education and Research, Medical Faculty of University of Cologne, and Oncosuisse (Switzerland).

Risk of acute kidney injury in patients with severe aortic valve stenosis undergoing transcatheter valve replacement

BACKGROUND: Transcatheter aortic valve implantation (TAVI) for high-risk and inoperable patients with severe aortic stenosis is an emerging procedure in cardiovascular medicine. Little is known of the impact of TAVI on renal function. METHODS: We analysed retrospectively renal baseline characteristics and outcome in 58 patients including 2 patients on chronic haemodialysis undergoing TAVI at our institution. Acute kidney injury (AKI) was defined according to the RIFLE classification. RESULTS: Fifty-eight patients with severe symptomatic aortic stenosis not considered suitable for conventional surgical valve replacement with a mean age of 83 +/- 5 years underwent TAVI. Two patients died during transfemoral valve implantation and two patients in the first month after TAVI resulting in a 30-day mortality of 6.9%. Vascular access was transfemoral in 46 patients and transapical in 12. Estimated glomerular filtration rate (eGFR) increased in 30 patients (56%). Fifteen patients (28%) developed AKI, of which four patients had to be dialyzed temporarily and one remained on chronic renal replacement therapy. Risk factors for AKI comprised, among others, transapical access, number of blood transfusions, postinterventional thrombocytopaenia and severe inflammatory response syndrome (SIRS). CONCLUSIONS: TAVI is feasible in patients with a high burden of comorbidities and in patients with pre-existing end-stage renal disease who would be otherwise not considered as candidates for conventional aortic valve replacement. Although GFR improved in more than half of the patients, this benefit was associated with a risk of postinterventional AKI. Future investigations should define preventive measures of peri-procedural kidney injury.

A comparison of patient characteristics and 30-day mortality outcomes after transcatheter aortic valve implantation and surgical aortic valve replacement for the treatment of aortic stenosis: a two-centre study

AIMS: It is unclear whether transcatheter aortic valve implantation (TAVI) addresses an unmet clinical need for those currently rejected for surgical aortic valve replacement (SAVR) and whether there is a subgroup of high-risk patients benefiting more from TAVI compared to SAVR. In this two-centre, prospective cohort study, we compared baseline characteristics and 30-day mortality between TAVI and SAVR in consecutive patients undergoing invasive treatment for aortic stenosis. METHODS AND RESULTS: We pre-specified different adjustment methods to examine the effect of TAVI as compared with SAVR on overall 30-day mortality: crude univariable logistic regression analysis, multivariable analysis adjusted for baseline characteristics, analysis adjusted for propensity scores, propensity score matched analysis, and weighted analysis using the inverse probability of treatment (IPT) as weights. A total of 1,122 patients were included in the study: 114 undergoing TAVI and 1,008 patients undergoing SAVR. The crude mortality rate was greater in the TAVI group (9.6% vs. 2.3%) yielding an odds ratio [OR] of 4.57 (95%-CI 2.17-9.65). Compared to patients undergoing SAVR, patients with TAVI were older, more likely to be in NYHA class III and IV, and had a considerably higher logistic EuroSCORE and more comorbid conditions. Adjusted OR depended on the method used to control for confounding and ranged from 0.60 (0.11-3.36) to 7.57 (0.91-63.0). We examined the distribution of propensity scores and found scores to overlap sufficiently only in a narrow range. In patients with sufficient overlap of propensity scores, adjusted OR ranged from 0.35 (0.04-2.72) to 3.17 (0.31 to 31.9). In patients with insufficient overlap, we consistently found increased odds of death associated with TAVI compared with SAVR irrespective of the method used to control confounding, with adjusted OR ranging from 5.88 (0.67-51.8) to 25.7 (0.88-750). Approximately one third of patients undergoing TAVI were found to be potentially eligible for a randomised comparison of TAVI versus SAVR. CONCLUSIONS: Both measured and unmeasured confounding limit the conclusions that can be drawn from observational comparisons of TAVI versus SAVR. Our study indicates that TAVI could be associated with either substantial benefits or harms. Randomised comparisons of TAVI versus SAVR are warranted.

A case-control study of sporadic Creutzfeldt-Jakob disease in Switzerland: analysis of potential risk factors with regard to an increased CJD incidence in the years 2001-2004

BACKGROUND: In 2001, the observed annual mortality from Creutzfeldt-Jakob disease (CJD) in Switzerland increased from less than 1.5 to 2.6 per million inhabitants. An underlying cause could not be identified. METHODS: To analyse potential risk factors for sCJD in Switzerland, close relatives of 69 sCJD-patients and 224 frequency age-matched controls were interviewed in a case-control study using a standardised questionnaire. 135 potential risk factors including socio-demographics, medical history, occupation and diet were analysed by logistic regression adjusting for age, sex and education. RESULTS: sCJD patients were more likely to have travelled abroad, worked at an animal laboratory, undergone invasive dental treatment, orthopaedic surgery, ophthalmologic surgery after 1980, regular GP visits, taken medication regularly, and consumed kidney. No differences between patients and controls were found for residency, family history, and exposure to environmental and other dietary factors. CONCLUSION: Although some factors were significantly more frequent among sCJD-cases, this study did not reveal specific explanations for the increased incidence of deaths due to sporadic CJD observed in Switzerland since 2001. Results have to be interpreted with caution due to multiple testing and possible recall bias in association with a long incubation period. The most plausible reason for the increase in Swiss sCJD cases after 2000 is an improved case ascertainment. Therefore, underreporting of cases might well have occurred before the year 2001, and the "real" yearly incidence of sCJD might not be lower than, but rather above 2 per million inhabitants.

Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial

INTRODUCTION: It is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock. METHODS: This is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP > or = 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles > or = 70 mmHg and mortality or the frequency and occurrence of disease-related events. RESULTS: There was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.28-2.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.38-2.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01). CONCLUSIONS: MAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. Elevating MAP >70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.

Quality controls for two heel bone ultrasounds used in the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk Study

Because of the important morbidity and mortality associated with osteoporosis, it is essential to detect subjects at risk by screening methods, such as bone quantitative ultrasounds (QUSs). Several studies showed that QUS could predict fractures. None, however, compared prospectively different QUS devices, and few data of quality controls (QCs) have been published. The Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk is a prospective multicenter study that compared three QUSs for the assessment of hip fracture risk in a population of 7609 women age >/=70 yr. Because the inclusion phase lasted 20 mo, and because 10 centers participated in this study, QC became a major issue. We therefore developed a QC procedure to assess the stability and precision of the devices, and for their cross-calibration. Our study focuses on the two heel QUSs. The water bath system (Achilles+) had a higher precision than the dry system (Sahara). The QC results were highly dependent on temperature. QUS stability was acceptable, but Sahara must be calibrated regularly. A sufficient homogeneity among all the Sahara devices could be demonstrated, whereas significant differences were found among the Achilles+ devices. For speed of sound, 52% of the differences among the Achilles+ was explained by the water s temperature. However, for broadband ultrasound attenuation, a maximal difference of 23% persisted after adjustment for temperature. Because such differences could influence measurements in vivo, it is crucial to develop standardized phantoms to be used in prospective multicenter studies.

Treatment response and mortality among patients starting antiretroviral therapy with and without Kaposi sarcoma: a cohort study

BACKGROUND Improved survival among HIV-infected individuals on antiretroviral therapy (ART) has focused attention on AIDS-related cancers including Kaposi sarcoma (KS). However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART. METHODS We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment. RESULTS Between January 2001-January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n = 247, 2%) were similar to those without KS (n = 13600,98%) with respect to age (35 vs. 35yrs), presenting CD4 count (74 vs. 85cells/mm³) and proportion on TB treatment (37% vs. 30%). In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71-4.84) than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95-5.55) and attenuated thereafter (HR: 2.30; 95% CI: 1.08-4.89). Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7-52cells/mm³) and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99-2.06) within the first 6-months of treatment. CONCLUSIONS HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS demonstrated a poorer immunologic response to ART than those without KS.

CD4 count slope and mortality in HIV-infected patients on antiretroviral therapy: multicohort analysis from South Africa

BACKGROUND In many resource-limited settings monitoring of combination antiretroviral therapy (cART) is based on the current CD4 count, with limited access to HIV RNA tests or laboratory diagnostics. We examined whether the CD4 count slope over 6 months could provide additional prognostic information. METHODS We analyzed data from a large multicohort study in South Africa, where HIV RNA is routinely monitored. Adult HIV-positive patients initiating cART between 2003 and 2010 were included. Mortality was analyzed in Cox models; CD4 count slope by HIV RNA level was assessed using linear mixed models. RESULTS About 44,829 patients (median age: 35 years, 58% female, median CD4 count at cART initiation: 116 cells/mm) were followed up for a median of 1.9 years, with 3706 deaths. Mean CD4 count slopes per week ranged from 1.4 [95% confidence interval (CI): 1.2 to 1.6] cells per cubic millimeter when HIV RNA was <400 copies per milliliter to -0.32 (95% CI: -0.47 to -0.18) cells per cubic millimeter with >100,000 copies per milliliter. The association of CD4 slope with mortality depended on current CD4 count: the adjusted hazard ratio (aHRs) comparing a >25% increase over 6 months with a >25% decrease was 0.68 (95% CI: 0.58 to 0.79) at <100 cells per cubic millimeter but 1.11 (95% CI: 0.78 to 1.58) at 201-350 cells per cubic millimeter. In contrast, the aHR for current CD4 count, comparing >350 with <100 cells per cubic millimeter, was 0.10 (95% CI: 0.05 to 0.20). CONCLUSIONS Absolute CD4 count remains a strong risk for mortality with a stable effect size over the first 4 years of cART. However, CD4 count slope and HIV RNA provide independently added to the model.

Incidence and risk factors of homicide-suicide in Swiss households: National Cohort study

BACKGROUND Homicide-suicides are rare but catastrophic events. This study examined the epidemiology of homicide-suicide in Switzerland. METHODS The study identified homicide-suicide events 1991-2008 in persons from the same household in the Swiss National Cohort, which links census and mortality records. The analysis examined the association of the risk of dying in a homicide-suicide event with socio-demographic variables, measured at the individual-level, household composition variables and area-level variables. Proportional hazards regression models were calculated for male perpetrators and female victims. Results are presented as age-adjusted hazard ratios (HR) with 95% confidence intervals (95%CI). RESULTS The study identified 158 deaths from homicide-suicide events, including 85 murder victims (62 women, 4 men, 19 children and adolescents) and 68 male and 5 female perpetrators. The incidence was 3 events per million households and year. Firearms were the most prominent method for both homicides and suicides. The risk of perpetrating homicide-suicide was higher in divorced than in married men (HR 3.64; 95%CI 1.56-8.49), in foreigners without permanent residency compared to Swiss citizens (HR 3.95; 1.52-10.2), higher in men without religious affiliations than in Catholics (HR 2.23; 1.14-4.36) and higher in crowded households (HR 4.85; 1.72-13.6 comparing ≥2 with <1 persons/room). There was no association with education, occupation or nationality, the number of children, the language region or degree of urbanicity. Associations were similar for female victims. CONCLUSIONS This national longitudinal study shows that living conditions associated with psychological stress and lower levels of social support are associated with homicide-suicide events in Switzerland.

Risk factors for death and unwanted early slaughter in Swiss veal calves kept at a specific animal welfare standard

Calf losses (CL, mortality and unwanted early slaughter) in veal production are of great economic importance and an indicator of welfare. The objective of the present study was to evaluate CL and the causes of death on farms with a specific animal welfare standard (SAW) which exceeds the Swiss statutory regulations. Risk factors for CL were identified based on information about management, housing, feeding, and medication. In total, 74 production cohorts (2783 calves) of 15 farms were investigated. CL was 3.6%, the main causes of death were digestive disorders (52%), followed by respiratory diseases (28%). Factors significantly associated with an increased risk for CL were a higher number of individual daily doses of antibiotics (DDA), insufficient wind deflection in winter, and male gender. For administration of antibiotics to all calves of the cohort, a DDA of 14-21 was associated with a decreased risk for CL compared to a DDA of 7-13 days.

Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe

Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death. This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (<3 months, 3-12 months or >12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three- to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died <3 months, 3-12 months or >12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p<0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death. Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region.

Reduced estimated GFR and cancer mortality.

BACKGROUND Chronic kidney disease is associated with an increased risk of cancer, but whether reduced kidney function also leads to increased cancer mortality is uncertain. The aim of our study was to assess the independent effects of reduced kidney function on the risk of cancer deaths. STUDY DESIGN Prospective population-based cohort study. SETTING & PARTICIPANTS Participants of the Blue Mountains Eye Study (n=4,077; aged 49-97 years). PREDICTOR Estimated glomerular filtration rate (eGFR). OUTCOMES Overall and site-specific cancer mortality. RESULTS During a median follow-up of 12.8 (IQR, 8.6-15.8) years, 370 cancer deaths were observed in our study cohort. For every 10-mL/min/1.73 m(2) reduction in eGFR, there was an increase in cancer-specific mortality of 18% in the fully adjusted model (P<0.001). Compared with participants with eGFR ≥ 60 mL/min/1.73 m(2), the adjusted HR for cancer-specific mortality for those with eGFR<60 mL/min/1.73 m(2) was 1.27 (95% CI, 1.00-1.60; P=0.05). This excess cancer mortality varied with site, with the greatest risk for breast and urinary tract cancer deaths (adjusted HRs of 1.99 [95% CI, 1.05-3.85; P=0.01] and 2.54 [95% CI, 1.02-6.44; P=0.04], respectively). LIMITATIONS Residual confounding, such as from unmeasured socioeconomic factors and the potential effects of erythropoiesis-stimulating agents on cancer deaths, may have occurred. CONCLUSIONS eGFR<60 mL/min/1.73m(2) appears to be a significant risk factor for death from cancer. These effects appear to be site specific, with breast and urinary tract cancers incurring the greatest risk of death among those with reduced kidney function.