Socioeconomic gradients in mortality in the oldest old: a review.

This review aims at identifying gaps in knowledge on socioeconomic gradients in mortality in the oldest old. The authors review literature on oldest old population with a focus on unanswered questions: do socioeconomic status (SES) gradients in mortality persist after 80; does the magnitude of the gradient change as compared with younger populations; which socioeconomic/socio-demographic determinants should be used in this population with specific characteristics (e.g., with respect to sex ratio and household type)? Results are often inconsistent while conclusions drawn by selected studies are generally limited by the difficulty of disentangling the effects of age and cohort, and of generalizing results observed in preponderantly small, selected samples (which typically exclude institutionalized persons). Future research should explore the effects of socio-demographic indicators other than education and social class (e.g., marital status, loss of the partner) and adequately differentiate the social position of oldest old women. The authors recommend that research applies a life-course perspective combined with an interdisciplinary perspective to improve our understanding of the SES gradients in later life. Research is needed to elucidate which causal pathways depending on SES in younger age impact on mortality in higher ages up to oldest old.

Trends in cancer mortality in Mexico, 1981-2007.

The objective of this study was to provideinformation on recent trends in cancer mortality in Mexico. We analyzed data provided by the World Health Organization, using joinpoint analysis to detect changes in trends between 1981 and 2007. For most cancers, mortality was upward but started to decline in the late 1980's/early 1990's for both sexes. Overall cancer mortality was 75.53/100 000 men, world standard, and 69.2/100 000 women in 2005-2007. Mortality from uterine cancer declined by approximately 2.5% per year in the 1990s, and by approximately 5% per year in the last decade, but its rates remained exceedingly high (9.7/100 000 in 2005-2007). Other major declines over recent years were those of stomach cancer (approximately 2.5% per year, with rates of 6.6/100 000 in men and 4.9/100 000 in women in 2005-2007) and lung cancer (2-2.5% per year, 11.0/100 000 in men and 4.5/100 000 in women in 2005-2007). Mortality leveled off only since the early 1990s for breast and prostate, and since the late 1990s for colorectal cancer. Death rates from cancer in Mexico remained low on a worldwide scale and showed favorable trends over more recent calendar years. Mortality from (cervix) uterine cancer still represents a major public health priority in this country.

Less mortality but more relapses in experimental allergic encephalomyelitis in CD8-/- mice.

Mice lacking in CD8 were generated from homologous recombination in embryonal stem cells at the CD8 locus and bred with the experimental allergic encephalomyelitis (EAE)-susceptible PL/JH-2u through four backcross generations to investigate the role of CD8+ T cells in this model of multiple sclerosis. The disease onset and susceptibility were similar to those of wild-type mice. However, the mutant mice had a milder acute EAE, reflected by fewer deaths, but more chronic EAE, reflected by a higher frequency of relapse. This suggests that CD8+ T lymphocytes may participate as both effectors and regulators in this animal model.

Weekend versus weekday admission and mortality after acute pulmonary embolism.

BACKGROUND: Optimal management of acute pulmonary embolism (PE) requires medical expertise, diagnostic testing, and therapies that may not be available consistently throughout the entire week. We sought to assess whether associations exist between weekday or weekend admission and mortality and length of hospital stay for patients hospitalized with PE. METHODS AND RESULTS: We evaluated patients discharged with a primary diagnosis of PE from 186 acute care hospitals in Pennsylvania (January 2000 to November 2002). We used random-effect logistic models to study the association between weekend admission and 30-day mortality and used discrete survival models to study the association between weekend admission and time to hospital discharge, adjusting for hospital (region, size, and teaching status) and patient factors (race, insurance, severity of illness, and use of thrombolytic therapy). Among 15 531 patient discharges with PE, 3286 patients (21.2%) had been admitted on a weekend. Patients admitted on weekends had a higher unadjusted 30-day mortality rate (11.1% versus 8.8%) than patients admitted on weekdays, with no difference in length of stay. Patients admitted on weekends had significantly greater adjusted odds of dying (odds ratio 1.17, 95% confidence interval 1.03 to 1.34) than patients admitted on weekdays. The higher mortality among patients hospitalized on weekends was driven by the increased mortality rate among the most severely ill patients. CONCLUSIONS: Patients with PE who are admitted on weekends have a significantly higher short-term mortality than patients admitted on weekdays. Quality-improvement efforts should aim to ensure a consistent approach to the management of PE 7 days a week.

Two alpha1-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation.

To study the functional role of individual alpha1-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the alpha1B-AR and/or alpha1D-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the alpha1D-AR knockout and alpha1B-/alpha1D-AR double knockout mice, but not the alpha1B-AR knockout mice, had significantly (p < 0.05) lower levels of basal systolic and mean arterial BP than wild-type mice in nonanesthetized condition, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. All mutants showed a significantly (p < 0.05) reduced catecholamine-induced pressor and vasoconstriction responses. It is noteworthy that the infusion of norepinephrine did not elicit any pressor response at all in alpha1B-/alpha1D-AR double knockout mice. In an attempt to further examine alpha1-AR subtype, which is involved in the genesis or maintenance of hypertension, BP after salt loading was monitored by tail-cuff readings and confirmed at the endpoint by direct intra-arterial recording. After salt loading, alpha1B-AR knockout mice developed a comparable level of hypertension to wild-type mice, whereas mice lacking alpha1D-AR had significantly (p < 0.05) attenuated BP and lower levels of circulating catecholamines. Our data indicated that alpha1B- and alpha1D-AR subtypes participate cooperatively in BP regulation; however, the deletion of the functional alpha1D-AR, not alpha1B-AR, leads to an antihypertensive effect. The study shows differential contributions of alpha1B- and alpha1D-ARs in BP regulation.

Estimating attributable mortality due to nosocomial infections acquired in intensive care units.

BACKGROUND: The strength of the association between intensive care unit (ICU)-acquired nosocomial infections (NIs) and mortality might differ according to the methodological approach taken. OBJECTIVE: To assess the association between ICU-acquired NIs and mortality using the concept of population-attributable fraction (PAF) for patient deaths caused by ICU-acquired NIs in a large cohort of critically ill patients. SETTING: Eleven ICUs of a French university hospital. DESIGN: We analyzed surveillance data on ICU-acquired NIs collected prospectively during the period from 1995 through 2003. The primary outcome was mortality from ICU-acquired NI stratified by site of infection. A matched-pair, case-control study was performed. Each patient who died before ICU discharge was defined as a case patient, and each patient who survived to ICU discharge was defined as a control patient. The PAF was calculated after adjustment for confounders by use of conditional logistic regression analysis. RESULTS: Among 8,068 ICU patients, a total of 1,725 deceased patients were successfully matched with 1,725 control patients. The adjusted PAF due to ICU-acquired NI for patients who died before ICU discharge was 14.6% (95% confidence interval [CI], 14.4%-14.8%). Stratified by the type of infection, the PAF was 6.1% (95% CI, 5.7%-6.5%) for pulmonary infection, 3.2% (95% CI, 2.8%-3.5%) for central venous catheter infection, 1.7% (95% CI, 0.9%-2.5%) for bloodstream infection, and 0.0% (95% CI, -0.4% to 0.4%) for urinary tract infection. CONCLUSIONS: ICU-acquired NI had an important effect on mortality. However, the statistical association between ICU-acquired NI and mortality tended to be less pronounced in findings based on the PAF than in study findings based on estimates of relative risk. Therefore, the choice of methods does matter when the burden of NI needs to be assessed.

Latitude gradients in melanoma incidence and mortality in the non-Maori population of New Zealand

The variation with latitude of incidence and mortality for cutaneous malignant melanoma (CMM) in the non-Maori population of New Zealand was assessed. For those aged 20 to 74 years, the effects of age, time period, birth-cohort, gender, and region (latitude), and some interactions between them were evaluated by log-linear regression methods. Increasing age-standardized incidence and mortality rates with increasing proximity to the equator were found for men and women. These latitude gradients were greater for males than females. The relative risk of melanoma in the most southern part of New Zealand (latitude 44 degrees S) compared with the most northern region (latitude 36 degrees S) was 0.63 (95 percent confidence interval [CI] = 0.60-0.67) for incidence and 0.76 (CI = 0.68-0.86) for mortality, both genders combined. The mean percentage change in CMM rates per degree of latitude for males was greater than those reported in other published studies. Differences between men and women in melanoma risk with latitude suggest that regional sun-behavior patterns or other risk factors may contribute to the latitude gradient observed.

Hypertension et diabète ADVANCE : une étude de morbidité-mortalité : nouveautés en médecine 2007 [ADVANCE: a morbidity mortality study of diabetes and hypertension]

The ADVANCE study is a morbidity-mortality double-blind trial carried out in normotensive or hypertensive patients with type 2 diabetes. The patients were randomly assigned to receive containing a fixed-combination tablet of an ACE inhibitor (perindopril) with a diuretic (indapamide) (4 mg/l,250 mg, n=5569), or placebo (n=5571), administered if needed on top of other blood pressure lowering agents. Significant reductions in the relative risk of death from cardiovascular disease (18%), total coronary events (14%), and total renal events (21%) were observed. Thus, in patients with type 2 diabetes, a drug regimen based on a fixed-dose combination of perindopril/ indapamide affords major protection against both the macro and microvascular complications. L'étude ADVANCE est un essai clinique de morbidité-mortalité réalisé en double insu chez des malades avec diabète de type 2 normo ou hypertendus. Les malades ont été alloués au hasard pour un suivi moyen de 4,3 ans à un traitement comportant soit une association fixe de l'inhibiteur de l'ECA périndopril et du diurétique indapamide (4 mg/1,250 mg, n = 5569), soit un placebo (n = 5571), ceci en plus si nécessaire d'autres médicaments antihypertenseurs. Des réductions significatives du risque relatif ont été observées sous périndopril/indapamide, en particulier de la mortalité cardiovasculaire (18%), de l'ensemble des événements coronaires (14%) et rénaux (21%). Ainsi chez le malade avec diabète de type 2, un traitement basé sur une association de périndopril et d'indapamide à doses fixes a un effet protecteur majeur contre les complications macro et microvasculaires.

Analysing trends in cardiovascular mortality: some methodological points.

This paper comments on the drop in coronary heart disease mortality observed in Switzerland among middle-aged men since the mid-seventies. Several methodological points are made regarding the consistency of this decline (relationships with mortality from other causes), and the reasons for this drop (possible change in population mix). It is suggested that a more complete use of vital statistics is still possible and that this can provide useful clues for the assessment and the interpretation of mortality trends in the field of cardiovascular epidemiology.

Trends in mortality from major cancers in the americas : 1980-2010

BACKGROUND: Between the 1970's and 2000 mortality in Latin America showed favorable trends for some common cancer sites, including stomach and male lung cancer in most countries. However, major concerns were related to mortality patterns from other cancers, particularly in women. We provide an up-to-date picture of patterns and trends in cancer mortality in Latin America. METHODS: We analyzed data from the World Health Organization mortality database in 2005-2009 for 20 cancer sites in 11 Latin American countries and, for comparative purposes, in the USA and Canada. We computed age-standardized (world) rates (per 100 000 person-year) and provided an overview of trends since 1980 using joinpoint regression models. RESULTS: Cancer mortality from some common cancers (including colorectum and lung) is still comparatively low in Latin America, and decreasing trends continue for some cancer sites (including stomach, uterus, male lung cancers) in several countries. However, there were upward trends for colorectal cancer for both sexes, and for women lung and breast cancer mortality in most countries. During the last decade, lung cancer mortality in women rose by 1-3% per year in all Latin American countries except Mexico and Costa Rica, whereas rises of about 1% were registered for breast cancer in Brazil, Colombia and Venezuela. Moreover, high mortality from cancer of the cervix uteri was recorded in most countries, with rates over 13/100 000 women in Cuba and Venezuela. In men, upward trends were registered in prostate cancer mortality in Brazil and Colombia, but also in Cuba, where the rate in 2005-2009 was more than twice that in the USA (23.6 versus 10/100 000). CONCLUSIONS: Tobacco control, efficient screening programs, early cancer detection and widespread access to treatments continue to be a major priority for most Latin American countries.

European cancer mortality predictions for the year 2013.

Background Estimated cancer mortality statistics were published for the years 2011 and 2012 for the European Union (EU) and its six more populous countries. Patients and methods Using logarithmic Poisson count data joinpoint models and the World Health Organization mortality and population database, we estimated numbers of deaths and age-standardized (world) mortality rates (ASRs) in 2013 from all cancers and selected cancers. Results The 2013 predicted number of cancer deaths in the EU is 1 314 296 (737 747 men and 576 489 women). Between 2009 and 2013, all cancer ASRs are predicted to fall by 6% to 140.1/100 000 in men, and by 4% to 85.3/100 000 in women. The ASRs per 100 000 are 6.6 men and 2.9 women for stomach, 16.7 men and 9.5 women for intestines, 8.0 men and 5.5 women for pancreas, 37.1 men and 13.9 women for lung, 10.5 men for prostate, 14.6 women for breast, and 4.7 for uterine cancer, and 4.2 and 2.6 for leukaemia. Recent trends are favourable except for pancreatic cancer and lung cancer in women. Conclusions Favourable trends will continue in 2013. Pancreatic cancer has become the fourth cause of cancer death in both sexes, while in a few years lung cancer will likely become the first cause of cancer mortality in women as well, overtaking breast cancer.

The alpha 1a and alpha 1b-adrenergic receptor subtypes: molecular mechanisms of receptor activation and of drug action.

In this chapter we summarize some aspects of the structure-functional relationship of the alpha 1a and alpha 1b-adrenergic receptor subtypes related to the receptor activation process as well as the effect of different alpha-blockers on the constitutive activity of the receptor. Molecular modeling of the alpha 1a and alpha 1b-adrenergic receptor subtypes and computational simulation of receptor dynamics were useful to interpret the experimental findings derived from site directed mutagenesis studies.

Signifiant decrease in in-hospital mortality and major adverse cardiac events in Swiss STEMI patients between 2000 and December 2007

Rapport de synthèse : Objectifs : évaluer la survie intra-hospitalière des patients présentant un infarctus du myocarde avec sus-décalage du segment ST admis dans les hôpitaux suisses entre 2000 et 2007, et identifier les paramètres prédictifs de mortalité intra-hospitalière et d'événements cardio-vasculaires majeurs (infarctus, réinfarctus, attaque cérébrale). Méthode : utilisation des données du registre national suisse AMIS Plus (Acute Myocardial lnfarction and Unstable Angina in Switzerland). Tous les patients admis pour un infarctus du myocarde avec sus-décalage du segment ST ou bloc de branche gauche nouveau dans un hôpital suisse participant au registre entre janvier 2000 et décembre 2007 ont été inclus. Résultats: nous avons étudié 12 026 patients présentant un infarctus du myocarde avec sus-décalage du segment ST ou bloc de branche gauche nouveau admis dans 54 hôpitaux suisses différents. L'âge moyen est de 64+-13 ans et 73% des patients inclus sont des hommes. L'incidence de mortalité intra-hospitalière est de 7.6% en 2000 et de 6% en 2007. Le taux de réinfarctus diminue de 3.7% en 2000 à 0.9% en 2007. L'utilisation de médicaments thrombolytiques chute de 40.2% à 2% entre 2000 et 2007. Les paramètres prédictifs cliniques de mortalité sont : un âge> 65-ans, une classe Killips Ill ou IV, un diabète et un infarctus du myocarde avec onde Q (au moment de la présentation). Les patients traités par revascularisation coronarienne percutanée ont un taux inférieur de mortalité et de réinfarctus (3.9% versus 11.2% et 1.1% versus 3.1%, respectivement, p<0.001) sur la période de temps étudiée. Le nombre de patients traités par revascularisation coronarienne percutanée augmente de 43% en 2000 à 85% en 2007. Les patients admis dans les hôpitaux bénéficiant d'une salle de cathétérisme cardiaque ont un taux de mortalité plus bas que les patients hopitalisés dans les centres sans salle de cathétérisme cardiaque. Mais les caractéristiques démographiques de ces deux populations sont très différentes. La mortalité intra-hospitalière ainsi que le taux de réinfarctus diminuent significativement au cours y de la période étudiée, parallèlement à l'augmentation de |'utilisation de la revascularisation coronarienne percutanée. La revascularisation coronarienne percutanée est le paramètre prédictif de survie le plus important. Conclusion: la mortalité intra-hospitalière et le taux de réinfarctus du myocarde ont diminué de manière significative chez les patients souffrant d'un infarctus du myocarde avec sus-décalage du segment ST au cours de ces sept dernières années, parallèlement à l'augmentation significative de la revascularisation coronarienne percutanée en plus de la thérapie médicamenteuse. La survie n'est È pas liée au lieu d'hospitalisation mais à l'accès à une revascularisation coronarienne percutanée.

European cancer mortality predictions for the year 2014.

BACKGROUND: From most recent available data, we projected cancer mortality statistics for 2014, for the European Union (EU) and its six more populous countries. Specific attention was given to pancreatic cancer, the only major neoplasm showing unfavorable trends in both sexes. PATIENTS AND METHODS: Population and death certification data from stomach, colorectum, pancreas, lung, breast, uterus, prostate, leukemias and total cancers were obtained from the World Health Organisation database and Eurostat. Figures were derived for the EU, France, Germany, Italy, Poland, Spain and the UK. Projected 2014 numbers of deaths by age group were obtained by linear regression on estimated numbers of deaths over the most recent time period identified by a joinpoint regression model. RESULTS: In the EU in 2014, 1,323,600 deaths from cancer are predicted (742,500 men and 581,100 women), corresponding to standardized death rates of 138.1/100,000 men and 84.7/100,000 women, falling by 7% and 5%, respectively, since 2009. In men, predicted rates for the three major cancers (lung, colorectum and prostate cancer) are lower than in 2009, falling by 8%, 4% and 10%, respectively. In women, breast and colorectal cancers had favorable trends (-9% and -7%), but female lung cancer rates are predicted to rise 8%. Pancreatic cancer is the only neoplasm with a negative outlook in both sexes. Only in the young (25-49 years), EU trends become more favorable in men, while women keep registering slight predicted rises. CONCLUSIONS: Cancer mortality predictions for 2014 confirm the overall favorable cancer mortality trend in the EU, translating to an overall 26% fall in men since its peak in 1988, and 20% in women, and the avoidance of over 250,000 deaths in 2014 compared with the peak rate. Notable exceptions are female lung cancer and pancreatic cancer in both sexes.

Subclinical hypothyroidism and the risk of coronary heart disease and mortality.

CONTEXT: Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease. OBJECTIVE: To assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched. DATA EXTRACTION: Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations. RESULTS: Among 55,287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51,837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age- and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval [CI], 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n = 70 events/235; 38.4/1000 person-years; P <.001 for trend). The corresponding HRs for CHD mortality were 1.09 (95% CI, 0.91-1.30; 5.3 vs 4.9/1000 person-years for participants with euthyroidism), 1.42 (95% CI, 1.03-1.95; 6.9/1000 person-years), and 1.58 (95% CI, 1.10-2.27, n = 28 deaths/333; 7.7/1000 person-years; P = .005 for trend). Total mortality was not increased among participants with subclinical hypothyroidism. Results were similar after further adjustment for traditional cardiovascular risk factors. Risks did not significantly differ by age, sex, or preexisting cardiovascular disease. CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater.