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Competing causes of death: a death certificate study.

BACKGROUND: Despite the widespread interest in competing causes of death, empirical information on interrelationships between causes of death is scarce. We have used death certificate information to estimate the prevalence of competing causes of death at the moment of dying from specific underlying causes of death. MATERIALS AND METHODS: In a stratified sample of 5975 deaths occurring in The Netherlands in 1990, information contained in the death certificate was used to determine the presence of diseases which, in the hypothetical case of elimination of the underlying cause of death, could develop into a new underlying cause of death. Poisson regression analysis was used to describe variation in age- and sex-adjusted prevalence of competing causes of death between different underlying causes. RESULTS: Per 100 deaths, 46.2 competing causes were identified (52.0 after reweighting to take away the effects of stratification). The most frequent competing causes, all occurring in more than 2% of deaths, were: senile dementia, diabetes mellitus, ischemic heart disease, cerebrovascular disease, chronic obstructive lung disease, hypertensive disease, and arteriosclerosis. The overall prevalence of competing causes is relatively high among deaths from respiratory diseases (relative risk for respiratory diseases as compared with all underlying causes (RR) = 1.42 (95% CI, 1.25-1.62)), relatively low among deaths from neoplasms (RR = 0.54 (95% CI, 0.47-0.62)), and in between among deaths from cardiovascular diseases (RR = 1.08 (95% CI, 0.95-1.22)). CONCLUSION: Although it cannot be excluded that some of the variation in prevalence of competing causes by underlying cause is due to selective underregistration of coexisting diseases on death certificates, the results of this study suggest that conventional estimates of gains in life expectancy after elimination of neoplasms are much less biased by the effect of competing causes than the corresponding estimates for cardiovascular diseases and particularly respiratory diseases.

Adolescent↗

[Diabetes as primary or associated cause of death in the state of São Paulo, Brazil, 1992].

INTRODUCTION: Analysis of mortality data are usually performed with reference to the underlying cause of death. The importance of diabetes as a cause of death is always underestimated, because diabetics generally die from chronic complications of the disease, these being considered as the underlying cause of the death. To attenuate this problem, mortality data should be analyzed on the basis of all the causes listed on the death certificate. Frequency of references to diabetes on death certificates and the principal associated causes were evaluated as a contribution to the solution of this problem. METHODOLOGY: Specific death rates and proportional mortality by diabetes, as underlying or associated cause, were calculated on the basis of information derived from death certificates by the ACME program (Automated Classification of Medical Entities), for the State of S. Paulo, in 1992. RESULTS AND CONCLUSIONS: Of a total of 202,141 deaths, diabetes was mentioned in 13,786 (6.8%) and as being the underlying cause in 5,305(2.6%). The proportion was higher for women than men (10.1 vs. 4.6% as mentioned, and 6.1 vs 2.9% as underlying cause). Among deaths with a mention of diabetes on the certificate, the main underlying causes were: diabetes (38.5%), cardiovascular (37.2%) and respiratory (8.5%) diseases, and neoplasias (4.8%). When diabetes was the underlying cause, the main associated causes were: cardiovascular (42.2%), respiratory (10.7%) and genitourinary (10.1%) diseases. When diabetes was an associated cause, the main underlying causes were: cardiovascular (60.5%) and respiratory (13.8%) diseases, and neoplasias (7.9%). In spite of the limitation of the data from death certificates, it is possible to observe the importance of diabetes as cause of death, reflecting its magnitude as a health problem. Also, the analysis by multiple causes of deaths gives an idea of the morbidity profile associated with diabetes at the time of death, showing the importance of the group of cardiovascular diseases.

Adolescent↗

Outcomes of renal transplantation among patients with end-stage renal disease caused by lupus nephritis.

BACKGROUND: Although the outcomes of renal transplantation among patients with end-stage renal disease (ESRD) caused by lupus nephritis have generally been found to be comparable to those of patients with other causes of ESRD, some studies indicate that cadaveric graft failure is more common among these patients. However, most previous studies examined small numbers of patients and did not adjust for important confounding factors. METHODS: Graft failure and patient mortality after the first cadaveric renal transplantation were compared between 772 adults with ESRD caused by lupus nephritis and 32,644 adults with ESRD caused by other causes who received a transplant between 1987 and 1994 and were included in the United States Renal Data System. The median follow-up times were 4.9 and 5.0 years in the two groups, respectively. Multivariate Cox regression models were used to adjust the risks of graft failure and mortality for group differences in recipient and donor characteristics. Similar comparisons were performed between 390 adults with ESRD caused by lupus nephritis and 10,512 adults with ESRD caused by other causes after first living-related renal transplantation. RESULTS: In an unadjusted analysis, the risk of graft failure after first cadaveric transplant was slightly but significantly greater among patients with ESRD caused by lupus nephritis than among those with ESRD caused by other causes [hazard ratio (HR), 1.13; 95% CI, 1.01 to 1. 26, P = 0.04]. However, after adjustment for potential confounding factors, the risk of graft failure was not increased in patients with ESRD caused by lupus nephritis (HR, 1.08; 95% CI, 0.94 to 1.23, P = 0.28). Mortality after the first cadaveric transplantation did not differ between groups. The adjusted risks of graft failure (HR, 1.06; 95% CI, 0.84 to 1.32, P = 0.62) and patient mortality (HR = 0. 69; 95% CI, 0.45 to 1.05, P = 0.09) after the first living-related renal transplant were also not significantly higher among patients with ESRD caused by lupus nephritis. CONCLUSIONS: Graft and patient survival after first cadaveric and first living-related renal transplants are similar in patients with ESRD caused by lupus nephritis and patients with ESRD from other causes.

Adolescent↗

Ill-defined and multiple causes on death certificates--a study of misclassification in mortality statistics.

Biases can distort, limit or inhibit the value of mortality data as an epidemiological re source. From 9500 deaths occurring in Naples (Italy during 1994, a random sample of 372 death certificates reporting ill-defined causes and multiple causes of death was extracted. The code for the underlying cause on the death certificate (assigned code) was compared with the cause reattributed with the aid of interview of the certifying physician or clinical records (modified code). The aim was to investigate the extent of misclassification of 'underlying cause' in deaths attributed to ill-defined and/or multiple causes and the shortcomings in the ICD-IX. Ill-defined underlying causes of death (7.0% of death certificates) were cardiovascular diseases, tumours with no specified site or nature, symptoms, signs, ill-defined conditions and senility. There was disagreement between the initially assigned code and the modified code in 53.8% of ill-defined underlying causes; discordance was high for the certificates filled in by the family physician. Multiple causes of death were observed in 23.6% of certificates; of these 59.2% concerned subjects aged 75 years and over at death. Diabetes was always listed in association with other pathologies but neoplasms and traumas were generally listed alone. Disagreement between codes occurred in 48 (54.5%) certificates indicating multiple causes. In 10 of them, death was established as due to a concurrence of causes. As regards ill-defined causes of death, the authors concluded that specific training on certifying procedures would be insufficient on their own; the physician should be made aware that certification is a fundamental requirement for building up epidemiological data. Evidence-based educational interventions are needed. As regards multiple causes of death, multicausal analysis may be indicated for deaths due to a concurrence of causes.

Age Factors↗

[Multiple-causes-of-death related to tuberculosis in the State of São Paulo, Brazil, 1998].

OBJECTIVES: The goal of this paper is to investigate mortality related to tuberculosis in the state of S o Paulo, southeastern Brazil, according to multiple causes of death and their interrelation with other underlying causes. METHODS: The study investigated deaths related to tuberculosis that occurred in the state of S o Paulo in 1998. Data were obtained from the Fundação Sistema Estadual de Análise de Dados (State System for Data Analysis Foundation - SEADE) database. Causes of death by clinical forms of TB were coded in block A15-A19, and by its sequelae in category B90, according to the guidelines proposed by the Tenth Revision of the International Statistical Classification of Diseases and Related Health Problems. Tabulador de Causas Múltiplas (Multiple Cause Tabulator - TCM) software was used for processing associated causes of death. Statistical analysis included analysis of variance, Student's t -distribution, and chi-squared tests. RESULTS: TB was the underlying cause of 1,644 deaths, a 4.6/100,000 population mortality rate. Main associated causes were respiratory failure (46,9%), pneumonias (16.5%), other specified symptoms and signs involving circulatory and respiratory systems (13.9%), cachexia (12.9%), diseases of the circulatory system (10.3%), conditions due to alcohol use (8.4%), septicemias (7.2%) and malnutrition (7.1%). Tuberculosis occurred as an associated cause in another 1,388 deaths. The mortality rate including TB as a both underlying and associated cause was 8.9/100,000 population, practically twice the classical rate. Deaths whose associated cause was reported as being TB had as underlying causes: AIDS (65.3%), diseases of the circulatory system (8.9%), neoplasms (7.5%), and diseases of the digestive system (4.8%). Clinical forms of nervous system and miliary TB were more frequent as a cause associated with AIDS than with other underlying causes (p<0,001). CONCLUSIONS: Total reports of TB-related death practically doubled its mortality rate as an underlying cause. The increase in TB mortality was demonstrated to be influenced by the AIDS epidemic.

Acquired Immunodeficiency Syndrome↗

Accuracy and impact of presumed cause in patients with cardiac arrest.

BACKGROUND: International guidelines recommend differentiation between cardiac and noncardiac causes of cardiac arrest. The aim of this study was to find the rate of agreement between primarily postulated and definitive causes of cardiac arrest. METHODS AND RESULTS: We retrospectively analyzed the primarily presumed cause of cardiac arrest as determined by the emergency room physician on admission in all patients admitted to the emergency department of one urban tertiary care hospital. This was compared with the definitive cause as established by clinical evidence or autopsy. Within 4 years, the initially presumed cause was unclear in 24 (4%) of 593 patients. In the remaining 569 patients, the presumed cause was correct in 509 (89%) and wrong in 60 (11%) cases. Cardiac origin was presumed in 421 (71%) and the definitive cause in 408 (69%) cases. Noncardiac origin was presumed in 148 (25%) and the definitive cause in 185 (31%) patients. Presumed cardiac cause was sensitive (96%) but less specific (77%). Noncardiac causes such as pulmonary embolism, cerebral disorders, or exsanguination were those most frequently overlooked. Asystole occurred significantly more often in patients in whom presumed cause remained undetermined or differed from the definitive cause. CONCLUSIONS: Cause of cardiac arrest is not as easily recognized as anticipated, especially when the initial rhythm is different from ventricular fibrillation. This might affect comparability of study results, therapeutic strategies, prognosis, and outcome. Patients in whom the presumed cause was confirmed as being correct had significantly better survival and neurological outcome.

Aged↗

Mortality from violent causes in the Americas.

This article provides an assessment of 1986 mortality from violent causes in the Americas. Directed at assisting with development of preventive public health measures, it employs data available in the PAHO data base to focus on the under-25 year age group, compare mortality from violent causes with mortality from infectious and parasitic diseases, and evaluate the relative role of motor vehicle traffic accidents, other accidents, suicide, homicide, and deaths from unknown causes in mortality from violent causes. The study uses the classification of causes presented in the International Classification of Diseases, Ninth Revision. The results show that 517,465 deaths from violent causes were registered in 28 countries and political units of the Americas in 1986, mortality from these causes ranging from 19.3 deaths per 100,000 inhabitants in Jamaica to 125 in El Salvador. Examination of available 1980-1986 data from five countries points to steady increases in mortality from violent causes in Brazil and Cuba that began respectively in 1983 and 1984. Assessment of male and female 1986 mortality from these causes in nine countries showed male mortality to be substantially higher, the lowest male:female ratio (in Cuba) being 1.9:1. Among infants, infectious and parasitic disease mortality was greater than mortality from violent causes in most countries. However, from age 1 to the study's 25-year cutoff, mortality from violent causes was found to exceed infectious and parasitic disease mortality in most countries and to play an especially large role in deaths among those 19-24 years old. Data from eight countries suggested that accidents other than motor vehicle traffic accidents were accounting for much of the mortality from violent causes among infants and the 1-4 year age group in 1986, while motor vehicle traffic accidents rivaled other accidents in importance among the older (5-9, 10-14, 15-19, and 19-24) age groups. It appears that the information presented could prove of considerable use in developing policies designed to reduce morbidity and mortality from violent causes (1).

Adolescent↗

Relationship of dose of hemodialysis and cause-specific mortality.

A number of studies have found a relationship of lower all-cause mortality risk for ESRD patients treated with increasing dose of dialysis. The objective of this study was to determine the relationship of delivered dose of dialysis with cause-specific mortality. Data from the USRDS Case Mix Adequacy Study, which includes a national random sample of hemodialysis patients, were utilized. To minimize the contribution of unmeasured residual renal function, the sample used in this analysis (N = 2479) included only patients on dialysis for one year or more. Cox proportional hazards models, stratified for diabetes, were used to analyze the effect of delivered dose of dialysis (measured and reported by both Kt/V and URR) on major causes of death and withdrawal from dialysis, adjusting for other covariates including demographics, comorbid diseases present at start of study, functional status, laboratory values and other dialysis parameters. Patient follow-up for mortality was censored at the earliest of time of transplantation, 60 days after a switch to peritoneal dialysis or at the time of data abstraction. For each 0.1 higher Kt/V, the adjusted relative risk of death due to coronary artery disease was 9% lower (RR = 0.91, P < 0.05), due to other cardiac causes was 12% lower (RR = 0.88, P < 0.01), due to cerebrovascular disease (CVD) was 14% lower (RR = 0.86, P < 0.05), due to infection was 9% lower (RR = 0.91, P = 0.05), and due to other known causes was 6% lower (RR = 0.94, P < 0.05). There was no statistically significant relationship of Kt/V and risk of death among patients who died of malignancy (RR = 0.84, P = 0.10) or among patients whose death cause was missing (RR = 0.95, P = 0.41). The risk of withdrawal from dialysis prior to death due to any cause was 9% lower (RR = 0.91, P < 0.05) for each 0.1 higher Kt/V. The relationships of delivered dose of dialysis, as measured by URR, and cause-specific mortality were essentially similar in relative magnitude and statistical significance as the relationships observed using Kt/V as the measurement of dialysis dose, with the exception that the relationship was less significant for cerebrovascular disease and withdrawal from dialysis. The relationship of dialysis dose with risk of death due to each cause of death category except other cardiac causes and "other" causes appeared to be of greater magnitude and of greater statistical significance among diabetics than non-diabetics. These results indicate that low dose of dialysis is not associated with mortality due to just one isolated cause of death, but rather is due to a number of the major causes of death in this population. This study is consistent with hypotheses that low doses of dialysis may promote atherogenesis, infection, malnutrition and failure to thrive through a variety of pathophysiologic mechanisms. Further study is necessary to confirm these results and to test hypotheses that are developed.

Adult↗

Use of multiple-cause mortality data in epidemiologic analyses: US rate and proportion files developed by the National Institute for Occupational Safety and Health and the National Cancer Institute.

The authors have created US mortality rates (age, sex, race, and calendar-time specific) and proportions, using multiple cause-of-death data, for the years 1960-1989. Multiple cause-of-death data include the usual underlying cause of death from the death certificate as well as contributory causes and other significant conditions. US multiple-cause rates and proportions enable the user to calculate the expected occurrences of disease on the death certificates of a cohort under study. There is an average of 2.66 causes and/or contributory conditions listed on US death certificates, increasing over time from 2.54 in the 1960s to 2.76 in the 1980s. The ratio of multiple-cause listings to underlying cause listings varies by disease, from low ratios for cancers to high ratios for diseases such as diabetes, arthritis, prostate disease, hypertension, pneumoconiosis, and renal disease. Use of these data is illustrated with two cohorts. Multiple-cause analysis (but not underlying cause analysis) revealed twofold significant excesses of renal disease and arthritis among granite cutters. For workers exposed to dioxin, neither multiple-cause nor underlying cause analysis indicated any excess of diabetes, an outcome of a priori interest. Good candidates for multiple-cause analysis are diseases that are of long duration, not necessarily fatal, yet serious enough to be listed on the death certificate.

Cause of Death↗

Contribution of developmental disabilities to childhood mortality in the United States: a multiple-cause-of-death analysis.

Although developmental disabilities are among the major chronic health problems affecting children in the United States, the contribution of developmental disabilities to childhood mortality is unknown. To investigate the magnitude of this contribution, multiple cause-of-death data were examined for US children, aged 1-19 years, for 1980 and 1983-1989. The following conditions were included as developmental disabilities: autism, attention deficit disorder, learning disorders, mental retardation, cerebral palsy, epilepsy, muscular dystrophy, blindness and deafness. Based on underlying cause only, it was found that developmental disabilities were the fifth leading cause of nontraumatic death for children between 1 and 14 years of age and the third leading cause of non-traumatic death for children between 15 and 19 years. When a multiple cause approach was used to define developmental disability-related deaths (i.e. when contributing as well as underlying cause was considered), the number of such deaths nearly doubled. On the basis of both underlying- and multiple-cause analyses, cerebral palsy was the developmental disability most frequently cited as a cause of death. Mental retardation ranked second according to the multiple-cause approach but only fourth according to the underlying-cause approach. The least frequent causes of death (autism, attention deficit disorder, learning disorders, blindness, and deafness) were the ones most likely to be coded as contributing rather than underlying causes. Developmental disability-related mortality rates were highest among children aged 1-4 and 15-19 years, highest among blacks and lowest among racial groups other than blacks and whites, and higher among males than females. Although results of multiple-cause-of-death analyses more accurately reflect the proportion of deaths related to developmental disabilities, even this approach may underestimate the degree to which mortality is associated with a developmental disability.

Adolescent↗

Factors associated with reporting multiple causes of death.

BACKGROUND: There is analytical potential for multiple cause of death data collected from death certificates. This study examines relationships of multiple causes of death as a function of factors available on the death certificate (demographics of decedent, place of death, type of certifier, disposal method, whether an autopsy was performed, and year of death). METHODS: Data from 326,332 Minnesota death certificates from 1990-1998 are examined. Underlying and non-underlying causes of death are examined (based on record axis codes) as well as demographic and death-related covariates. Associations between covariates and prevalence of multiple causes of death and conditional probability of underlying compared to non-underlying causes of death are examined. The occurrence of ischemic heart disease or diabetes as underlying causes are specifically examined. RESULTS: Both the probability of multiple causes of death and the proportion of underlying cause compared to non-underlying cause of death are associated with demographic characteristics of the deceased and other non-medical conditions related to filing death certificate such as place of death. CONCLUSIONS: Multiple cause of death data provide a potentially useful way of looking for inaccuracies in reporting of causes of death. Differences across demographics in the proportion of time a cause is selected as underlying compared to non-underlying exist and can potentially provide useful information about the overall impact of causes of death in different populations.

Adolescent↗

Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New York City.

BACKGROUND: Monitoring the full spectrum of causes of death among persons with AIDS is increasingly important as survival improves because of highly active antiretroviral therapy. OBJECTIVE: To describe recent trends in deaths due to HIV-related and non-HIV-related causes among persons with AIDS, identify factors associated with these deaths, and identify leading causes of non-HIV-related deaths. DESIGN: Population-based cohort analysis. SETTING: New York City. PATIENTS: All adults (age > or =13 years) living with AIDS between 1999 and 2004 who were reported to the New York City HIV/AIDS Reporting System and Vital Statistics Registry through 2004 (n = 68,669). MEASUREMENTS: Underlying cause of death on the death certificate. RESULTS: Between 1999 and 2004, the percentage of deaths due to non-HIV-related causes increased by 32.8% (from 19.8% to 26.3%; P = 0.015). The age-adjusted mortality rate decreased by 49.6 deaths per 10,000 persons with AIDS (P < 0.001) annually for HIV-related causes but only by 7.5 deaths per 10 000 persons with AIDS (P = 0.004) annually for non-HIV-related causes. Of deaths due to non-HIV-related causes, 76% could be attributed to substance abuse, cardiovascular disease, or a non-AIDS-defining type of cancer. Compared with men who have sex with men, injection drug users had a statistically significantly increased risk for death due to HIV-related causes (hazard ratio, 1.59 [95% CI, 1.49 to 1.70]) and non-HIV-related causes (hazard ratio, 2.54 [CI, 2.24 to 2.87]). LIMITATIONS: Compared with autopsy and chart review, death certificates may lack specificity in the underlying cause of death or detailed clinical and treatment-related information. CONCLUSIONS: Non-HIV-related causes of death account for one fourth of all deaths of persons with AIDS. Cardiovascular disease, non-AIDS-defining cancer, and substance abuse account for most non-HIV-related deaths. Reducing deaths from these causes requires a shift in the health care model for persons with AIDS from a primary focus on managing HIV infection to providing care that addresses all aspects of physical and mental health.

Acquired Immunodeficiency Syndrome↗

[An analysis of the main causes of death in different industrial systems in Guangzhou].

OBJECTIVE: To study the main causes of death in workers from different industries in Guangzhou. METHODS: The industrial systems in Guangzhou were classified into six categories according to the Chinese Public Health Inspection Statistical Report. Baseline data on 79,547 workers, age > or = 35, were retrieved from individual health records under the Guangzhou Occupational Health Surveillance Record System established in 1989-1992. In this prospective cohort study, the workers' vital status and causes of death were followed up until 31 December 1998. Using SPSS 10.0, crude death rates were calculated and relative risks(RR) (95% CI) were estimated using Cox proportional-hazard models. RESULTS: (1) Among 79,547 workers were 49,355 men and 30,192 women, with mean age of (43.8 +/- 6.5) years, and 64% were aged 35-44. The mean age difference of workers in different industries was +/- 1 year. At baseline, 41% had been exposed to occupational hazards. Exposure was most prevalent in petroleum chemical industry(53.9%), followed by metallurgical industry, and the lowest exposure was in mechanical industry (30.2%). (2) The mean follow-up period was (8.0 +/- 1.3) years with 633,510 person-years. 1,577 workers had died with a total death rate of 248.9 per 100,000 person-years. The death rate in rubber industry was the highest, followed by metallurgical and petroleum chemical industries. Malignant neoplasms, vascular and respiratory diseases were most common, constituting 80.3% of all causes of death. (3) For all causes of death and the three main categories, the top three crude death rates were observed in rubber and petroleum chemical industries, and in the metallurgical industry except for vascular causes. The rubber industry had the highest crude death rate for all and vascular causes, and the metallurgical industry for malignant neoplasms and respiratory causes. (4) With the light industry as a reference (RR = 1.0), the metallurgical industry had the highest adjusted relative risks (RR) (95% CI) of 1.62(1.20-2.18) and 7.42(3.38-16.31) for malignant neoplasms and respiratory causes, respectively. The rubber industry had the highest RR of 1.69(1.40-2.04) for all causes. A significant RR of 2.03(1.43-2.88) for vascular causes was observed only in the rubber industry. CONCLUSIONS: The main causes of death varied from industry. Malignant neoplasms and respiratory diseases were the leading causes in metallurgical and petroleum chemical industries. In rubber industry, vascular and respiratory causes were most common. Preventive measures for disease control should be tailor-made for each industry.

Adult↗

[Induction mechanism of shock: applying the etiology in judgment of the cause of death in forensic practice].

In the field of forensic medicine, shock has been identified as a cause of death owing to various kinds of exogenous insults. The etiology and pathogenesis of shock cannot be explained well by the usual gross appearance in medicolegal autopsies, because it is now generally established that the shock is a functional reaction of the vascular system to bodily injury, and that several organs are secondarily impaired during shock. Thus it seemed to forensic pathologists that these morphological changes in several organs after shock did not reveal any significant differences among the causes of death. We approached to the induction mechanism of shock, and we investigated what etiology induced these morphological changes after shock in order to identify shock as the cause of death. It is now generally accepted that the kidney is a target organ of shock, so we mainly investigated the cause of kidney disorder in a case of burn shock and hemorrhagic shock. 1. Consequences of bacterial translocation (BT) in the shock. The concept of BT indicates that the beginning of shock is induced by the loss of gut barrier function and consequent translocation of bacteria. In general, impaired gut barrier function can be caused either during the shock period by decreased intestinal blood flow and reduced oxygen delivery, resulting during reperfusion in a stage of increased intestinal blood flow, or at a later stage again by reduced flow. A variety of physiological stresses, such as trauma, hemorrhage, thermal injury, surgical operation, various kinds of drags and mental stress, have been shown to cause failure of the gut mucosal barrier, with translocation of bacteria/endotoxin from the gastrointestinal into the mesenteric lymph nodes, and translocation into remote organs and systemic circulation. 2. Burn shock. We designed to evaluate the BT in a burn shock rat model (following 20% full-thickness scald injury). The p38 MAPK pathway is an important stress-responsive signal molecule pathway, and it is responsible for the production and signal transduction of cytokines. This pathway is activated by the bacterial LPS or ischemia, so we examined the effects of FR167653, a specific inhibitor of p38 MAPK, on the development of renal failure after the burn-induced intestinal barrier damage. Our study demonstrated that viable bacteria reached the remote organs after burn by quantitative bacterial culture data and FR167653 blocked the burn-induced intestinal barrier damage, and the immunohistochemical data showed that FR167653 prevented the accumulation of polymorphonuclear leukocytes (PMNs) in the glomerular capillaries after burn, and blockaded the burn-induced renal failure by serum UN assay. FR167653 especially decreased the phosphorylation levels of p38 MAPK in the infant kidney after burn, and TNF-alpha and IL-1beta mRNA decreased through the p38 MAPK pathway. The above-mentioned facts do provide additional support for the hypothesis that postburn renal failure is mediated by endotoxin associated with the bacterial translocation, and we identified the pathophysiologic role of p38 MAPK pathway in the development of renal failure after the burn-induced intestinal barrier damage. 3. Hemorrhagic shock. We evaluated the role of endogenous TNF-alpha in the renal failure and gut bacterial translocation induced by mild hemorrhagic shock (16.7% bleeding of total body blood via a common carotid catheter without fluid resuscitation). FR167653, a potent inhibitor of TNF-alpha up regulation through p38 MAPK pathway, significantly inhibited these increases of TNF-alpha. Adding to this, our study demonstrated that FR167653 prevented renal failure, such as the infiltration of inflammatory cells and tubular cell necrosis after hemorrhage, and the intestinal barrier damage was also dramatically improved by FR167653 treatment. These results show that derived endogenous TNF-alpha plays a key role in renal failure through p38 MAPK activation during the early phase of mild hemorrhagic shock, including the possible participation of BT. According to these results, we hypothesized that the invading leukocytes induced these organs failures after hemorrhagic shock, so we examined the appearances of leukocytes by the immunohistochemical myeloperoxidase (MPO) staining (marker staining for PMNs). The incidences of PMNs in these organs after mild hemorrhagic shock increased significantly, and FR157653 prevented the appearance of PMNs. These results showed the possible effective role of the PMNs on the occurrence of organ failure caused by mild hemorrhagic shock. 4. Forensic practice. Six hundred and seven forensic autopsy cases in our department of forensic medicine during the past 11 years between 1992 and 2002 were analyzed with regard to the cause of death. Shock cases accounted for 18% of all forensic autopsy cases, and among them 65% of cases identified hemorrhagic shock as the cause of death. So we investigated what good grounds to clearly identify the cause of death induced by hemorrhagic shock. Our experimental hemorrhagic shock data showed PMNs activation and priming during hemorrhagic shock, and it might be closely related to BT and remote organ failure. Consequently, we used the MPO staining method, and we immunohistochemically investigated several organs of our practical autopsy cases to detect the appearance of PMNs as a marker of shock induction. We compared the hemorrhagic shock with other causes of death, such as blood loss, asphyxia, drawing and head injury (intracranial hemorrhage). In every organ, a significant appearance of PMNs was observed in the hemorrhagic shock compared to the other causes of death. Especially, the appearance of PMNs in the heart was clear than that of the other organs in the hemorrhagic shock cases. Therefore, detecting the appearance of PMNs as a marker of shock induction is a very useful and significant method forjudging the cause of death in forensic practice.

Animals↗

Concurrence of monthly variations of mortality related to underlying cause in Europe.

STUDY OBJECTIVE: The study aimed to examine the concurrence in the variation of monthly numbers of deaths in summer and winter from the four main underlying causes - respiratory, circulatory, neoplastic, and all others - in four countries. In particular, the hypothesis that most non-respiratory concurrent deaths are miscoded respiratory deaths and that a large proportion of the winter mortality currently attributed to circulatory disorders should be attributed to respiratory causes was considered. DESIGN: Mortality data were analysed graphically in relation to cause. Each of the four series of monthly data underwent time series analysis to remove auto-correlation, seasonality, and secular trends. Associations between paired causes of death and between multiple series (using Kendall's coefficient of concordance) were then examined after modelling. SETTING: Monthly deaths (65 years and over) related to underlying cause were examined for England and Wales (nine years), The Netherlands (nine years), Denmark (10 years), and Portugal (10 years - all ages). Weekly data for England and Wales (51 weeks) were also analysed. MAIN RESULTS: All combinations of monthly deaths related to underlying cause were strongly associated in all four countries. This concurrence was evident down to the lowest monthly values so that all seasonally related deaths above the minimum monthly value can be used as an estimate of the "concurrent" proportion. Associations involving deaths from neoplasm were weakest. Concurrence was evident even on a weekly analysis (England and Wales). Concurrent deaths in England and Wales accounted for 31.1% of respiratory, 16.0% of circulatory, 3.5% of neoplastic, 14.1% of deaths from other causes and 14.2% for all deaths combined. The equivalent percentages for concurrent deaths from all causes were 8.4% in the Netherlands, 9.3% in Denmark, and 16.8% in Portugal. CONCLUSIONS: Concurrence, which was present in each of the underlying causal groups in each of the four national data sets examined, suggests a common cause separate from the underlying cause that has been used in the presentation of mortality statistics. If the person concerned had not died at that time, as a result of this cause, he would not have died from the recorded underlying cause. Most of these non-respiratory concurrent deaths are miscoded. As a consequence, a large proportion of winter mortality currently attributed to circulatory disorders should be attributed to other causes, probably respiratory. More intensive research into the contribution made by acute respiratory diseases is proposed. The proportion of concurrent deaths varied in the four countries thereby limiting the validity of simple comparisons of national mortality statistics.

Adolescent↗

Causes and effects.

Most companies make charitable donations, but few approach their contributions with an eye toward enhancing their brands. Those that do take such an approach commit talent and know-how, not just dollars, to a pressing but carefully chosen social need and then tell the world about the cause and their service to it. Through the association, both the business and the cause benefit in ways they could not otherwise. Organizations such as Avon, ConAgra Foods, and Chevrolet have recognized that a sustained cause-branding program can improve their reputations, boost their employees' morale, strengthen relations with business partners, and drive sales. And the targeted causes receive far more money than they could have from direct corporate gifts alone. The authors examine these best practices and offer four principles for building successful cause-branding programs. First, they say, a company should select a cause that advances its corporate goals. That is, unless the competitive logic for supporting the cause is clear, a company shouldn't even consider putting its finite resources behind it. Second, a business should commit to a cause before picking its charitable partners. Otherwise, a cause-branding program may become too dependent on its partners. Third, a company should put all its assets to work, especially its employees. It should leverage the professional skills of its workers as well as its other assets such as distribution networks. And fourth, a company should promote its philanthropic initiatives through every possible channel. In addition to using the media, it should communicate its efforts through the Web, annual reports, direct mail, and so on. Cause branding is a way to turn the obligations of corporate citizenship into a valuable asset. When the cause is well chosen, the commitment genuine, and the program well executed, the cause helps the company, and the company helps the cause.

Commerce↗

[Bacterial causes of meningitis in newborns].

INTRODUCTION: Bacterial meningitis jeopardizes the life of affected newborns and in survived children often leaves permanent sequels. The sooner the diagnosis is established and the therapy is started, the more a prosperous outcome can be expected. When the indication is established, lumbar punction should be performed. On the basis of the results of cytological and biochemical analyses of the cerebrospinal fluid (CSF) that point to bacterial meningitis, the initial therapy should begin even before the results of bacteriological analyses. It is important to know which causes are to be expected in order to make an adequate choice of antibiotics for initial therapy. The AIM of this study is to identify the causes of meningitis, frequency of their occurrings and mortality-rate in the affected newborns. PATIENTS AND METHODS: A prospective study was carried out in the Paediatric Department of the Institute from January 1, 1978 to December 31, 2000. Patients originated from all parts of Yugoslavia. After the establishing of indication, lumbar punction was performed. CSF was sent to cytological, biochemical and bacteriological analyses. Diagnosis of meningitis was established when at least two criteria of four were fulfilled: 1. isolation of the cause by CSF culture; 2. elevation of CSF leukocyte count more than 20 with predominance of polymorphonuclear leukocytes; 3. hypoglucorrhachia (glycaemia less than 40 mg percent or less than 50 percent of glycaemia); 4. identification of bacteria by the Gram stain of CSF sediment. In 173 newborns the cause of bacterial meningitis was confirmed. RESULTS AND DISCUSSION: Causes of meningitis were as follows: E. coli in 46 newborns (N) (26.5%), Streptococcus B haemolyticus group B in 35 N (20.2%), K. pneumoniae in 27 N (15.6%), K. oxytoca in 3 N (1.7%), Proteus spp in 14 N (8%), Salmonella spp in 12 N, Pseudomonas spp in 9 N, Streptococcus pneumoniae in 9 N, Acinetobacter calcoaceticus in 4 N, Enterobacter spp in 3 N, L. monocytogenes and Serratia marcescens and Staphylococcus aureus in 2 N each, and in one N. meningitidis, Streptococcus group D, Citrobacter, Morganella morganii and Alkaligenes xilosoxidans. Over the period 1978-1987, the most frequent causes were: E. coli (28.2%), SBHB (26.8%) and Klebsiella spp (11.3%). Over the period 1991-2000, order and frequency of causes had been changed: Klebsiella spp (26.8%), E. coli (19.2%), SBHB (14.1%), etc. In addition, new causes appeared, namely: Morganella morganii, Citrobacter, K. oxitoca and Alkaligenes xylosoxidans (Table 2). Of a total of 173 patients, 52 (30.1%) died: of 124 children with meningitis caused by gram-negative bacteria, 39 (31.4%) died, and of 49 children with gram-positive bacteria, 13 (26.5%) died (Table 1). Comparing the first and the last decade, mortality decreased by only 0.2% (Table 2). The explanation might be that the patients came to the Institute too late, and after manifestation of resistant and multiresistant causes that obscured the appropriate selection of antibiotics for initial therapy. The precious time between the onset of the disease and start of the therapy was lost in this way. Newborns with bacterial meningitis should be treated only in health institutions where the intensive care units for newborns exist. CONCLUSION: The most frequent causes of meningitis are the following: E. coli, SBHB and Klebsiella pn. Frequency of causes of meningitis changed with time. New uncommon causes have appeared. The mortality-rate remained very high.

Bacteria↗

Predictive values of the character, timing, and complications of chronic cough in diagnosing its cause.

BACKGROUND: It is not clear whether careful history taking with detailed questioning of the characteristics of cough is diagnostically useful. OBJECTIVE: To determine if the character, timing, or complications of chronic cough were helpful in determining its cause. METHODS: A prospective, descriptive study of consecutive, unselected, immunocompetent patients referred to our university outpatient clinic because of chronic cough. All patients were evaluated by a previously published and validated systematic diagnostic protocol, a self-administered questionnaire, and by observing the character of involuntary and voluntary coughs. The final diagnosis of the cause of cough required fulfillment of pretreatment criteria plus having cough disappear or substantially improve as a complaint with specific therapy. RESULTS: Eighty-eight patients met inclusion criteria and were fully evaluated. The mean +/- SD age was 53.1 +/- 16 years (range, 15-83 years) and 24 were males and 64 were females with a mean +/- SD history of cough for 6.6 +/- 9.8 years (range, 1 month-44 years). The cause of chronic cough was established in 86 (98%) of 88 patients. Eighty-one (92%) of 88 had cough disappear as a complaint. Cough was as a result of a single cause in 39% and multiple causes in 59%. Gastroesophageal reflux disease, postnasal drip syndrome, and asthma were the 3 most common causes of chronic cough and accounted for 90% of diagnoses. Gastroesophageal reflux disease, postnasal drip syndrome, and asthma were again found to be the 3 most common causes of chronic cough irrespective of patient estimated quantity of daily sputum production. These 3 conditions caused chronic cough in 99.4% of patients with the following characteristics: (1) nonsmoker; (2) not receiving an angiotensin-converting enzyme inhibitor drug; and (3) normal or nearly normal and stable chest radiograph. With respect to the spectrum and frequency of diagnoses and their interrelationships with the character, timing, and complications of cough, multiple stepwise linear regression analysis showed that none of the variability of the character, timing, or complications of cough could be explained by any specific diagnosis. CONCLUSIONS: A carefully taken history with detailed questioning of the character, timing, and complications of chronic cough is not likely to be useful in diagnosing the cause of cough. The cause can be determined and successfully treated with specific therapy in the greatest majority of cases. Chronic cough is often caused by multiple, simultaneously contributing causes. Postnasal drip syndrome, asthma, and gastroesophageal reflux disease remain the 3 most common causes of chronic cough and there is a clinical profile that nearly always predicts their presence in immunocompetent patients.

Adolescent↗