Increase In Death Rate Research Articles

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Drug-eluting Coronary Stents

Hepatocellular carcinoma in an Australian tertiary referral hospital 1975–2002: Change in epidemiology and clinical presentation

We compared the epidemiology and clinical features of hepatocellular carcinoma (HCC) cases diagnosed between 1975 and 2002. Retrospective and prospective analysis was performed of HCC cases diagnosed at The Alfred during the time periods 1975-1983 and 1995-2002. Demographic, epidemiological, clinical and laboratory data were recorded and compared between the two periods. Comparing the 1995-2002 cohort to the 1975-1983 cohort, patients were older (64 years vs 60 years; P = 0.02), and were more likely to be non-Caucasian (25%vs 9%; P = 0.003) and born overseas (57%vs 40%; P = 0.03) particularly from Asia. In addition, hepatitis C virus (HCV) (35%), hepatitis B virus (HBV) (22%), and alcoholic liver disease (29%) were the major etiological factors for HCC with alcohol less likely the cause of underlying liver disease (33%vs 55%; P < 0.01). Among the 1995-2002 cohort, overseas-born patients were more likely to be infected with HBV (P < 0.001) and HCV (P = 0.01), while alcohol was more likely to be the etiological factor in Australian-born cases (P = 0.02), particularly among males. Detection of HCC by screening was the initial presentation in 38% of patients, and diagnosis of HCC was often by non-invasive means. The epidemiology of HCC has changed in Australia over the past 20 years with hepatitis C and hepatitis B now major etiological factors, and an increase in cases born overseas particularly from areas where HCV and HBV are endemic. This suggests the recent increase in incidence and death rates due to HCC in Australia relate to HCV and HBV infection.

Carotid artery stenting in octogenarians: results from the ALKK Carotid Artery Stent (CAS) Registry

We tried to determine the influence of age on complication rates of carotid artery stenting (CAS). Two thousand seven hundred eighty CAS procedures were included in the registry. Median age of the patients was 70.8 years, with a proportion of octogenarians of 11.2% and a significant increase between 1996 (5.9%) and 2005 (13.7%; P for trend = 0.002). In octogenarians, a symptomatic stenosis was a more frequent indication for CAS (60.7% vs. 48%, P < 0.001), the CAS procedure was aborted more frequently (6.9% vs. 2.2%; P < 0.001) and the duration of intervention was longer (Median 45 vs. 40 min; P = 0.008). Increasing age was associated with a significant increase in the in-hospital death or stroke rate (P for trend: 0.001). In-hospital death or stroke rate was also higher in octogenarians compared with younger patients (5.5 vs. 3.2%; P = 0.032, OR = 1.79; 95%CI: 1.04-3.06). Logistic regression analysis showed that age analysed as a continuous variable was a strong predictor of in-hospital death or stroke (P < 0.001), whereas octogenarians had only a trend towards a higher event rate (P = 0.062). CAS in octogenarians is performed in an increasing proportion of patients. In-hospital stroke or death rates increase significantly with older age; however, there was no excess complication rate in octogenarians.

The Rise of Occult Powers, AIDS and the Roman Catholic Church in Western Uganda

AbstractTaking as my example a lay organisation of the Roman Catholic Church, the Uganda Martyrs Guild, which entered the public domain in western Uganda in the 1990s and started to organise witch and cannibal hunts, I offer two arguments to the ongoing debate on the rise of occult forces in Africa. First, against the tendency to find the origin of the rise of occult forces in the invisible hand of capital, I relate the dramatic activation and rise of occult forces in Africa to the large increase in death rates caused by the AIDS epidemic (and to a lesser extent local wars). Although various scholars have shown in detail that in Africa contemporary Christianity has not put an end to witchcraft and the occult, but instead provided a new context in which they make perfect sense, they missed the point that precisely the fight against the occult reproduces and strengthens the 'enemy'. As I try to show, Christian anti-witchcraft movements are instrumental in reinstating the occult powers they fight against.

Does age matter? Comparing case fatality rates for selected poisonings reported to U.S. poison centers

Background. As the elderly population continues to grow, the number of geriatric patients reported to poison centers continues to increase. We believe that older poisoned patients are at an increased risk of death compared to younger adult patients. The objective of this study was to compare the risk of death from selected poisoning between younger (<59) and older (>59) adults. Methods. We included adult cases reported to U.S. poison centers between 1995 and 2002. To limit potential confounders, our analysis included single substance ingestions of theophylline, digoxin, benzodiazepines, tricyclic antidepressants, calcium channel antagonists, acetaminophen, and salicylate. We determined the case fatality rate for each poisoning for younger and older adults. We calculated crude odds ratios for each poison and then used logistic regression to adjust for covariates. Results. Overall we found an increase in the relative rate of death for each poison (range 1.2 to 7.1). After adjustment, each 10-year increase in age was associated with a 36% increase in the odds ratio for death as an outcome. Our findings were limited by the use of poison center data, which does not include data on covariates that may be potential confounders.

Electric vehicle: a futuristic approach to reduce pollution (A case study of Delhi)

In developing countries, city traffic is growing at a very fast rate. Rapid urbanisation, industrialisation, insurance and loan facilities etc., are some of the important factors which accelerate the growth of traffic in urban areas. The city of Delhi, like other cities in developing countries, is facing an acute transport management problem. This primary transport management problem leads to many more secondary problems such as traffic congestion, high energy consumption, loss of productivity, increase in accidental death rates, vehicular parking problem and deterioration of the environment. In this paper, we conducted a survey based on a structured questionnaire for the need for electric vehicles. By analysis of the data collected, we found that if the people opt for the Electric Vehicle (EV), the pollution emitted by all the cars and jeeps will be reduced to 75,991 tonnes from 1,01,051 tonnes per year. Similarly, on the adoption of EV cars in Delhi, an amount of Rs. 4940.51 − 3715.26 = Rs. 1225.25 crores (Approx. USD 28,16,663) can be reduced, which is now being annually spent on petrol.

Population-Based Case-Control Study of Risk Factors for Unintentional Mortality from Carbon Monoxide Poisoning in Taiwan

We carried out a population-based case-control study to identify people in Taiwan who are at increased risk of unintentional mortality from carbon monoxide (CO) poisoning (ICD-9 CM: 986 or E868). The study included all 439 deaths from unintentional CO poisoning registered in Taiwan's National Mortality Registry during 1997–2003, whereas 878 control subjects were randomly selected, with a control/case ratio of 2, from all deceased individuals from other causes during the same period. The annual mortality rate of CO poisoning significantly increased in Taiwan over the 7-yr period from 1.6 to 3.5 per 106 person-years. Thirty-six percent (n = 160) of the deaths occurred at home, and 21% (n = 93) were registered as in-hospital mortalities. A multivariate logistic regression analysis indicated that married people had a significantly reduced mortality odds ratio (MOR) of 0.50 (95% CI = 0.30–0.82) compared to single individuals. Additionally, residents of northern Taiwan (which is relatively urban) had a notably higher MOR of CO poisoning (MOR = 3.44, 95% CI = 1.40–8.44) than people residing in eastern Taiwan (which is relatively rural). Moreover, the MOR peaked in cold periods. A daily maximum temperature of < 18.4°C was associated with a 2.15-fold increase in the MOR compared to a daily maximum temperature of ≥ 27.1°C. This study demonstrates an alarming increase in the unintentional death rate from CO poisoning in Taiwan between 1997 and 2003. Certain demographic and geographic characteristics were significant predictors for CO poisoning, suggesting a need for preventive strategies targeting these high-risk populations. Precautions should also be taken during periods of low temperatures.

Mortality, Mass-Layoffs, and Career Outcomes: An Analysis Using Administrative Data

This paper uses administrative data on quarterly employment and earnings matched to death records to estimate the effects of job displacement on mortality. We find that job displacement leads to a 15-20% increase in death rates during the following 20 years. If such increases were sustained beyond this period, they would imply a loss in life expectancy of about 1.5 years for a worker displaced at age 40. These results are robust to extensive controls for sorting and selection, and are consistent with estimates of the effects of job loss on mortality pooling displaced workers and stayers that are not affected by selective job displacement. To examine the channels through which mass layoffs raise mortality, we exploit the panel nature of our data -- covering over 15 years of earnings -- to analyze the correlation of long-run career outcomes, such as the mean and standard deviation of earnings, with mortality at the individual and group level, something not possible with typical data sets. Our findings suggest that factors correlated with a decrease in mean earnings and a rise in standard deviation of earnings have the potential to explain an important fraction of the effect of a job displacement on mortality.

High Plasma Aldosterone Levels on Admission Are Associated With Death in Patients Presenting With Acute ST-Elevation Myocardial Infarction

Aldosterone, the final mediator of the renin-angiotensin-aldosterone pathway, is at its highest plasma levels at presentation for ST-elevation myocardial infarction (STEMI). Whether aldosterone level at presentation for STEMI is associated with adverse outcome remains unknown. Plasma aldosterone levels were measured at presentation in consecutive patients referred for primary percutaneous coronary intervention for STEMI. We assessed the association between aldosterone levels and in-hospital events and mortality during a 6-month follow-up. Of 356 STEMI patients, 23 and 36 died during the hospital stay and 6-month follow-up period, respectively. Nine other patients survived in-hospital cardiac arrest. High aldosterone levels were associated with an almost stepwise increase in rates of in-hospital death (P=0.01), cardiovascular death (P=0.03), heart failure (P=0.005), ventricular fibrillation (P=0.02), and resuscitated cardiac arrest (P=0.01). After adjustment for age, Killip class, and reperfusion status, compared with patients in the first aldosterone quartile group, those in the highest quartile were at higher risk of death (hazard ratio 3.28, 95% CI 1.09 to 9.89, P=0.035) and death or resuscitated cardiac arrest (hazard ratio 3.74, 95% CI 1.40 to 9.98, P=0.008) during the follow-up. Plasma aldosterone levels on admission among patients referred for primary percutaneous coronary intervention for STEMI are associated with early and late adverse clinical outcomes, including mortality. The association between high aldosterone levels and late mortality is independent of age, heart failure, and reperfusion status. Such results underline the pivotal role of aldosterone and justify a randomized trial to assess the early administration of aldosterone antagonists in the setting of STEMI.

Evaluation of Developmental Toxicity of Amitraz in Sprague-Dawley Rats

This study investigated the potential adverse effects of amitraz on the initiation and maintenance of pregnancy in Sprague-Dawley rats as well as its effects on embryo-fetal development after maternal exposure during the entire pregnancy period. Amitraz was administered to pregnant rats by gavage from days 1 to 19 of gestation at dose levels of 0, 3, 10, and 30 mg/kg/day. All dams underwent a caesarean section on day 20 of gestation and their fetuses were examined for any external, visceral, and skeletal abnormalities. At 30 mg/kg, maternal toxicity manifested as an increase in the incidence of abnormal clinical signs and a lower body weight gain and food intake. Developmental toxicity included an increase in the fetal death rate, a decrease in the litter size, and a reduction in the fetal body weight. In addition, there was an increase in the incidence of fetal external, visceral, and skeletal abnormalities. At 10 mg/kg, maternal toxicity observed included a decrease in the body weight gain and a decrease in food intake. In addition, minimal developmental toxicity, including a decrease in the fetal body weight, an increase in the visceral and skeletal aberrations, and a delay in fetal ossification. There were no signs of either maternal toxicity or developmental toxicity at 3 mg/kg. These results show that amitraz administered during the entire pregnancy period in rats is embryotoxic and teratogenic at the maternally toxic dose (i.e., 30 mg/kg/day) and is minimally embryotoxic at a minimally maternally toxic dose (i.e., 10 mg/kg/day). Under these experimental conditions, the no-observed-adverse-effect level of amitraz for both dams and embryo-fetal development is estimated to be 3 mg/kg/day.

Are Cardiopulmonary Patients More Susceptible to Acute Effects of Air Pollutants?

P-725 Introduction: People with existing respiratory and cardiac conditions may be more susceptible to the acute effects of air pollutants. We tested this hypothesis using a novel approach: a cohort design with nested case-control analysis was used to measure the association between black smoke (BS) and mortality rates among subjects previously admitted to hospital for an emergency respiratory condition, an emergency cardiac condition or a digestive condition. Patients were followed for up to 15 years but attention was restricted to acute effects of pollution. Methods: Three cohorts of patients aged < 90 years admitted to hospitals in Edinburgh, Scotland between 1981 and 1996 were identified: emergency admissions for respiratory conditions, emergency cardiac admissions and any admission for digestive disease. To be eligible, patients also had to be discharged alive and to survive at least 30 days. Follow-up was from day 30 until death or 30/9/1996. For the nested case-control analyses, cases were members of the cohorts who died. For each case, up to 5 controls were chosen at random from patients in the same cohort of the same age and sex, who left hospital on the same day of the week and survived longer after hospitalisation than the case. For cases and matching controls, point source exposure to black smoke (BS) was averaged across the 30 days preceding the case's death. Analysis was by conditional logistic regression with adjustment for calendar year, month and temperature lagged to 30 days. Results were compared with other ‘time series’ estimates of risk for the Edinburgh population. Results There were 34,204 cardiac admissions, 12,422 respiratory admissions and 92,865 digestive admissions of which 45%, 39% and 19% respectively died during follow-up. For the three cohorts combined, the percentage increase in death rate associated with a 10μg/m3 increase in BS was 5.6% (95% CI: 2.7, 8.6), compared with 3.7% for the whole population estimated using time series methods. The increases were 9.5% (95% CI: 5.6, 13.4) for cardiac patients, 7.9% (95% CI: 2.4, 13.7) for respiratory patients and 1.6% (95% CI: -1.8, 5.1) for digestive admissions; differences were statistically significant (p=0.0004) With BS modelled as a categorical variable, dose-response relationships were evident in the cardiac and respiratory groups. Conclusions and discussion The results support the original hypothesis but it should be remembered that there was no adjustment for traditional risk factors. Further work is under way to estimate degree of life shortening and risk of readmission to hospital.

Polynomial Distributed Lag Models of Short Term Air Pollution Effects on Lung Function

P-040 Introduction: We recently reported a panel study (Moshammer et al. Eur Respir J, in press) on pupils at an elementary school in Linz, the capital of Upper Austria. A total of 163 children underwent lung function testing every 2–3 weeks and 11–12 times during one school year. Lung function testing was performed between 8:30 am and 11:00 am. Air pollution levels at the monitoring station in close vicinity of the school were usually below current and proposed limit values. Nevertheless the 8-hour average concentrations between midnight and school start at 8 o'clock in the morning had a significant effect on lung function results. No such associations was seen for the 8 hour mean values between 4 and 12 pm on the previous day indicating a rather acute and reversible effect. Polynomial distributed lag models have been successfully applied in time series studies on air pollution and daily deaths. In that case an increase of pollution followed by an early increase in death rates reaching a maximum and afterwards a minimum due to “harvesting” could well be modelled by a 3rd degree polynom. For the time course of lung function changes, however, shorter time intervals (e.g. half hour means) should be considered and more complex functions than 3rd degree polynoms. Two distinct modes of action with different time courses were expected: One very acute reaction due to nerval stimulation (reflectory vagal response) and a slower reaction mediated by an inflammatory tissue response. To model such a time course with at least 2 maxima polynoms of higher degree were necessary. Methods: Because lung function testing was on average performed at 9 o'clock and we had noticed an effect of the air pollution levels between 0 and 8 o'clock in the morning (and not the previous evening hours)we decided to study 34 half hour means (17 hours) as distributed lag before each individual lung function test. A general linear model (xtgee in STATA Vers. 9) was prepared as in the previous study: The logs of the various lung function parameters served as dependent variables, gender and the logs of age, height, and weight as independent variables and a forced autoregressive correlation of order 1 as the basic model. Additionally 5 to 7 variables were added that resulted from a transformation of the lag values applying polynomial models of the 4th to 6th degree. Results: Upon back-transformation polynomial models of the 5th and 6th degree gave the most consistent results, in accordance with the a priori hypothesis on the temporal course of the effect. As an additional check of internal consistency the air pollution levels at the half hour mean values with the maximal effect were added to the basic model.

Radiation effects to acupuncture in mice embryos

We examined the radioprotection effects of acupoint (acupuncture point) stimulation during organogenesis stages of ICR mice. Pregnant mice received 1.5 Gy whole body X-irradiation on day 8 of gestation, which is the early stage of organogenesis. The embryonic death rate and teratogenesis rate by radiation were examined. Electroacupuncture to the leg acupoints and/ or transcutaneous stimulation to the back acupoints on the pregnant mice showed no protective effect against irradiation on embryonic or fetal death rate. On the contrary, the strong stimulation resulted in increase in the mortality after irradiation rather than protection. However acupoint stimulation to the pregnant mice never showed harmful effects by itself on embryos. It tended to reduce the skeletal malformations induced by X-ray irradiation. We suspect that acupoint stimulation removed the cells injured by irradiation during embryonic development, resulting in an increase in embryonic death rate and reduction in skeletal anomalies.

Acute hypoxia and programmed cell death in developing CNS: Differential vulnerability of chick optic tectum layers

The chick optic tectum displays an alternating pattern of cellular and plexiform layers and at embryonic day (ED) 12 there are mainly four cellular layers: transient cell compartment 3 (TCC3), compartment “h-i-j”(C“h-i-j”), stratum griseum centrale (SGC) and subventricular zone (SvZ). In the present work we characterized the programmed cell death (PCD) of these layers and their vulnerability to acute hypoxia at ED12, and also identified the main cellular type involved in hypoxic cell death. The colocalization of three independent markers of cell degeneration: pyknotic nuclei by Hoechst staining, fragmented DNA by TdT-mediated dUTP nick-end labeling (TUNEL), and presence of active caspase-3 by immunofluorescence, was analyzed in embryos that developed in normoxic conditions (control embryos) and embryos that were subjected to hypoxia (8% O 2/92% N 2) for 60 min (hypoxic embryos), followed by 0–12 h of normoxic recovery. In control embryos cell death rate within each layer was constant through time, but there were significant differences ( P<0.01) in cell death rates among the different layers. In contrast, in hypoxic embryos, a significant increase ( P<0.01) in cell death rate was observed in layers TCC3, C“h-i-j” and SGC. This change was evident only at 6 h post-hypoxia, and at later time points cell death rate was similar to control values. Each of these layers had a different vulnerability to the hypoxic event while the SvZ layer was not affected. In addition, the significant colocalization between the neuron specific nuclear protein (NeuN) and TUNEL signal showed that hypoxia affected primarily neurons. In conclusion, our findings demonstrate that in the chick optic tectum at ED12, PCD is layer dependent and that acute hypoxia causes a transient increase in neuronal death in a delayed fashion, which is also layer dependent. The morphological features of the neuronal death process at the light microscope level resembled apoptosis.

A Liquid Path to Lung Disease: EarlyArsenicExposureand EffectsinYoung Adults

Vol. 114, No. 8 EnvironewsOpen AccessA Liquid Path to Lung Disease: EarlyArsenicExposureand EffectsinYoung Adultsis accompanied byIncreased Mortality from Lung Cancer and Bronchiectasis in Young Adults after Exposure to Arsenic in Utero and in Early Childhood Tanya Tillett Tanya Tillett Search for more papers by this author Published:1 August 2006https://doi.org/10.1289/ehp.114-a486aAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Increased rates of cancer and mortality have been documented in areas of the world where drinking water contains high concentrations of naturally occurring arsenic. A new study by a group of Californian and Chilean researchers now provides strong evidence of a link in humans between prenatal and early childhood arsenic exposure and significantly higher rates of lung disease in young adulthood [EHP 114:1293–1296; Smith et al.].Both malignant and nonmalignant lung disease are known to develop with exposure to arsenic in drinking water. Recent evidence from a project in India by the same research group showed decreased lung function similar to that of smokers in adults exposed to the semimetallic carcinogen.The current study took advantage of a unique opportunity to study the long-term health effects of a discrete prenatal and early childhood exposure. From 1958 to 1970, the water supply for the neighboring Chilean cities of Antofagasta and Mejillones was supplemented with water from rivers with arsenic concentrations near 1,000 μg/L, 100 times the current acceptable standard for arsenic concentration in the United States. With the 1971 activation of an arsenic removal plant, however, levels plummeted to about 90 μg/L and have continued to drop ever since.The research team studied mortality data obtained from Chile’s Ministry of Health for the years 1989 through 2000 for all 13 regions of the country. They divided the population into two groups: individuals born between 1958 and 1970 (who likely would have had prenatal arsenic exposure if their mothers lived in Antofagasta or Mejillones) and those born between 1950 and 1957 (who likely would have had childhood but not prenatal exposure if they lived in either of the two cities). The researchers also divided overall deaths for Chile into two groups: residents of Antofagasta and Mejillones, and residents of all other regions. They used the International Classification of Diseases, Ninth Revision, to code causes of death, including lung cancer and bronchiectasis, a form of chronic respiratory disease.The investigators’ findings show a distinct connection between prenatal and early childhood exposure to arsenic and lung disease–related mortality before age 50. Lung cancer death rates for those exposed to arsenic in early childhood were 7 times higher than those for the rest of the Chilean population, and bronchiectasis death rates were 12 times higher. In cases where exposure occurred both prenatally and in early childhood, lung cancer death rates were 6 times higher and bronchiectasis death rates were 46 times higher than those for the rest of the population.The authors believe these results describe the highest increase in death rates for arsenic-related lung cancer and bronchiectasis ever documented among young adults, and add that this study is one of the first to provide evidence of human adult disease resulting from prenatal and early childhood exposure to any environmental toxicant. They conclude that an increase in young adult mortality should be of concern to public health officials, and should influence future decisions regarding sources of drinking water.A big gulp of newsThe link between early arsenic exposure and later lung disease is the first such association to be confirmed in humans.FiguresReferencesRelatedDetailsRelated articlesIncreased Mortality from Lung Cancer and Bronchiectasis in Young Adults after Exposure to Arsenic in Utero and in Early Childhood27 March 2006Environmental Health Perspectives Vol. 114, No. 8 August 2006Metrics About Article Metrics Publication History Originally published1 August 2006Published in print1 August 2006 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Natural Background Radioactive Carbon and the Natural Death Rate of People

A brief analysis of the known data on the potential danger of radiocarbon incorporation into DNA structure shows that the great genetic importance of transmutational transformations of DNA-incorporated 14C is theoretically and experimentally proved. This effect exists both in huge and small radiation doses (similar to doses of 14C natural background radiation). Therefore, the human death rate can be assumed to be dependent on natural and anthropogenous fluctuations of atmospheric 14C. Calculation methods of the age parameter dynamics of the natural human death rate are offered. It is shown that when calculating the parameters of the natural death rate, the use of Gompertz's formula is reasonable provided that the data on the general death rate are taken for the age interval "60 to 85 years." The ratios reflecting the regular and casual errors of the parameters R and a of Gompertz's equation, caused by people's casual deaths, were determined. A comparison of the historical dynamics of people's natural death rates in the last 150 years with the variations of 14C of the natural background during the same period showed that these are coordinated phenomena, the strong correlation of which indicates the possibility of their functional dependence. The 14C-concentration increase in an organism is the result of its increase in the surrounding biospheric composition, causing an increase in the natural death rate and vice versa: The increase of a person's life expectancy is caused by a decrease of 14C concentration.

Arrhythmic death and ICD implantation after myocardial infarction

Arrhythmic death remains one of the most important causes of mortality after an acute myocardial infarction also in the revascularization era. As a consequence, identification of patients at risk should be performed before discharge. Unfortunately, in the clinical practice, this evaluation is mainly based on detection of a depressed left ventricular ejection. This approach, however, cannot adequately distinguish arrhythmic versus non-arrhythmic risk.This issue is of critical relevance when considering that arrhythmic death can be significantly reduced by appropriate interventions of implantable cardioverter defibrillator. Available evidence, however, indicates that in the first month after myocardial infarction, device implantation does not significantly reduce cardiac mortality: it seems that the reduction of arrhythmic death is counterbalanced by an increase in rate of death from non arrhythmic cause. It is therefore to be hoped that, in the future, arrhythmic risk evaluation will be based not only on the extent of left ventricular dysfunction but also on the analysis of other risk markers such as those reflecting autonomic dysfunction, cardiac electrical instability and presence of subclinical inflammation.

Understanding the Coronary Heart Disease Versus Total Cardiovascular Mortality Paradox

Coronary heart disease (CHD) represents the largest share of cardiovascular disease in the United States, but there are conspicuous discrepancies between CHD and total cardiovascular death rates across the states, possibly due in part to variations in physician assignment of causes of death. Our aim was to identify exogenous individual- and community-level predictors of cause-of-death assignment and variability and to use these predictors to improve the comparability of CHD mortality estimates across states. We performed a multinomial logistic regression analysis to estimate the effect of individual- and community-level factors on the likelihood of a death being certified as 1 of 3 ill-defined clusters (general atherosclerosis and unspecified heart disease, heart failure, and cardiac arrest) relative to being certified as CHD. The individual-level variables were the decedent's race, sex, age, education, and place of death; the community-level variable was the number of cardiologists per capita. We used the model to estimate state-level CHD rates that are standardized with regard to the levels of individual- and community-level determinants of cause-of-death assignment. Decedents who died in hospitals and in counties with more cardiologists per capita were more likely to be assigned to CHD than to the ill-defined categories, as were white males relative to other race-sex combinations. Adjustment for these factors resulted in substantially improved correlation between death rates for CHD and all cardiovascular causes. Increases in CHD death rates across states after adjustment for external predictors of cause-of-death assignment ranged from 2% (North Dakota) to 72% (Washington, DC); New York had a decrease (1%) in CHD death rates after adjustment. Nationally, CHD death rates increased 10% for males and 15% for females. The total number of deaths in 2001 attributed to CHD in patients over 30 years of age rose from 433,625 to 489,836 after adjustment. Greater presence of medical knowledge at the time of death, reflected by place of death and cardiologists per capita, reduces the use of the ill-defined cardiovascular clusters. Racial and gender effects on CHD assignment may reflect disparities in access to care and quality of care. By adjusting for differentials in these parameters, a comparable and consistent set of CHD mortality estimates can be created. The role of the exogenous predictors in validity and comparability of cause-of-death statistics should be confirmed in carefully designed validation autopsy studies.

Trends in AIDS and Mortality in HIV-Infected Subjects With Hemophilia From 1985 to 2003

To study trends in progression to AIDS, all-cause mortality, and cause-specific mortality (AIDS-related, liver disease, and hemorrhagic complications) over calendar periods with different exposure to highly active antiretroviral therapy (HAART) in a cohort of hemophiliacs in Spain, taking into account the competing risks of the causes of death. Multicenter cohort of HIV-infected hemophiliacs. HIV seroconversion was estimated using mathematic techniques for interval-censored data from 1979 through 1985. Rates of AIDS and cause-specific death were calculated by Poisson regression, allowing for late entry, for the periods 1985 through 1992, 1993 through 1996, 1997 through 2000 (early HAART), and 2001 through 2003 (late HAART), also allowing for competing risks. Of 585 subjects, 44% were younger than 15 years of age, 82% had severe hemophilia, 86% had type A hemophilia, and the median seroconversion date was October 1982. Calendar period and age at HIV seroconversion strongly influenced AIDS and death rates. Compared with 1993 through 1996, decreases of 75% (relative risk [RR] = 0.25, 95% confidence interval [CI]: 0.14 to 0.43) and 72% (RR = 0.28, 95% CI: 0.12 to 0.63) in the RR of AIDS were observed in early and late HAART. For all-cause mortality, 72% (RR = 0.28, 95% CI: 0.18 to 0.42) and 83% (RR = 0.17, 95% CI: 0.09 to 0.33) decreases were observed by 1997 through 2000 and 2001 through 2003. For liver-related deaths, increases were observed in the late-HAART period (RR = 2.80, 95% CI: 0.94 to 8.36) compared with 1993 through 1996, but using competing risks, this RR was substantially reduced (RR = 1.70, 95% CI: 0.57 to 5.04). Major reductions in AIDS and death rates were observed from 1997 to 2003 in hemophiliacs. These survival improvements are largely attributable to decreases in AIDS-related deaths and have been accompanied by increases in liver disease death rates, which are overestimated if competing risks are not taken into account.

Pharmacogenomics in the Clinic: New Questions About Tamoxifen

To the Editor: I enjoyed the excellent summary of recent insights regarding tamoxifen's pharmacogenomics,1 its essential activation to endoxifen by CYP2D6, the poor metabolizer (PM) phenotypes that cannot perform this step, and the unintended blockade of this activation by commonly prescribed drugs.2 The study of North Central Cancer Treatment Group (NCCTG) tissues showing a marked survival decrement for PM phenotypes3 is rich with implications for practice. Additionally, one can't help but grin at the authors' assiduously politically correct way of handling the use of selective serotonin reuptake inhibitors (SSRIs) to treat hot flashes, a colossal therapeutic misadventure for breast cancer patients in retrospect. After all, it is remarkable how many ways we shoot ourselves in the foot, proverbially speaking. Yet application of these new insights promises better results from tamoxifen. Have we arrived at the threshold for routine pharmacogenomic testing? Some provocative issues were not addressed by the authors. First, the science is either retrospective or based on relatively few patients. But would it be ethical to study the questions of genotype and drug interaction in a large, prospective, controlled trial? Such a trial would stipulate a control group with survival outcomes of 1980s placebo groups. Arguably, clinicians don't need absolute scientific rigor to practice common-sense medicine. Limited although compelling anecdotal or scientific observations akin to the admonition against putting one's finger in the electric socket can suffice for adopting a pharmacogenetic approach to endocrine therapy without a prospective trial. The weightiest questions spawned by tamoxifen's pharmacogenomics pertain to the aromatase inhibitors (AIs). Eliminate PMs and those taking CYP2D6 inhibitors from randomized AI studies: Would there still be an advantage for AIs? One would anticipate that endoxifen-poor patients make up the lion's share of treatment failures among the tamoxifen-treated control arms, and that therapeutic outcomes could be equivalent for appropriately selected and coached (i.e., instructed not to take 2D6 inhibitors) patients receiving tamoxifen. By extension, absence of a survival disadvantage for patients who generate sufficient endoxifen would raise reservations about the skeletal consequences of AIs, especially in low-risk women. Moreover, appropriately selected premenopausal women would not be missing out on the benefit of AIs, the common exclusionary wince for estrogen receptor–positive premenopausal women. Possibly, such a re-evaluation of the AI data could end up reaffirming tamoxifen's central role, PMs and SSRI users aside. Conversely, the decision to avoid AIs would be inappropriate for patients who cannot get by without an SSRI or for PMs. Hopefully, this work on PMs will spur new correlative science initiatives in already completed trials and in those currently underway. This represents a challenge for the vested interests of companies who sell AIs, and provokes a question of whether society can pursue questions that are clinically necessary but potentially adverse to industry. Most likely, the U.S. Food and Drug Administration's leadership will be needed to compel such inquiries, particularly since AI commercial licensing has long been a done deal. Should all patients considered for endocrine therapy and prevention of breast cancer be tested for the CYP2D6 PM polymorphisms? In the white population, 5% to 10% of patients unable to derive a benefit from tamoxifen would be identified. In my experience, informed patients will not accept a 5% to 10% chance of receiving a drug that is ineffective if they can be identified up front, particularly given the risks of adverse consequences from tamoxifen and potential for an alternative strategy. Is testing cost-effective? The CYP2D6 test is commercially available for about $250. By comparison, a 5-year course of tamoxifen costs roughly $5,000. Thus, women who would not receive tamoxifen produce a savings for the health care system even after testing for PMs prospectively, to say nothing of avoiding the suffering and salvage maneuvers of administering ineffective therapy upfront. Not least, liability pressures coming from those with relapsed disease in the adjuvant tamoxifen setting are probably indefensible, given the easy availability of CYP2D6 testing already. The authors did not mention the sulfonotransferase work. This enzyme plays a rate-limiting role in activating 4-hydroxy-tamoxifen, and defective trans-sulfation from SULT1A1★2 homozygosity yields a three-fold increase in death rate,4 suggesting another crucial mechanism of tamoxifen resistance. Hopefully commercialization of this test will be accomplished soon to further help in refining clinical decision making. In the meantime, oncologists should embrace the new insights about tamoxifen and make CYP2D6 testing routine. It is an approach with huge potential benefits for some, and thus represents another incremental improvement in the outcome for breast cancer patients on the whole.