Glucocorticoid Replacement and Mortality in Patients with Nonfunctioning Pituitary Adenoma

Current treatment guidelines generally suggest using lower and weight-adjusted glucocorticoid replacement doses in patients with insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis. Although data in patients with acromegaly revealed a positive association between glucocorticoid dose and mortality, no comparable results exist in patients with nonfunctioning pituitary adenomas (NFPA).

Complicated intra-abdominal infections in Europe: preliminary data from the first three months of the CIAO Study

The CIAO Study is a multicenter observational study currently underway in 66 European medical institutions over the course of a six-month study period (January-June 2012).This preliminary report overviews the findings of the first half of the study, which includes all data from the first three months of the six-month study period.Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.912 patients with a mean age of 54.4 years (range 4-98) were enrolled in the study during the first three-month period. 47.7% of the patients were women and 52.3% were men. Among these patients, 83.3% were affected by community-acquired IAIs while the remaining 16.7% presented with healthcare-associated infections. Intraperitoneal specimens were collected from 64.2% of the enrolled patients, and from these samples, 825 microorganisms were collectively identified.The overall mortality rate was 6.4% (58/912). According to univariate statistical analysis of the data, critical clinical condition of the patient upon hospital admission (defined by severe sepsis and septic shock) as well as healthcare-associated infections, non-appendicular origin, generalized peritonitis, and serious comorbidities such as malignancy and severe cardiovascular disease were all significant risk factors for patient mortality.White Blood Cell counts (WBCs) greater than 12,000 or less than 4,000 and core body temperatures exceeding 38°C or less than 36°C by the third post-operative day were statistically significant indicators of patient mortality.

Subclinical hyperthyroidism and the risk of coronary heart disease and mortality

Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting.We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts.

Impact of left ventricular hypertrophy late after aortic valve replacement for aortic stenosis on cardiovascular morbidity and mortality

AIMS: The goal of this study was to assess the prevalence of left ventricular (LV) hypertrophy in patients with aortic stenosis late (>6 months) after aortic valve replacement and its impact on cardiac-related morbidity and mortality. METHODS AND RESULTS: In a single tertiary centre, echocardiographic data of LV muscle mass were collected. Detailed information of medical history and angiographic data were gathered. Ninety-nine of 213 patients (46%) had LV hypertrophy late (mean 5.8 +/- 5.4 years) after aortic valve replacement. LV hypertrophy was associated with impaired exercise capacity, higher New York Heart Association dyspnoea class, a tendency for more frequent chest pain expressed as higher Canadian Cardiovascular Society class, and more rehospitalizations. 24% of patients with normal LV mass vs. 39% of patients with LV hypertrophy reported cardiac-related morbidity (p = 0.04). In a multivariate logistic regression model, LV hypertrophy was an independent predictor of cardiac-related morbidity (odds ratio 2.31, 95% CI 1.08 to 5.41), after correction for gender, baseline ejection fraction, and coronary artery disease and its risk factors. Thirty seven deaths occurred during a total of 1959 patient years of follow-up (mean follow-up 9.6 years). Age at aortic valve replacement (hazard ratio 1.85, 95% CI 1.39 to 2.47, for every 5 years increase in age), coexisting coronary artery disease at the time of surgery (hazard ratio 3.36, 95% CI 1.31 to 8.62), and smoking (hazard ratio 4.82, 95% CI 1.72 to 13.45) were independent predictors of overall mortality late after surgery, but not LV hypertrophy. CONCLUSIONS: In patients with aortic valve replacement for isolated aortic stenosis, LV hypertrophy late after surgery is associated with increased morbidity.

A simple presurgical necrotizing enterocolitis-mortality scoring system

OBJECTIVE: To assess the relationship between early laboratory parameters, disease severity, type of management (surgical or conservative) and outcome in necrotizing enterocolitis (NEC). STUDY DESIGN: Retrospective collection and analysis of data from infants treated in a single tertiary care center (1980 to 2002). Data were collected on disease severity (Bell stage), birth weight (BW), gestational age (GA) and pre-intervention laboratory parameters (leukocyte and platelet counts, hemoglobin, lactate, C-reactive protein). RESULTS: Data from 128 infants were sufficient for analysis. Factors significantly associated with survival were Bell stage (P<0.05), lactate (P<0.05), BW and GA (P<0.01, P<0.001, respectively). From receiver operating characteristics curves, the highest predictive value resulted from a score with 0 to 8 points combining BW, Bell stage, lactate and platelet count (P<0.001). At a cutoff level of 4.5 sensitivity and specificity for predicting survival were 0.71 and 0.72, respectively. CONCLUSION: Some single parameters were associated with poor outcome in NEC. Optimal risk stratification was achieved by combining several parameters in a score.

Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries

BACKGROUND: Highly active antiretroviral therapy (HAART) is being scaled up in developing countries. We compared baseline characteristics and outcomes during the first year of HAART between HIV-1-infected patients in low-income and high-income settings. METHODS: 18 HAART programmes in Africa, Asia, and South America (low-income settings) and 12 HIV cohort studies from Europe and North America (high-income settings) provided data for 4810 and 22,217, respectively, treatment-naive adult patients starting HAART. All patients from high-income settings and 2725 (57%) patients from low-income settings were actively followed-up and included in survival analyses. FINDINGS: Compared with high-income countries, patients starting HAART in low-income settings had lower CD4 cell counts (median 108 cells per muL vs 234 cells per muL), were more likely to be female (51%vs 25%), and more likely to start treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (70%vs 23%). At 6 months, the median number of CD4 cells gained (106 cells per muL vs 103 cells per muL) and the percentage of patients reaching HIV-1 RNA levels lower than 500 copies/mL (76%vs 77%) were similar. Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20,532 person-years). The adjusted hazard ratio (HR) of mortality comparing low-income with high-income settings fell from 4.3 (95% CI 1.6-11.8) during the first month to 1.5 (0.7-3.0) during months 7-12. The provision of treatment free of charge in low-income settings was associated with lower mortality (adjusted HR 0.23; 95% CI 0.08-0.61). INTERPRETATION: Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries. Timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART, might reduce this excess mortality.

Cellular telephone use and time trends in brain tumour mortality in Switzerland from 1969 to 2002

A rising concern exists that with the widespread use of mobile communication technologies, the incidence of brain tumours may increase. On the basis of data from the Swiss national mortality registry from 1969 to 2002, annual age-standardized brain tumour mortality rates per 100,000 person-years were calculated using the European standard population. Time trend analyses were performed by the Poisson regression for six different age groups in men and women separately. The study period was divided into two intervals: before and after 1987, when the analogue mobile technology was introduced in Switzerland. Age-standardized brain tumour mortality rates ranged between 3.7 and 6.7 for men and 2.5 and 4.4 for women per 100,000 person-years. For the whole study period, a significant increase in brain tumour mortality was observed for men and women in the older age groups (60-74 and 75+ years) but not in the younger ones in whom mobile phone use was more prevalent. Time trend analyses restricted to data from 1987 onwards revealed relatively stable brain tumour mortality rates in all age groups. For instance, the annual change in brain tumour mortality rate for the 45-59-year age group was -0.3% (95% confidence interval: -1.7; 1.1) for men and -0.4% (95% confidence interval:-2.2; 1.3) for women. We conclude that after the introduction of mobile phone technology in Switzerland, brain tumour mortality rates remained stable in all age groups. Our results suggest that mobile phone use is not a strong risk factor in the short term for mortality from brain tumours. Ecological analyses like this, however, are limited in their ability to reveal potentially small increases in risk for diseases with a long latency period.

[Survival, clinical data and quality of life 10 years after heart transplantation: a prospective study]

AIM: To study prospectively patients after heart transplantation with respect to quality of life, mortality, morbidity, and clinical parameters before and up to 10 years after the operation. METHODS: Sixty patients (47.9 +/- 10.9 years, 57 men, 3 women) were transplanted at the University of Vienna Hospital, Department for Heart and Thorax Surgery and were included in this study. They were assessed when set on the waiting list, then exactly one, 5 and 10 years after the transplantation. The variables evaluated included physical and emotional complaints, well-being, mortality and morbidity. In the sample of patients who survived 10 years (n = 23), morbidity (infections, malignancies, graft arteriosclerosis, and rejection episodes) as well as quality of life were evaluated. RESULTS: Actuarial survival rates were 83.3, 66.7, 48.3% at 1, 5, and 10 years after transplantation, respectively. During the first year, infections were the most important reasons for premature death. As a cause of mortality, malignancies were found between years 1 and 5, and graft arteriosclerosis between years 5 and 10. Physical complaints diminished significantly after the operation, but grew significantly during the period from 5 to 10 years (p < 0.001). However, trembling (p < 0.05) and paraesthesies (p < 0.01) diminished continuously. Emotional complaints such as depression and dysphoria (both p < 0.05) increased until the tenth year after their nadir at year 1. In long-time survivors, 3 malignancies (lung, skin, thyroidea) were diagnosed 6 to 9 years postoperatively. Three patients (13%) had signs of graft arteriosclerosis at year 10; 9 (40%) patients suffered from rejection episodes during the course of 10 years. There were no serious rejection episodes deserving immediate therapy. Quality of life at 10 years is good in these patients. CONCLUSIONS: Heart transplantation is a successful therapy for patients with terminal heart disease. Long-term survivors feel well after 10 years and report a good quality of life.

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.

Cardiovascular mortality and exposure to extremely low frequency magnetic fields: a cohort study of Swiss railway workers

BACKGROUND: Exposure to intermittent magnetic fields of 16 Hz has been shown to reduce heart rate variability, and decreased heart rate variability predicts cardiovascular mortality. We examined mortality from cardiovascular causes in railway workers exposed to varying degrees to intermittent 16.7 Hz magnetic fields. METHODS: We studied a cohort of 20,141 Swiss railway employees between 1972 and 2002, including highly exposed train drivers (median lifetime exposure 120.5 muT-years), and less or little exposed shunting yard engineers (42.1 muT-years), train attendants (13.3 muT-years) and station masters (5.7 muT-years). During 464,129 person-years of follow up, 5,413 deaths were recorded and 3,594 deaths were attributed to cardio-vascular diseases. We analyzed data using Cox proportional hazards models. RESULTS: For all cardiovascular mortality the hazard ratio compared to station masters was 0.99 (95%CI: 0.91, 1.08) in train drivers, 1.13 (95%CI: 0.98, 1.30) in shunting yard engineers, and 1.09 (95%CI: 1.00, 1.19) in train attendants. Corresponding hazard ratios for arrhythmia related deaths were 1.04 (95%CI: 0.68, 1.59), 0.58 (95%CI: 0.24, 1.37) and 10 (95%CI: 0.87, 1.93) and for acute myocardial infarction 1.00 (95%CI: 0.73, 1.36), 1.56 (95%CI: 1.04, 2.32), and 1.14 (95%CI: 0.85, 1.53). The hazard ratio for arrhythmia related deaths per 100 muT-years of cumulative exposure was 0.94 (95%CI: 0.71, 1.24) and 0.91 (95%CI: 0.75, 1.11) for acute myocardial infarction. CONCLUSION: This study provides evidence against an association between long-term occupational exposure to intermittent 16.7 Hz magnetic fields and cardiovascular mortality.

Long-term cardiovascular and non-cardiovascular mortality in women and men with type 1 and type 2 diabetes mellitus: a 30-year follow-up in Switzerland

While studies from other countries have shown an excess mortality in diabetic individuals when compared with the general population, comparable long-term data is not available for Switzerland.

Erythropoietin or Darbepoetin for patients with cancer--meta-analysis based on individual patient data

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) reduce anemia in cancer patients and may improve quality of life, but there are concerns that ESAs might increase mortality. OBJECTIVES: Our objectives were to examine the effect of ESAs and identify factors that modify the effects of ESAs on overall survival, progression free survival, thromboembolic and cardiovascular events as well as need for transfusions and other important safety and efficacy outcomes in cancer patients. SEARCH STRATEGY: We searched the Cochrane Library, Medline, Embase and conference proceedings for eligible trials. Manufacturers of ESAs were contacted to identify additional trials. SELECTION CRITERIA: We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusions (as necessary) versus red blood cell transfusions (as necessary) alone, to prevent or treat anemia in adult or pediatric cancer patients with or without concurrent antineoplastic therapy. DATA COLLECTION AND ANALYSIS: We performed a meta-analysis of randomized controlled trials comparing epoetin alpha, epoetin beta or darbepoetin alpha plus red blood cell transfusions versus transfusion alone, for prophylaxis or therapy of anemia while or after receiving anti-cancer treatment. Patient-level data were obtained and analyzed by independent statisticians at two academic departments, using fixed-effects and random-effects meta-analysis. Analyses were according to the intention-to-treat principle. Primary endpoints were on study mortality and overall survival during the longest available follow-up, regardless of anticancer treatment, and in patients receiving chemotherapy. Tests for interactions were used to identify differences in effects of ESAs on mortality across pre-specified subgroups. The present review reports only the results for the primary endpoint. MAIN RESULTS: A total of 13933 cancer patients from 53 trials were analyzed, 1530 patients died on-study and 4993 overall. ESAs increased on study mortality (combined hazard ratio [cHR] 1.17; 95% CI 1.06-1.30) and worsened overall survival (cHR 1.06; 95% CI 1.00-1.12), with little heterogeneity between trials (I(2) 0%, p=0.87 and I(2) 7.1%, p=0.33, respectively). Thirty-eight trials enrolled 10441 patients receiving chemotherapy. The cHR for on study mortality was 1.10 (95% CI 0.98-1.24) and 1.04; 95% CI 0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients receiving different cancer treatments (P for interaction=0.42). AUTHORS' CONCLUSIONS: ESA treatment in cancer patients increased on study mortality and worsened overall survival. For patients undergoing chemotherapy the increase was less pronounced, but an adverse effect could not be excluded.

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).

Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal

BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a "rare ADEs" category. RESULTS: During a median follow-up period of 43 months (interquartile range, 19-70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin's lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84-22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70-14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin's lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55-9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76-3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08-2.00]). CONCLUSIONS: In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management.

Culture, risk factors and mortality: can Switzerland add missing pieces to the European puzzle?

BACKGROUND: The aim was to compare cause-specific mortality, self-rated health (SRH) and risk factors in the French and German part of Switzerland and to discuss to what extent variations between these regions reflect differences between France and Germany. METHODS: Data were used from the general population of German and French Switzerland with 2.8 million individuals aged 45-74 years, contributing 176 782 deaths between 1990 and 2000. Adjusted mortality risks were calculated from the Swiss National Cohort, a longitudinal census-based record linkage study. Results were contrasted with cross-sectional analyses of SRH and risk factors (Swiss Health Survey 1992/3) and with cross-sectional national and international mortality rates for 1980, 1990 and 2000. RESULTS: Despite similar all-cause mortality, there were substantial differences in cause-specific mortality between Swiss regions. Deaths from circulatory disease were more common in German Switzerland, while causes related to alcohol consumption were more prevalent in French Switzerland. Many but not all of the mortality differences between the two regions could be explained by variations in risk factors. Similar patterns were found between Germany and France. CONCLUSION: Characteristic mortality and behavioural differentials between the German- and the French-speaking parts of Switzerland could also be found between Germany and France. However, some of the international variations in mortality were not in line with the Swiss regional comparison nor with differences in risk factors. These could relate to peculiarities in assignment of cause of death. With its cultural diversity, Switzerland offers the opportunity to examine cultural determinants of mortality without bias due to different statistical systems or national health policies.