The effect of tobacco control measures during a period of rising cardiovascular disease risk in India: a mathematical model of myocardial infarction and stroke.

PubMed

Basu, Sanjay; Glantz, Stanton; Bitton, Asaf; Millett, Christopher

2013-01-01

We simulated tobacco control and pharmacological strategies for preventing cardiovascular deaths in India, the country that is expected to experience more cardiovascular deaths than any other over the next decade. A microsimulation model was developed to quantify the differential effects of various tobacco control measures and pharmacological therapies on myocardial infarction and stroke deaths stratified by age, gender, and urban/rural status for 2013 to 2022. The model incorporated population-representative data from India on multiple risk factors that affect myocardial infarction and stroke mortality, including hypertension, hyperlipidemia, diabetes, coronary heart disease, and cerebrovascular disease. We also included data from India on cigarette smoking, bidi smoking, chewing tobacco, and secondhand smoke. According to the model's results, smoke-free legislation and tobacco taxation would likely be the most effective strategy among a menu of tobacco control strategies (including, as well, brief cessation advice by health care providers, mass media campaigns, and an advertising ban) for reducing myocardial infarction and stroke deaths over the next decade, while cessation advice would be expected to be the least effective strategy at the population level. In combination, these tobacco control interventions could avert 25% of myocardial infarctions and strokes (95% CI: 17%-34%) if the effects of the interventions are additive. These effects are substantially larger than would be achieved through aspirin, antihypertensive, and statin therapy under most scenarios, because of limited treatment access and adherence; nevertheless, the impacts of tobacco control policies and pharmacological interventions appear to be markedly synergistic, averting up to one-third of deaths from myocardial infarction and stroke among 20- to 79-y-olds over the next 10 y. Pharmacological therapies could also be considerably more potent with further health system improvements. Smoke-free laws and substantially increased tobacco taxation appear to be markedly potent population measures to avert future cardiovascular deaths in India. Despite the rise in co-morbid cardiovascular disease risk factors like hyperlipidemia and hypertension in low- and middle-income countries, tobacco control is likely to remain a highly effective strategy to reduce cardiovascular deaths.

Relation of Total and Cardiovascular Death Rates to Climate System, Temperature, Barometric Pressure, and Respiratory Infection.

PubMed

Schwartz, Bryan G; Qualls, Clifford; Kloner, Robert A; Laskey, Warren K

2015-10-15

A distinct seasonal pattern in total and cardiovascular death rates has been reported. The factors contributing to this pattern have not been fully explored. Seven locations (average total population 71,354,000) were selected where data were available including relatively warm, cold, and moderate temperatures. Over the period 2004 to 2009, there were 2,526,123 all-cause deaths, 838,264 circulatory deaths, 255,273 coronary heart disease deaths, and 135,801 ST-elevation myocardial infarction (STEMI) deaths. We used time series and multivariate regression modeling to explore the association between death rates and climatic factors (temperature, dew point, precipitation, barometric pressure), influenza levels, air pollution levels, hours of daylight, and day of week. Average seasonal patterns for all-cause and cardiovascular deaths were very similar across the 7 locations despite differences in climate. After adjusting for multiple covariates and potential confounders, there was a 0.49% increase in all-cause death rate for every 1°C decrease. In general, all-cause, circulatory, coronary heart disease and STEMI death rates increased linearly with decreasing temperatures. The temperature effect varied by location, including temperature's linear slope, cubic fit, positional shift on the temperature axis, and the presence of circulatory death increases in locally hot temperatures. The variable effect of temperature by location suggests that people acclimatize to local temperature cycles. All-cause and circulatory death rates also demonstrated sizable associations with influenza levels, dew point temperature, and barometric pressure. A greater understanding of how climate, temperature, and barometric pressure influence cardiovascular responses would enhance our understanding of circulatory and STEMI deaths. Copyright © 2015 Elsevier Inc. All rights reserved.

Causes of death of prisoners of war during the Korean War (1950-1953).

PubMed

Lee, Myoung-Soon; Kang, Min-Jung; Huh, Sun

2013-03-01

This study aimed at analyzing the causes of death of prisoners of war (POWs) during the Korean War (1950-1953) who fought for the Communist side (North Korea and the People's Republic of China). In 1998, the United States Department of Defense released new information about the prisoners including, 7,614 deaths of the POW during the Korean War. The data on the causes of death of the POWs during the Korean War provides valuable information on the both the public health and history of the conflict. To analyze the causes of death of the POWs, we classified the clinical diagnosis and findings on 7,614 deaths into 22 chapters, as outlined in the International Statistical Classification of Diseases and Related Health Problems-10th Revision (ICD-10). Second, we traced changes in the monthly death totals of POWs as well as deaths caused by common infectious diseases and external causes of death including injury over time from August 1950 to September 1953. The most common category of causes of deaths of POWs was infectious disease, 5,013 (65.8%) out of 7,614 deaths, followed by external causes including injury, 817 (10.7%). Overall, tuberculosis and dysentery/diarrhea were the most common causes of death. Deaths caused by acute and chronic infection, or external causes showed different patterns of increases and decline over time during the Korean War. The information and data on POWs' deaths during the Korean War reflects the critical impact of the POWs' living conditions and the effect of public health measures implemented in POW camps during the war.

[Effect of family cohesion, subjective happiness and other factors on death anxiety in Korean elders].

PubMed

Jo, Kae Hwa; Song, Byung Sook

2012-10-01

The purposes of this study were to explore the effects of family cohesion and subjective happiness on death anxiety of Korean elders and to identify other factors contributing to death anxiety. The participants were 280 elders who lived in P metropolitan city. Data were collected between November 5, 2011 and January 12, 2012 using the Short Portable Mental Status Questionnaire (SPMSQ), Family Cohesion Evaluation Scale, Subjective Happiness Scale, and Fear of Death Scale (FODS). Data were analyzed using the SPSS/WIN 19.0 program. Family cohesion, marital status, religious activity, perceived health status, and subjective happiness were included in the factors affecting death anxiety of Korean elders. These variables explained 50.1% of death anxiety. The results of the study indicate that these variables should be considered in developing nursing intervention programs to decrease death anxiety and increase family cohesion and subjective happiness for life integration in Korean elders.

Capability for suicide interacts with states of heightened arousal to predict death by suicide beyond the effects of depression and hopelessness

PubMed Central

Ribeiro, Jessica D.; Yen, Shirley; Joiner, Thomas; Siegler, Ilene C.

2016-01-01

Background States of heightened arousal (e.g., agitation, sleep disturbance) have been repeatedly linked to suicidal thoughts and behaviors, including attempts and death. Studies have further indicated that these states may be particularly pernicious among individuals who evidence high suicidal capability. The objective of this study was to examine the interactive effects of heightened arousal and the capability for suicide in the prospective prediction of death by suicide. We examine this relation beyond the effects of robust predictors of suicide, namely depression and hopelessness. Methods Participants were drawn from a larger study of undergraduates who completed baseline assessments during their freshman year and were then followed to time of death. The sample in this study only included individuals who had died by suicide (n=96) or other causes (n=542). Proxy measures to assess predictor variables were constructed using items from the MMPI, which was administered at baseline. An independent sample of clinical outpatients (n=was used to evaluate the construct validity of the proxy measures). Results Results were in line with expectation: heightened arousal interacted with capability for suicide to prospectively predict death by suicide, such that, as severity of heightened arousal symptoms increased, the likelihood of death by suicide increased among individuals high but not low on capability for suicide. Limitations Limitations include the use of proxy measures, the extended length of follow-up, and the homogeneity of the sample (i.e., primarily White males). Conclusion These findings add to an emerging literature that supports the moderating influence of capability for suicide on the relationship between states of heightened arousal on the likelihood of death by suicide. PMID:26342889

Academic emergency physicians' experiences with patient death.

PubMed

Strote, Jared; Schroeder, Erika; Lemos, John; Paganelli, Ryan; Solberg, Jonathan; Range Hutson, H

2011-03-01

There is a growing awareness of the effects of patient death on physician well-being, and the importance of cultural and educational changes to improve coping mechanisms. The objective of this study was to explore both the effects of patient death on academic emergency physicians (EPs) and the coping mechanisms they use to deal with these events. Faculty at a convenience sample of four emergency medicine (EM) residency programs were questioned about their responses to patient death in a 15-question on-line survey. Descriptive analysis of the data was performed. Independent variables were analyzed for differences in complaints of physical symptoms or consideration of important life changes after patient death. Of 207 EPs surveyed, 145 (70%) responded. Patient death was experienced frequently, with 95 (66%) witnessing a death at least every month. No training on coping with patient death had occurred for 35 (24%); 93 (64%) had less than 6 hours of training. The most common coping mechanisms included talking with colleagues (113; 78%) or friends and family (100; 69%), as well as simply continuing to work (89; 61%). Postdeath debriefing occurred rarely or never for 93 (64%) of respondents. Most EPs had experienced physical responses to patient death, the most common being insomnia (54; 37%) and fatigue (21; 14%). Common emotional responses included sadness (112; 70%) and disappointment (55; 38%). No significant differences in response rates for physical symptoms or consideration of life changes were found for any of the variables. Patient death was reported to lead to both physical and emotional symptoms in academic EPs. Postdeath debriefing appears to happen infrequently in teaching settings, and most respondents reported that they themselves received limited training in coping with patient death. Further study is needed to both identify coping mechanisms that are feasible and effective in emergency department settings and develop teaching strategies to incorporate this information into EM residency training. © 2011 by the Society for Academic Emergency Medicine.

Suicide and media reporting: a longitudinal and spatial analysis.

PubMed

Yang, Albert C; Tsai, Shih-Jen; Yang, Cheng-Hung; Shia, Ben-Chang; Fuh, Jong-Ling; Wang, Shuu-Jiun; Peng, Chung-Kang; Huang, Norden E

2013-03-01

The impact of media reporting on copycat suicides has been well established in various cases of celebrity suicide. However, knowledge is limited about the spatial and temporal relationship between suicide death and media reporting over a long period of time. This study investigated the association of suicide deaths with suicide news in longitudinal and spatial dimensions. All suicides during 2003-2010 (n = 31,364) were included. Suicide news in the study period was retrieved from Google News, and included all available news media in Taiwan. Empirical mode decomposition was used to identify the main intrinsic oscillation, reflecting both major and minor suicide events, and time-dependent intrinsic correlation was used to quantify the temporal correlation between suicide deaths and suicide news. The media reporting of suicide was synchronized with increased suicide deaths during major suicide events such as celebrity death, and slightly lagged behind the suicide deaths for 1 month in other periods without notable celebrity deaths. The means of suicide reported in the media diversely affected the suicide models. Reports of charcoal burning suicide exhibited an exclusive copycat effect on actual charcoal burning deaths, whereas media reports of jumping had a wide association with various suicide models. Media reports of suicide had a higher association with suicide deaths in urban than in rural areas. This report suggested that a delayed effect of copycat suicide may exist in media reports of minor suicide events. The competitive reporting of minor suicide events must be avoided and addressed by media professionals.

Causes of Death of Prisoners of War during the Korean War (1950-1953)

PubMed Central

Lee, Myoung-Soon; Kang, Min-Jung

2013-01-01

Purpose This study aimed at analyzing the causes of death of prisoners of war (POWs) during the Korean War (1950-1953) who fought for the Communist side (North Korea and the People's Republic of China). In 1998, the United States Department of Defense released new information about the prisoners including, 7,614 deaths of the POW during the Korean War. The data on the causes of death of the POWs during the Korean War provides valuable information on the both the public health and history of the conflict. Materials and Methods To analyze the causes of death of the POWs, we classified the clinical diagnosis and findings on 7,614 deaths into 22 chapters, as outlined in the International Statistical Classification of Diseases and Related Health Problems-10th Revision (ICD-10). Second, we traced changes in the monthly death totals of POWs as well as deaths caused by common infectious diseases and external causes of death including injury over time from August 1950 to September 1953. Results The most common category of causes of deaths of POWs was infectious disease, 5,013 (65.8%) out of 7,614 deaths, followed by external causes including injury, 817 (10.7%). Overall, tuberculosis and dysentery/diarrhea were the most common causes of death. Deaths caused by acute and chronic infection, or external causes showed different patterns of increases and decline over time during the Korean War. Conclusion The information and data on POWs' deaths during the Korean War reflects the critical impact of the POWs' living conditions and the effect of public health measures implemented in POW camps during the war. PMID:23364985

Psychodrama and Moviemaking in a Death Education Course to Work Through a Case of Suicide Among High School Students in Italy.

PubMed

Testoni, Ines; Ronconi, Lucia; Palazzo, Lorenza; Galgani, Michele; Stizzi, Antonio; Kirk, Kate

2018-01-01

This study describes the psychological effects of an experience of death education (DE) used to explore a case of suicide in an Italian high school. DE activities included philosophical and religious perspectives of the relationships between death and the meaning of life, a visit to a local hospice, and psychodrama activities, which culminated in the production of short movies. The intervention involved 268 high school students (138 in the experimental group). Pre-test and post-test measures assessed ontological representations of death, death anxiety, alexithymia, and meaning in life. Results confirmed that, in the experimental group, death anxiety was significantly reduced as much as the representation of death as annihilation and alexithymia, while a sense of spirituality and the meaning of life were more enhanced, compared to the No DE group. These improvements in the positive meaning of life and the reduction of anxiety confirmed that it is possible to manage trauma and grief at school with death education interventions that include religious discussion, psychodrama and movie making activities.

Psychodrama and Moviemaking in a Death Education Course to Work Through a Case of Suicide Among High School Students in Italy

PubMed Central

Testoni, Ines; Ronconi, Lucia; Palazzo, Lorenza; Galgani, Michele; Stizzi, Antonio; Kirk, Kate

2018-01-01

This study describes the psychological effects of an experience of death education (DE) used to explore a case of suicide in an Italian high school. DE activities included philosophical and religious perspectives of the relationships between death and the meaning of life, a visit to a local hospice, and psychodrama activities, which culminated in the production of short movies. The intervention involved 268 high school students (138 in the experimental group). Pre-test and post-test measures assessed ontological representations of death, death anxiety, alexithymia, and meaning in life. Results confirmed that, in the experimental group, death anxiety was significantly reduced as much as the representation of death as annihilation and alexithymia, while a sense of spirituality and the meaning of life were more enhanced, compared to the No DE group. These improvements in the positive meaning of life and the reduction of anxiety confirmed that it is possible to manage trauma and grief at school with death education interventions that include religious discussion, psychodrama and movie making activities. PMID:29692745

Flavonoids in Ginkgo biloba fallen leaves induce apoptosis through modulation of p53 activation in melanoma cells.

PubMed

Park, Hye-Jung; Kim, Moon-Moo

2015-01-01

The aim of the present study was to examine the apoptotic effect of flavonoids in methanol extracts of Ginkgo biloba fallen leaves (MEGFL) on melanoma cells. Ginkgo biloba is a deciduous castle chaplain and its leaves include various types of flavonoids such as flavonol-O-glycosides. Ginkgo biloba is known to have therapeutic properties against a number of diseases such as cerebrovascular diseases, blood circulation disease and hypertension. In the present study MEGFL exhibited a higher cytotoxic effect on melanoma cells than Ginkgo biloba leaves (MEGL). It was also found that MEGFL induced apoptotic cell death which was characterized by DNA fragmentation. During the cell death process following treatment with MEGFL, the expression of a variety of death-associated proteins including p53, caspase-3, caspase-9, cytochrome c and Bax were analyzed in the cytosol of melanoma cells. MEGFL significantly increased the expression levels of caspase-3, caspase-9 and p53 in a dose-dependent manner. Our results indicate that MEGFL induced apoptotic cell death by increasing the expression of cell death-associated proteins in melanoma cells.

DISTINCT FUNCTIONS OF JNK AND C-JUN IN OXIDANT-INDUCED HEPATOCYTE DEATH

PubMed Central

Amir, Muhammad; Liu, Kun; Zhao, Enpeng; Czaja, Mark J.

2013-01-01

Overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling is a central mechanism of hepatocyte injury and death including that from oxidative stress. However, the functions of JNK and c-Jun are still unclear, and this pathway also inhibits hepatocyte death. Previous studies of menadione-induced oxidant stress demonstrated that toxicity resulted from sustained JNK/c-Jun activation as death was blocked by the c-Jun dominant negative TAM67. To further delineate the function of JNK/c-Jun signaling in hepatocyte injury from oxidant stress, the effects of direct JNK inhibition on menadione-induced death were examined. In contrast to the inhibitory effect of TAM67, pharmacological JNK inhibition by SP600125 sensitized the rat hepatocyte cell line RALA255-10G to death from menadione. SP600125 similarly sensitized mouse primary hepatocytes to menadione toxicity. Death from SP600125/menadione was c-Jun dependent as it was blocked by TAM67, but independent of c-Jun phosphorylation. Death occurred by apoptosis and necrosis and activation of the mitochondrial death pathway. Short hairpin RNA knockdowns of total JNK or JNK2 sensitized to death from menadione, whereas a jnk1 knockdown was protective. Jnk2 null mouse primary hepatocytes were also sensitized to menadione death. JNK inhibition magnified decreases in cellular ATP content and β-oxidation induced by menadione. This effect mediated cell death as chemical inhibition of β-oxidation also sensitized cells to death from menadione, and supplementation with the β-oxidation substrate oleate blocked death. Components of the JNK/c-Jun signaling pathway have opposing functions in hepatocyte oxidant stress with JNK2 mediating resistance to cell death and c-Jun promoting death. PMID:22644775

Effects of alcohol taxes on alcohol-related mortality in Florida: time-series analyses from 1969 to 2004.

PubMed

Maldonado-Molina, Mildred M; Wagenaar, Alexander C

2010-11-01

Over a hundred studies have established the effects of beverage alcohol taxes and prices on sales and drinking behaviors. Yet, relatively few studies have examined effects of alcohol taxes on alcohol-related mortality. We evaluated effects of multiple changes in alcohol tax rates in the state of Florida from 1969 to 2004 on disease (not injury) mortality. A time-series quasi-experimental research design was used, including non-alcohol deaths within Florida and other states' rates of alcohol-related mortality for comparison. A total of 432 monthly observations of mortality in Florida were examined over the 36-year period. Analyses included ARIMA, fixed-effects, and random-effects models, including a noise model, tax independent variables, and structural covariates. We found significant reductions in mortality related to chronic heavy alcohol consumption following legislatively induced increases in alcohol taxes in Florida. The frequency of deaths (t = -2.73, p = 0.007) and the rate per population (t = -2.06, p = 0.04) declined significantly. The elasticity effect estimate is -0.22 (t = -1.88, p = 0.06), indicating a 10% increase in tax is associated with a 2.2% decline in deaths. Increased alcohol taxes are associated with significant and sizable reductions in alcohol-attributable mortality in Florida. Results indicate that 600 to 800 lives per year could be saved if real tax rates were returned to 1983 levels (when the last tax increase occurred). Findings highlight the role of tax policy as an effective means for reducing deaths associated with chronic heavy alcohol use. Copyright © 2010 by the Research Society on Alcoholism.

Effects of alcohol taxes on alcohol-related mortality in Florida: Time-series analyses from 1969–2004

PubMed Central

Maldonado-Molina, Mildred M.; Wagenaar, Alexander C.

2010-01-01

Background Over a hundred studies have established the effects of beverage alcohol taxes and prices on sales and drinking behaviors. Yet, relatively few studies have examined effects of alcohol taxes on alcohol-related mortality. We evaluated effects of multiple changes in alcohol tax rates in the State of Florida from 1969–2004 on disease (not injury) mortality. Methods A time-series quasi-experimental research design was used, including non-alcohol deaths within Florida and other states’ rates of alcohol-related mortality for comparison. A total of 432 monthly observations of mortality in Florida were examined over the 36-year period. Analyses included ARIMA, fixed-effects, and random effects models, including a noise model, tax independent variables, and structural covariates. Results We found significant reductions in mortality related to chronic heavy alcohol consumption following legislatively induced increases in alcohol taxes in Florida. The frequency of deaths (t=−2.73, p=.007) and the rate per population (t=−2.06, p=.04) declined significantly. The elasticity effect estimate is −0.22 (t=−1.88, p=.06), indicating a 10% increase in tax is associated with a 2.2% decline in deaths. Conclusions Increased alcohol taxes are associated with significant and sizable reductions in alcohol-attributable mortality in Florida. Results indicate that 600–800 lives per year could be saved if real tax rates were returned to 1983 levels (when the last tax increase occurred). Findings highlight the role of tax policy as an effective means for reducing deaths associated with chronic heavy alcohol use. PMID:20659073

The Effect of Tobacco Control Measures during a Period of Rising Cardiovascular Disease Risk in India: A Mathematical Model of Myocardial Infarction and Stroke

PubMed Central

Basu, Sanjay; Glantz, Stanton; Bitton, Asaf; Millett, Christopher

2013-01-01

Background We simulated tobacco control and pharmacological strategies for preventing cardiovascular deaths in India, the country that is expected to experience more cardiovascular deaths than any other over the next decade. Methods and Findings A microsimulation model was developed to quantify the differential effects of various tobacco control measures and pharmacological therapies on myocardial infarction and stroke deaths stratified by age, gender, and urban/rural status for 2013 to 2022. The model incorporated population-representative data from India on multiple risk factors that affect myocardial infarction and stroke mortality, including hypertension, hyperlipidemia, diabetes, coronary heart disease, and cerebrovascular disease. We also included data from India on cigarette smoking, bidi smoking, chewing tobacco, and secondhand smoke. According to the model's results, smoke-free legislation and tobacco taxation would likely be the most effective strategy among a menu of tobacco control strategies (including, as well, brief cessation advice by health care providers, mass media campaigns, and an advertising ban) for reducing myocardial infarction and stroke deaths over the next decade, while cessation advice would be expected to be the least effective strategy at the population level. In combination, these tobacco control interventions could avert 25% of myocardial infarctions and strokes (95% CI: 17%–34%) if the effects of the interventions are additive. These effects are substantially larger than would be achieved through aspirin, antihypertensive, and statin therapy under most scenarios, because of limited treatment access and adherence; nevertheless, the impacts of tobacco control policies and pharmacological interventions appear to be markedly synergistic, averting up to one-third of deaths from myocardial infarction and stroke among 20- to 79-y-olds over the next 10 y. Pharmacological therapies could also be considerably more potent with further health system improvements. Conclusions Smoke-free laws and substantially increased tobacco taxation appear to be markedly potent population measures to avert future cardiovascular deaths in India. Despite the rise in co-morbid cardiovascular disease risk factors like hyperlipidemia and hypertension in low- and middle-income countries, tobacco control is likely to remain a highly effective strategy to reduce cardiovascular deaths. Please see later in the article for the Editors' Summary PMID:23874160

Florida's weakened motorcycle helmet law: effects on death rates in motorcycle crashes.

PubMed

Kyrychenko, Sergey Y; McCartt, Anne T

2006-03-01

Effective July 1, 2000, Florida's universal helmet law was amended to exclude riders ages 21 and older with insurance coverage providing at least 10,000 US dollars in medical benefits for injuries sustained in a motorcycle crash. Observed helmet use in Florida was reported to have declined from nearly 100% in 1998, before the law change, to 53% after. This study examined the effects of the law change on the likelihood of death, given involvement in a motorcycle crash. Rates of motorcyclist deaths per crash involvement in Florida for 2001-2002 (after the law change) were compared with those for 1998-1999 (before the law change). Before/after death rate ratios (95% CIs) were examined, and logistic regression models estimated the effect of the helmet law change on the odds of death in a crash, while controlling for rider gender, age, and seating position, and number of vehicles. The motorcyclist death rate increased significantly after the law change, from 30.8 to 38.8 deaths per 1,000 crash involvements. Motorcyclist death rates increased for single- and multiple-vehicle crashes, for male and female operators, and for riders of all ages including those younger than 21. After controlling for gender and age, the likelihood of death given involvement in a motorcycle crash was 25% higher than expected after the law change. It is estimated that 117 motorcyclist deaths could have been avoided during 2001-2002 if Florida's universal helmet law had remained in place. This study provides evidence of the life-saving benefits of universal helmet laws. The results also suggest that age-specific helmet laws are not effective in protecting the youngest drivers. This is not surprising, as these laws are largely unenforceable.

Genetic parameters for lamb birth weight, survival and death risk traits.

PubMed

Everett-Hincks, J M; Mathias-Davis, H C; Greer, G J; Auvray, B A; Dodds, K G

2014-07-01

This paper reports genetic parameters for lamb survival and mortality traits on sheep farms in New Zealand. Lamb survival and mortality records were obtained from 38 flocks (103,357 lambs) from 5 yr of lambing data (2007 to 2011) and include many breeds and their crosses (predominantly Romney, Perendale, Coopworth, and Texel). A number of models were tested, all including environmental weather effects and investigating the random environmental effect of dam and litter (dam/year) as well as logit transformation for binary traits. Total heritability (direct + maternal) estimates were low for lamb viability at birth (0.01), lamb death risk to dystocia (0.01), and lamb death risk to starvation exposure (0.01) from birth to 3 d of age in an analysis accounting for direct and maternal genetic effects and the maternal environmental effects. Lamb survival heritabilities reported are very low (total heritabilities range from 0.02 to 0.06). The total heritabilities for the lamb death risk traits are lower than reported estimates of survival to 3 d of age or to weaning suggesting selection for the postmortem traits are not warranted at this time within these flocks. The total heritability for lamb birth weight was moderate (0.38) and the genetic correlations with the lamb death risk traits suggested that directional selection on lamb birth weight would have an effect on survival, although it is likely to have a nonlinear effect and therefore an optimum birth weight at which survival is maximized. This study has also shown that the total heritabilities may be overestimated when not accounting for maternal genetic and environment effects and in particular not accounting for the random environmental effect of litter (dam/year).

Impact of an effective multidrug-resistant tuberculosis control programme in the setting of an immature HIV epidemic: system dynamics simulation model.

PubMed

Atun, Rifat A; Lebcir, Reda; Drobniewski, Francis; Coker, Richard J

2005-08-01

This study sought to determine the impact of an effective programme of multidrug resistant tuberculosis control (MDRTB) on a population that is witnessing an explosive HIV epidemic among injecting drug users (IDUs), where the prevalence of MDRTB is already high. A transmission model was constructed that represents the dynamics of the drug-susceptible tuberculosis (DSTB), MDRTB and HIV spread among the adult population of Samara Oblast, Russia: from official notifications of tuberculosis and of HIV infection, estimates of MDRTB derived from surveillance studies, population data from official regional statistics, data on transmission probabilities from peer-reviewed publications and informed estimates, and policy-makers' estimates of IDU populations. Two scenarios of programme effectiveness for MDRTB were modelled and run over a period of 10 years to predict cumulative deaths. In a population of 3.3 million with a high prevalence of MDRTB, an emerging epidemic of HIV among IDUs, and a functioning directly observed therapy-short course (DOTS) programme, the model predicts that under low cure rates for MDRTB the expected cumulative deaths from tuberculosis will reach 6303 deaths including 1900 deaths from MDRTB at 10 years. Under high cure rate for MDRTB 4465 deaths will occur including 134 deaths from MDRTB. At 10 years there is little impact on HIV-infected populations from the MDRTB epidemic, but as the HIV epidemic matures the impact becomes substantial. When the model is extended to 20 years cumulative deaths from MDRTB become very high if cure rates for MDRTB are low and cumulative deaths in the HIV-infected population, likewise, are profoundly affected. In the presence of an immature HIV epidemic failure to actively control MDRTB may result in approximately a third more deaths than if effective treatment is given. As the HIV epidemic matures then the impact of MDRTB grows substantially if MDRTB control strategies are ineffective. The epidemiological starting point for these scenarios is present in many regions within the former Soviet Union and this analysis suggests control of MDRTB should be an urgent priority.

Ethical issues in critical care and cardiac arrest: clinical research, brain death, and organ donation.

PubMed

Donatelli, Luke A; Geocadin, Romergryko G; Williams, Michael A

2006-09-01

Cardiac arrest results in global hypoxic-ischemic brain injury from which there is a range of possible neurological outcomes. In most cases, patients may require a surrogate to make decisions regarding end-of-life care, including the withdrawal of life-sustaining therapies. This article reviews ethical considerations that arise in the clinical care of patients following cardiac arrest, including decisions to continue or withdraw life-sustaining therapies; brain death determination; and organ donation in the context of brain death and cardiac death (so-called non-heart-beating donation). This article also discusses ethical concerns pertaining to the design and conduct of resuscitation research that is necessary for the development of effective therapies to prevent anoxic brain injury or promote neurological recovery.

Electroconvulsive Therapy and All-Cause Mortality in Texas, 1998-2013.

PubMed

Dennis, Nora M; Dennis, Paul A; Shafer, Alan; Weiner, Richard D; Husain, Mustafa M

2017-03-01

Electroconvulsive therapy (ECT) remains an effective treatment for major depressive disorder. Since 1995, Texas has maintained an ECT database including patient diagnoses and outcomes, and reporting any deaths within 14 days of receiving an ECT treatment, encompassing a total of 166,711 ECT treatments administered in Texas over the previously unreported period of 1998 to 2013. Descriptive analysis summarized information on deaths reported during the 16-year period-cause of death, type of treatment (index or maintenance) and patient demographics. Multiple logistic regression of death incidence by treatment session was performed to determine whether patient age, sex, race, diagnosis, or year of treatment was associated with death after ECT. Of those deaths occurring within 1 day of an ECT treatment, the death rate was 2.4 per 100,000 treatments. Looking at all deaths within 14 days of an ECT treatment, the death rate increased to 18 per 100,000 treatments but included all deaths regardless of likelihood of causal association with ECT, for example, accidents and suicides, the latter a leading cause of death among individuals with severe major depression or other disorders for which ECT is indicated. Death rate increased significantly with increasing patient age (P = 0.001) and male sex (P = 0.009), and there was a nonsignificant trend toward increased death amongst patients with bipolar disorder or schizophrenia (P = 0.058) versus depression. Our data indicate that ECT is in general a safe procedure with respect to the likelihood of immediate death. Suicide remains a significant risk in ECT patients, despite evidence that ECT reduces suicidal ideation.

Tobacco as a Reproductive and Developmental Toxicant

EPA Science Inventory

Maternal cigarette smoking has long been known to result in effects on offspring including lower birthweight and neurobehavioral effects. Continuing studies have expanded the list of adverse outcomes in offspring to include Sudden Infant Death Syndrome, impaired lung function, an...

Immunopathogenesis of Dengue Virus-Induced Redundant Cell Death: Apoptosis and Pyroptosis.

PubMed

Suwanmanee, San; Luplertlop, Natthanej

Dengue virus infection is a self-limited condition, which is of particular importance in tropical and subtropical regions and for which no specific treatment or effective vaccine is available. There are several hypotheses explaining dengue pathogenesis. These usually refer to host immune responses, including antibody-dependent enhancement, cytokine expression, and dengue virus particles including NS1 protein, which lead to cell death by both apoptosis and pyroptosis. A clear understanding of the pathogenesis should facilitate the development of vaccines and therapies. This review focuses on the immunopathogenesis in relation to clinical manifestations and patterns of cell death, focusing on the pathogenesis of severe dengue.

A prospective study of arm circumference and risk of death in Bangladesh.

PubMed

Chen, Yu; Ge, Wenzhen; Parvez, Faruque; Bangalore, Sripal; Eunus, Mahbub; Ahmed, Alauddin; Islam, Tariqul; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Argos, Maria; Levy, Diane; Sarwar, Golam; Ahsan, Habibul

2014-08-01

Epidemiological studies have observed protective effects of mid-upper arm circumference (MUAC) against all-cause mortality mostly in Western populations. However, evidence on cause-specific mortality is limited. The sample included 19 575 adults from a population-based cohort study in rural Bangladesh, who were followed up for an average of 7.9 years for mortality. Cox proportional hazards regression was used to evaluate the effect of MUAC, as well as the joint effect of body mass index (BMI) and MUAC, on the risk of death from any cause, cancer and cardiovascular disease (CVD). During 154 664 person-years of follow-up, 744 deaths including 312 deaths due to CVD and 125 deaths due to cancer were observed. There was a linear inverse relationship of MUAC with total and CVD mortality. Each 1-cm increase in MUAC was associated a reduced risk of death from any cause [hazard ratio (HR) = 0.85; 95% confidence interval (C), 0.81-0.89) and CVD (HR = 0.87; 95% CI, 0.80-0.94), after controlling for potential confounders. No apparent relationship between MUAC and the risk of death from cancer was observed. Among individuals with a low BMI (<18.5 kg/m(2)), a MUAC less than 24 cm was associated with increased risk for all-cause (HR = 1.81; 95% CI, 1.52-2.17) and CVD mortality (HR = 1.45; 95% CI, 1.11-1.91). MUAC may play a critical role on all-cause and CVD mortality in lean Asians. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Six-Year Follow-Up of Impact of Co-proxamol Withdrawal in England and Wales on Prescribing and Deaths: Time-Series Study

PubMed Central

Hawton, Keith; Bergen, Helen; Simkin, Sue; Wells, Claudia; Kapur, Navneet; Gunnell, David

2012-01-01

Background The analgesic co-proxamol (paracetamol/dextropropoxyphene combination) has been widely involved in fatal poisoning. Concerns about its safety/effectiveness profile and widespread use for suicidal poisoning prompted its withdrawal in the UK in 2005, with partial withdrawal between 2005 and 2007, and full withdrawal in 2008. Our objective in this study was to assess the association between co-proxamol withdrawal and prescribing and deaths in England and Wales in 2005–2010 compared with 1998–2004, including estimation of possible substitution effects by other analgesics. Methods and Findings We obtained prescribing data from the NHS Health and Social Care Information Centre (England) and Prescribing Services Partneriaeth Cydwasanaethau GIG Cymru (Wales), and mortality data from the Office for National Statistics. We carried out an interrupted time-series analysis of prescribing and deaths (suicide, open verdicts, accidental poisonings) involving single analgesics. The reduction in prescribing of co-proxamol following its withdrawal in 2005 was accompanied by increases in prescribing of several other analgesics (co-codamol, paracetamol, codeine, co-dydramol, tramadol, oxycodone, and morphine) during 2005–2010 compared with 1998–2004. These changes were associated with major reductions in deaths due to poisoning with co-proxamol receiving verdicts of suicide and undetermined cause of −21 deaths (95% CI −34 to −8) per quarter, equating to approximately 500 fewer suicide deaths (−61%) over the 6 years 2005–2010, and −25 deaths (95% CI −38 to −12) per quarter, equating to 600 fewer deaths (−62%) when accidental poisoning deaths were included. There was little observed change in deaths involving other analgesics, apart from an increase in oxycodone poisonings, but numbers were small. Limitations were that the study was based on deaths involving single drugs alone and changes in deaths involving prescribed morphine could not be assessed. Conclusions During the 6 years following the withdrawal of co-proxamol in the UK, there was a major reduction in poisoning deaths involving this drug, without apparent significant increase in deaths involving other analgesics. Please see later in the article for the Editors' Summary PMID:22589703

Vital signs: restraint use and motor vehicle occupant death rates among children aged 0-12 years - United States, 2002-2011.

PubMed

Sauber-Schatz, Erin K; West, Bethany A; Bergen, Gwen

2014-02-07

Motor vehicle crashes are a leading cause of death among children in the United States. Age- and size-appropriate child restraint use is the most effective method for reducing these deaths. CDC analyzed 2002–2011 data from the Fatality Analysis Reporting System to determine the number and rate of motor-vehicle occupant deaths, and the proportion of unrestrained child deaths among children aged <1 year, 1–3 years , 4–7 years, 8–12 years, and for all children aged 0–12 years. Age group–specific death rates and proportions of unrestrained child motor vehicle deaths for 2009–2010 were further stratified by race/ethnicity. Motor vehicle occupant death rates for children declined significantly from 2002 to 2011. However, one third (33%) of children who died in 2011 were unrestrained. Compared with white children for 2009–2010, black children had significantly higher death rates, and black and Hispanic children both had significantly higher proportions of unrestrained child deaths. Motor vehicle occupant deaths among children in the United States have declined in the past decade, but more deaths could be prevented if restraints were always used. Effective interventions, including child passenger restraint laws (with child safety seat/ booster seat coverage through at least age 8 years) and child safety seat distribution plus education programs, can increase restraint use and reduce child motor vehicle deaths.

Vital Signs: Restraint Use and Motor Vehicle Occupant Death Rates Among Children Aged 0–12 Years — United States, 2002–2011

PubMed Central

Sauber-Schatz, Erin K.; West, Bethany A.; Bergen, Gwen

2014-01-01

Background Motor vehicle crashes are a leading cause of death among children in the United States. Age- and size-appropriate child restraint use is the most effective method for reducing these deaths. Methods CDC analyzed 2002–2011 data from the Fatality Analysis Reporting System to determine the number and rate of motor-vehicle occupant deaths, and the proportion of unrestrained child deaths among children aged <1 year, 1–3 years, 4–7 years, 8–12 years, and for all children aged 0–12 years. Age group–specific death rates and proportions of unrestrained child motor vehicle deaths for 2009–2010 were further stratified by race/ethnicity. Results Motor vehicle occupant death rates for children declined significantly from 2002 to 2011. However, one third (33%) of children who died in 2011 were unrestrained. Compared with white children for 2009–2010, black children had significantly higher death rates, and black and Hispanic children both had significantly higher proportions of unrestrained child deaths. Conclusions Motor vehicle occupant deaths among children in the United States have declined in the past decade, but more deaths could be prevented if restraints were always used. Implications for Public Health Effective interventions, including child passenger restraint laws (with child safety seat/booster seat coverage through at least age 8 years) and child safety seat distribution plus education programs, can increase restraint use and reduce child motor vehicle deaths. PMID:24500292

Quantifying the indirect effects of key child survival interventions for pneumonia, diarrhoea, and measles.

PubMed

Fischer Walker, C L; Munos, M K; Black, R E

2013-01-01

To date many studies have measured the effect of key child survival interventions on the main cause of mortality while anecdotally reporting effects on all-cause mortality. We conducted a systematic literature review and abstracted cause-specific and all-cause mortality data from included studies. We then estimated the effect of the intervention on the disease of primary interest and calculated the additional deaths prevented (i.e. the indirect effect). We calculated that insecticide-treated nets have been shown to result in a 12% reduction [95% confidence interval (CI) 0·0-23] among non-malaria deaths. We found pneumonia case management to reduce non-pneumonia mortality by 20% (95% CI 8-22). For measles vaccine, seven of the 10 studies reporting an effect on all-cause mortality demonstrated an additional benefit of vaccine on all-cause mortality. These interventions may have benefits on causes of death beyond the specific cause of death they are targeted to prevent and this should be considered when evaluating the effects of implementation of interventions.

Electronic Certification of Death in Slovenia - System Considerations and Development Opportunities.

PubMed

Stanimirovic, Dalibor

2016-01-01

Accurate and consistent death certification facilitates morbidity and mortality surveillance, and consequently supports evidence-informed health policies. The paper initially explores the current death certification practice in Slovenia, and identifies related deficiencies and system inconsistencies. Finally, the paper outlines a conceptualization of ICT-based model of death certification including renovation of business processes and organizational changes. The research is based on focus group methodology. Structured discussions were conducted with 29 experts from cross-sectional areas related to death certification. Research results imply that effective ICT-based transformation of the existing death certification model should involve a redefinition of functions and relationships between the main actors, as well as a reconfiguration of the technological, organizational, and regulatory elements in the field. The paper provides an insight into the complexities of the death certification and may provide the groundwork for ICT-based transformation of the death certification model in Slovenia.

Effectiveness of inactivated influenza vaccines in preventing influenza-associated deaths and hospitalizations among Ontario residents aged ≥ 65 years: estimates with generalized linear models accounting for healthy vaccinee effects.

PubMed

Ridenhour, Benjamin J; Campitelli, Michael A; Kwong, Jeffrey C; Rosella, Laura C; Armstrong, Ben G; Mangtani, Punam; Calzavara, Andrew J; Shay, David K

2013-01-01

Estimates of the effectiveness of influenza vaccines in older adults may be biased because of difficulties identifying and adjusting for confounders of the vaccine-outcome association. We estimated vaccine effectiveness for prevention of serious influenza complications among older persons by using methods to account for underlying differences in risk for these complications. We conducted a retrospective cohort study among Ontario residents aged ≥ 65 years from September 1993 through September 2008. We linked weekly vaccination, hospitalization, and death records for 1.4 million community-dwelling persons aged ≥ 65 years. Vaccine effectiveness was estimated by comparing ratios of outcome rates during weeks of high versus low influenza activity (defined by viral surveillance data) among vaccinated and unvaccinated subjects by using log-linear regression models that accounted for temperature and time trends with natural spline functions. Effectiveness was estimated for three influenza-associated outcomes: all-cause deaths, deaths occurring within 30 days of pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations. During weeks when 5% of respiratory specimens tested positive for influenza A, vaccine effectiveness among persons aged ≥ 65 years was 22% (95% confidence interval [CI], -6%-42%) for all influenza-associated deaths, 25% (95% CI, 13%-37%) for deaths occurring within 30 days after an influenza-associated pneumonia/influenza hospitalization, and 19% (95% CI, 4%-31%) for influenza-associated pneumonia/influenza hospitalizations. Because small proportions of deaths, deaths after pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations were associated with influenza virus circulation, we estimated that vaccination prevented 1.6%, 4.8%, and 4.1% of these outcomes, respectively. By using confounding-reducing techniques with 15 years of provincial-level data including vaccination and health outcomes, we estimated that influenza vaccination prevented ~4% of influenza-associated hospitalizations and deaths occurring after hospitalizations among older adults in Ontario.

Implantable cardioverter-defibrillator implantation for primary and secondary prevention: indications and outcomes.

PubMed

Pick, Justin M; Batra, Anjan S

2017-01-01

Implantable cardioverter-defibrillators effectively reduce the rate of sudden cardiac death in children. Significant efforts have been made to better characterise the indications for their placement, and over the past two decades there has been a shift in their use from secondary to primary prevention. Primary prevention includes placement in patients thought to be at high risk of sudden cardiac death before the patient experiences any event. Secondary prevention includes placement after a high-risk event including sustained ventricular tachycardia or resuscitated cardiac arrest. Although liberal device implantation may be appealing even in patients having marginal indications, studies have shown high rates of adverse effects including inappropriate device discharges and the need for re-intervention because of hardware malfunction. The indications for placement of an implantable cardioverter-defibrillator, whether for primary or secondary prevention of sudden cardiac death, vary based on cardiac pathology. This review will assist the provider in understanding the risks and benefits of device implantation in order to enhance the shared decision-making capacity of patients, families, and providers.

Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular disease, death and safety outcomes in type 2 diabetes - A systematic review.

PubMed

Rådholm, Karin; Wu, Jason Hy; Wong, Muh Geot; Foote, Celine; Fulcher, Gregory; Mahaffey, Kenneth W; Perkovic, Vlado; Neal, Bruce

2018-06-01

Sodium glucose co-transporter 2 (SGLT2) inhibitors appear to protect against increased risks of cardiovascular and kidney disease in patients with type 2 diabetes but also cause some harms. Whether effects are comparable across drug class or specific to individual compounds is unclear. This meta-analysis assessed the class and individual compound effects of SGLT2 inhibition versus control on cardiovascular events, death, kidney disease and safety outcomes in patients with type 2 diabetes. MEDLINE, EMBASE, the Cochrane Library and regulatory databases were systematically searched for data from randomized clinical trials that included reporting of cardiovascular events, deaths or safety outcomes. We used fixed effects models and inverse variance weighting to calculate relative risks with the 95% confidence intervals. The analyses included data from 82 trials, four overviews and six regulatory reports and there were 1,968 major cardiovascular events identified for analysis. Patients randomly assigned to SGLT2 had lower risks of major cardiovascular events (RR 0.85, 95%CI 0.77-0.93), heart failure (RR 0.67, 95%CI 0.55-0.80), all-cause death (RR 0.79, 95%CI 0.70-0.88) and serious decline in kidney function (RR 0.59, 0.49-0.71). Significant adverse effects were observed for genital infections (RR 3.06, 95%CI 2.73-4.43), volume depletion events (RR 1.24, 95%CI 1.07-1.43) and amputation (RR 1.44 95%CI 1.13-1.83). There was a high likelihood of differences in the associations of the individual compounds with cardiovascular death, hypoglycaemia and amputation (all I 2  > 80%) and a moderate likelihood of differences in the associations with non-fatal stroke, all-cause death, urinary tract infection and fracture (all I 2  > 30%). There are strong overall associations of SGLT2 inhibition with protection against major cardiovascular events, heart failure, serious decline in kidney function and all-cause death. SGLT2 inhibitors were also associated with infections, volume depletion effects and amputation. Some associations appear to differ between compounds. Copyright © 2018 Elsevier B.V. All rights reserved.

The impact of parental death on child well-being: evidence from the Indian Ocean tsunami.

PubMed

Cas, Ava Gail; Frankenberg, Elizabeth; Suriastini, Wayan; Thomas, Duncan

2014-04-01

Identifying the impact of parental death on the well-being of children is complicated because parental death is likely to be correlated with other, unobserved factors that affect child well-being. Population-representative longitudinal data collected in Aceh, Indonesia, before and after the December 2004 Indian Ocean tsunami are used to identify the impact of parental deaths on the well-being of children aged 9-17 at the time of the tsunami. Exploiting the unanticipated nature of parental death resulting from the tsunami in combination with measuring well-being of the same children before and after the tsunami, models that include child fixed effects are estimated to isolate the causal effect of parental death. Comparisons are drawn between children who lost one or both parents and children whose parents survived. Shorter-term impacts on school attendance and time allocation one year after the tsunami are examined, as well as longer-term impacts on education trajectories and marriage. Shorter- and longer-term impacts are not the same. Five years after the tsunami, there are substantial deleterious impacts of the tsunami on older boys and girls, whereas the effects on younger children are more muted.

The Impact of Parental Death on Child Well-being: Evidence From the Indian Ocean Tsunami

PubMed Central

Cas, Ava Gail; Frankenberg, Elizabeth; Suriastini, Wayan; Thomas, Duncan

2014-01-01

Identifying the impact of parental death on the well-being of children is complicated because parental death is likely to be correlated with other, unobserved factors that affect child well-being. Population-representative longitudinal data collected in Aceh, Indonesia, before and after the December 2004 Indian Ocean tsunami are used to identify the impact of parental deaths on the well-being of children aged 9–17 at the time of the tsunami. Exploiting the unanticipated nature of parental death resulting from the tsunami in combination with measuring well-being of the same children before and after the tsunami, models that include child fixed effects are estimated to isolate the causal effect of parental death. Comparisons are drawn between children who lost one or both parents and children whose parents survived. Shorter-term impacts on school attendance and time allocation one year after the tsunami are examined, as well as longer-term impacts on education trajectories and marriage. Shorter- and longer-term impacts are not the same. Five years after the tsunami, there are substantial deleterious impacts of the tsunami on older boys and girls, whereas the effects on younger children are more muted. PMID:24573765

20 CFR 410.450 - Death due to pneumoconiosis, including statutory presumption.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Death due to pneumoconiosis, including... Death Due to Pneumoconiosis § 410.450 Death due to pneumoconiosis, including statutory presumption... at the time of his death, or whose death is determined to have been due to pneumoconiosis. (For...

20 CFR 410.450 - Death due to pneumoconiosis, including statutory presumption.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Death due to pneumoconiosis, including... Death Due to Pneumoconiosis § 410.450 Death due to pneumoconiosis, including statutory presumption... at the time of his death, or whose death is determined to have been due to pneumoconiosis. (For...

Harnessing tumor necrosis factor receptors to enhance antitumor activities of drugs.

PubMed

Muntané, Jordi

2011-10-17

Cancer is the second-leading cause of death in the U.S. behind heart disease and over stroke. The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The inhibition of cell death pathways is one of these tumor characteristics which also include sustained proliferative signaling, evading growth suppressor signaling, replicative immortality, angiogenesis, and promotion of invasion and metastasis. Cell death is mediated through death receptor (DR) stimulation initiated by specific ligands that transmit signaling to the cell death machinery or through the participation of mitochondria. Cell death involving DR is mediated by the superfamily of tumor necrosis factor receptor (TNF-R) which includes TNF-R type I, CD95, DR3, TNF-related apoptosis-inducing ligand (TRAIL) receptor-1 (TRAIL-R1) and -2 (TRAIL-R2), DR6, ectodysplasin A (EDA) receptor (EDAR), and the nerve growth factor (NGF) receptor (NGFR). The expression of these receptors in healthy and tumor cells induces treatment side effects that limit the systemic administration of cell death-inducing therapies. The present review is focused on the different therapeutic strategies such as targeted antibodies or small molecules addressed to selective stimulated DR-mediated apoptosis or reduce cell proliferation in cancer cells.

Effects of Phytophthora ramorum infection on hydraulic conductivity and tylosis formation in Tanoak sapwood

Treesearch

Jennifer Parke; Bradley Collins; Barb Lachenbruch; Everett Hansen

2010-01-01

Tanoak (Lithocarpus densiflorus) is highly susceptible to sudden oak death caused by Phytophthora ramorum. Symptoms include dying crowns, bleeding cankers, and, eventually, death of infected trees. The cause of mortality is not well understood, but we showed previously that naturally infected mature trees have reduced sap...

Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death

PubMed Central

Narayanan, Kannan Badri; Ali, Manaf; Barclay, Barry J.; Cheng, Qiang (Shawn); D’Abronzo, Leandro; Dornetshuber-Fleiss, Rita; Ghosh, Paramita M.; Gonzalez Guzman, Michael J.; Lee, Tae-Jin; Leung, Po Sing; Li, Lin; Luanpitpong, Suidjit; Ratovitski, Edward; Rojanasakul, Yon; Romano, Maria Fiammetta; Romano, Simona; Sinha, Ranjeet K.; Yedjou, Clement; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Brown, Dustin G.; Ryan, Elizabeth P.; Colacci, Anna Maria; Hamid, Roslida A.; Mondello, Chiara; Raju, Jayadev; Salem, Hosni K.; Woodrick, Jordan; Scovassi, A.Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Kim, Seo Yun; Bisson, William H.; Lowe, Leroy; Park, Hyun Ho

2015-01-01

Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis. PMID:26106145

The combined effects of single-nucleotide polymorphisms, tobacco products, and ethanol on normal resting blood mononuclear cells.

PubMed

Cederblad, Lena; Thunberg, Ulf; Engström, Mats; Castro, Juan; Rutqvist, Lars Erik; Laytragoon-Lewin, Nongnit

2013-05-01

Tobacco and ethanol consumption are crucial factors in the development of various diseases including cancer. In this investigation, we evaluated the combined effects of a number of single nucleotide polymorphisms (SNPs), with ethanol and tobacco products on healthy individuals. Pure nicotine, cigarette smoke extract, and Swedish snuff (snus) extract were used. The effects were examined by means of in vitro cell cycle progression and cell death of peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. After 3 days, in vitro, resting PBMCs entered the S and G2 stage in the presence of 100 µM nicotine. The PBMCs only proceeded to S stage, in the presence of 0.2% ethanol. The nicotine- and ethanol-induced normal cell cycle progression correlated to a number of SNPs in the IL12RB2, Rad 52, XRCC2, P53, CCND3, and ABCA1 genes. Certain SNPs in Caspases 8, IL12RB2, Rad 52, MMP2, and MDM2 genes appeared to significantly influence the effects of EtOH-, snus-, and snus + EtOH-induced cell death. Importantly, the highest degree of cell death was observed in the presence of smoke + EtOH. The amount of cell death under this treatment condition also correlated to specific SNPs, located in the MDM2, ABCA1, or GASC1 genes. Cigarette smoke in combination with ethanol strongly induced massive cell death. Long-term exposure to smoke and ethanol could provoke chronic inflammation, and this could be the initiation of disease including the development of cancer at various sites.

Radiation Therapy and Cardiac Death in Long-Term Survivors of Esophageal Cancer: An Analysis of the Surveillance, Epidemiology, and End Result Database.

PubMed

Gharzai, Laila; Verma, Vivek; Denniston, Kyle A; Bhirud, Abhijeet R; Bennion, Nathan R; Lin, Chi

2016-01-01

Radiation therapy (RT) for esophageal cancer often results in unintended radiation doses delivered to the heart owing to anatomic proximity. Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined late cardiac death in survivors of esophageal cancer that had or had not received RT. 5,630 patients were identified that were diagnosed with esophageal squamous cell carcinoma (SCC) or adenocarcinoma (AC) from 1973-2012, who were followed for at least 5 years after therapy. Examined risk factors for cardiac death included age (≤55/56-65/66-75/>75), gender, race (white/non-white), stage (local/regional/distant), histology (SCC/AC), esophageal location (<18cm/18-24cm/25-32cm/33-40cm from incisors), diagnosis year (1973-1992/1993-2002/2003-2012), and receipt of surgery and/or RT. Time to cardiac death was evaluated using the Kaplan-Meier method. A Cox model was used to evaluate risk factors for cardiac death in propensity score matched data. Patients who received RT were younger, diagnosed more recently, had more advanced disease, SCC histology, and no surgery. The RT group had higher risk of cardiac death than the no-RT group (log-rank p<0.0001). The median time to cardiac death in the RT group was 289 months (95% CI, 255-367) and was not reached in the no-RT group. The probability of cardiac death increased with age and decreased with diagnosis year, and this trend was more pronounced in the RT group. Multivariate analysis found RT to be associated with higher probability of cardiac death (OR 1.23, 95% CI 1.03-1.47, HR 1.961, 95% CI 1.466-2.624). Lower esophageal subsite (33-40 cm) was also associated with a higher risk of cardiac death. Other variables were not associated with cardiac death. Recognizing the limitations of a SEER analysis including lack of comorbidity accountability, these data should prompt more definitive study as to whether a possible associative effect of RT on cardiac death could potentially be a causative effect.

Fasting boosts sensitivity of human skin melanoma to cisplatin-induced cell death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Antunes, Fernanda; Corazzari, Marco; National Institute for Infectious Diseases IRCCS “Lazzaro Spallanzani”

Melanoma is one of leading cause of tumor death worldwide. Anti-cancer strategy includes combination of different chemo-therapeutic agents as well as radiation; however these treatments have limited efficacy and induce significant toxic effects on healthy cells. One of most promising novel therapeutic approach to cancer therapy is the combination of anti-cancer drugs with calorie restriction. Here we investigated the effect Cisplatin (CDDP), one of the most potent chemotherapeutic agent used to treat tumors, in association with fasting in wild type and mutated BRAF{sup V600E} melanoma cell lines. Here we show that nutrient deprivation can consistently enhance the sensitivity of tumormore » cells to cell death induction by CDDP, also of those malignancies particularly resistant to any treatment, such as oncogenic BRAF melanomas. Mechanistic studies revealed that the combined therapy induced cell death is characterized by ROS accumulation and ATF4 in the absence of ER-stress. In addition, we show that autophagy is not involved in the enhanced sensitivity of melanoma cells to combined CDDP/EBSS-induced apoptosis. While, the exposure to 2-DG further enhanced the apoptotic rate observed in SK Mel 28 cells upon treatment with both CDDP and EBSS. - Highlights: • Calorie restriction associated to chemo-therapeutic drugs enhance cell death induction in many resistant malignancies • Cisplatin in association with starvation significantly increases cell death also in those high resistant melanoma cells bearing BRAF mutations • Combined treatment also including 2-DG results in similar cell death levels in both wild type and mutated BRAF cells.« less

Tobacco smoking and the risk of sudden cardiac death: a systematic review and meta-analysis of prospective studies.

PubMed

Aune, Dagfinn; Schlesinger, Sabrina; Norat, Teresa; Riboli, Elio

2018-06-01

Smoking is an established risk factor for cardiovascular disease including coronary heart disease and stroke, however, data regarding smoking and sudden cardiac death have not been summarized in a meta-analysis previously. We therefore conducted a systematic review and meta-analysis to clarify this association. We searched the PubMed and Embase databases for studies of smoking and sudden cardiac death up to July 20th 2017. Prospective studies were included if they reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for smoking and sudden cardiac death. Summary RRs were estimated by use of a random effects model. Twelve prospective studies were included. The summary RR was 3.06 (95% CI 2.46-3.82, I 2  = 41%, p heterogeneity  = 0.12, n = 7) for current smokers and 1.38 (95% CI 1.20-1.60, I 2  = 0%, p heterogeneity  = 0.55, n = 7) for former smokers compared to never smokers. For four studies using non-current (never + former) smokers as the reference category the summary RR among current smokers was 2.08 (95% CI 1.70-2.53, I 2  = 18%, p heterogeneity  = 0.30). The results persisted in most of the subgroup analyses. There was no evidence of publication bias. These results confirm that smoking increases the risk of sudden cardiac death. Any further studies should investigate in more detail the effects of duration of smoking, number of cigarettes per day, pack-years, and time since quitting smoking and sudden cardiac death.

Exposure of Bacterial Biofilms to Electrical Current Leads to Cell Death Mediated in Part by Reactive Oxygen Species.

PubMed

Brinkman, Cassandra L; Schmidt-Malan, Suzannah M; Karau, Melissa J; Greenwood-Quaintance, Kerryl; Hassett, Daniel J; Mandrekar, Jayawant N; Patel, Robin

2016-01-01

Bacterial biofilms may form on indwelling medical devices such as prosthetic joints, heart valves and catheters, causing challenging-to-treat infections. We have previously described the 'electricidal effect', in which bacterial biofilms are decreased following exposure to direct electrical current. Herein, we sought to determine if the decreased bacterial quantities are due to detachment of biofilms or cell death and to investigate the role that reactive oxygen species (ROS) play in the observed effect. Using confocal and electron microscopy and flow cytometry, we found that direct current (DC) leads to cell death and changes in the architecture of biofilms formed by Gram-positive and Gram-negative bacteria. Reactive oxygen species (ROS) appear to play a role in DC-associated cell death, as there was an increase in ROS-production by Staphylococcus aureus and Staphylococcus epidermidis biofilms following exposure to DC. An increase in the production of ROS response enzymes catalase and superoxide dismutase (SOD) was observed for S. aureus, S. epidermidis and Pseudomonas aeruginosa biofilms following exposure to DC. Additionally, biofilms were protected from cell death when supplemented with antioxidants and oxidant scavengers, including catalase, mannitol and Tempol. Knocking out SOD (sodAB) in P. aeruginosa led to an enhanced DC effect. Microarray analysis of P. aeruginosa PAO1 showed transcriptional changes in genes related to the stress response and cell death. In conclusion, the electricidal effect results in death of bacteria in biofilms, mediated, at least in part, by production of ROS.

Classification systems for causes of stillbirth and neonatal death, 2009-2014: an assessment of alignment with characteristics for an effective global system.

PubMed

Leisher, Susannah Hopkins; Teoh, Zheyi; Reinebrant, Hanna; Allanson, Emma; Blencowe, Hannah; Erwich, Jan Jaap; Frøen, J Frederik; Gardosi, Jason; Gordijn, Sanne; Gülmezoglu, A Metin; Heazell, Alexander E P; Korteweg, Fleurisca; Lawn, Joy; McClure, Elizabeth M; Pattinson, Robert; Smith, Gordon C S; Tunçalp, Ӧzge; Wojcieszek, Aleena M; Flenady, Vicki

2016-09-15

To reduce the burden of 5.3 million stillbirths and neonatal deaths annually, an understanding of causes of deaths is critical. A systematic review identified 81 systems for classification of causes of stillbirth (SB) and neonatal death (NND) between 2009 and 2014. The large number of systems hampers efforts to understand and prevent these deaths. This study aimed to assess the alignment of current classification systems with expert-identified characteristics for a globally effective classification system. Eighty-one classification systems were assessed for alignment with 17 characteristics previously identified through expert consensus as necessary for an effective global system. Data were extracted independently by two authors. Systems were assessed against each characteristic and weighted and unweighted scores assigned to each. Subgroup analyses were undertaken by system use, setting, type of death included and type of characteristic. None of the 81 systems were aligned with more than 9 of the 17 characteristics; most (82 %) were aligned with four or fewer. On average, systems were aligned with 19 % of characteristics. The most aligned system (Frøen 2009-Codac) still had an unweighted score of only 9/17. Alignment with individual characteristics ranged from 0 to 49 %. Alignment was somewhat higher for widely used as compared to less used systems (22 % v 17 %), systems used only in high income countries as compared to only in low and middle income countries (20 % vs 16 %), and systems including both SB and NND (23 %) as compared to NND-only (15 %) and SB-only systems (13 %). Alignment was higher with characteristics assessing structure (23 %) than function (15 %). There is an unmet need for a system exhibiting all the characteristics of a globally effective system as defined by experts in the use of systems, as none of the 81 contemporary classification systems assessed was highly aligned with these characteristics. A particular concern in terms of global effectiveness is the lack of alignment with "ease of use" among all systems, including even the most-aligned. A system which meets the needs of users would have the potential to become the first truly globally effective classification system.

Assessing health and economic outcomes of interventions to reduce pregnancy-related mortality in Nigeria.

PubMed

Erim, Daniel O; Resch, Stephen C; Goldie, Sue J

2012-09-14

Women in Nigeria face some of the highest maternal mortality risks in the world. We explore the benefits and cost-effectiveness of individual and integrated packages of interventions to prevent pregnancy-related deaths. We adapt a previously validated maternal mortality model to Nigeria. Model outcomes included clinical events, population measures, costs, and cost-effectiveness ratios. Separate models were adapted to Southwest and Northeast zones using survey-based data. Strategies consisted of improving coverage of effective interventions, and could include improved logistics. Increasing family planning was the most effective individual intervention to reduce pregnancy-related mortality, was cost saving in the Southwest zone and cost-effective elsewhere, and prevented nearly 1 in 5 abortion-related deaths. However, with a singular focus on family planning and safe abortion, mortality reduction would plateau below MDG 5. Strategies that could prevent 4 out of 5 maternal deaths included an integrated and stepwise approach that includes increased skilled deliveries, facility births, access to antenatal/postpartum care, improved recognition of referral need, transport, and availability quality of EmOC in addition to family planning and safe abortion. The economic benefits of these strategies ranged from being cost-saving to having incremental cost-effectiveness ratios less than $500 per YLS, well below Nigeria's per capita GDP. Early intensive efforts to improve family planning and control of fertility choices, accompanied by a stepwise effort to scale-up capacity for integrated maternal health services over several years, will save lives and provide equal or greater value than many public health interventions we consider among the most cost-effective (e.g., childhood immunization).

TRAIL enhances paracetamol-induced liver sinusoidal endothelial cell death in a Bim- and Bid-dependent manner

PubMed Central

Badmann, A; Langsch, S; Keogh, A; Brunner, T; Kaufmann, T; Corazza, N

2012-01-01

Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic alterations. Although hepatocytes represent the main target of the cytotoxic effect of paracetamol overdose, perturbations within the endothelium involving morphological changes of liver sinusoidal endothelial cells (LSECs) have also been described in paracetamol-induced liver disease. Recently, we have shown that paracetamol-induced liver damage is synergistically enhanced by the TRAIL signaling pathway. As LSECs are constantly exposed to activated immune cells expressing death ligands, including TRAIL, we investigated the effect of TRAIL on paracetamol-induced LSEC death. We here demonstrate for the first time that TRAIL strongly enhances paracetamol-mediated LSEC death with typical features of apoptosis. Inhibition of caspases using specific inhibitors resulted in a strong reduction of cell death. TRAIL appears to enhance paracetamol-induced LSEC death via the activation of the pro-apoptotic BH3-only proteins Bid and Bim, which initiate the mitochondrial apoptotic pathway. Taken together this study shows that the liver endothelial layer, mainly LSECs, represent a direct target of the cytotoxic effect of paracetamol and that activation of TRAIL receptor synergistically enhances paracetamol-induced LSEC death via the mitochondrial apoptotic pathway. TRAIL-mediated acceleration of paracetamol-induced cell death may thus contribute to the pathogenesis of paracetamol-induced liver damage. PMID:23254290

Universal Motorcycle Helmet Laws to Reduce Injuries: A Community Guide Systematic Review.

PubMed

Peng, Yinan; Vaidya, Namita; Finnie, Ramona; Reynolds, Jeffrey; Dumitru, Cristian; Njie, Gibril; Elder, Randy; Ivers, Rebecca; Sakashita, Chika; Shults, Ruth A; Sleet, David A; Compton, Richard P

2017-06-01

Motorcycle crashes account for a disproportionate number of motor vehicle deaths and injuries in the U.S. Motorcycle helmet use can lead to an estimated 42% reduction in risk for fatal injuries and a 69% reduction in risk for head injuries. However, helmet use in the U.S. has been declining and was at 60% in 2013. The current review examines the effectiveness of motorcycle helmet laws in increasing helmet use and reducing motorcycle-related deaths and injuries. Databases relevant to health or transportation were searched from database inception to August 2012. Reference lists of reviews, reports, and gray literature were also searched. Analysis of the data was completed in 2014. A total of 60 U.S. studies qualified for inclusion in the review. Implementing universal helmet laws increased helmet use (median, 47 percentage points); reduced total deaths (median, -32%) and deaths per registered motorcycle (median, -29%); and reduced total injuries (median, -32%) and injuries per registered motorcycle (median, -24%). Repealing universal helmet laws decreased helmet use (median, -39 percentage points); increased total deaths (median, 42%) and deaths per registered motorcycle (median, 24%); and increased total injuries (median, 41%) and injuries per registered motorcycle (median, 8%). Universal helmet laws are effective in increasing motorcycle helmet use and reducing deaths and injuries. These laws are effective for motorcyclists of all ages, including younger operators and passengers who would have already been covered by partial helmet laws. Repealing universal helmet laws decreased helmet use and increased deaths and injuries. Published by Elsevier Inc.

Stimulation of suicidal erythrocyte death by sulforaphane.

PubMed

Alzoubi, Kousi; Calabrò, Salvatrice; Faggio, Caterina; Lang, Florian

2015-03-01

Sulforaphane, an isothiocyanate from cruciferous vegetable, counteracts malignancy. The effect is at least in part due to the stimulation of suicidal death or apoptosis of tumour cells. Mechanisms invoked in sulforaphane-induced apoptosis include mitochondrial depolarization and altered gene expression. Despite the lack of mitochondria and nuclei, erythrocytes may, similar to apoptosis of nucleated cells, enter eryptosis, a suicidal cell death characterized by cell shrinkage and phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca(2+)-activity ([Ca(2+)]i). This study explored whether sulforaphane stimulates eryptosis. Cell volume was estimated from forward scatter, phosphatidylserine exposure at the cell surface from annexin V binding and [Ca(2+)]i from Fluo-3 fluorescence. A 48-hr treatment of human erythrocytes with sulforaphane (50-100 μM) significantly decreased forward scatter, significantly increased the percentage of annexin V binding cells and significantly increased [Ca(2+)]i. The effect of sulforaphane (100 μM) on annexin V binding was significantly blunted but not abrogated by the removal of extracellular Ca(2+). Sulforaphane (100 μM) significantly increased ceramide formation. In conclusion, sulforaphane stimulates suicidal erythrocyte death or eryptosis, an effect at least partially, but not exclusively, due to the stimulation of Ca(2+) entry and ceramide formation. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Modelling Future Cardiovascular Disease Mortality in the United States: National Trends and Racial and Ethnic Disparities

PubMed Central

Pearson-Stuttard, Jonathan; Guzman-Castillo, Maria; Penalvo, Jose L.; Rehm, Colin D.; Afshin, Ashkan; Danaei, Goodarz; Kypridemos, Chris; Gaziano, Tom; Mozaffarian, Dariush; Capewell, Simon; O’Flaherty, Martin

2016-01-01

Background Accurate forecasting of cardiovascular disease (CVD) mortality is crucial to guide policy and programming efforts. Prior forecasts have often not incorporated past trends in rates of reduction in CVD mortality. This creates uncertainties about future trends in CVD mortality and disparities. Methods and Results To forecast US CVD mortality and disparities to 2030, we developed a hierarchical Bayesian model to determine and incorporate prior age, period and cohort (APC) effects from 1979–2012, stratified by age, gender and race; which we combined with expected demographic shifts to 2030. Data sources included the National Vital Statistics System, SEER single year population estimates, and US Bureau of Statistics 2012 National Population projections. We projected coronary disease and stroke deaths to 2030, first based on constant APC effects at 2012 values, as most commonly done (conventional); and then using more rigorous projections incorporating expected trends in APC effects (trend-based). We primarily evaluated absolute mortality. The conventional model projected total coronary and stroke deaths by 2030 to increase by approximately 18% (67,000 additional coronary deaths/year) and 50% (64,000 additional stroke deaths/year). Conversely, the trend-based model projected that coronary mortality would fall by 2030 by approximately 27% (79,000 fewer deaths/year); and stroke mortality would remain unchanged (200 fewer deaths/year). Health disparities will be improved in stroke deaths, but not coronary deaths. Conclusions After accounting for prior mortality trends and expected demographic shifts, total US coronary deaths are expected to decline, while stroke mortality will remain relatively constant. Health disparities in stroke, but not coronary, deaths will be improved but not eliminated. These APC approaches offer more plausible predictions than conventional estimates. PMID:26846769

Terbutaline Injection

MedlinePlus

... caused serious side effects, including death, in pregnant women who took the medication for this purpose. Terbutaline has also caused serious side effects in newborns whose mothers took the medication to stop or prevent labor.

Modeling causes of death: an integrated approach using CODEm

PubMed Central

2012-01-01

Background Data on causes of death by age and sex are a critical input into health decision-making. Priority setting in public health should be informed not only by the current magnitude of health problems but by trends in them. However, cause of death data are often not available or are subject to substantial problems of comparability. We propose five general principles for cause of death model development, validation, and reporting. Methods We detail a specific implementation of these principles that is embodied in an analytical tool - the Cause of Death Ensemble model (CODEm) - which explores a large variety of possible models to estimate trends in causes of death. Possible models are identified using a covariate selection algorithm that yields many plausible combinations of covariates, which are then run through four model classes. The model classes include mixed effects linear models and spatial-temporal Gaussian Process Regression models for cause fractions and death rates. All models for each cause of death are then assessed using out-of-sample predictive validity and combined into an ensemble with optimal out-of-sample predictive performance. Results Ensemble models for cause of death estimation outperform any single component model in tests of root mean square error, frequency of predicting correct temporal trends, and achieving 95% coverage of the prediction interval. We present detailed results for CODEm applied to maternal mortality and summary results for several other causes of death, including cardiovascular disease and several cancers. Conclusions CODEm produces better estimates of cause of death trends than previous methods and is less susceptible to bias in model specification. We demonstrate the utility of CODEm for the estimation of several major causes of death. PMID:22226226

Prevention of motor‐vehicle deaths by changing vehicle factors

PubMed Central

Robertson, Leon S

2007-01-01

Objective To estimate the effect of changing vehicle factors to reduce mortality in a comprehensive study. Design/methods Odds of death in the United States during 2000–2005 were analyzed, involving specific makes and models of 1999–2005 model year cars, minivans, and sport utility vehicles using logistic regression after selection of factors to be included by examination of least‐squares correlations of vehicle factors to maximize independence of predictors. Based on the regression coefficients, percentages of deaths preventable by changes in selected factors were calculated. Correlations of vehicle characteristics to environmental and behavioral risk factors were also examined to assess any potential confounding. Results Deaths in the studied vehicles would have been 42% lower had all had electronic stability control (ESC) systems. Improved crashworthiness as measured by offset frontal and side crash tests would have produced an additional 28% reduction, and static stability improvement would have reduced the deaths 11%. Although weight–power that reduces fuel economy is associated with lower risk to drivers, it increases risk of deaths to pedestrians and bicyclists but has an overall minor effect compared to the other factors. Conclusion A large majority of motor‐vehicle‐related fatalities could be avoided by universal adoption of the most effective technologies. PMID:17916886

Fight or Flight - Regulation of Emergency Hematopoiesis by Pyroptosis and Necroptosis

PubMed Central

Croker, Ben A.; Silke, John; Gerlic, Motti

2015-01-01

Purpose of review A feature of the innate immune response that is conserved across kingdoms is the induction of cell death. In this review, we discuss the direct and indirect effects of increased inflammatory cell death, including pyroptosis, a caspase-1-dependent cell death, and necroptosis, a RIPK3/MLKL-dependent, caspase-independent cell death, on emergency hematopoiesis. Recent findings Activation of non-apoptotic cell death pathways during infection can trigger release of cytokines and/or damage-associated molecular patterns (DAMPs) such as IL-1α, IL-1β, IL-18, IL-33, HMGB1 and mtDNA to promote emergency hematopoiesis. During systemic infection, pyroptosis and necroptosis can directly kill hematopoietic stem and progenitor cells, which results in impaired hematopoiesis, cytopenia and immunosuppression. Although originally described as discrete entities, there now appears to be more intimate connections between the non-apoptotic and death receptor signaling pathways. Summary The choice to undergo pyroptotic and necroptotic cell death constitutes a rapid response system serving to eliminate infected cells, including hematopoietic stem and progenitor cells. This system has the potential to be detrimental to emergency hematopoiesis during severe infection. We discuss the potential of pharmacological intervention for the pyroptosis and necroptosis pathways that may be beneficial during periods of infection and emergency hematopoiesis. PMID:26049749

Caring at home until death: enabled determination.

PubMed

Robinson, Carole A; Bottorff, Joan L; McFee, Erin; Bissell, Laura J; Fyles, Gillian

2017-04-01

The importance of family caregivers in providing palliative care at home and in supporting a home death is well supported. Gaining a better understanding of what enables palliative family caregivers to continue caring at home for their family members until death is critical to providing direction for more effective support. The purpose of the study was to describe the experiences of bereaved family caregivers whose terminally ill family members with advanced cancer were successful in achieving a desired home death. A qualitative interpretive descriptive approach was used. Data were collected using semi-structured, audio-recorded interviews conducted in-person or via telephone in addition to field notes and reflective journaling. The study took place in British Columbia, Canada, and included 29 bereaved adult family caregivers who had provided care for a family member with advanced cancer and experienced a home death. Four themes captured the experience of caring at home until death: context of providing care, supportive antecedents to providing care, determination to provide care at home, and enabled determination. Factors that enabled determination to achieve a home death included initiation of formal palliative care, asking for and receiving help, augmented care, relief or respite, and making the healthcare system work for the ill person. Clarifying caregiving goals and supporting the factors that enable caregiver determination appear to be critical in enhancing the likelihood of a desired home death.

Death related to dental treatment: a systematic review.

PubMed

Reuter, Nathan G; Westgate, Philip M; Ingram, Mark; Miller, Craig S

2017-02-01

The aim of this study was to identify factors associated with death in relation to dental care. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Dental and Oral Sciences Source, Web of Science, and the Cochrane database were searched, and the references of all retrieved articles were analyzed. Studies were included if death had occurred within 90 days of the dental appointment, and if the patient's age, procedure, and information regarding cause or time of death were provided. Factors associated with death were assessed by multivariate analyses and logistic regression. Fifty-six publications, including retrospective studies and case reports/series that reported 148 fatalities, were analyzed. On average, 2.6 deaths were reported per year. The leading cause of deaths was anesthesia/sedation/medication-related complications (n = 70). Other causes were cardiovascular events (n = 31), infection (n = 19), airway-respiratory complications (n = 18), bleeding (n = 5), and others (n = 5). Age (P < .0001), disease severity (P < .02), disease stability (P < .006), dental provider characteristics (P < .05), level of consciousness/sedation (P < .02), and drug effects (P < .03) had significant associations with death. Reports of death were rare; however, specific risk factors associated with dentistry were identified. A better understanding of these factors is important for the development of guidelines that help prevent fatalities in dentistry. Copyright © 2016 Elsevier Inc. All rights reserved.

Outcome in 55 dogs with pulmonic stenosis that did not undergo balloon valvuloplasty or surgery.

PubMed

Francis, A J; Johnson, M J S; Culshaw, G C; Corcoran, B M; Martin, M W S; French, A T

2011-06-01

To determine the outcome, independent predictors of cardiac death, and the Doppler-derived pressure gradient cut-off for predicting cardiac death in dogs with pulmonic stenosis, with or without tricuspid regurgitation, that do not undergo balloon valvuloplasty or valve surgery. Review of medical records of two UK referral centres between July 1997 and October 2008 for all cases of pulmonic stenosis that had no balloon valvuloplasty or valve surgery. Inclusion criteria included a diagnosis of pulmonic stenosis; spectral Doppler pulmonic velocity greater than 1·6 m/s; characteristic valve leaflet morphological abnormalities. Exclusion criteria included concurrent significant cardiac defects, including tricuspid dysplasia. Dogs with tricuspid regurgitation were included. Dogs were classified according to Doppler-derived pressure gradients into mild, moderate or severe pulmonic stenosis categories. Presence of tricuspid regurgitation and severe stenosis were independent predictors of cardiac death. A pulmonic pressure gradient of more than 60 mmHg was associated with 86% sensitivity, and 71% specificity of predicting cardiac death. There is an increased probability of cardiac death in those cases which have a pulmonary pressure gradient greater than 60 mmHg and tricuspid regurgitation, though the effect of severity of tricuspid regurgitation on outcome was not measurable because of small sample sizes. These animals might benefit from intervention. © 2011 British Small Animal Veterinary Association.

Servo-control for maintaining abdominal skin temperature at 36C in low birth weight infants.

PubMed

Sinclair, J C

2002-01-01

Randomized trials have shown that the neonatal mortality rate of low birth-weight babies can be reduced by keeping them warm. For low birth-weight babies nursed in incubators, warm conditions may be achieved either by heating the air to a desired temperature, or by servo-controlling the baby's body temperature at a desired set-point. In low birth weight infants, to determine the effect on death and other important clinical outcomes of targeting body temperature rather than air temperature as the end-point of control of incubator heating. Standard search strategy of the Cochrane Neonatal Review Group. Searches were made of the Cochrane Controlled Trials Register (CCTR) (Cochrane Library, Issue 4, 2001) and MEDLINE, 1966 to November 2001. Randomized or quasi-randomized trials which test the effects of having the heat output of the incubator servo-controlled from body temperature compared with setting a constant incubator air temperature. Trial methodologic quality was systematically assessed. Outcome measures included death, timing of death, cause of death, and other clinical outcomes. Categorical outcomes were analyzed using relative risk and risk difference. Meta-analysis assumed a fixed effect model. Two eligible trials were found. In total, they included 283 babies and 112 deaths. Compared to setting a constant incubator air temperature of 31.8C, servo-control of abdominal skin temperature at 36C reduces the neonatal death rate among low birth weight infants: relative risk 0.72 (95% CI 0.54, 0.97); risk difference -12.7% (95% CI -1.6, -23.9). This effect is even greater among VLBW infants. During at least the first week after birth, low birth weight babies should be provided with a carefully regulated thermal environment that is near the thermoneutral point. For LBW babies in incubators, this can be achieved by adjusting incubator temperature to maintain an anterior abdominal skin temperature of at least 36C, using either servo-control or frequent manual adjustment of incubator air temperature.

Effect of Shenzhu Guanxin Recipe () on patients with angina pectoris after percutaneous coronary intervention: A prospective, randomized controlled trial.

PubMed

Xu, Dan-Ping; Wu, Huan-Lin; Lan, Tao-Hua; Wang, Xia; Sheng, Xiao-Gang; Lin, Yu; Li, Song; Zheng, Chao-Yang

2015-06-01

To evaluate the efficacy and safety of a combination therapy using Chinese medicine (CM) Shenzhu Guanxin Recipe (, SGR) and standard Western medicine treatment (SWMT) in patients with angina pectoris after percutaneous coronary intervention (PCI). Double-blind randomized controlled trial was used in this experimental procedure. One hundred and eighty-seven patients with coronary heart disease receiving SWMT after PCI were randomly assigned to the treatment (SGR) and control (placebo) groups. Outcome measures including angina pectoris score (APS), CM symptom score, and Seattle Angina Questionnaire (SAQ) score were evaluated in 1, 2, 3 and 12 months, and the death rate, restenosis and other emergency treatments were observed. The mixed-effects models were employed for the data analysis. In the treatment group, a larger within-treatment effect size (d=1.74) was found, with a 76.7% reduction in APS from pretreatment to 12-month follow-up assessment compared with the control group (d=0.83, 53.8% symptom reduction); betweentreatment (BT) effect size was d=0.66. CM symptom scores included an 18.3% reduction in the treatment group (d=0.46), and a 16.1% decrease in the control group (d=0.31); d=0.62 for BT effect size. In regard to scores of SAQ, the BT effect size of cognition level of disease was larger in the treatment group (d=0.63), followed by the level of body limitation of activity (d=0.62), condition of angina pectoris attacks (d=0.55), satisfaction level of treatments (d=0.31), and steady state of angina pectoris (d=0.30). Two cardiovascular related deaths and one incidental death were recorded in the control and treatment groups, respectively. No significant difference in any cardiovascular event (including death toll, frequency of cardiovascular hospitalization or emergency room visits) was found between the two groups. The combination therapy of SGR and SWMT is effective and safe in patients with angina pectoris after PCI when compared with SWMT alone.

ATTITUDES TOWARD SUICIDE: THE EFFECT OF SUICIDE DEATH IN THE FAMILY*

PubMed Central

Zhang, Jie; Jia, Cun-Xian

2011-01-01

There have been few reports on the effect of suicide death on family members’ attitudes toward suicide. In order to estimate the extent to which suicide death affects attitudes toward suicide among family members of suicides, data of 264 informants from a case-control psychological autopsy study were analyzed. The results showed that there were no significant differences in attitudes toward suicide, measured by the General Social Survey’s (GSS) four questions, between informants of suicides and informants of living controls, between family members of suicides and family members of living controls, or between family members of suicides and non-family members of suicides. Our findings did not support the hypothesis that suicide death affects the attitudes toward suicide in suicides’ family members. However, some factors were found to be related to the pro-suicide attitudes measured by the four questions included in the GSS. PMID:20397616

The Effect of Widowhood on Husbands’ and Wives’ Physical Activity: The Cardiovascular Health Study

PubMed Central

Stahl, Sarah T.; Schulz, Richard

2013-01-01

This prospective study examined the effect of widowhood on physical activity by comparing widowed elders to health status-, age-, and sex-matched married controls. Participants included 396 married controls and 396 widows/widowers age 64 to 91 (M age = 72.7 years) who experienced the death of their spouse while participating in the Cardiovascular Health Study (CHS). Compared to married controls, widowed men, but not women, were more likely to increase their physical activity following the death of their spouse. However, this increased level of activity was not sustained and declines as time since spousal death passes. Moreover, during the year before spousal death, soon-to-be widowed men, but not women, increase their physical activity. Our results suggest that widowed men experience significant changes in physical activity and that the transition to widowhood contribute to these changes. PMID:23975417

Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death

PubMed Central

Parra, Valentina; Moraga, Francisco; Kuzmicic, Jovan; López-Crisosto, Camila; Troncoso, Rodrigo; Torrealba, Natalia; Criollo, Alfredo; Díaz-Elizondo, Jessica; Rothermel, Beverly A.; Quest, Andrew F.G.; Lavandero, Sergio

2014-01-01

Ceramides are important intermediates in the biosynthesis and degradation of sphingolipids that regulatenumerous cellular processes, including cell cycle progression, cell growth, differentiation and death. In cardiomyocytes, ceramides induce apoptosis by decreasing mitochondrial membrane potential and promoting cytochrome-c release. Ca2+ overload is a common feature of all types of cell death. The aim of this study was to determine the effect of ceramides on cytoplasmic Ca2+ levels, mitochondrial function and cardiomyocyte death. Our data show that C2-ceramide induces apoptosis and necrosis in cultured cardiomyocytes by a mechanism involving increased Ca2+ influx, mitochondrial network fragmentation and loss of the mitochondrial Ca2+ buffer capacity. These biochemical events increase cytosolic Ca2+ levels and trigger cardiomyocyte death via the activation of calpains. PMID:23602992

An anatomy of the autopsy, Olmsted County, 1935 through 1985.

PubMed

Nemetz, P N; Ballard, D J; Beard, C M; Ludwig, J; Tangalos, E G; Kokmen, E; Weigel, K M; Belau, P G; Bourne, W M; Kurland, L T

1989-09-01

In this study, we examined in detail the patterns of autopsy rates for a half century (1935 through 1985) among residents of Olmsted County, Minnesota. The time trend of the autopsy in this community represents, in many respects, a microcosm of national trends. In the process of this analysis, we identified several medical and socioeconomic variables that may influence the rate of autopsy, including the age at death, physical location of death, gender, surgical procedures preceding death, immediate cause of death, and direct and indirect costs of the autopsy. In particular, the advancing mean age at death and the increase of the nursing home as a social phenomenon seem to have had a profound effect on autopsy rates both in Olmsted County and throughout the United States.

Distinct Effects of Rotenone, 1-methyl-4-phenylpyridinium and 6-hydroxydopamine on Cellular Bioenergetics and Cell Death

PubMed Central

Giordano, Samantha; Lee, Jisun; Darley-Usmar, Victor M.; Zhang, Jianhua

2012-01-01

Parkinson’s disease is characterized by dopaminergic neurodegeneration and is associated with mitochondrial dysfunction. The bioenergetic susceptibility of dopaminergic neurons to toxins which induce Parkinson’s like syndromes in animal models is then of particular interest. For example, rotenone, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP+), and 6-hydroxydopamine (6-OHDA), have been shown to induce dopaminergic cell death in vivo and in vitro. Exposure of animals to these compounds induce a range of responses characteristics of Parkinson’s disease, including dopaminergic cell death, and Reactive Oxygen Species (ROS) production. Here we test the hypothesis that cellular bioenergetic dysfunction caused by these compounds correlates with induction of cell death in differentiated dopaminergic neuroblastoma SH-SY5Y cells. At increasing doses, rotenone induced significant cell death accompanied with caspase 3 activation. At these concentrations, rotenone had an immediate inhibition of mitochondrial basal oxygen consumption rate (OCR) concomitant with a decrease of ATP-linked OCR and reserve capacity, as well as a stimulation of glycolysis. MPP+ exhibited a different behavior with less pronounced cell death at doses that nearly eliminated basal and ATP-linked OCR. Interestingly, MPP+, unlike rotenone, stimulated bioenergetic reserve capacity. The effects of 6-OHDA on bioenergetic function was markedly less than the effects of rotenone or MPP+ at cytotoxic doses, suggesting a mechanism largely independent of bioenergetic dysfunction. These studies suggest that these dopaminergic neurotoxins induce cell death through distinct mechanisms and differential effects on cellular bioenergetics. PMID:22970265

Leprosy-related mortality in Brazil: a neglected condition of a neglected disease.

PubMed

Martins-Melo, Francisco Rogerlândio; Assunção-Ramos, Adriana Valéria; Ramos, Alberto Novaes; Alencar, Carlos Henrique; Montenegro, Renan Magalhães; Wand-Del-Rey de Oliveira, Maria Leide; Heukelbach, Jorg

2015-10-01

Leprosy is a public health problem and a neglected condition of morbidity and mortality in several countries of the world. We analysed time trends and spatiotemporal patterns of leprosy-related mortality in Brazil. We performed a nationwide population-based study using secondary mortality data. We included all deaths that occurred in Brazil between 2000 and 2011, in which leprosy was mentioned in any field of death certificates. Leprosy was identified in 7732/12 491 280 deaths (0.1%). Average annual age-adjusted mortality rate was 0.43 deaths/100 000 inhabitants (95% CI 0.40-0.46). The burden of leprosy deaths was higher among males, elderly, black race/colour and in leprosy-endemic regions. Lepromatous leprosy was the most common clinical form mentioned. Mortality rates showed a significant nationwide decrease over the period (annual percent change [APC]: -2.8%; 95% CI -4.2 to -2.4). We observed decreasing mortality rates in the South, Southeast and Central-West regions, while the rates remained stable in North and Northeast regions. Spatial and spatiotemporal high-risk clusters for leprosy-related deaths were distributed mainly in highly endemic and socio-economically deprived regions. Leprosy is a neglected cause of death in Brazil since the disease is preventable, and a cost-effective treatment is available. Sustainable control measures should include appropriate management and systematic monitoring of leprosy-related complications, such as severe leprosy reactions and adverse effects to multidrug therapy. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Palliative sedation for terminally ill cancer patients in a tertiary cancer center in Shanghai, China.

PubMed

Gu, Xiaoli; Cheng, Wenwu; Chen, Menglei; Liu, Minghui; Zhang, Zhe

2015-01-01

There are a number of studies dedicated to characteristics of sedation, but these studies are mostly bound to western country practices. The aim of this study is to describe the characteristics of patients who suffered from cancer and who had been sedated until their death in Shanghai, China. Retrospective medical data of 244 terminally ill cancer patients including 82 sedated patients were collected. Data collected included demographic characteristics, disease-related characteristics and details of the sedation. In sedated cases, patients and/or caregivers gave the consent to start palliative sedation due to unmanageable symptoms. On average, sedation was performed 24.65(±1.78)hours before death. Agitated delirium and dyspnea were the most frequent indications for palliative sedation. There was no significant difference in survival time from admission till death between sedated and non-sedated patients (p > 0.05). Palliative sedation is effective for reducing terminally ill cancer patients' suffering without hastening death. Prospective research is needed to determine the optimal conditions for Chinese patients including indications, decision making process, informed consent, cultural and ethical issues, type of sedation and drugs.

Communication About Dying, Death, and Bereavement: A Systematic Review of Children's Literature

PubMed Central

Arruda-Colli, Marina N. F.; Weaver, Meaghann S.

2017-01-01

Abstract Background: Children's books have the potential to facilitate communication about death for children living with a serious illness and for children coping with the death of a loved one. Objectives: This study examines the content of children's literature relevant to the topic of dying and death and identifies books providers can share with children and their families. Design: A search of children's literature was conducted using four electronic databases and one additional search engine using the word “Death” or “Dying.” Storybooks about dying, death, and bereavement published in English, French, or Spanish between 1995 and 2015 were included. Measurements: Each book underwent content analysis by at least two independent reviewers. Strict PRISMA standard was followed. Full protocol is available as PROSPERO #CRD42016042129. Results: Two hundred ten books met inclusion criteria. The dying subject was primarily a grandparent (n = 78) or pet (n = 44). Books on the experience of a child dying were scarce (n = 5). The word death or dying was used in 75% of the books (n = 158), while others utilized euphemisms. The majority of books featured animals (n = 40) or Caucasian subjects (n = 122) and included spiritual elements such as heaven (n = 122). Less than one-quarter of the books included tools for readers to address the topic of death. Conclusions: Storybooks can be a helpful tool to introduce communication about dying and death with children. Gaps exist in current children's literature to effectively enable children to reflect on their own dying process. A general summary of available books is provided to assist those caring for children and families facing end-of-life issues. PMID:28346862

Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death.

PubMed

Narayanan, Kannan Badri; Ali, Manaf; Barclay, Barry J; Cheng, Qiang Shawn; D'Abronzo, Leandro; Dornetshuber-Fleiss, Rita; Ghosh, Paramita M; Gonzalez Guzman, Michael J; Lee, Tae-Jin; Leung, Po Sing; Li, Lin; Luanpitpong, Suidjit; Ratovitski, Edward; Rojanasakul, Yon; Romano, Maria Fiammetta; Romano, Simona; Sinha, Ranjeet K; Yedjou, Clement; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Brown, Dustin G; Ryan, Elizabeth P; Colacci, Annamaria; Hamid, Roslida A; Mondello, Chiara; Raju, Jayadev; Salem, Hosni K; Woodrick, Jordan; Scovassi, A Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Kim, Seo Yun; Bisson, William H; Lowe, Leroy; Park, Hyun Ho

2015-06-01

Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Insensitive dependence of delay-induced oscillation death on complex networks

NASA Astrophysics Data System (ADS)

Zou, Wei; Zheng, Xing; Zhan, Meng

2011-06-01

Oscillation death (also called amplitude death), a phenomenon of coupling induced stabilization of an unstable equilibrium, is studied for an arbitrary symmetric complex network with delay-coupled oscillators, and the critical conditions for its linear stability are explicitly obtained. All cases including one oscillator, a pair of oscillators, regular oscillator networks, and complex oscillator networks with delay feedback coupling, can be treated in a unified form. For an arbitrary symmetric network, we find that the corresponding smallest eigenvalue of the Laplacian λN (0 >λN ≥ -1) completely determines the death island, and as λN is located within the insensitive parameter region for nearly all complex networks, the death island keeps nearly the largest and does not sensitively depend on the complex network structures. This insensitivity effect has been tested for many typical complex networks including Watts-Strogatz (WS) and Newman-Watts (NW) small world networks, general scale-free (SF) networks, Erdos-Renyi (ER) random networks, geographical networks, and networks with community structures and is expected to be helpful for our understanding of dynamics on complex networks.

Assault Injury and Homicide Death Profile in Rhode Island, 2004-2014.

PubMed

Jiang, Yongwen; Ranney, Megan L; Seaberry, Jordan; Shea, Lynne-Marie; Sullivan, Brian; Viner-Brown, Samara

2017-04-03

Community violence, including assault and homicide, is a public health problem. We provide a profile of assault-related injury and homicide death in Rhode Island to better understand assault/homicide. The 2014 emergency department (ED) visit data, hospital discharge (HD) data, and 2004-2014 Rhode Island Violent Death Reporting System (RIVDRS) data were used for this study. Most assault injuries and homicide deaths were among persons who were 25-44 years old, male, black and Hispanic, living in urban regions, self-pay or public insurance user, and never married. Almost 63% of the homicide decedents tested positive for some illicit substance. Precipitating circumstances include a preceding argument or a conflict, another crime, intimate partner violence, and drug involvement. RIVDRS did not provide an estimate for mental illness related homicides (e.g. command hallucinations). ED, HD, and RIVDRS data can provide a profile of assault injury and homicide death for public health authorities in RI. Interventions need to focus on high-risk populations and areas to effectively prevent assault-related injury and homicide. [Full article available at http://rimed.org/rimedicaljournal-2017-04.asp].

Inner ear supporting cells protect hair cells by secreting HSP70

PubMed Central

May, Lindsey A.; Kramarenko, Inga I.; Brandon, Carlene S.; Voelkel-Johnson, Christina; Roy, Soumen; Truong, Kristy; Francis, Shimon P.; Monzack, Elyssa L.; Lee, Fu-Shing; Cunningham, Lisa L.

2013-01-01

Mechanosensory hair cells are the receptor cells of hearing and balance. Hair cells are sensitive to death from exposure to therapeutic drugs with ototoxic side effects, including aminoglycoside antibiotics and cisplatin. We recently showed that the induction of heat shock protein 70 (HSP70) inhibits ototoxic drug–induced hair cell death. Here, we examined the mechanisms underlying the protective effect of HSP70. In response to heat shock, HSP70 was induced in glia-like supporting cells but not in hair cells. Adenovirus-mediated infection of supporting cells with Hsp70 inhibited hair cell death. Coculture with heat-shocked utricles protected nonheat-shocked utricles against hair cell death. When heat-shocked utricles from Hsp70–/– mice were used in cocultures, protection was abolished in both the heat-shocked utricles and the nonheat-shocked utricles. HSP70 was detected by ELISA in the media surrounding heat-shocked utricles, and depletion of HSP70 from the media abolished the protective effect of heat shock, suggesting that HSP70 is secreted by supporting cells. Together our data indicate that supporting cells mediate the protective effect of HSP70 against hair cell death, and they suggest a major role for supporting cells in determining the fate of hair cells exposed to stress. PMID:23863716

Should we use standard survival models or the illness-death model for interval-censored data to investigate risk factors of chronic kidney disease progression?

PubMed

Boucquemont, Julie; Metzger, Marie; Combe, Christian; Stengel, Bénédicte; Leffondre, Karen

2014-01-01

In studies investigating risk factors of chronic kidney disease (CKD) progression, one may be interested in estimating factors effects on both a fall of glomerular filtration rate (GFR) below a specific level (i.e., a CKD stage) and death. Such studies have to account for the fact that GFR is measured at intermittent visit only, which implies that progression to the stage of interest is unknown for patients who die before being observed at that stage. Our objective was to compare the results of an illness-death model that handles this uncertainty, with frequently used survival models. This study included 1,519 patients from the NephroTest cohort with CKD stages 1-4 at baseline (69% males, 59±15 years, median protein/creatinine ratio [PCR] 27.4 mg/mmol) and subsequent annual measures of GFR (follow-up time 4.3±2.7 years). Each model was used to estimate the effects of sex, age, PCR, and GFR at baseline on the hazards of progression to CKD stage 5 (GFR<15 mL/min/1.73 m2, n = 282 observed) and death (n = 168). For progression to stage 5, there were only minor differences between results from the different models. The differences between results were higher for the hazard of death before or after progression. Our results also suggest that previous findings on the effect of age on end-stage renal disease are more likely due to a strong impact of age on death than to an effect on progression. The probabilities of progression were systematically under-estimated with the survival model as compared with the illness-death model. This study illustrates the advantages of the illness-death model for accurately estimating the effects of risk factors on the hazard of progression and death, and probabilities of progression. It avoids the need to choose arbitrary time-to-event and time-to-censoring, while accounting for both interval censoring and competition by death, using a single analytical model.

Effect of calf death loss on cloned cattle herd derived from somatic cell nuclear transfer: clones with congenital defects would be removed by the death loss.

PubMed

Watanabe, Shinya

2013-09-01

To increase public understanding on cloned cattle derived from somatic cell nuclear transfer (SCNT), the present review describes the effect of calf death loss on an SCNT cattle herd. The incidence of death loss in SCNT cattle surviving more than 200 days reached the same level as that in conventionally bred cattle. This process could be considered as removal of SCNT cattle with congenital defects caused by calf death loss. As a result of comparative studies of SCNT cattle and conventionally bred cattle, the substantial equivalences in animal health status, milk and meat productive performance have been confirmed. Both sexes of SCNT cattle surviving to adulthood were fertile and their reproductive performance, including efficiency of progeny production, was the same as that in conventionally bred cattle. The presence of substantial equivalence between their progeny and conventionally bred cattle also existed. Despite these scientific findings, the commercial use of food products derived from SCNT cattle and their progeny has not been allowed by governments for reasons including the lack of public acceptance of these products and the low efficiency of animal SCNT. To overcome this situation, communication of the low risk of SCNT technology and research to improve SCNT efficiency are required. © 2013 Japanese Society of Animal Science.

Improving observational study estimates of treatment effects using joint modeling of selection effects and outcomes: the case of AAA repair.

PubMed

O'Malley, A James; Cotterill, Philip; Schermerhorn, Marc L; Landon, Bruce E

2011-12-01

When 2 treatment approaches are available, there are likely to be unmeasured confounders that influence choice of procedure, which complicates estimation of the causal effect of treatment on outcomes using observational data. To estimate the effect of endovascular (endo) versus open surgical (open) repair, including possible modification by institutional volume, on survival after treatment for abdominal aortic aneurysm, accounting for observed and unobserved confounding variables. Observational study of data from the Medicare program using a joint model of treatment selection and survival given treatment to estimate the effects of type of surgery and institutional volume on survival. We studied 61,414 eligible repairs of intact abdominal aortic aneurysms during 2001 to 2004. The outcome, perioperative death, is defined as in-hospital death or death within 30 days of operation. The key predictors are use of endo, transformed endo and open volume, and endo-volume interactions. There is strong evidence of nonrandom selection of treatment with potential confounding variables including institutional volume and procedure date, variables not typically adjusted for in clinical trials. The best fitting model included heterogeneous transformations of endo volume for endo cases and open volume for open cases as predictors. Consistent with our hypothesis, accounting for unmeasured selection reduced the mortality benefit of endo. The effect of endo versus open surgery varies nonlinearly with endo and open volume. Accounting for institutional experience and unmeasured selection enables better decision-making by physicians making treatment referrals, investigators evaluating treatments, and policy makers.

Mortality audit of the Finnish cervical cancer screening program.

PubMed

Lönnberg, Stefan; Nieminen, Pekka; Luostarinen, Tapio; Anttila, Ahti

2013-05-01

Incidence-based evaluations of cervical cancer screening programs have suggested age-specific impacts and there is uncertainty regarding the effectiveness of screening outside the ages of 30-60 years. We audited the screening histories of cervical cancer deaths and conducted a case-control evaluation of the effectiveness of organized screening in different ages with mortality as outcome. We included all 506 cervical cancer deaths in Finland in 2000-2009 due to cancers diagnosed in 1990 or later, and 3,036 controls matched by age at diagnosis to the cases. Squamous cell carcinoma constituted 59% of the cases, adenocarcinomas 29%, and the remaining 12% were other specified and unspecified cervical malignancies. Most deaths (54%) were due to cancers diagnosed more than 5 years after last screening invitation, 24% were diagnosed among nonattenders and only 14% of deaths occurred among women who had attended invitational screening. The risk reduction associated with attending a single program screen at an age below 40 was nonsignificant (OR 0.70; 95% CI 0.33-1.48), while clear risk reductions were observed after screening at the age of 40-54 (OR 0.33; CI 0.20-0.56) and 55-69 (OR 0.29; CI 0.16-0.54). This study also provides some indication of a long-lasting additional effect of screening at the age of 65. Possible avenues for improving the effectiveness of the Finnish screening program include efforts to increase attendance and an extension of the target ages to include 65-to 69-year-old women. The potential benefit of increasing the sensitivity of the screening test or shortening the screening interval is smaller. Copyright © 2012 UICC.

The interaction effect between low income and severe illness on the risk of death by suicide after self-harm.

PubMed

Chung, Chi-Hsiang; Pai, Lu; Kao, Senyeong; Lee, Meei-Shyuan; Yang, Tsung-Tsair; Chien, Wu-Chien

2013-01-01

Previous Western studies have reported that the prevalence of death by suicide within 1 year after self-harm was 0.5-2%; however, no studies have focused on the Far East. To calculate the prevalence of death by suicide after self-harm over different lengths of follow-up time and to determine the predictors of death by suicide after self-harm. Our study was based on 3,388 inpatients hospitalized between 2000 and 2007 in any of the 1,230 hospitals in Taiwan. Death by suicide after self-harm among the members of this cohort was tracked after 3 months, 6 months, and 1-8 years. The tracking continued until December 31, 2008. We analyzed the prevalence and risk factors of death by suicide after self-harm using Cox's regression model. Of the 3,388 individuals with a history of self-harm included in the study, 48 (1.4%) died by suicide after self-harm within 3 months and 97 (2.9%) within 1 year. In all, 144 (4.3%) died by suicide after self-harm within 8 years. The predictors of death by suicide were violent methods (such as hanging, drowning, firearms, and jumping), low income, and severe illness. Moreover, an interaction effect was noted between low income and severe illness on the outcome (death by suicide). It seems that effective healthcare for individuals who engage in self-harming behavior would benefit from supplementing medical care with social assistance, such as the support of a social worker.

Characteristics and Factors Associated with Death among Patients Hospitalized for Severe Fever with Thrombocytopenia Syndrome, South Korea, 2013.

PubMed

Shin, Jaeseung; Kwon, Donghyok; Youn, Seung-Ki; Park, Ji-Hyuk

2015-10-01

In South Korea, nationwide surveillance for severe fever with thrombocytopenia syndrome (SFTS) began during 2013. Among 301 surveillance cases, 35 hospitalized case-patients in 25 areas were confirmed by using virologic testing, and 16 (46%) case-patients subsequently died. The SFTS cases occurred during May-November and peaked during June (9 cases, 26%). The incidence of SFTS was higher in the southern regions of South Korea. Age and neurologic symptoms, including decreased level of consciousness and slurred speech, were heavily associated with death; neurologic symptoms during the first week after disease onset were also associated with death. Although melena was common among patients who died, no other hemorrhagic manifestations were substantively more common among those who died. No effective treatments, including ribavirin, were identified. Expansion of SFTS surveillance to include the outpatient sector and development of an antibody test would enhance completeness of SFTS detection in South Korea.

Prevention of sudden death in adolescent athletes: Incremental diagnostic value and cost-effectiveness of diagnostic tests.

PubMed

Grazioli, Gonzalo; Sanz de la Garza, Maria; Vidal, Barbara; Montserrat, Silvia; Sarquella-Brugada, Georgia; Pi, Ramon; Til, Lluis; Gutierrez, Josep; Brugada, Josep; Sitges, Marta

2017-09-01

Introduction Pre-participation screening in athletes attempts to reduce the incidence of sudden death during sports by identifying susceptible individuals. The objective of this study was to evaluate the diagnostic capacity of the different pre-participation screening points in adolescent athletes and the cost effectiveness of the programme. Methods Athletes were studied between 12-18 years old. Pre-participation screening included the American Heart Association questionnaire, electrocardiogram, echocardiogram, and stress test. The cost of test was established by the Catalan public health system. Results Of 1650 athletes included, 57% were men and mean age was 15.09 ± 1.82 years. Positive findings were identified as follows: in American Heart Association questionnaire 5.09% of subjects, in electrocardiogram 3.78%, in echocardiogram 4.96%, and in exercise test 1.75%. Six athletes (0.36%) were disqualified from participation and 10 (0.60%) were referred for interventional treatment. Diagnostic capacity was assessed by the area under the curve for detection of diseases that motivated disqualification for sport practice (American Heart Association questionnaire, 0.55; electrocardiogram, 0.72; echocardiogram, 0.88; stress test, 0.57). The cost for each athlete disqualified from the sport for a disease causing sudden death was €45,578. Conclusion The electrocardiogram and echocardiogram were the most useful studies to detect athletes susceptible to sudden death, and the stress test best diagnosed arrhythmias with specific treatment. In our country, pre-participatory screening was cost effective to detect athletes who might experience sudden death in sports.

Risk of Death for Veterans on Release From Prison

PubMed Central

Wortzel, Hal S.; Blatchford, Patrick; Conner, Latoya; Adler, Lawrence E.; Binswanger, Ingrid A.

2017-01-01

We sought to determine, among veterans released from Washington state prisons from 1999 through 2003, the risk of death from all causes, whether those veterans have faced a higher risk of death than have nonveterans, and whether having VA benefits decreased the risk of death. We linked data from a retrospective cohort study to data from the Veterans Benefit Administration. Mortality rates were compared between veteran and nonveteran former inmates. The crude rate of veteran mortality was 1,195 per 100,000 person-years, significantly higher than that of nonveterans (p < .001), but adjustment for demographic factors demonstrated no significant increased risk. VA benefits were associated with a reduced risk for all-cause deaths (hazard ratio, .376; 95% confidence interval, 0.18–0.79). Veterans share the heightened risk of death after release from prison faced by all released inmates and should be included in efforts to reduce the risks associated with transitioning from prison to the community. VA benefits appear to offer a protective effect, particularly against medical deaths. PMID:22960917

Astaxanthin Protects Against Retinal Damage: Evidence from In Vivo and In Vitro Retinal Ischemia and Reperfusion Models.

PubMed

Otsuka, Tomohiro; Shimazawa, Masamitsu; Inoue, Yuki; Nakano, Yusuke; Ojino, Kazuki; Izawa, Hiroshi; Tsuruma, Kazuhiro; Ishibashi, Takashi; Hara, Hideaki

2016-11-01

Astaxanthin exhibits various pharmacological activities, including anti-oxidative, anti-tumor, and anti-inflammatory effects, and is thought to exert a neuroprotective effect via these mechanisms. The purpose of this study was to investigate the protective effects of astaxanthin on neuronal cell death using a retinal ischemia/reperfusion model. In vivo, retinal ischemia was induced by 5 h unilateral ligation of the pterygopalatine artery (PPA) and the external carotid artery (ECA) in ddY mice. Astaxanthin (100 mg/kg) was administered orally 1 h before induction of ischemia, immediately after reperfusion, at 6 or 12 h after reperfusion, and twice daily for the following 4 days. Histological analysis and an electroretinogram (ERG) were performed 5 days after ischemia/reperfusion. In vitro, cell death was induced in the RGC-5 (retinal precursor cells) by oxygen-glucose deprivation (OGD), and the rates of cell death and production of intracellular reactive oxygen species (ROS) were measured using nuclear staining and a ROS reactive reagent, CM-H 2 DCFDA. Histological studies revealed that astaxanthin significantly reduced retinal ischemic damage and ERG reduction. In in vitro studies, astaxanthin inhibited cell death and ROS production in a concentration-dependent manner. Collectively, these results indicate that astaxanthin inhibits ischemia-induced retinal cell death via its antioxidant effect. Hence, astaxanthin might be effective in treating retinal ischemic pathologies.

Parents' Death and its Implications for Child Survival.

PubMed

Atrash, Hani K

Reduction of child mortality is a global public health priority. Parents can play an important role in reducing child mortality. The inability of one or both parents to care for their children due to death, illness, divorce or separation increases the risk of death of their children. There is increasing evidence that the health, education, and socioeconomic status of mothers and fathers have significant impact on the health and survival of their children. We conducted a literature review to explore the impact of the death of parents on the survival and wellbeing of their children and the mechanisms through which this impact is mediated. Studies have generally concluded that the death of a mother significantly increased the risk of death of her children, especially during the early years; the effect continues but is significantly reduced with increasing age through the age of 15 years. The effect of the loss of a father had less impact than the effect of losing a mother although it too had negative consequences for the survival prospect of the child. A mother's health, education, socioeconomic status, fertility behavior, environmental health conditions, nutritional status and infant feeding, and the use of health services all play an important role in the level of risk of death of her children. Efforts to achieve the Millennium Development Goal No. 4 of reducing children's under-5 mortality in developing countries by two thirds by 2015 should include promoting the health and education of women.

The Effects of Maternal Mortality on Infant and Child Survival in Rural Tanzania: A Cohort Study.

PubMed

Finlay, Jocelyn E; Moucheraud, Corrina; Goshev, Simo; Levira, Francis; Mrema, Sigilbert; Canning, David; Masanja, Honorati; Yamin, Alicia Ely

2015-11-01

The full impact of a maternal death includes consequences faced by orphaned children. This analysis adds evidence to a literature on the magnitude of the association between a woman's death during or shortly after childbirth, and survival outcomes for her children. The Ifakara and Rufiji Health and Demographic Surveillance Sites in rural Tanzania conduct longitudinal, frequent data collection of key demographic events at the household level. Using a subset of the data from these sites (1996-2012), this survival analysis compared outcomes for children who experienced a maternal death (42 and 365 days definitions) during or near birth to those children whose mothers survived. There were 111 maternal deaths (or 229 late maternal deaths) during the study period, and 46.28 % of the index children also subsequently died (40.73 % of children in the late maternal death group) before their tenth birthday-a much higher prevalence of child mortality than in the population of children whose mothers survived (7.88 %, p value <0.001). Children orphaned by early maternal deaths had a 51.54 % chance of surviving to their first birthday, compared to a 94.42 % probability for children of surviving mothers. A significant, but lesser, child survival effect was also found for paternal deaths in this study period. The death of a mother compromises the survival of index children. Reducing maternal mortality through improved health care-especially provision of high-quality skilled birth attendance, emergency obstetric services and neonatal care-will also help save children's lives.

Embryo deaths in reproduction and embryo research: a reply to Murphy's double effect argument.

PubMed

Devolder, Katrien

2013-08-01

The majority of embryos created in natural reproduction die spontaneously within a few weeks of conception. Some have argued that, therefore, if one believes the embryo is a person (in the normative sense) one should find 'natural' reproduction morally problematic. An extension of this argument holds that, if one accepts embryo deaths in natural reproduction, consistency requires that one also accepts embryo deaths that occur in (i) assisted reproduction via in vitro fertilisation (IVF) and (ii) embryo research. In a recent paper in this journal, Timothy Murphy criticises both the initial argument and its extension. Murphy argues that double-effect reasoning can justify embryo deaths both in natural reproduction and IVF, but not in embryo research. Thus, according to Murphy, one can, without being inconsistent, (1) believe the embryo is a person and accept natural reproduction and IVF, and (2) accept natural reproduction and IVF, while rejecting embryo research on the ground that it involves embryo deaths. I show that Murphy's argument is problematic because double effect cannot justify embryo deaths in standard IVF practices. The problem is that the proportionality criterion of double effect is not met by such practices. Thus, Murphy's argument fails to support (1) and (2). An implication of his argument failing to support (2) is that it does not defeat the position I have defended in the past-that if one accepts standard IVF practices one should also accept embryo research, including research with embryos created solely for that purpose.

Development and validation of a prognostic model to predict death in patients with traumatic bleeding, and evaluation of the effect of tranexamic acid on mortality according to baseline risk: a secondary analysis of a randomised controlled trial.

PubMed

Perel, P; Prieto-Merino, D; Shakur, H; Roberts, I

2013-06-01

Severe bleeding accounts for about one-third of in-hospital trauma deaths. Patients with a high baseline risk of death have the most to gain from the use of life-saving treatments. An accurate and user-friendly prognostic model to predict mortality in bleeding trauma patients could assist doctors and paramedics in pre-hospital triage and could shorten the time to diagnostic and life-saving procedures such as surgery and tranexamic acid (TXA). The aim of the study was to develop and validate a prognostic model for early mortality in patients with traumatic bleeding and to examine whether or not the effect of TXA on the risk of death and thrombotic events in bleeding adult trauma patients varies according to baseline risk. Multivariable logistic regression and risk-stratified analysis of a large international cohort of trauma patients. Two hundred and seventy-four hospitals in 40 high-, medium- and low-income countries. We derived prognostic models in a large placebo-controlled trial of the effects of early administration of a short course of TXA [Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial]. The trial included 20,127 trauma patients with, or at risk of, significant bleeding, within 8 hours of injury. We externally validated the model on 14,220 selected trauma patients from the Trauma Audit and Research Network (TARN), which included mainly patients from the UK. We examined the effect of TXA on all-cause mortality, death due to bleeding and thrombotic events (fatal and non-fatal myocardial infarction, stroke, deep-vein thrombosis and pulmonary embolism) within risk strata in the CRASH-2 trial data set and we estimated the proportion of premature deaths averted by applying the odds ratio (OR) from the CRASH-2 trial to each of the risk strata in TARN. For the stratified analysis according baseline risk we considered the intervention TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo. For the prognostic models we included predictors for death in hospital within 4 weeks of injury. For the stratified analysis we reported ORs for all causes of death, death due to bleeding, and fatal and non-fatal thrombotic events associated with the use of TXA according to baseline risk. A total of 3076 (15%) patients died in the CRASH-2 trial and 1705 (12%) in the TARN data set. Glasgow Coma Scale score, age and systolic blood pressure were the strongest predictors of mortality. Discrimination and calibration were satisfactory, with C-statistics > 0.80 in both CRASH-2 trial and TARN data sets. A simple chart was constructed to readily provide the probability of death at the point of care, while a web-based calculator is available for a more detailed risk assessment. TXA reduced all-cause mortality and death due to bleeding in each stratum of baseline risk. There was no evidence of heterogeneity in the effect of TXA on all-cause mortality (p-value for interaction = 0.96) or death due to bleeding (p= 0.98). There was a significant reduction in the odds of fatal and non-fatal thrombotic events with TXA (OR = 0.69, 95% confidence interval 0.53 to 0.89; p= 0.005). There was no evidence of heterogeneity in the effect of TXA on the risk of thrombotic events (p= 0.74). This prognostic model can be used to obtain valid predictions of mortality in patients with traumatic bleeding. TXA can be administered safely to a wide spectrum of bleeding trauma patients and should not be restricted to the most severely injured. Future research should evaluate whether or not the use of this prognostic model in clinical practice has an impact on the management and outcomes of trauma patients.

The effects of Phytophthora ramorum infection on hydraulic conductivity and tylosis formation in tanoak sapwood

Treesearch

Bradley R. Collins; Jennifer L. Parke; Barb Lachenbruch; Everett M. Hansen

2009-01-01

Tanoak (Lithocarpus densiflorus (Hook. and Arn.) Rehder) is highly susceptible to sudden oak death, a disease caused by the oomycete Phytophthora ramorum Werres, De Cock & Man in’t Veld. Symptoms include a dying crown, bleeding cankers, and, eventually, death of infected trees. The cause of mortality is not well understood, but recent research indicates that...

Alterations in comprehensive geriatric assessment decrease survival of elderly patients with cancer.

PubMed

Frasca, M; Soubeyran, P; Bellera, C; Rainfray, M; Leffondre, K; Mathoulin-Pélissier, S

2018-02-01

A comprehensive geriatric assessment (CGA) evaluating several domains of health is recommended for elderly patients with cancer. Effects of altered domains on the risk of death in this population need to be clarified. The aim of this study was to estimate the independent association of each CGA domain to overall survival (OS). Patients included in the ONCODAGE cohort completed a CGA at baseline. Cox models (one per domain) estimated the hazard ratio (HR) of death for each CGA domain. Directed Acyclic Graphs (DAGs) selected specific sets of adjustment factors for each model. The analysis included 1264 patients (mean age: 78 years, women: 70%). Median follow-up was 5.2 years, and 446 patients died. Each altered domain had a detrimental effect on survival, sometimes dependent on gender, age, education or time from inclusion. Nutritional status had a time-varying effect, with higher mortality rates if altered only within the first 3 years of follow-up. In case of altered mobility, the risk of death was higher only for the youngest patients and, in case of altered autonomy, only for the youngest women. An altered neurological state led to higher mortality rates; this effect increased with the level of education. Patients with altered psychological status or more than four comorbidities at baseline had also higher mortality rates. Patients with an altered CGA domain have a higher risk of death than those without any alteration. The effect of some alterations is different in some subgroups or at a given time of the treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mental disorders and vulnerability to homicidal death: Swedish nationwide cohort study.

PubMed

Crump, Casey; Sundquist, Kristina; Winkleby, Marilyn A; Sundquist, Jan

2013-03-04

To determine the risk of people with mental disorders being victims of homicide. National cohort study. Sweden. Entire adult population (n = 7,253,516). Homicidal death during eight years of follow-up (2001-08); hazard ratios for the association between mental disorders and homicidal death, with adjustment for sociodemographic confounders; potential modifying effect of comorbid substance use. 615 homicidal deaths occurred in 54.4 million person years of follow-up. Mortality rates due to homicide (per 100,000 person years) were 2.8 among people with mental disorders compared with 1.1 in the general population. After adjustment for sociodemographic confounders, any mental disorder was associated with a 4.9-fold (95% confidence interval 4.0 to 6.0) risk of homicidal death, relative to people without mental disorders. Strong associations were found irrespective of age, sex, or other sociodemographic characteristics. Although the risk of homicidal death was highest among people with substance use disorders (approximately ninefold), the risk was also increased among those with personality disorders (3.2-fold), depression (2.6-fold), anxiety disorders (2.2-fold), or schizophrenia (1.8-fold) and did not seem to be explained by comorbid substance use. Sociodemographic risk factors included male sex, being unmarried, and low socioeconomic status. In this large cohort study, people with mental disorders, including those with substance use disorders, personality disorders, depression, anxiety disorders, or schizophrenia, had greatly increased risks of homicidal death. Interventions to reduce violent death among people with mental disorders should tackle victimisation and homicidal death in addition to suicide and accidents, which share common risk factors.

Risk of Death in Infants Who Have Experienced a Brief Resolved Unexplained Event: A Meta-Analysis.

PubMed

Brand, Donald A; Fazzari, Melissa J

2018-06-01

To estimate an upper bound on the risk of death after a brief resolved unexplained event (BRUE), a sudden alteration in an infant's breathing, color, tone, or responsiveness, previously labeled "apparent life-threatening event" (ALTE). The meta-analysis incorporated observational studies of patients with ALTE that included data on in-hospital and post-discharge deaths with at least 1 week of follow-up after hospital discharge. Pertinent studies were identified from a published review of the literature from 1970 through 2014 and a supplementary PubMed query through February 2017. The 12 included studies (n = 3005) reported 12 deaths, of which 8 occurred within 4 months of the event. Applying a Poisson-normal random effects model to the 8 proximate deaths using a 4-month time horizon yielded a post-ALTE mortality rate of about 1 in 800, which constitutes an upper bound on the risk of death after a BRUE. This risk is about the same as the baseline risk of death during the first year of life. The meta-analysis therefore supports the return-home approach advocated in a recently published clinical practice guideline-not routine hospitalization-for BRUE patients who have been evaluated in the emergency department and determined to be at lower risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Which strategies reduce breast cancer mortality most? Collaborative modeling of optimal screening, treatment, and obesity prevention.

PubMed

Mandelblatt, Jeanne; van Ravesteyn, Nicolien; Schechter, Clyde; Chang, Yaojen; Huang, An-Tsun; Near, Aimee M; de Koning, Harry; Jemal, Ahmedin

2013-07-15

US breast cancer mortality is declining, but thousands of women still die each year. Two established simulation models examine 6 strategies that include increased screening and/or treatment or elimination of obesity versus continuation of current patterns. The models use common national data on incidence and obesity prevalence, competing causes of death, mammography characteristics, treatment effects, and survival/cure. Parameters are modified based on obesity (defined as BMI  ≥  30 kg/m(2) ). Outcomes are presented for the year 2025 among women aged 25+ and include numbers of cases, deaths, mammograms and false-positives; age-adjusted incidence and mortality; breast cancer mortality reduction and deaths averted; and probability of dying of breast cancer. If current patterns continue, the models project that there would be about 50,100-57,400 (range across models) annual breast cancer deaths in 2025. If 90% of women were screened annually from ages 40 to 54 and biennially from ages 55 to 99 (or death), then 5100-6100 fewer deaths would occur versus current patterns, but incidence, mammograms, and false-positives would increase. If all women received the indicated systemic treatment (with no screening change), then 11,400-14,500 more deaths would be averted versus current patterns, but increased toxicity could occur. If 100% received screening plus indicated therapy, there would be 18,100-20,400 fewer deaths. Eliminating obesity yields 3300-5700 fewer breast cancer deaths versus continuation of current obesity levels. Maximal reductions in breast cancer deaths could be achieved through optimizing treatment use, followed by increasing screening use and obesity prevention. © 2013 American Cancer Society.

A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score

PubMed Central

Hijazi, Ziad; Oldgren, Jonas; Lindbäck, Johan; Alexander, John H; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Held, Claes; Hylek, Elaine M; Lopes, Renato D; Yusuf, Salim; Granger, Christopher B; Siegbahn, Agneta; Wallentin, Lars

2018-01-01

Abstract Aims In atrial fibrillation (AF), mortality remains high despite effective anticoagulation. A model predicting the risk of death in these patients is currently not available. We developed and validated a risk score for death in anticoagulated patients with AF including both clinical information and biomarkers. Methods and results The new risk score was developed and internally validated in 14 611 patients with AF randomized to apixaban vs. warfarin for a median of 1.9 years. External validation was performed in 8548 patients with AF randomized to dabigatran vs. warfarin for 2.0 years. Biomarker samples were obtained at study entry. Variables significantly contributing to the prediction of all-cause mortality were assessed by Cox-regression. Each variable obtained a weight proportional to the model coefficients. There were 1047 all-cause deaths in the derivation and 594 in the validation cohort. The most important predictors of death were N-terminal pro B-type natriuretic peptide, troponin-T, growth differentiation factor-15, age, and heart failure, and these were included in the ABC (Age, Biomarkers, Clinical history)-death risk score. The score was well-calibrated and yielded higher c-indices than a model based on all clinical variables in both the derivation (0.74 vs. 0.68) and validation cohorts (0.74 vs. 0.67). The reduction in mortality with apixaban was most pronounced in patients with a high ABC-death score. Conclusion A new biomarker-based score for predicting risk of death in anticoagulated AF patients was developed, internally and externally validated, and well-calibrated in two large cohorts. The ABC-death risk score performed well and may contribute to overall risk assessment in AF. ClinicalTrials.gov identifier NCT00412984 and NCT00262600 PMID:29069359

[Cause-of-death statistics and ICD, quo vadis?

PubMed

Eckert, Olaf; Vogel, Ulrich

2018-07-01

The International Statistical Classification of Diseases and Related Health Problems (ICD) is the worldwide binding standard for generating underlying cause-of-death statistics. What are the effects of former revisions of the ICD on underlying cause-of-death statistics and which opportunities and challenges are becoming apparent in a possible transition process from ICD-10 to ICD-11?This article presents the calculation of the exploitation grade of ICD-9 and ICD-10 in the German cause-of-death statistics and quality of documentation. Approximately 67,000 anonymized German death certificates are processed by Iris/MUSE and official German cause-of-death statistics are analyzed.In addition to substantial changes in the exploitation grade in the transition from ICD-9 to ICD-10, regional effects become visible. The rate of so-called "ill-defined" conditions exceeds 10%.Despite substantial improvement of ICD revisions there are long-known deficits in the coroner's inquest, filling death certificates and quality of coding. To make better use of the ICD as a methodological framework for mortality statistics and health reporting in Germany, the following measures are necessary: 1. General use of Iris/MUSE, 2. Establishing multiple underlying cause-of-death statistics, 3. Introduction of an electronic death certificate, 4. Improvement of the medical assessment of cause of death.Within short time the WHO will release the 11th revision of the ICD that will provide additional opportunities for the development of underlying cause-of-death statistics and their use in science, public health and politics. A coordinated effort including participants in the process and users is necessary to meet the related challenges.

Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death.

PubMed

Parra, Valentina; Moraga, Francisco; Kuzmicic, Jovan; López-Crisosto, Camila; Troncoso, Rodrigo; Torrealba, Natalia; Criollo, Alfredo; Díaz-Elizondo, Jessica; Rothermel, Beverly A; Quest, Andrew F G; Lavandero, Sergio

2013-08-01

Ceramides are important intermediates in the biosynthesis and degradation of sphingolipids that regulate numerous cellular processes, including cell cycle progression, cell growth, differentiation and death. In cardiomyocytes, ceramides induce apoptosis by decreasing mitochondrial membrane potential and promoting cytochrome-c release. Ca(2+) overload is a common feature of all types of cell death. The aim of this study was to determine the effect of ceramides on cytoplasmic Ca(2+) levels, mitochondrial function and cardiomyocyte death. Our data show that C2-ceramide induces apoptosis and necrosis in cultured cardiomyocytes by a mechanism involving increased Ca(2+) influx, mitochondrial network fragmentation and loss of the mitochondrial Ca(2+) buffer capacity. These biochemical events increase cytosolic Ca(2+) levels and trigger cardiomyocyte death via the activation of calpains. Copyright © 2013 Elsevier B.V. All rights reserved.

VX-induced cell death involves activation of caspase-3 in cultured rat cortical neurons.

PubMed

Tenn, Catherine C; Wang, Yushan

2007-05-01

Exposure of cell cultures to organophosphorous compounds such as VX can result in cell death. However, it is not clear whether VX-induced cell death is necrotic or involves programmed cell death mechanisms. Activation of caspases, a family of cysteine proteases, is often involved in cell death, and in particular, caspase-3 activation appears to be a key event in programmed cell death processes including apoptosis. In this study, we investigated VX-induced neuronal cell death, as well as the underlying mechanism in terms of its effect on caspase-3 activity. Primary cortical neuronal cultures were prepared from gestational days 17 to 19 Sprague Dawley rat fetuses. At maturation, the cells were treated with varying concentrations of VX and cell death was evaluated by lactate dehydrogenase (LDH) release. VX induced an increase in LDH release in a concentration-dependent manner. Morphological VX-induced cell death was also characterized by using nuclear staining with propidium iodide and Hoechst 33342. VX induced a concentration- and time-dependent increase in caspase-3 activation. Caspase-3 activation was also confirmed by the proteolytic cleavage of poly(ADP-ribose)polymerase (PARP), an endogenous caspase-3 substrate. These data suggested that in rat cortical neurons, VX-induced cell death via a programmed cell death pathway that involves changes in caspase-3 protease.

Meaning of death: an exploration of perception of elderly in a Bangladeshi village.

PubMed

Joarder, Taufique; Cooper, Alicia; Zaman, Shahaduz

2014-09-01

The aim of this qualitative study was to explore the perceptions of meaning of death among the elderly in a Bangladeshi community, and to understand how the meaning of death affects one's overall well-being. Understandings of death were explored through the explanations respondents provided on the journey of the soul during lifetime and the afterlife, concepts of body-soul duality, and perceived "good" and "bad" deaths. The relationship to well-being was expressed in terms of longevity, anxiety/acceptance of death, and preferred circumstances for death. Seven in-depth interviews and one informal discussion session provided the bulk of the data, while Participatory Rapid Appraisal (PRA) tools, including daily routines and body mapping, supplemented our findings. Elderly members of the community had very specific ideas about the meaning of death, and provided clear explanations regarding the journey of the soul, drawing on ideas of body-soul duality to substantiate claims. Due to long coexistence fusion of Hindu and Muslim ideas around death was found. Anxiety/fear of death was associated with some secular issues, on the contrary the perception of longevity was found linked with spirituality. Insights revealed from this study of subtle differences in the perceptions regarding issues around death may aid the policy makers develop effective end-of-life interventions.

[Death rate by malnutrition in children under the age of five, Colombia].

PubMed

Quiroga, Edwin Fernando

2012-01-01

Much higher mortalities occur in children under five in developing countries with high poverty rates compared with developed countries. Causes of death are related to perinatal conditions, measles, HIV/AIDS, diarrhea, respiratory diseases and others. Throughout the world, malnutrition has been identified as the underlying cause of approximately half of these deaths. Death rate due to malnutrition was described using an adjusted method that takes into account the difficulties of identifying malnutrition as a direct cause of death. A descriptive study included analysis of the International Classification of Diseases (ICD-10) vital statistics from 2003-2007. Death rates were estimated, a method of analysis of multiple causes was applied for infectious diseases, along with calculations of death probabilities. Malnutrition was associated with infectious diseases. The frequency of infectious disease as a direct cause of death was almost seven times higher in cases with the antecedent of malnutrition. When adjusted death rate values were used, the initial value increased nearly five times. The probability of death after the adjustment for inadequate classification increased approximately four times. The Analysis of Multiple Causes Method was established as an effective method in analyzing malnutrition and infectious diesease mortality in Colombia. Malnutrition may be a direct underlying cause of death in one of eight deaths in children <1 year old and one of three deaths in 1-4-year-olds.

Additive Effects of Cointoxicants in Single-Opioid Induced Deaths

PubMed Central

Sorg, Marcella H.; Long, D. Leann; Abate, Marie A.; Kaplan, James A.; Kraner, James C.; Greenwald, Margaret S.; Andrew, Thomas A.; Shapiro, Steven L.; Wren, Jamie A.

2017-01-01

A forensic drug database (FDD) was used to capture comprehensive data from all drug-related deaths in West Virginia, with deaths also included from the northern New England states of Maine, Vermont, and New Hampshire. All four states serve predominantly rural populations under two million and all have similar state medical examiner systems that employ statewide uniform death certification policies and practices. This study focused on 1482 single opioid deaths (fentanyl, hydrocodone, methadone, and oxycodone) in the FDD from 2007–2011. We modeled relationships between the opioid concentrations and the presence or absence of the following commonly occurring non-opioid cointoxicants: benzodiazepines (alprazolam and diazepam), alcohol, tricyclic antidepressants, selective serotonin reuptake inhibitors, and diphenhydramine. Additional covariates of state, age, body mass index, and sex were included. Results showed that the presence of alcohol, benzodiazepines, and antidepressants were each associated with statistically significant lower concentrations of some but not all of the opioids studied, which may obscure the interpretation of postmortem toxicology results alone. Fentanyl concentrations appeared to be the least associated with the presence or absence of the variables studied, and cointoxicant alcohol appeared to be associated with lower concentrations in opioid concentrations than were most of the other factors in the model studied. These findings underscore the importance of documenting all potential cointoxicants in opioid-related deaths. PMID:29399239

The Role of Public Policies in Reducing Smoking

PubMed Central

Levy, David T.; Boyle, Raymond G.; Abrams, David B.

2015-01-01

Background Following the landmark lawsuit and settlement with the tobacco industry, Minnesota pursued the implementation of stricter tobacco control policies, including tax increases, mass media campaigns, smokefree air laws, and cessation treatment policies. Modeling is used to examine policy effects on smoking prevalence and smoking-attributable deaths. Purpose To estimate the effect of tobacco control policies in Minnesota on smoking prevalence and smoking-attributable deaths using the SimSmoke simulation model. Methods Minnesota data starting in 1993 are applied to SimSmoke, a simulation model used to examine the effect of tobacco control policies over time on smoking initiation and cessation. Upon validating the model against smoking prevalence, SimSmoke is used to distinguish the effect of policies implemented since 1993 on smoking prevalence. Using standard attribution methods, SimSmoke also estimates deaths averted as a result of the policies. Results SimSmoke predicts smoking prevalence accurately between 1993 and 2011. Since 1993, a relative reduction in smoking rates of 29% by 2011 and of 41% by 2041 can be attributed to tobacco control policies, mainly tax increases, smokefree air laws, media campaigns, and cessation treatment programs. Moreover, 48,000 smoking-attributable deaths will be averted by 2041. Conclusions Minnesota SimSmoke demonstrates that tobacco control policies, especially taxes, have substantially reduced smoking prevalence and smoking-attributable deaths. Taxes, smokefree air laws, mass media, cessation treatment policies, and youth-access enforcement contributed to the decline in prevalence and deaths averted, with the strongest component being taxes. With stronger policies, for example, increasing cigarette taxes to $4.00 per pack, Minnesota’s smoking rate could be reduced by another 13%, and 7200 deaths could be averted by 2041. PMID:23079215

The role of public policies in reducing smoking: the Minnesota SimSmoke tobacco policy model.

PubMed

Levy, David T; Boyle, Raymond G; Abrams, David B

2012-11-01

Following the landmark lawsuit and settlement with the tobacco industry, Minnesota pursued the implementation of stricter tobacco control policies, including tax increases, mass media campaigns, smokefree air laws, and cessation treatment policies. Modeling is used to examine policy effects on smoking prevalence and smoking-attributable deaths. To estimate the effect of tobacco control policies in Minnesota on smoking prevalence and smoking-attributable deaths using the SimSmoke simulation model. Minnesota data starting in 1993 are applied to SimSmoke, a simulation model used to examine the effect of tobacco control policies over time on smoking initiation and cessation. Upon validating the model against smoking prevalence, SimSmoke is used to distinguish the effect of policies implemented since 1993 on smoking prevalence. Using standard attribution methods, SimSmoke also estimates deaths averted as a result of the policies. SimSmoke predicts smoking prevalence accurately between 1993 and 2011. Since 1993, a relative reduction in smoking rates of 29% by 2011 and of 41% by 2041 can be attributed to tobacco control policies, mainly tax increases, smokefree air laws, media campaigns, and cessation treatment programs. Moreover, 48,000 smoking-attributable deaths will be averted by 2041. Minnesota SimSmoke demonstrates that tobacco control policies, especially taxes, have substantially reduced smoking prevalence and smoking-attributable deaths. Taxes, smokefree air laws, mass media, cessation treatment policies, and youth-access enforcement contributed to the decline in prevalence and deaths averted, with the strongest component being taxes. With stronger policies, for example, increasing cigarette taxes to $4.00 per pack, Minnesota's smoking rate could be reduced by another 13%, and 7200 deaths could be averted by 2041. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Deaths averted by influenza vaccination in the U.S. during the seasons 2005/06 through 2013/14.

PubMed

Foppa, Ivo M; Cheng, Po-Yung; Reynolds, Sue B; Shay, David K; Carias, Cristina; Bresee, Joseph S; Kim, Inkyu K; Gambhir, Manoj; Fry, Alicia M

2015-06-12

Excess mortality due to seasonal influenza is substantial, yet quantitative estimates of the benefit of annual vaccination programs on influenza-associated mortality are lacking. We estimated the numbers of deaths averted by vaccination in four age groups (0.5 to 4, 5 to 19, 20 to 64 and ≥65 yrs.) for the nine influenza seasons from 2005/6 through 2013/14. These estimates were obtained using a Monte Carlo approach applied to weekly U.S. age group-specific estimates of influenza-associated excess mortality, monthly vaccination coverage estimates and summary seasonal influenza vaccine effectiveness estimates to obtain estimates of the number of deaths averted by vaccination. The estimates are conservative as they do not include indirect vaccination effects. From August, 2005 through June, 2014, we estimated that 40,127 (95% confidence interval [CI] 25,694 to 59,210) deaths were averted by influenza vaccination. We found that of all studied seasons the most deaths were averted by influenza vaccination during the 2012/13 season (9398; 95% CI 2,386 to 19,897) and the fewest during the 2009/10 pandemic (222; 95% CI 79 to 347). Of all influenza-associated deaths averted, 88.9% (95% CI 83 to 92.5%) were in people ≥65 yrs. old. The estimated number of deaths averted by the US annual influenza vaccination program is considerable, especially among elderly adults and even when vaccine effectiveness is modest, such as in the 2012/13 season. As indirect effects ("herd immunity") of vaccination are ignored, these estimates represent lower bound estimates and are thus conservative given valid excess mortality estimates. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Effects of NAD+ on Apoptotic Neuronal Death and Mitochondrial Biogenesis and Function after Glutamate Excitotoxicity

PubMed Central

Wang, Xiaowan; Li, Hailong; Ding, Shinghua

2014-01-01

NAD+ is an essential co-enzyme for cellular energy metabolism and is also involved as a substrate for many cellular enzymatic reactions. It has been shown that NAD+ has a beneficial effect on neuronal survival and brain injury in in vitro and in vivo ischemic models. However, the effect of NAD+ on mitochondrial biogenesis and function in ischemia has not been well investigated. In the present study, we used an in vitro glutamate excitotoxicity model of primary cultured cortical neurons to study the effect of NAD+ on apoptotic neuronal death and mitochondrial biogenesis and function. Our results show that supplementation of NAD+ could effectively reduce apoptotic neuronal death, and apoptotic inducing factor translocation after neurons were challenged with excitotoxic glutamate stimulation. Using different approaches including confocal imaging, mitochondrial DNA measurement and Western blot analysis of PGC-1 and NRF-1, we also found that NAD+ could significantly attenuate glutamate-induced mitochondrial fragmentation and the impairment of mitochondrial biogenesis. Furthermore, NAD+ treatment effectively inhibited mitochondrial membrane potential depolarization and NADH redistribution after excitotoxic glutamate stimulation. Taken together, our results demonstrated that NAD+ is capable of inhibiting apoptotic neuronal death after glutamate excitotoxicity via preserving mitochondrial biogenesis and integrity. Our findings provide insights into potential neuroprotective strategies in ischemic stroke. PMID:25387075

The effect of tranexamic acid on the risk of death and hysterectomy in women with post-partum haemorrhage: statistical analysis plan for the WOMAN trial.

PubMed

Shakur, Haleema; Roberts, Ian; Edwards, Philip; Elbourne, Diana; Alfirevic, Zarko; Ronsmans, Carine

2016-05-17

Severe haemorrhage is a leading cause of maternal death worldwide. Most haemorrhage deaths occur soon after childbirth. Severe post-partum bleeding is sometimes managed by the surgical removal of the uterus (hysterectomy). Death and hysterectomy are important health consequences of post-partum haemorrhage, and clinical trials of interventions aimed at preventing these outcomes are needed. The World Maternal Antifibrinolytic trial aims to determine the effect of tranexamic acid on death, hysterectomy and other health outcomes in women with post-partum haemorrhage. It is an international, multicentre, randomised trial. Approximately 20,000 women with post-partum haemorrhage will be randomly allocated to receive an intravenous injection of either tranexamic acid or matching placebo in addition to usual care. The primary outcome measure is a composite of death in hospital or hysterectomy within 42 days of delivery. The cause of death will be described. Secondary outcomes include death, death due to bleeding, hysterectomy, thromboembolic events, blood transfusion, surgical and radiological interventions, complications, adverse events and quality of life. The health status and occurrence of thromboembolic events in breastfed babies will also be reported. We will conduct subgroup analyses for the primary outcome by time to treatment, type of delivery and cause of haemorrhage. We will conduct an analysis of treatment effect adjusted for baseline risk. The World Maternal Antifibrinolytic trial should provide reliable evidence for the efficacy of tranexamic acid in the prevention of death, hysterectomy and other outcomes that are important to patients. We present a protocol update and the statistical analysis plan for the trial. Current Controlled Trials ISRCTN76912190 (Registration date 08 December 2008), Clinicaltrials.gov NCT00872469 (Registration date 30 March 2009) and Pan African Clinical Trials Registry: PACTR201007000192283 (Registration date 02 September 2010).

Social Autopsy of maternal, neonatal deaths and stillbirths in rural Bangladesh: qualitative exploration of its effect and community acceptance.

PubMed

Biswas, Animesh; Rahman, Fazlur; Eriksson, Charli; Halim, Abdul; Dalal, Koustuv

2016-08-23

Social Autopsy (SA) is an innovative strategy where a trained facilitator leads community groups through a structured, standardised analysis of the physical, environmental, cultural and social factors contributing to a serious, non-fatal health event or death. The discussion stimulated by the formal process of SA determines the causes and suggests preventative measures that are appropriate and achievable in the community. Here we explored individual experiences of SA, including acceptance and participant learning, and its effect on rural communities in Bangladesh. The present study had explored the experiences gained while undertaking SA of maternal and neonatal deaths and stillbirths in rural Bangladesh. Qualitative assessment of documents, observations, focus group discussions, group discussions and in-depth interviews by content and thematic analyses. Each community's maternal and neonatal death was a unique, sad story. SA undertaken by government field-level health workers were well accepted by rural communities. SA had the capability to explore the social reasons behind the medical cause of the death without apportioning blame to any individual or group. SA was a useful instrument to raise awareness and encourage community responses to errors within the society that contributed to the death. People participating in SA showed commitment to future preventative measures and devised their own solutions for the future prevention of maternal and neonatal deaths. SA highlights societal errors and promotes discussion around maternal or newborn death. SA is an effective means to deliver important preventative messages and to sensitise the community to death issues. Importantly, the community itself is enabled to devise future strategies to avert future maternal and neonatal deaths in Bangladesh. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Photoreceptor cell death and rescue in retinal detachment and degenerations

PubMed Central

Murakami, Yusuke; Notomi, Shoji; Hisatomi, Toshio; Nakazawa, Toru; Ishibashi, Tatsuro; Miller, Joan W.; Vavvas, Demetrios G.

2013-01-01

Photoreceptor cell death is the ultimate cause of vision loss in various retinal disorders, including retinal detachment (RD). Photoreceptor cell death has been thought to occur mainly through apoptosis, which is the most characterized form of programmed cell death. The caspase family of cysteine proteases plays a central role for inducing apoptosis, and in experimental models of RD, dying photoreceptor cells exhibit caspase activation; however, there is a paradox that caspase inhibition alone does not provide a sufficient protection against photoreceptor cell loss, suggesting that other mechanisms of cell death are involved. Recent accumulating evidence demonstrates that non-apoptotic forms of cell death, such as autophagy and necrosis, are also regulated by specific molecular machinery, such as those mediated by autophagy-related proteins and receptor-interacting protein kinases, respectively. Here we summarize the current knowledge of cell death signaling and its roles in photoreceptor cell death after RD and other retinal degenerative diseases. A body of studies indicate that not only apoptotic but also autophagic and necrotic signaling are involved in photoreceptor cell death, and that combined targeting of these pathways may be an effective neuroprotective strategy for retinal diseases associated with photoreceptor cell loss. PMID:23994436

Comparative effectiveness of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers in patients with type 2 diabetes and retinopathy

PubMed Central

Shih, Chia-Jen; Chen, Hung-Ta; Kuo, Shu-Chen; Li, Szu-Yuan; Lai, Pi-Hsiang; Chen, Shu-Chen; Ou, Shuo-Ming; Chen, Yung-Tai

2016-01-01

Background: Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective treatments for diabetic retinopathy, but randomized trials and meta-analyses comparing their effects on macrovascular complications have yielded conflicting results. We compared the effectiveness of these drugs in patients with pre-existing diabetic retinopathy in a large population-based cohort. Methods: We conducted a propensity score–matched cohort study using Taiwan’s National Health Insurance Research Database. We included adult patients prescribed an ACE inhibitor or ARB within 90 days after diagnosis of diabetic retinopathy between 2000 and 2010. Primary outcomes were all-cause death and major adverse cardiovascular events (myocardial infarction, ischemic stroke or cardiovascular death). Secondary outcomes were hospital admissions with acute kidney injury or hyperkalemia. Results: We identified 11 246 patients receiving ACE inhibitors and 15 173 receiving ARBs, of whom 9769 patients in each group were matched successfully by propensity scores. In the intention-to-treat analyses, ARBs were similar to ACE inhibitors in risk of all-cause death (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.87–1.01) and major adverse cardiovascular events (HR 0.95, 95% CI 0.87–1.04), including myocardial infarction (HR 1.03, 95% CI 0.88–1.20), ischemic stroke (HR 0.94, 95% CI 0.85–1.04) and cardiovascular death (HR 1.01, 95% CI 0.88–1.16). They also did not differ from ACE inhibitors in risk of hospital admission with acute kidney injury (HR 1.01, 95% CI 0.91–1.13) and hospital admission with hyperkalemia (HR 1.01, 95% CI 0.86–1.18). Results were similar in as-treated analyses. Interpretation: Our study showed that ACE inhibitors were similar to ARBs in risk of all-cause death, major adverse cardiovascular events and adverse effects among patients with pre-existing diabetic retinopathy. PMID:27001739

Comparative effectiveness of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers in patients with type 2 diabetes and retinopathy.

PubMed

Shih, Chia-Jen; Chen, Hung-Ta; Kuo, Shu-Chen; Li, Szu-Yuan; Lai, Pi-Hsiang; Chen, Shu-Chen; Ou, Shuo-Ming; Chen, Yung-Tai

2016-05-17

Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective treatments for diabetic retinopathy, but randomized trials and meta-analyses comparing their effects on macrovascular complications have yielded conflicting results. We compared the effectiveness of these drugs in patients with pre-existing diabetic retinopathy in a large population-based cohort. We conducted a propensity score-matched cohort study using Taiwan's National Health Insurance Research Database. We included adult patients prescribed an ACE inhibitor or ARB within 90 days after diagnosis of diabetic retinopathy between 2000 and 2010. Primary outcomes were all-cause death and major adverse cardiovascular events (myocardial infarction, ischemic stroke or cardiovascular death). Secondary outcomes were hospital admissions with acute kidney injury or hyperkalemia. We identified 11 246 patients receiving ACE inhibitors and 15 173 receiving ARBs, of whom 9769 patients in each group were matched successfully by propensity scores. In the intention-to-treat analyses, ARBs were similar to ACE inhibitors in risk of all-cause death (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.87-1.01) and major adverse cardiovascular events (HR 0.95, 95% CI 0.87-1.04), including myocardial infarction (HR 1.03, 95% CI 0.88-1.20), ischemic stroke (HR 0.94, 95% CI 0.85-1.04) and cardiovascular death (HR 1.01, 95% CI 0.88-1.16). They also did not differ from ACE inhibitors in risk of hospital admission with acute kidney injury (HR 1.01, 95% CI 0.91-1.13) and hospital admission with hyperkalemia (HR 1.01, 95% CI 0.86-1.18). Results were similar in as-treated analyses. Our study showed that ACE inhibitors were similar to ARBs in risk of all-cause death, major adverse cardiovascular events and adverse effects among patients with pre-existing diabetic retinopathy. © 2016 Canadian Medical Association or its licensors.

Effects of alcohol taxes on alcohol-related disease mortality in New York State from 1969 to 2006.

PubMed

Delcher, Chris; Maldonado-Molina, Mildred M; Wagenaar, Alexander C

2012-07-01

The relationship of increased alcohol taxes to reductions in alcohol-related harm is well established. Few studies, however, have examined the effects of sudden decreases in alcohol tax rates or effects of narrow tax changes limited to specific beverage types. In the current study, we: (1) examine whether tax increases on spirits have similar effects in reducing alcohol-related disease mortality as increasing taxes on all types of alcoholic beverages simultaneously, and (2) evaluate effects of beer-specific tax decreases in New York State on mortality. We used a time-series, quasi-experimental research design, including non-alcohol deaths within New York State and other states' rates of alcohol-related disease mortality for comparison. The dataset included 456 monthly observations of mortality in New York State over a 38-year period (1969-2006). We used a random-effects approach and included several other important covariates. Alcohol-related disease mortality declined by 7.0% after a 1990 tax increase for spirits and beer. A spirits-only tax increase (in 1972) was not significantly associated with mortality but a data anomaly increased error in this effect estimate. Small tax decreases on beer between 1996 and 2006 had no measurable effect on mortality. Doubling the beer tax from $0.11 to $0.22 per gallon, a return to New York State's 1990 levels, would decrease deaths by an estimated 250 deaths per year. Excise tax increases on beer and spirits were associated with reductions in alcohol-related disease mortality. Modifying tax rates on a single beverage type does not appear to be as effective as doing so on multiple alcoholic beverages simultaneously. In New York, small decreases in beer taxes were not significantly associated with alcohol-related disease mortality. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of alcohol taxes on alcohol-related disease mortality in New York State from 1969 to 2006

PubMed Central

Delcher, Chris; Maldonado-Molina, Mildred M.; Wagenaar, Alexander C.

2013-01-01

Objective The relationship of increased alcohol taxes to reductions in alcohol-related harm is well established. Few studies, however, have examined the effects of sudden decreases in alcohol tax rates or effects of narrow tax changes limited to specific beverage types. In the current study, we: (1) examine whether tax increases on spirits have similar effects in reducing alcohol-related disease mortality as increasing taxes on all types of alcoholic beverages simultaneously, and (2) evaluate effects of beer-specific tax decreases in New York State on mortality. Method We used a time-series, quasi-experimental research design, including non-alcohol deaths within New York State and other states’ rates of alcohol-related disease mortality for comparison. The dataset included 456 monthly observations of mortality in New York State over a 38-year period (1969–2006). We used a random-effects approach and included several other important covariates. Results Alcohol-related disease mortality declined by 7.0% after a 1990 tax increase for spirits and beer. A spirits-only tax increase (in 1972) was not significantly associated with mortality but a data anomaly increased error in this effect estimate. Small tax decreases on beer between 1996 and 2006 had no measurable effect on mortality. Doubling the beer tax from $0.11 to $0.22 per gallon, a return to New York State’s 1990 levels, would decrease deaths by an estimated 250 deaths per year. Conclusions Excise tax increases on beer and spirits were associated with reductions in alcohol-related disease mortality. Modifying tax rates on a single beverage type does not appear to be as effective as doing so on multiple alcoholic beverages simultaneously. In New York, small decreases in beer taxes were not significantly associated with alcohol-related disease mortality. PMID:22436591

Neuroprotective Compound from an Endophytic Fungus, Colletotrichum sp. JS-0367.

PubMed

Song, Ji Hoon; Lee, Changyeol; Lee, Dahae; Kim, Soonok; Bang, Sunghee; Shin, Myoung-Sook; Lee, Jun; Kang, Ki Sung; Shim, Sang Hee

2018-05-23

Colletotrichum sp. JS-0367 was isolated from Morus alba (mulberry), identified, and cultured on a large scale for chemical investigation. One new anthraquinone (1) and three known anthraquinones (2-4) were isolated and identified using spectroscopic methods including 1D/2D-NMR and HRESIMS. Although the neuroprotective effects of some anthraquinones have been reported, the biological activities of the four anthraquinones isolated in this study have not been reported. Therefore, the neuroprotective effects of these compounds were determined against murine hippocampal HT22 cell death induced by glutamate. Compound 4, evariquinone, showed strong protective effects against HT22 cell death induced by glutamate by the inhibition of intracellular ROS accumulation and Ca 2+ influx triggered by glutamate. Immunoblot analysis revealed that compound 4 reduced the phosphorylation of MAPKs (JNK, ERK1/2, and p38) induced by glutamate. Furthermore, compound 4 strongly attenuated glutamate-mediated apoptotic cell death.

Alkaloids from the hook-bearing branch of Uncaria rhynchophylla and their neuroprotective effects against glutamate-induced HT22 cell death

PubMed Central

Qi, Wen; Yue, Si-Jia; Sun, Jia-Hong; Simpkins, James W.; Zhang, Lin; Yuan, Dan

2015-01-01

One new alkaloid, 4-geissoschizine N-oxide methyl ether (1), was isolated from the EtOH extract of the hook-bearing branch of Uncaria rhynchophylla, together with 10 known alkaloids, 3-epi-geissoschizine methyl ether (2) isolated from U. rhynchophylla for the first time, geissoschizine methyl ether (3), 4-hirsuteine N-oxide (4), hirsuteine (5), hirsutine (6), 3α-dihydro-cadambine (7), 3β-isodihydro-cadambine (8), cadambine (9), strictosamide (10), and akuammigine (11). The structures were elucidated by spectroscopic methods including UV, ESI-QTOF MS, NMR, and circular dichroism experiments. Neuroprotective effects of 1–9 were investigated against 3 mM glutamate-induced HT22 cell death. The activity assay showed that 2, 3, 5, and 6 exhibited potent neuroprotective effects against glutamate-induced HT22 cell death. However, only weak neuroprotective activities were observed for 1, 4, 7, 8, and 9. PMID:24899363

Alkaloids from the hook-bearing branch of Uncariarhynchophylla and their neuroprotective effects against glutamate-induced HT22 cell death.

PubMed

Qi, Wen; Yue, Si-Jia; Sun, Jia-Hong; Simpkins, James W; Zhang, Lin; Yuan, Dan

2014-01-01

One new alkaloid, 4-geissoschizine N-oxide methyl ether (1), was isolated from the EtOH extract of the hook-bearing branch of Uncariarhynchophylla, together with 10 known alkaloids, 3-epi-geissoschizine methyl ether (2) isolated from U.rhynchophylla for the first time, geissoschizine methyl ether (3), 4-hirsuteine N-oxide (4), hirsuteine (5), hirsutine (6), 3α-dihydro-cadambine (7), 3β-isodihydro-cadambine (8), cadambine (9), strictosamide (10), and akuammigine (11). The structures were elucidated by spectroscopic methods including UV, ESI-QTOF MS, NMR, and circular dichroism experiments. Neuroprotective effects of 1-9 were investigated against 3 mM glutamate-induced HT22 cell death. The activity assay showed that 2, 3, 5, and 6 exhibited potent neuroprotective effects against glutamate-induced HT22 cell death. However, only weak neuroprotective activities were observed for 1, 4, 7, 8, and 9.

Vitamin K3 triggers human leukemia cell death through hydrogen peroxide generation and histone hyperacetylation.

PubMed

Lin, Changjun; Kang, Jiuhong; Zheng, Rongliang

2005-10-01

Vitamin K3 (VK3) is a well-known anticancer agent, but its mechanism remains elusive. In the present study, VK3 was found to simultaneously induce cell death, reactive oxygen species (ROS) generation, including superoxide anion (O2*-) and hydrogen peroxide (H2O2) generation, and histone hyperacetylation in human leukemia HL-60 cells in a concentration- and time-dependent manner. Catalase (CAT), an antioxidant enzyme that specifically scavenges H2O2, could significantly diminish both histone acetylation increase and cell death caused by VK3, whereas superoxide dismutase (SOD), an enzyme that specifically eliminates O2*-, showed no effect on both of these, leading to the conclusion that H2O2 generation, but not O2*- generation, contributes to VK3-induced histone hyperacetylation and cell death. This conclusion was confirmed by the finding that enhancement of VK3-induced H2O2 generation by vitamin C (VC) could significantly promote both the histone hyperacetylation and cell death. Further studies suggested that histone hyperacetylation played an important role in VK3-induced cell death, since sodium butyrate, a histone deacetylase (HDAC) inhibitor, showed no effect on ROS generation, but obviously potentiated VK3-induced histone hyperacetylation and cell death. Collectively, these results demonstrate a novel mechanism for the anticancer activity of VK3, i.e., VK3 induced tumor cell death through H2O2 generation, which then further induced histone hyperacetylation.

Kill and spread the word: stimulation of antitumor immune responses in the context of radiotherapy.

PubMed

Gaipl, Udo S; Multhoff, Gabriele; Scheithauer, Heike; Lauber, Kirsten; Hehlgans, Stefanie; Frey, Benjamin; Rödel, Franz

2014-01-01

Besides the direct, targeted effects of ionizing irradiation (x-ray) on cancer cells, namely DNA damage and cell death induction, indirect, nontargeted ones exist, which are mediated in large part by the immune system. Immunogenic forms of tumor cell death induced by x-ray, including immune modulating danger signals like the heat shock protein 70, adenosine triphosphate, and high-mobility group box 1 protein are presented. Further, antitumor effects exerted by cells of the innate (natural killer cells) as well as adaptive immune system (T cells activated by dendritic cells) are outlined. Tumor cell death inhibiting molecules such as survivin are introduced as suitable target for molecularly tailored therapies in combination with x-ray. Finally, reasonable combinations of immune therapies with radiotherapy are discussed.

Pomegranate Juice Polyphenols Induce Macrophage Death via Apoptosis as Opposed to Necrosis Induced by Free Radical Generation: A Central Role for Oxidative Stress.

PubMed

Rom, Oren; Volkova, Nina; Nandi, Sukhendu; Jelinek, Raz; Aviram, Michael

2016-08-01

At high concentrations, polyphenols induce cell death, and the polyphenols-rich pomegranate juice (PJ), known for its antioxidative/antiatherogenic properties, can possibly affect cell death, including macrophage death involved in atherogenesis. In the present study, apoptotic/necrotic macrophage death was analyzed in J774A.1 macrophages and in peritoneal macrophages isolated from atherosclerotic apoE-/- mice treated with PJ. The effects of PJ were compared with those of the free radical generator 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH). Both PJ and AAPH significantly increased J774A.1 macrophage death; however, flow cytometric and microscopic analyses using annexin V/propidium iodide revealed that PJ increased the early apoptosis of the macrophage dose dependently (up to 2.5-fold, P < 0.01), whereas AAPH caused dose-dependent increases in late apoptosis/necrosis (up to 12-fold, P < 0.001). Unlike PJ, AAPH-induced macrophage death was associated with increased intracellular oxidative stress (up to 7-fold, P < 0.001) and with lipid stress demonstrated by triglyceride accumulation (up to 3-fold, P < 0.01) and greater chromatic vesicle response to culture medium (up to 5-fold, P < 0.001). Accordingly, recombinant paraoxonase 1, which hydrolyzes oxidized lipids, attenuated macrophage death induced by AAPH, but not by PJ. Similar apoptotic and oxidative effects were found in macrophages from apoE-/- mice treated with PJ or AAPH. As macrophage apoptotic/necrotic death has considerable impact on atherosclerosis progression, these findings may provide novel mechanisms for the antiatherogenicity of PJ.

Exposure of Bacterial Biofilms to Electrical Current Leads to Cell Death Mediated in Part by Reactive Oxygen Species

PubMed Central

Brinkman, Cassandra L.; Schmidt-Malan, Suzannah M.; Karau, Melissa J.; Greenwood-Quaintance, Kerryl; Hassett, Daniel J.; Mandrekar, Jayawant N.

2016-01-01

Bacterial biofilms may form on indwelling medical devices such as prosthetic joints, heart valves and catheters, causing challenging-to-treat infections. We have previously described the ‘electricidal effect’, in which bacterial biofilms are decreased following exposure to direct electrical current. Herein, we sought to determine if the decreased bacterial quantities are due to detachment of biofilms or cell death and to investigate the role that reactive oxygen species (ROS) play in the observed effect. Using confocal and electron microscopy and flow cytometry, we found that direct current (DC) leads to cell death and changes in the architecture of biofilms formed by Gram-positive and Gram-negative bacteria. Reactive oxygen species (ROS) appear to play a role in DC-associated cell death, as there was an increase in ROS-production by Staphylococcus aureus and Staphylococcus epidermidis biofilms following exposure to DC. An increase in the production of ROS response enzymes catalase and superoxide dismutase (SOD) was observed for S. aureus, S. epidermidis and Pseudomonas aeruginosa biofilms following exposure to DC. Additionally, biofilms were protected from cell death when supplemented with antioxidants and oxidant scavengers, including catalase, mannitol and Tempol. Knocking out SOD (sodAB) in P. aeruginosa led to an enhanced DC effect. Microarray analysis of P. aeruginosa PAO1 showed transcriptional changes in genes related to the stress response and cell death. In conclusion, the electricidal effect results in death of bacteria in biofilms, mediated, at least in part, by production of ROS. PMID:27992529

Potential combined effects of maternal smoking and coffee intake on foetal death within the Danish National Birth Cohort.

PubMed

Morales-Suárez-Varela, Maria; Nohr, Ellen A; Olsen, Jørn; Bech, Bodil H

2018-04-01

Several studies have linked coffee intake and smoking to foetal death, but a possible interaction between both exposures remains unknown. We studied, within the Danish National Birth Cohort, the potential interaction between smoking and coffee drinking while pregnant on the risk of foetal (early and late) death. The study included 90 086 pregnant women, with information about their smoking habit and coffee intake in early pregnancy, and several potential confounding factors. Interaction was studied by calculating both the hazard ratio (HR) in Cox's regression (linear and smoothed restricted cubic spline) and the interaction contrast ratio (ICR). Women who neither smoked nor drank coffee were used as the reference group. Drinking more than 3 cups/d of coffee was associated with the highest risk of foetal death, spontaneous abortion and stillbirth for all smoking status (non-smoker, ≤10 or > 10 cigarettes/d). Among smokers, the combination with drinking <3 cups/d of coffee presented the lowest HRa for foetal death, spontaneous abortion and stillbirth. The ICRs were negative when considering smokers who had a coffee intake up to 3 cups/d, but they were positive for those who had a higher coffee intake, suggesting the effect of coffee intake may be non-linear. Our results suggest that the combined effect of smoking and coffee intake during pregnancy on the risk of foetal death is coffee-dose-dependent. A low coffee intake may reduce the risk of foetal death associated with smoking while a high coffee intake increases the risk.

Antihelminthic benzimidazoles are novel HIF activators that prevent oxidative neuronal death via binding to tubulin.

PubMed

Aleyasin, Hossein; Karuppagounder, Saravanan S; Kumar, Amit; Sleiman, Sama; Basso, Manuela; Ma, Thong; Siddiq, Ambreena; Chinta, Shankar J; Brochier, Camille; Langley, Brett; Haskew-Layton, Renee; Bane, Susan L; Riggins, Gregory J; Gazaryan, Irina; Starkov, Anatoly A; Andersen, Julie K; Ratan, Rajiv R

2015-01-10

Pharmacological activation of the adaptive response to hypoxia is a therapeutic strategy of growing interest for neurological conditions, including stroke, Huntington's disease, and Parkinson's disease. We screened a drug library with known safety in humans using a hippocampal neuroblast line expressing a reporter of hypoxia-inducible factor (HIF)-dependent transcription. Our screen identified more than 40 compounds with the ability to induce hypoxia response element-driven luciferase activity as well or better than deferoxamine, a canonical activator of hypoxic adaptation. Among the chemical entities identified, the antihelminthic benzimidazoles represented one pharmacophore that appeared multiple times in our screen. Secondary assays confirmed that antihelminthics stabilized the transcriptional activator HIF-1α and induced expression of a known HIF target gene, p21(cip1/waf1), in post-mitotic cortical neurons. The on-target effect of these agents in stimulating hypoxic signaling was binding to free tubulin. Moreover, antihelminthic benzimidazoles also abrogated oxidative stress-induced death in vitro, and this on-target effect also involves binding to free tubulin. These studies demonstrate that tubulin-binding drugs can activate a component of the hypoxic adaptive response, specifically the stabilization of HIF-1α and its downstream targets. Tubulin-binding drugs, including antihelminthic benzimidazoles, also abrogate oxidative neuronal death in primary neurons. Given their safety in humans and known ability to penetrate into the central nervous system, antihelminthic benzimidazoles may be considered viable candidates for treating diseases associated with oxidative neuronal death, including stroke.

Mortality on match days of the German national soccer team: a time series analysis from 1995 to 2009.

PubMed

Medenwald, D; Kuss, O

2014-09-01

There is inconsistent evidence on population mortality, especially cardiovascular disease mortality, on match days of national soccer teams during particular international tournaments. This study examines the number of deaths in Germany on match days of the national soccer team during a long-term period including several tournaments. We analysed all registered daily deaths in Germany from 1995 to 2009 (11 225 966 cases) using time series analysis methods. Following the Box/Jenkins approach, we applied a seasonal autoregressive integrated moving average model. To assess the effect of match days, we performed an intervention analysis by including a transfer function model representing match days of the national team in the statistical analyses. We conducted separate analyses for all matches and for matches during international tournaments (European and World Championships) only. Time series and results were stratified in terms of sex, age (<50 years, 50-70 years, >70 years) and cause of death (cardiovascular deaths, injuries, others). We performed a further independent analysis focusing only on the effect of match results (victory, loss, draw) and kind of tournament (international championships, qualifications, friendly matches). Most of the results did not indicate a distinct effect of matches of the national team on general mortality. Moreover, all null value deviations were small when compared with the average number of daily deaths (n=2270). There is no relevant increase or decrease in mortality on match days of the German national soccer team. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effects of intracellular iron overload on cell death and identification of potent cell death inhibitors.

PubMed

Fang, Shenglin; Yu, Xiaonan; Ding, Haoxuan; Han, Jianan; Feng, Jie

2018-06-11

Iron overload causes many diseases, while the underlying etiologies of these diseases are unclear. Cell death processes including apoptosis, necroptosis, cyclophilin D-(CypD)-dependent necrosis and a recently described additional form of regulated cell death called ferroptosis, are dependent on iron or iron-dependent reactive oxygen species (ROS). However, whether the accumulation of intracellular iron itself induces ferroptosis or other forms of cell death is largely elusive. In present study, we study the role of intracellular iron overload itself-induced cell death mechanisms by using ferric ammonium citrate (FAC) and a membrane-permeable Ferric 8-hydroxyquinoline complex (Fe-8HQ) respectively. We show that FAC-induced intracellular iron overload causes ferroptosis. We also identify 3-phosphoinositide-dependent kinase 1 (PDK1) inhibitor GSK2334470 as a potent ferroptosis inhibitor. Whereas, Fe-8HQ-induced intracellular iron overload causes unregulated necrosis, but partially activates PARP-1 dependent parthanatos. Interestingly, we identify many phenolic compounds as potent inhibitors of Fe-8HQ-induced cell death. In conclusion, intracellular iron overload-induced cell death form might be dependent on the intracellular iron accumulation rate, newly identified cell death inhibitors in our study that target ferroptosis and unregulated oxidative cell death represent potential therapeutic strategies against iron overload related diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Influence of Training on First-Year Nursing Department Students' Attitudes on Death and Caring for Dying Patients: A Single-Group Pretest-Posttest Experimental Study.

PubMed

Cerit, Birgül

2017-01-01

The study examined the influence of training on first-year nursing department students' attitudes on death and caring for dying patients. Utilizing the experimental model, the study sample consisted of 81 first-year students attending the nursing department of a university. Death Attitude Profile-Revised and Frommelt Attitude toward Care of the Dying Scale were used for data collection. Data analysis included means, standard deviation, and t test for related samples. Student attitudes toward death were measured as 146.43 (16.741) and 152.75 (15.132) for pre- and posttraining, respectively. Student attitudes toward caring for dying patients were established to be 103.02 (7.655) during pretraining period and 111.02 (10.359) at posttraining period. The difference between pre- and posttests for mean attitudes toward death and caring for the dying patient was statistically significant. Study results determined that training was effective in forming positive student attitudes toward death and caring for dying patients.

Transduced human copper chaperone for Cu,Zn-SOD (PEP-1-CCS) protects against neuronal cell death.

PubMed

Choi, Soo Hyun; Kim, Dae Won; Kim, So Young; An, Jae Jin; Lee, Sun Hwa; Choi, Hee Soon; Sohn, Eun Jung; Hwang, Seok-Il; Won, Moo Ho; Kang, Tae-Cheon; Kwon, Hyung Joo; Kang, Jung Hoon; Cho, Sung-Woo; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

2005-12-31

Reactive oxygen species (ROS) contribute to the development of various human diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS. SOD activity is dependent upon bound copper ions supplied by its partner metallochaperone protein, copper chaperone for SOD (CCS). In the present study, we investigated the protective effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1-CCS was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Moreover, transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells. Immunohistochemical analysis revealed that it prevented neuronal cell death in the hippocampus in response to transient forebrain ischemia. These results suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS provides a potential strategy for therapeutic delivery in various human diseases including stroke related to SOD or ROS.

Glyceraldehyde-3-phosphate dehydrogenase aggregation inhibitor peptide: A potential therapeutic strategy against oxidative stress-induced cell death.

PubMed

Itakura, Masanori; Nakajima, Hidemitsu; Semi, Yuko; Higashida, Shusaku; Azuma, Yasu-Taka; Takeuchi, Tadayoshi

2015-11-13

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has multiple functions, including mediating oxidative stress-induced neuronal cell death. This process is associated with disulfide-bonded GAPDH aggregation. Some reports suggest a link between GAPDH and the pathogenesis of several oxidative stress-related diseases. However, the pathological significance of GAPDH aggregation in disease pathogenesis remains unclear due to the lack of an effective GAPDH aggregation inhibitor. In this study, we identified a GAPDH aggregation inhibitor (GAI) peptide and evaluated its biological profile. The decapeptide GAI specifically inhibited GAPDH aggregation in a concentration-dependent manner. Additionally, the GAI peptide did not affect GAPDH glycolytic activity or cell viability. The GAI peptide also exerted a protective effect against oxidative stress-induced cell death in SH-SY5Y cells. This peptide could potentially serve as a tool to investigate GAPDH aggregation-related neurodegenerative and neuropsychiatric disorders and as a possible therapy for diseases associated with oxidative stress-induced cell death. Copyright © 2015 Elsevier Inc. All rights reserved.

Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations*†‡

PubMed Central

Fields, Marcia D.; Abate, Marie A.; Hu, Lan; Long, D. Leann; Blommel, Matthew L.; Haikal, Nabila A.; Kraner, James C.

2016-01-01

Effects of benzodiazepines on postmortem opioid parent and parent/metabolite blood concentration ratios were determined for fentanyl-, hydrocodone-, methadone-, or oxycodone-related accidental deaths. These opioids are partially metabolized by the CYP3A4 enzyme system, which is also affected by diazepam and alprazolam. Opioid/metabolite combinations examined were as follows: fentanyl/norfentanyl, hydrocodone/dihydrocodeine, methadone/EDDP, and oxycodone/oxymorphone. Parent opioid concentrations were analyzed for 877 deaths. Parent/metabolite concentration ratios were analyzed for 349 deaths, excluding cases with co-intoxicants present known to interfere with opioid elimination. Alprazolam in combination with diazepam significantly decreased median hydrocodone concentrations by 48% (p = 0.01) compared to hydrocodone alone. The methadone parent/metabolite concentration ratio was reduced by 35% in the presence of diazepam compared to methadone alone (p = 0.03). Benzodiazepines did not statistically significantly affect fentanyl or oxycodone concentrations. Possible factors affecting opioid concentrations and possible toxicity development, including any differential effects on specific opioids, should continue to be explored. PMID:26223761

Neighborhood Effects on Heat Deaths: Social and Environmental Predictors of Vulnerability in Maricopa County, Arizona

PubMed Central

Declet-Barreto, Juan H.; Stefanov, William L.; Petitti, Diana B.

2012-01-01

Background: Most heat-related deaths occur in cities, and future trends in global climate change and urbanization may amplify this trend. Understanding how neighborhoods affect heat mortality fills an important gap between studies of individual susceptibility to heat and broadly comparative studies of temperature–mortality relationships in cities. Objectives: We estimated neighborhood effects of population characteristics and built and natural environments on deaths due to heat exposure in Maricopa County, Arizona (2000–2008). Methods: We used 2000 U.S. Census data and remotely sensed vegetation and land surface temperature to construct indicators of neighborhood vulnerability and a geographic information system to map vulnerability and residential addresses of persons who died from heat exposure in 2,081 census block groups. Binary logistic regression and spatial analysis were used to associate deaths with neighborhoods. Results: Neighborhood scores on three factors—socioeconomic vulnerability, elderly/isolation, and unvegetated area—varied widely throughout the study area. The preferred model (based on fit and parsimony) for predicting the odds of one or more deaths from heat exposure within a census block group included the first two factors and surface temperature in residential neighborhoods, holding population size constant. Spatial analysis identified clusters of neighborhoods with the highest heat vulnerability scores. A large proportion of deaths occurred among people, including homeless persons, who lived in the inner cores of the largest cities and along an industrial corridor. Conclusions: Place-based indicators of vulnerability complement analyses of person-level heat risk factors. Surface temperature might be used in Maricopa County to identify the most heat-vulnerable neighborhoods, but more attention to the socioecological complexities of climate adaptation is needed. PMID:23164621

Assessment of potential public health impact of a quadrivalent inactivated influenza vaccine in Thailand.

PubMed

Kittikraisak, Wanitchaya; Chittaganpitch, Malinee; Gregory, Christopher J; Laosiritaworn, Yongjua; Thantithaveewat, Thanawadee; Dawood, Fatimah S; Lindblade, Kim A

2016-05-01

Each year, an influenza B strain representing only one influenza B lineage is included in the trivalent inactivated influenza vaccine (IIV3); a mismatch between the selected lineage and circulating viruses can result in suboptimal vaccine effectiveness. We modeled the added potential public health impact of a quadrivalent inactivated influenza vaccine (IIV4) that includes strains from both influenza B lineages compared to IIV3 on influenza-associated morbidity and mortality in Thailand. Using data on the incidence of influenza-associated hospitalizations and deaths, vaccine effectiveness, and vaccine coverage from the 2007-2012 influenza seasons in Thailand, we estimated rates of influenza-associated outcomes that might be averted using IIV4 instead of IIV3. We then applied these rates to national population estimates to calculate averted illnesses, hospitalizations, and deaths for each season. We assumed that the influenza B lineage included in IIV3 would provide a relative vaccine effectiveness of 75% against the other B lineage. Compared to use of IIV3, use of IIV4 might have led to an additional reduction ranging from 0·4 to 14·3 influenza-associated illnesses per 100 000 population/year, <0·1 to 0·5 hospitalizations per 100 000/year, and <0·1 to 0·4 deaths per 1000/year. Based on extrapolation to national population estimates, replacement of IIV3 with IIV4 might have averted an additional 267-9784 influenza-associated illnesses, 9-320 hospitalizations, and 0-3 deaths. Compared to use of IIV3, IIV4 has the potential to further reduce the burden of influenza-associated morbidity and mortality in Thailand. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Mexico SimSmoke: how changes in tobacco control policies would impact smoking prevalence and smoking attributable deaths in Mexico.

PubMed

Fleischer, Nancy L; Thrasher, James F; Reynales-Shigematsu, Luz Myriam; Cummings, K Michael; Meza, Rafael; Zhang, Yian; Levy, David T

2017-07-01

We examined the effect of tobacco control policies in Mexico on smoking prevalence and smoking-related deaths using the Mexico SimSmoke model. The model is based on the previously developed SimSmoke simulation model of tobacco control policy, and uses population size, smoking rates and tobacco control policy data for Mexico. It assesses, individually, and in combination, the effect of six tobacco control policies on smoking prevalence and smoking-related deaths. Policies included: cigarette excise taxes, smoke-free laws, anti-smoking public education campaigns, marketing restrictions, access to tobacco cessation treatments and enforcement against tobacco sales youth. The model estimates that, if Mexico were to adopt strong tobacco control policies compared to current policy levels, smoking prevalence could be reduced by 30% in the next decade and by 50% by 2053; an additional 470,000 smoking-related premature deaths could be averted over the next 40 years. The greatest impact on smoking and smoking-related deaths would be achieved by raising excise taxes on cigarettes from 55% to at least 70% of the retail price, followed by strong youth access enforcement and access to cessation treatments. Implementing tobacco control policies in Mexico could reduce smoking prevalence by 50%, and prevent 470,000 smoking-related deaths by 2053.

[EARLY IN-HOSPITAL MORTALITY IN INTERNAL MEDICINE WARDS (WITHIN 24 HOURS): A POTENTIAL QUALITY INDICATOR OR A VARIABLE AFFECTED BY MULTIPLE FACTORS?

PubMed

Niv, Yaron; Berkov, Evgeny; Kanter, Pazit; Abrahmson, Evgeny; Gabbay, Uri

2017-04-01

To evaluate in-hospital mortality rate within 24 hours in internal medicine wards and to evaluate if it may be used as quality indicator. In-hospital mortality rate is an outcome measure which apparently reflects quality of care. There are debates on whether it may be considered a quality indicator since it is difficult to compare different case-mixes between hospitals. Research on mortality within 24 hours had not been published. An historical prospective study was conducted including the entire internal wards admissions to the Rabin Medical Center between 1/7/14 and 30/6/15. We evaluated inhospital deaths and 7 days post discharge deaths. We focused on deaths within 24 hours, patients' characteristics, the primary diagnosis (which we assumed is the cause of death) and co-morbidity. The analysis includes descriptive statistics and mortality rates performed with SPSS version 22. Overall, 25,414 patients were admitted to internal wards during the study period. There were 1,620 in-hospitals deaths (6.37%) among which 164 deaths occurred within 24 hours (0.65%), which is 10.1% of in-hospital deaths. These patients were very old (median 82), many were residents of nursing homes and nearly all were brought to the hospital by ambulance. The most frequent primary diagnoses were sepsis (24%), pneumonia (22%), metastatic cancer (10%) and acute neurologic event (5%). The results exclude excessive inhospital mortality within 24 hours. The patients' characteristics enable researchers to assume that these deaths were expected and not preventable. There is no excessive mortality within 24 hours, the deaths were expected and a seasonal modifying effect was evident. All this and the different case mix in between hospitals suggest that early in-hospital mortality seems inadequate as a quality measure.

Pushing up daisies: implicit and explicit language in oncologist-patient communication about death.

PubMed

Rodriguez, Keri L; Gambino, Frank J; Butow, Phyllis; Hagerty, Rebecca; Arnold, Robert M

2007-02-01

Although there are guidelines regarding how conversations with patients about prognosis in life-limiting illness should occur, there are little data about what doctors actually say. This study was designed to qualitatively analyze the language that oncologists and cancer patients use when talking about death. We recruited 29 adults who had incurable forms of cancer, were scheduled for a first-time visit with one of six oncologists affiliated with a teaching hospital in Australia, and consented to having their visit audiotaped and transcribed. Using content analytic techniques, we coded various features of language usage. Of the 29 visits, 23 (79.3%) included prognostic utterances about treatment-related and disease-related outcomes. In 12 (52.2%) of these 23 visits, explicit language about death ("terminal," variations of "death") was used. It was most commonly used by the oncologist after the physical examination, but it was sometimes used by patients or their kin, usually before the examination and involving emotional questioning about the patient's future. In all 23 (100%) visits, implicit language (euphemistic or indirect talk) was used in discussing death and focused on an anticipated life span (mentioned in 87.0% of visits), estimated time frame (69.6%), or projected survival (47.8%). Instead of using the word "death," most participants used some alternative phrase, including implicit language. Although oncologists are more likely than patients and their kin to use explicit language in discussing death, the oncologists tend to couple it with implicit language, possibly to mitigate the message effects.

The Relationship Between Poor Quality of Life and Desire to Hasten Death: A Multiple Mediation Model Examining the Contributions of Depression, Demoralization, Loss of Control, and Low Self-worth.

PubMed

Robinson, Sophie; Kissane, David W; Brooker, Joanne; Hempton, Courtney; Burney, Susan

2017-02-01

The risk of suicide is elevated in palliative care patients compared with the general population. Various psychological factors, including depression, demoralization, loss of control, and low self-worth, have been associated with a desire to hasten death. The aim of this study was to investigate whether depression, demoralization, loss of control, and low self-worth mediated the relationship between global quality of life and desire to hasten death. A sample of 162 palliative care patients completed measures of global quality of life, depression, demoralization, perceived control, self-worth, and desire to hasten death. A multiple mediation model with bootstrapping sampling tested the total (combined) indirect effect and individual indirect effects of depression, the two subscales of demoralization (Meaning and Purpose, and Distress and Coping Ability), perceived control, and self-worth. Depressive symptoms, loss of meaning and purpose, loss of control, and low self-worth mediated the direct effect of global quality of life on desire to hasten death. The Distress and Coping Ability component of demoralization was not a significant mediator. Depression, loss of meaning and purpose, loss of control, and low self-worth are strong clinical markers for desire to hasten death. Targeting these symptoms through existentially oriented therapies, such as meaning-centered therapy, may ameliorate suicidal thinking. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Suggested guidelines for the management of high-profile fatality cases.

PubMed

Perper, Joshua A; Juste, Gertrude M; Schueler, Harold E; Motte, Reinhard W; Cina, Stephen J

2008-10-01

The investigation of high-profile fatalities poses special challenges to medical examiners and coroners. Most high-profile cases can be readily recognized early in the course of the investigation. Commonly encountered examples include police-related fatalities or deaths in custody, deaths of celebrities, and mass fatalities or clustered deaths (eg, serial killers). Medical examiner and coroner offices should have policies and procedures in place for adequately handling such cases. A rational approach to these high-profile cases includes activating medical examiner or coroner investigative teams, preplanning before the autopsy, using special autopsy techniques and toxicology procedures, skillful questioning of key witnesses, preparing detailed and comprehensive reports, and planning effective communication with the media. The investigation of the sudden and unexpected death of Anna Nicole Smith, an entertainment personality, is presented as an example of how to address the challenging issues inherent in high-profile fatalities and how to adequately prepare for the forensic investigation of high-profile cases. This article presents a methodical approach to the investigation of high-profile deaths. A comprehensive, preplanned forensic investigation and autopsy (including use of adjunctive studies) following the death of Anna Nicole Smith resulted in the accurate determination of the cause and manner of her death while adequately convincing the public of the objectivity and reliability of the Medical Examiners Office with respect to its conclusions. The forensic investigation of death in high-profile cases can be much more tedious and demanding than the investigation of routine cases. It requires more stringent safekeeping of the body and its evidence, more extensive and sophisticated dissection techniques on occasion, and exhaustive toxicologic analysis to exclude low-probability allegations. Procedures for honest, unbiased, and judicious communication with outside agencies and the media must be followed. Failure to follow such procedures might have serious consequences for the medical examiner, the family of the deceased, and the community at large. Adherence to these suggested guidelines may resolve most of the intricate problems involved in the investigation of these types of cases.

The divided self: near death experiences of resuscitated patients--a review of literature.

PubMed

Cant, Robyn; Cooper, Simon; Chung, Catherine; O'Connor, Margaret

2012-04-01

This paper explores the prevalence of 'near death experience' phenomena associated with a resuscitation event and examines the current state of evidence for causation. Patients' reports of unusual recollections associated with a period of unconsciousness (perceived as approaching death) have fascinated individuals and the medical fraternity. Near death experiences (NDE) are reported in 4-9% of general community members and up to 23% of critical illness patients, although they can occur in healthy individuals who may think they are in peril. One explanation is that paranormal visions that include seeing bright lights, a tunnel and having feelings of peace may be a stage of enlightenment as death approaches. More objective explanations point to neuro-chemical changes in a stressed or dying brain as explanation for nearly all the elements of near death experience. However if this is so, NDE should occur in all patients who are critically ill and near death. In general, patients report positive psychological outcomes after a near death experience. Nurses can support patients during a time of crisis by assisting them and their families to comprehend the experiential event using effective communication and listening skill. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cost-effectiveness of using a social franchise network to increase uptake of oral rehydration salts and zinc for childhood diarrhea in rural Myanmar.

PubMed

Bishai, David; Sachathep, Karampreet; LeFevre, Amnesty; Thant, Hnin New Nwe; Zaw, Min; Aung, Tin; McFarland, Willi; Montagu, Dominic

2015-01-01

This paper examines the cost-effectiveness of achieving increases in the use of oral rehydration solution and zinc supplementation in the management of acute diarrhea in children under 5 years through social franchising. The study uses cost and outcome data from an initiative by Population Services International (PSI) in 3 townships of Myanmar in 2010 to promote an ORS-Zinc product called ORASEL. The objective of this study was to determine the incremental cost-effectiveness of a strategy to promote ORS-Z use through private sector franchising compared to standard government and private sector practices. Costing from a societal perspective included program, provider, and household costs for the 2010 calendar year. Program costs including ORASEL program launch, distribution, and administration costs were obtained through a retrospective review of financial records and key informant interviews with staff in the central Yangon office. Household out of pocket payments for diarrheal episodes were obtained from a household survey conducted in the study area and additional estimates of household income lost due to parental care-giving time for a sick child were estimated. Incremental cost-effectiveness relative to status quo conditions was calculated per child death and DALY averted in 2010. Health effects included deaths and DALYs averted; the former modeled based on coverage estimates from a household survey that were entered into the Lives Saved Tool (LiST). Uncertainty was modeled with Monte Carlo methods. Based on the model, the promotional strategy would translate to 2.85 (SD 0.29) deaths averted in a community population of 1 million where there would be 81,000 children under 5 expecting 48,373 cases of diarrhea. The incremental cost effectiveness of the franchised approach to improving ORASEL coverage is estimated at a median $5,955 (IQR: $3437-$7589) per death averted and $214 (IQR: $127-$287) per discounted DALY averted. Investing in developing a network of private sector providers and keeping them stocked with ORS-Z as is done in a social franchise can be a highly cost-effective in terms of dollars per DALY averted.

Research design in end-of-life research: state of science.

PubMed

George, Linda K

2002-10-01

The volume of research on end-of-life care, death, and dying has exploded during the past decade. This article reviews the conceptual and methodological adequacy of end-of-life research to date, focusing on limitations of research to date and ways of improving future research. A systematic search was conducted to identify the base of end-of-life research. Approximately 400 empirical articles were identified and are the basis of this review. Although much has been learned from research to date, limitations in the knowledge base are substantial. The most fundamental problems identified are conceptual and include failure to define dying; neglect of the distinctions among quality of life, quality of death, and quality of end-of-life care. Methodologically, the single greatest problem is the lack of longitudinal studies that cover more than the time period immediately before death. Gaps in the research base include insufficient attention to psychological and spiritual issues, the prevalence of psychiatric disorder and the effectiveness of the treatment of such disorders among dying persons, provider and health system variables, social and cultural diversity, and the effects of comorbidity on trajectories of dying.

Meta‐analysis of the procedural risks of carotid endarterectomy and carotid artery stenting over time

PubMed Central

Lokuge, K.; de Waard, D. D.; Halliday, A.; Gray, A.; Bulbulia, R.

2017-01-01

Background Stroke/death rates within 30 days of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in RCTs inform current clinical guidelines. However, the risks may have changed in recent years with wider use of effective stroke prevention therapies, especially statins, improved patient selection and growing operator expertise. The aim of this study was to investigate whether the procedural stroke/death risks from CEA and CAS have changed over time. Methods MEDLINE and Embase were searched systematically from inception to May 2016 for observational cohort studies of CEA and CAS. Studies included reported on more than 1000 patients, with 30‐day outcomes after the procedure according to patients' symptom status (recent stroke or transient ischaemic attack). Restricted maximum likelihood random‐effects and meta‐regressions methods were used to synthesize procedural stroke/death rates of CEA and CAS according to year of study recruitment completion. Results Fifty‐one studies, including 223 313 patients undergoing CEA and 72 961 undergoing CAS, were reviewed. Procedural stroke/death risks of CEA decreased over time in symptomatic and asymptomatic patients. Risks were substantially lower in studies completing recruitment in 2005 or later, both in symptomatic (5·11 per cent before 2005 versus 2·68 per cent from 2005 onwards; P = 0·002) and asymptomatic (3·17 versus 1·50 per cent; P < 0·001) patients. Procedural stroke/death rates of CAS did not change significantly over time (4·77 per cent among symptomatic and 2·59 per cent among asymptomatic patients). There was substantial heterogeneity in event rates and recruitment periods were long. Conclusions Risks of procedural stroke/death following CEA appear to have decreased substantially. There was no evidence of a change in stroke/death rates following CAS. PMID:29205297

Long-Term Survival and Death Causes of Systemic Lupus Erythematosus in China

PubMed Central

Wang, Ziqian; Wang, Yanhong; Zhu, Rongrong; Tian, Xinping; Xu, Dong; Wang, Qian; Wu, Chanyuan; Zhang, Shangzhu; Zhao, Jiuliang; Zhao, Yan; Li, Mengtao; Zeng, Xiaofeng

2015-01-01

Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with an increased risk of death compared to general population. Although previous studies showed improvement in survival of SLE, the long-term prognosis has not been elaborated in China. This study aims to integrate the observational studies estimating current long-term survival of Chinese SLE patients and analyze the death-cause situation of SLE in China. The study is a systemic review of English and non-English articles using MEDLINE, EMBASE, CNKI, WANFANG, and SINOMED databases. Additional studies were found by consultation with clinical experts, browse of references in selected papers, and search of related textbooks. Our major search terms were SLE, follow-up, prognosis, survival, mortality, and China. We included cohort studies for survival analysis, and both cohort studies and case series for death-cause analysis in China. The extraction of the articles were done by 2 authors independently using predesigned charts, including characteristics of study, clinical data, analyzing data, and study quality indicators. All pooled analyses were conducted both for random-effects model and fixed-effects model. Funnel plots and Egger regression tests were applied to check potential publication bias. Heterogeneity was tested by sensitivity analysis. We identified 5 studies for survival analysis comprising 4469 Chinese patients with SLE (380 observed deaths). Thirty-six studies were suitable for death-cause analysis with 2179 observed deaths (derived from more than 20,000 Chinese patients with SLE). The overall pooled survival rates for SLE in China were 94% for 5-year survival rate and 89% for 10-year survival rate after disease onset from the year 1995 to 2013, which were similar with previous publications in Asia-Pacific area. The proportions of different causes of death showed infection (33.2%), renal involvement (18.7%), lupus encephalopathy (13.8%), and cardiovascular disease (11.5%) as the top 4 causes. The overall survival rates for Chinese patients with SLE resembled previous publications in Asia-Pacific area. But the death causes of SLE in China were of some differences indicating relatively higher proportion of infection and lupus encephalopathy and lower cardiovascular disease. Ethnicity and more aggressive treatment might have contributed to the difference in death composition. PMID:25929930

Does marital status predict the odds of suicidal death in taiwan? A seven-year population-based study.

PubMed

Yeh, Jui-Yuan; Xirasagar, Sudha; Liu, Tsai-Ching; Li, Chong-Yi; Lin, Herng-Ching

2008-06-01

Using nationwide, 7-year population-based data for 1997-2003, we examined marital status to see if it predicted suicide among the ethnic Chinese population of Taiwan. Using cause of death data, with a case-control design, two groups-total adult suicide deaths, n = 17,850, the study group, and adult deaths other than suicide, n = 71,400 (randomly selected from age, sex, and geographic region matched controls, four per suicide)-were studied. Using multiple logistic regression analysis including age-marital status interaction, adjusted estimates show divorced status to be the most detrimental for suicide propensity, with males showing stronger effect size. Females never married, aged below 35 and 65-plus, and widowed 65-plus had lower suicide odds.

Synergistic cellular effects including mitochondrial destabilization, autophagy and apoptosis following low-level exposure to a mixture of lipophilic persistent organic pollutants.

PubMed

Rainey, Nathan E; Saric, Ana; Leberre, Alexandre; Dewailly, Etienne; Slomianny, Christian; Vial, Guillaume; Zeliger, Harold I; Petit, Patrice X

2017-07-05

Humans are exposed to multiple exogenous environmental pollutants. Many of these compounds are parts of mixtures that can exacerbate harmful effects of the individual mixture components. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is primarily produced via industrial processes including incineration and the manufacture of herbicides. Both endosulfan and TCDD are persistent organic pollutants which elicit cytotoxic effects by inducing reactive oxygen species generation. Sublethal concentrations of mixtures of TCDD and endosulfan increase oxidative stress, as well as mitochondrial homeostasis disruption, which is preceded by a calcium rise and, in fine, induce cell death. TCDD+Endosulfan elicit a complex signaling sequence involving reticulum endoplasmic destalilization which leads to Ca 2+ rise, superoxide anion production, ATP drop and late NADP(H) depletion associated with a mitochondrial induced apoptosis concomitant early autophagic processes. The ROS scavenger, N-acetyl-cysteine, blocks both the mixture-induced autophagy and death. Calcium chelators act similarly and mitochondrially targeted anti-oxidants also abrogate these effects. Inhibition of the autophagic fluxes with 3-methyladenine, increases mixture-induced cell death. These findings show that subchronic doses of pollutants may act synergistically. They also reveal that the onset of autophagy might serve as a protective mechanism against ROS-triggered cytotoxic effects of a cocktail of pollutants in Caco-2 cells and increase their tumorigenicity.

Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data.

PubMed

Gyöngyösi, Mariann; Wojakowski, Wojciech; Lemarchand, Patricia; Lunde, Ketil; Tendera, Michal; Bartunek, Jozef; Marban, Eduardo; Assmus, Birgit; Henry, Timothy D; Traverse, Jay H; Moyé, Lemuel A; Sürder, Daniel; Corti, Roberto; Huikuri, Heikki; Miettinen, Johanna; Wöhrle, Jochen; Obradovic, Slobodan; Roncalli, Jérome; Malliaras, Konstantinos; Pokushalov, Evgeny; Romanov, Alexander; Kastrup, Jens; Bergmann, Martin W; Atsma, Douwe E; Diederichsen, Axel; Edes, Istvan; Benedek, Imre; Benedek, Theodora; Pejkov, Hristo; Nyolczas, Noemi; Pavo, Noemi; Bergler-Klein, Jutta; Pavo, Imre J; Sylven, Christer; Berti, Sergio; Navarese, Eliano P; Maurer, Gerald

2015-04-10

The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy. We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization). The secondary end point was freedom from hard clinical end points (death, AMI recurrence, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy end points included changes in end-diastolic volume, end-systolic volume, and ejection fraction, analyzed with random-effects meta-analyses and ANCOVA. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on major adverse cardiac and cerebrovascular events (14.0% versus 16.3%; hazard ratio, 0.86; 95% confidence interval, 0.63-1.18) or death (1.4% versus 2.1%) or death/AMI recurrence/stroke (2.9% versus 4.7%) was identified in comparison with controls. No changes in ejection fraction (mean difference: 0.96%; 95% confidence interval, -0.2 to 2.1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters. This meta-analysis of individual patient data from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098591. © 2015 American Heart Association, Inc.

Revisiting the Decision of Death in Hurst v. Florida.

PubMed

Cooke, Brian K; Ginory, Almari; Zedalis, Jennifer

2016-12-01

The United States Supreme Court has considered the question of whether a judge or a jury must make the findings necessary to support imposition of the death penalty in several notable cases, including Spaziano v. Florida (1984), Hildwin v. Florida (1989), and Ring v. Arizona (2002). In 2016, the U.S. Supreme Court revisited the subject in Hurst v. Florida Florida Statute § 921.141 allows the judge, after weighing aggravating and mitigating circumstances, to enter a sentence of life imprisonment or death. Before Hurst, Florida's bifurcated sentencing proceedings included an advisory sentence from jurors and a separate judicial hearing without juror involvement. In Hurst, the Court revisited the question of whether Florida's capital sentencing scheme violates the Sixth Amendment, which requires a jury, not a judge, to find each fact necessary to impose a sentence of death in light of Ring In an eight-to-one decision, the Court reversed the judgment of the Florida Supreme Court, holding that the Sixth Amendment requires a jury to find the aggravating factors necessary for imposing the death penalty. The role of Florida juries in capital sentencing proceedings was thereby elevated from advisory to determinative. We examine the Court's decision and offer commentary regarding this shift from judge to jury in the final imposition of the death penalty and the overall effect of this landmark case. © 2016 American Academy of Psychiatry and the Law.

Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death

PubMed Central

Kenyon, Emma J.; Kirkwood, Nerissa K.; Kitcher, Siân R.; O’Reilly, Molly; Cantillon, Daire M.; Goodyear, Richard J.; Secker, Abigail; Baxendale, Sarah; Bull, James C.; Waddell, Simon J.; Whitfield, Tanya T.; Ward, Simon E.; Kros, Corné J.; Richardson, Guy P.

2017-01-01

Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro. Using zebrafish, 72 compounds were identified that either reduced loading of the MET-channel blocker FM 1-43FX, decreased Texas red–conjugated neomycin labeling, or reduced neomycin-induced hair cell death. After testing these 72 compounds, and 6 structurally similar compounds that failed in zebrafish, 13 were found that protected against gentamicin-induced death of OHCs in mouse cochlear cultures, 6 of which are permeant blockers of the hair cell MET channel. None of these compounds abrogated aminoglycoside antibacterial efficacy. By selecting those without adverse effects at high concentrations, 5 emerged as leads for developing pharmaceutical otoprotectants to alleviate an increasing clinical problem. PMID:29263311

Necroptosis: a potential, promising target and switch in acute pancreatitis.

PubMed

Wang, Gang; Qu, Feng-Zhi; Li, Le; Lv, Jia-Chen; Sun, Bei

2016-02-01

Pancreatic acinar cell death is the major pathophysiological change in early acute pancreatitis (AP), and the death modalities are important factors determining its progression and prognosis. During AP, acinar cells undergo two major modes of death, including necrosis and apoptosis. Acinar necrosis can lead to intensely local and systemic inflammatory responses, which both induce and aggravate the lesion. Necrosis has long been considered an unregulated, and passive cell death process. Since the effective interventions of necrosis are difficult to perform, its relevant studies have not received adequate attention. Necroptosis is a newly discovered cell death modality characterized by both necrosis and apoptosis, i.e., it is actively regulated by special genes, while has the typical morphological features of necrosis. Currently, necroptosis is gradually becoming an important topic in the fields of inflammatory diseases. The preliminary results from necroptosis in AP have confirmed the existence of acinar cell necroptosis, which may be a potential target for effectively regulating inflammatory injuries and improving its outcomes; however, the functional changes and mechanisms of necroptosis still require further investigation. This article reviewed the progress of necroptosis in AP to provide a reference for deeply understanding the pathogenic mechanisms of AP and identifying new therapeutic targets.

Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death.

PubMed

Kenyon, Emma J; Kirkwood, Nerissa K; Kitcher, Siân R; O'Reilly, Molly; Derudas, Marco; Cantillon, Daire M; Goodyear, Richard J; Secker, Abigail; Baxendale, Sarah; Bull, James C; Waddell, Simon J; Whitfield, Tanya T; Ward, Simon E; Kros, Corné J; Richardson, Guy P

2017-12-21

Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro. Using zebrafish, 72 compounds were identified that either reduced loading of the MET-channel blocker FM 1-43FX, decreased Texas red-conjugated neomycin labeling, or reduced neomycin-induced hair cell death. After testing these 72 compounds, and 6 structurally similar compounds that failed in zebrafish, 13 were found that protected against gentamicin-induced death of OHCs in mouse cochlear cultures, 6 of which are permeant blockers of the hair cell MET channel. None of these compounds abrogated aminoglycoside antibacterial efficacy. By selecting those without adverse effects at high concentrations, 5 emerged as leads for developing pharmaceutical otoprotectants to alleviate an increasing clinical problem.

Exploring the Association of Hospice Care on Patient Experience and Outcomes of Care

PubMed Central

Kleinpell, Ruth; Vasilevskis, Eduard E.; Fogg, Louis; Ely, E. Wesley

2016-01-01

Objective To examine the association of the use of hospice care on patient experience and outcomes of care. Promoting high-value, safe, and effective care is an international healthcare imperative. However, the extent to which hospice care may improve the value of care is not well characterized. Methods A secondary analysis of variations in care was conducted using the Dartmouth Atlas Report, matched to the American Hospital Association Annual Survey Database to abstract organizational characteristics for 236 US hospitals to examine the relationship between hospice utilization and a number of variables that represent care value including hospital care intensity index, hospital deaths, ICU deaths, patient satisfaction, and a number of patient quality indicators. Structural equation modeling was used to demonstrate the effect of hospice use on patient experience of care variables, clinical outcomes of care variables, and efficiency of care variables. Results Hospice admissions in the last 6 months of life were correlated with a number of variables including increases in patient satisfaction ratings (r=0.448, p=0.01) and better pain control (r=0.491, p=0.01), and reductions in hospital days (r=−0.517, p=0.01), fewer deaths in the hospital (r=−0.842, p=0.01), and fewer deaths occurring with an ICU admission during hospitalization (r=−0.358, p=0.01). The structural equation model identified use of hospice care was inversely related to both hospital mortality (−.885) and ICU mortality rate (−.457). Conclusions The results of this investigation demonstrate that greater utilization of hospice care during the last 6-months of life is associated with improved patient experience of care including satisfaction and pain control, as well as clinical outcomes of care including decreased ICU and hospital mortality. PMID:27531840

Agent Orange exposure and risk of death in Korean Vietnam veterans: Korean Veterans Health Study.

PubMed

Yi, Sang-Wook; Ryu, So-Yeon; Ohrr, Heechoul; Hong, Jae-Seok

2014-12-01

Agent Orange (AO) was a mixture of phenoxy herbicides, containing several dioxin impurities including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Various military herbicides, including AO, were sprayed by the US military and allied forces for military purposes during the Vietnam War. This study was performed to identify the associations between the AO exposure and mortality in Korean Vietnam veterans. From 1 January 1992 to 31 December 2005, 180 639 Korean Vietnam veterans were followed up for vital status and cause of death. The AO exposure index was based on the proximity of the veteran's unit to AO-sprayed areas, using a geographical information system-based model. The adjusted hazard ratios and 95% confidence intervals were calculated by Cox's proportional hazard model. The mortality from all causes of death was elevated with AO exposure. The deaths due to all sites of cancers combined and some specific cancers, including cancers of the stomach, small intestine, liver, larynx, lung, bladder and thyroid gland, as well as chronic myeloid leukaemia, were positively associated with AO exposure. The deaths from angina pectoris, chronic obstructive pulmonary disease and liver disease including liver cirrhosis were also increased with an increasing AO exposure. Overall, this study suggests that AO/TCDD exposure may account for mortality from various diseases even several decades after exposure. Further research is needed to better understand the long-term effects of AO/TCDD exposure on human health. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Rates of and factors associated with delivery-related perinatal death among term infants in Scotland.

PubMed

Pasupathy, Dharmintra; Wood, Angela M; Pell, Jill P; Fleming, Michael; Smith, Gordon C S

2009-08-12

Rates of obstetric intervention in labor, including cesarean delivery, have increased significantly in most developed countries. It is, however, unclear if this has been paralleled by decreased rates of perinatal and neonatal death associated with complications of labor at term. To determine whether rates of perinatal death at term, either during labor or in the neonatal period, have changed in Scotland during the last 20 years and whether this was associated with a reduction in deaths ascribed to intrapartum anoxia. A population-based, retrospective cohort study of linked data from a registry of births (Scottish Morbidity Record 02) and a registry of perinatal deaths (Scottish Stillbirth and Infant Death Survey) between 1988 and 2007. Participants included all births of a singleton infant in a cephalic presentation at term (N = 1,012,266), excluding those with perinatal death due to congenital anomaly or antepartum stillbirth. Delivery-related perinatal death, defined as intrapartum stillbirth or neonatal death unrelated to congenital abnormality. These events were also subdivided into those events ascribed to intrapartum anoxia and all other causes. The risk of death was modeled using logistic regression and analyses were adjusted for maternal age, height, parity, socioeconomic deprivation status, gestational age, birth weight percentile, fetal sex, onset of labor, and the annual number of births per hospital. During the study period, the risk of delivery-related perinatal death decreased from 8.8 to 5.5 per 10,000 births (unadjusted change, -38%; 95% confidence interval [CI], -51% to -21%). When analyzed by the cause of death, there was a significant decrease in the risk of death ascribed to intrapartum anoxia (5.7 to 3.0 per 10,000 births; unadjusted change, -48%; 95% CI, -62% to -29%), but no significant change in the risk of death ascribed to other causes. When deaths ascribed to intrapartum anoxia were analyzed by the time of death in relation to delivery, the reduction was similar comparing intrapartum stillbirths (2.6 to 1.1 per 10,000 births; unadjusted change, -60%; 95% CI, -75% to -34%) and neonatal deaths (3.1 to 1.9 per 10,000 births; unadjusted change, -38%; 95% CI, -59% to -7%). Adjustment for maternal, fetal, and obstetric factors was without material effect. Rates of intrapartum stillbirth and neonatal death at term decreased in Scotland between 1988 and 2007. This decrease was only significant for deaths ascribed to intrapartum anoxia.

Lives saved from malaria prevention in Africa--evidence to sustain cost-effective gains.

PubMed

Korenromp, Eline L

2012-03-28

Lives saved have become a standard metric to express health benefits across interventions and diseases. Recent estimates of malaria-attributable under-five deaths prevented using the Lives Saved tool (LiST), extrapolating effectiveness estimates from community-randomized trials of scale-up of insecticide-treated nets (ITNs) in the 1990s, confirm the substantial impact and good cost-effectiveness that ITNs have achieved in high-endemic sub-Saharan Africa. An even higher cost-effectiveness would likely have been found if the modelling had included the additional indirect mortality impact of ITNs on preventing deaths from other common child illnesses, to which malaria contributes as a risk factor. As conventional ITNs are being replaced by long-lasting insecticidal nets and scale-up is expanded to target universal coverage for full, all-age populations at risk, enhanced transmission reduction may--above certain thresholds--enhance the mortality impact beyond that observed in the trials of the 1990s. On the other hand, lives saved by ITNs might fall if improved malaria case management with artemisinin-based combination therapy averts the deaths that ITNs would otherwise prevent.Validation and updating of LiST's simple assumption of a universal, fixed coverage-to-mortality-reduction ratio will require enhanced national programme and impact monitoring and evaluation. Key indicators for time trend analysis include malaria-related mortality from population-based surveys and vital registration, vector control and treatment coverage from surveys, and parasitologically-confirmed malaria cases and deaths recorded in health facilities. Indispensable is triangulation with dynamic transmission models, fitted to long-term trend data on vector, parasite and human populations over successive phases of malaria control and elimination.Sound, locally optimized budget allocation including on monitoring and evaluation priorities will benefit much if policy makers and programme planners use planning tools such as LiST - even when predictions are less certain than often understood. The ultimate success of LiST for supporting malaria prevention may be to prove its linear predictions less and less relevant.

Drug-related celebrity deaths: A cross-sectional study.

PubMed

Just, Johannes M; Bleckwenn, Markus; Schnakenberg, Rieke; Skatulla, Philipp; Weckbecker, Klaus

2016-12-09

Celebrities are at risk for premature mortality as well as drug-related death. Despite being a vulnerable patient group, celebrities influence people's health behaviours through biological, psychological and social processes. Therefore, celebrity endorsement of the topic could be one way to challenge the current "opioid endemic". Our aim was to better understand the factors surrounding drug-related celebrity deaths by investigating the incidence as well as substances used between 1970 and 2015 using a cross-sectional study design. We searched public databases for drug-related celebrity deaths between 1970 and 2015. They were categorized for sex, profession, age at death, year of death and substances involved. The main outcome measures are descriptive values including number of drug deaths per year and substances involved. Secondary outcome measures are analytical questions to examine whether and which factors influence age at death and year of death (e.g. type of substance use disorder). We identified 220 celebrities who died a drug-related death with a clear indication of involved substances between 1970 and 2015. The average age at death was 38.6 years; 75% were male. Most celebrities died between the age of 25 and 40. The number of drug-related deaths increased in the 21st century, with a significant increase in the use of prescription opioids. Deaths involving prescription opioids and heroin were associated with a significantly lower mean age at death compared to deaths where these substances were not involved. Compared to the 20th century, the total number of celebrities who died from a drug-related death in the 21st century increased, possibly due to an increased involvement of prescription opioids. Negative effects on individual health decisions of celebrity's followers could be the result.

CHILDHOOD PARENTAL LOSS AND ADULT PSYCHOPATHOLOGY: EFFECTS OF LOSS CHARACTERISTICS AND CONTEXTUAL FACTORS*

PubMed Central

TYRKA, AUDREY R.; WIER, LAUREN; PRICE, LAWRENCE H.; ROSS, NICOLE S.; CARPENTER, LINDA L.

2013-01-01

The purpose of this study was to determine whether childhood parental death and childhood parental separation are linked to lifetime depressive and anxiety disorders after controlling for related risk factors. Participants were 105 individuals from the community, including a group with separation/desertion from a parent, a group with childhood parental death, and a matched control group whose parents remained married and living together. Participants completed interviews and questionnaires assessing symptoms of anxiety and depression, family psychiatric history, childhood maltreatment, and childhood parental relationships. Participants with separation/desertion and those with parental death were significantly more likely than the control subjects to report the subsequent onset of symptoms of a depressive or anxiety disorder. These effects were not fully explained by parental relationships or childhood maltreatment. However, in the group with parental separation only, family history of depressive and anxiety disorders accounted for the apparent effect of parental separation. These findings indicate that parental death may be a specific risk factor for depressive and anxiety disorders. For parental separation/desertion, our results highlight the overriding influence of risk factors that commonly co-occur with this form of parental loss. PMID:19069576

Mixed Impact of Firearms Restrictions on Fatal Firearm Injuries in Males: A National Observational Study

PubMed Central

Gjertsen, Finn; Leenaars, Antoon; Vollrath, Margarete E.

2013-01-01

Introduction: Public health organizations have recommended restricted access and safe storage practices as means to reduce firearm injuries and deaths. We aimed to assess the effect of four firearm restrictions on firearm deaths in Norway 1969–2009. Methods: All deaths due to firearm discharge were included (5,660 deaths, both sexes). The statistical analysis to assess impact of firearm legislations was restricted to males because of the sex disproportionality (94% were males). Results: A total of 89% of firearm deaths (both sexes) were classified as suicide, 8% as homicide, and 3% as unintentional (accident). During the past four decades, male accidental firearm death rates were reduced significantly by 90%. Male firearms suicide rates increased from 1969 to 1991 by 166%, and decreased by 62% from 1991 to 2009. Despite the great reduction in male accidental firearm deaths, we were unable to demonstrate effects of the laws. In contrast, we found that a 1990 regulation, requiring a police permit before acquiring a shotgun, had a beneficial impact on suicide in the total sample and in those aged 15–34 years. Male firearm homicides decreased post-2003 regulation regarding storing home guard weapons in private homes. Conclusions: Our findings suggest that two laws could have contributed to reduce male firearm mortality. It is, however, a challenge to measure the role of four firearm restrictions. The null findings are inconclusive, as they may reflect no true impact or study limitations. PMID:24380979

Combining lymphovascular invasion with reactive stromal grade predicts prostate cancer mortality.

PubMed

Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

2016-09-01

Previous studies suggest that lymphovascular invasion (LVI) has a weak and variable effect on prognosis. It is uncertain whether LVI, determined by diagnostic prostate biopsy, predicts prostate cancer death. Data from experimental studies have indicated that carcinoma-associated fibroblasts in the reactive stroma could promote LVI and progression to metastasis. Thus, combining LVI with reactive stromal grade may identify prostate cancer patients at high risk of an unfavorable outcome. The purpose of the present study was to examine if LVI, determined by diagnostic biopsy, alone and in combination with reactive stromal grade could predict prostate cancer death. This population-based study included 283 patients with prostate cancer diagnosed by needle biopsy in Aust-Agder County (Norway) from 1991 to 1999. Clinical data were obtained by medical charts review. Two uropathologists evaluated LVI and reactive stromal grade. The endpoint was prostate cancer death. Patients with LVI had marginally higher risk of prostate cancer death compared to patients without LVI (hazard ratio: 1.8, P-value = 0.04). LVI had a stronger effect on prostate cancer death risk when a high reactive stromal grade was present (hazard ratio: 16.0, P-value <0.001). Therefore, patients with concomitant LVI and high reactive stromal grade were at particularly high risk for prostate cancer death. Evaluating LVI together with reactive stromal grade on diagnostic biopsies could be used to identify patients at high risk of death from prostate cancer. Prostate 76:1088-1094, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Poisoning deaths involving opioid analgesics - New York State, 2003-2012.

PubMed

Sharp, Mark J; Melnik, Thomas A

2015-04-17

Deaths involving opioid analgesics have increased dramatically in the United States. Approximately 4,000 such deaths were documented in 1999, increasing to 16,235 in 2013, reflecting a nearly quadrupled death rate from 1.4 to 5.1 deaths per 100,000. To investigate this increase in New York state, trends in poisoning deaths involving opioid analgesics from 2003 to 2012 were examined. Data sources used were New York state vital statistics multiple-cause-of-death data, consisting of data from both the New York City (NYC)* and non-NYC reporting jurisdictions, as well as statewide Medicaid enrollment data. Deaths involving opioid analgesics increased both in number and as a percentage of all drug poisoning deaths, and rates were highest among men, whites, persons aged 45-64 years, persons residing outside of NYC, and Medicaid enrollees. The analysis found that, in 2012, 70.7% of deaths involving opioid analgesics also involved at least one other drug, most frequently a benzodiazepine. These results underscore the potential to mitigate the trend of increasing opioid analgesic-related mortality through initiatives such as New York state's Internet System for Tracking Over-Prescribing (I-STOP) law,† which took effect on August 27, 2013. Provisions under I-STOP include the requirements that providers consult the Prescription Monitoring Program (PMP) Registry when writing prescriptions for controlled substances, and that they use electronic prescribing.

Two programmed cell death systems in Escherichia coli: an apoptotic-like death is inhibited by the mazEF-mediated death pathway.

PubMed

Erental, Ariel; Sharon, Idith; Engelberg-Kulka, Hanna

2012-01-01

In eukaryotes, the classical form of programmed cell death (PCD) is apoptosis, which has as its specific characteristics DNA fragmentation and membrane depolarization. In Escherichia coli a different PCD system has been reported. It is mediated by the toxin-antitoxin system module mazEF. The E. coli mazEF module is one of the most thoroughly studied toxin-antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF. mazEF-mediated cell death is a population phenomenon requiring the quorum-sensing pentapeptide NNWNN designated Extracellular Death Factor (EDF). mazEF is triggered by several stressful conditions, including severe damage to the DNA. Here, using confocal microscopy and FACS analysis, we show that under conditions of severe DNA damage, the triggered mazEF-mediated cell death pathway leads to the inhibition of a second cell death pathway. The latter is an apoptotic-like death (ALD); ALD is mediated by recA and lexA. The mazEF-mediated pathway reduces recA mRNA levels. Based on these results, we offer a molecular model for the maintenance of an altruistic characteristic in cell populations. In our model, the ALD pathway is inhibited by the altruistic EDF-mazEF-mediated death pathway.

Dietary and supplemental calcium intakes in relation to mortality from cardiovascular diseases in the NIH-AARP Diet and Health Study

PubMed Central

Xiao, Qian; Murphy, Rachel A; Houston, Denise K.; Harris, Tamara B.; Chow, Wong-Ho; Park, Yikyung

2013-01-01

Background Calcium intake has been promoted due to its proposed benefit on bone health, particularly among the older population. However, concerns have been raised about the potential adverse effect of high calcium intake on cardiovascular health. Methods Dietary and supplemental calcium intakes were assessed at baseline (1995–96) in 388,229 men and women aged 50–71 years in the National Institutes of Health (NIH)–AARP Diet and Health Study. Supplemental calcium intake included calcium from multivitamins and individual calcium supplements. Cardiovascular disease (CVD) deaths were ascertained using the National Death Index. Multivariate Cox Proportional hazard models adjusted for demographic, lifestyle and dietary variables were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results During an average of 12 years of follow-up, 7904 and 3874 CVD deaths in men and women, respectively, were identified. Supplements containing calcium were used by 51% of men and 70% of women. In men supplemental calcium intake was associated with an elevated risk of CVD death (RR>1000 vs. 0 mg/day =1.20, 95% CI: 1.05–1.36), more specifically with heart disease death (RR=1.19, 95% CI: 1.03–1.37), but not significantly with cerebrovascular disease death (RR=1.14, 95% CI: 0.81–1.61). In women, supplemental calcium intake was not associated with CVD death (RR= 1.06, 95% CI: 0.96, 1.18), heart disease death (RR=1.05, 95% CI: 0.93–1.18) or cerebrovascular disease death (RR=1.08, 95% CI: 0.87–1.33). Dietary calcium intake was not related to CVD death in either men or women. Conclusion Our finding suggests that high intake of supplemental calcium is associated with an excess risk of CVD death in men, but not in women. Additional studies are needed to investigate the effect of supplemental calcium use beyond bone health. PMID:23381719

Cause-specific mortality among children and young adults with epilepsy: Results from the U.S. National Child Death Review Case Reporting System.

PubMed

Tian, Niu; Shaw, Esther C; Zack, Matthew; Kobau, Rosemarie; Dykstra, Heather; Covington, Theresa M

2015-04-01

We investigated causes of death in children and young adults with epilepsy by using data from the U.S. National Child Death Review Case Reporting System (NCDR-CRS), a passive surveillance system composed of comprehensive information related to deaths reviewed by local child death review teams. Information on a total of 48,697 deaths in children and young adults 28days to 24years of age, including 551 deaths with epilepsy and 48,146 deaths without epilepsy, was collected from 2004 through 2012 in 32 states. In a proportionate mortality analysis by official manner of death, decedents with epilepsy had a significantly higher percentage of natural deaths but significantly lower percentages of deaths due to accidents, homicide, and undetermined causes compared with persons without epilepsy. With respect to underlying causes of death, decedents with epilepsy had significantly higher percentages of deaths due to drowning and most medical conditions including pneumonia and congenital anomalies but lower percentages of deaths due to asphyxia, weapon use, and unknown causes compared with decedents without epilepsy. The increased percentages of deaths due to pneumonia and drowning in children and young adults with epilepsy suggest preventive interventions including immunization and better instruction and monitoring before or during swimming. State-specific and national population-based mortality studies of children and young adults with epilepsy are recommended. Published by Elsevier Inc.

Cause-specific mortality among children and young adults with epilepsy: Results from the U.S. National Child Death Review Case Reporting System ☆

PubMed Central

Tian, Niu; Shaw, Esther C.; Zack, Matthew; Kobau, Rosemarie; Dykstra, Heather; Covington, Theresa M.

2015-01-01

We investigated causes of death in children and young adults with epilepsy by using data from the U.S. National Child Death Review Case Reporting System (NCDR-CRS), a passive surveillance system composed of comprehensive information related to deaths reviewed by local child death review teams. Information on a total of 48,697 deaths in children and young adults 28 days to 24 years of age, including 551 deaths with epilepsy and 48,146 deaths without epilepsy, was collected from 2004 through 2012 in 32 states. In a proportionate mortality analysis by official manner of death, decedents with epilepsy had a significantly higher percentage of natural deaths but significantly lower percentages of deaths due to accidents, homicide, and undetermined causes compared with persons without epilepsy. With respect to underlying causes of death, decedents with epilepsy had significantly higher percentages of deaths due to drowning and most medical conditions including pneumonia and congenital anomalies but lower percentages of deaths due to asphyxia, weapon use, and unknown causes compared with decedents without epilepsy. The increased percentages of deaths due to pneumonia and drowning in children and young adults with epilepsy suggest preventive interventions including immunization and better instruction and monitoring before or during swimming. State-specific and national population-based mortality studies of children and young adults with epilepsy are recommended. PMID:25794682

Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death domains.

PubMed

Li, Shan; Zhang, Li; Yao, Qing; Li, Lin; Dong, Na; Rong, Jie; Gao, Wenqing; Ding, Xiaojun; Sun, Liming; Chen, Xing; Chen, She; Shao, Feng

2013-09-12

The tumour necrosis factor (TNF) family is crucial for immune homeostasis, cell death and inflammation. These cytokines are recognized by members of the TNF receptor (TNFR) family of death receptors, including TNFR1 and TNFR2, and FAS and TNF-related apoptosis-inducing ligand (TRAIL) receptors. Death receptor signalling requires death-domain-mediated homotypic/heterotypic interactions between the receptor and its downstream adaptors, including TNFR1-associated death domain protein (TRADD) and FAS-associated death domain protein (FADD). Here we discover that death domains in several proteins, including TRADD, FADD, RIPK1 and TNFR1, were directly inactivated by NleB, an enteropathogenic Escherichia coli (EPEC) type III secretion system effector known to inhibit host nuclear factor-κB (NF-κB) signalling. NleB contained an unprecedented N-acetylglucosamine (GlcNAc) transferase activity that specifically modified a conserved arginine in these death domains (Arg 235 in the TRADD death domain). NleB GlcNAcylation (the addition of GlcNAc onto a protein side chain) of death domains blocked homotypic/heterotypic death domain interactions and assembly of the oligomeric TNFR1 complex, thereby disrupting TNF signalling in EPEC-infected cells, including NF-κB signalling, apoptosis and necroptosis. Type-III-delivered NleB also blocked FAS ligand and TRAIL-induced cell death by preventing formation of a FADD-mediated death-inducing signalling complex (DISC). The arginine GlcNAc transferase activity of NleB was required for bacterial colonization in the mouse model of EPEC infection. The mechanism of action of NleB represents a new model by which bacteria counteract host defences, and also a previously unappreciated post-translational modification.

The cost of illness attributable to diabetic foot and cost-effectiveness of secondary prevention in Peru.

PubMed

Cárdenas, María Kathia; Mirelman, Andrew J; Galvin, Cooper J; Lazo-Porras, María; Pinto, Miguel; Miranda, J Jaime; Gilman, Robert H

2015-10-26

Diabetes mellitus is a public health challenge worldwide, and roughly 25% of patients with diabetes in developing countries will develop at least one foot ulcer during their lifetime. The gravest outcome of an ulcerated foot is amputation, leading to premature death and larger economic costs. This study aimed to estimate the economic costs of diabetic foot in high-risk patients in Peru in 2012 and to model the cost-effectiveness of a year-long preventive strategy for foot ulceration including: sub-optimal care (baseline), standard care as recommended by the International Diabetes Federation, and standard care plus daily self-monitoring of foot temperature. A decision tree model using a population prevalence-based approach was used to calculate the costs and the incremental cost-effectiveness ratio (ICER). Outcome measures were deaths and major amputations, uncertainty was tested with a one-way sensitivity analysis. The direct costs for prevention and management with sub-optimal care for high-risk diabetics is around US$74.5 million dollars in a single year, which decreases to US$71.8 million for standard care and increases to US$96.8 million for standard care plus temperature monitoring. The implementation of a standard care strategy would avert 791 deaths and is cost-saving in comparison to sub-optimal care. For standard care plus temperature monitoring compared to sub-optimal care the ICER rises to US$16,124 per death averted and averts 1,385 deaths. Diabetic foot complications are highly costly and largely preventable in Peru. The implementation of a standard care strategy would lead to net savings and avert deaths over a one-year period. More intensive prevention strategies such as incorporating temperature monitoring may also be cost-effective.

Minocycline causes widespread cell death and increases microglial labeling in the neonatal mouse brain.

PubMed

Strahan, J Alex; Walker, William H; Montgomery, Taylor R; Forger, Nancy G

2017-06-01

Minocycline, an antibiotic of the tetracycline family, inhibits microglia in many paradigms and is among the most commonly used tools for examining the role of microglia in physiological processes. Microglia may play an active role in triggering developmental neuronal cell death, although findings have been contradictory. To determine whether microglia influence developmental cell death, we treated perinatal mice with minocycline (45 mg/kg) and quantified effects on dying cells and microglial labeling using immunohistochemistry for activated caspase-3 (AC3) and ionized calcium-binding adapter molecule 1 (Iba1), respectively. Contrary to our expectations, minocycline treatment from embryonic day 18 to postnatal day (P)1 caused a > tenfold increase in cell death 8 h after the last injection in all brain regions examined, including the primary sensory cortex, septum, hippocampus and hypothalamus. Iba1 labeling was also increased in most regions. Similar effects, although of smaller magnitude, were seen when treatment was delayed to P3-P5. Minocycline treatment from P3 to P5 also decreased overall cell number in the septum at weaning, suggesting lasting effects of the neonatal exposure. When administered at lower doses (4.5 or 22.5 mg/kg), or at the same dose 1 week later (P10-P12), minocycline no longer increased microglial markers or cell death. Taken together, the most commonly used microglial "inhibitor" increases cell death and Iba1 labeling in the neonatal mouse brain. Minocycline is used clinically in infant and pediatric populations; caution is warrented when using minocycline in developing animals, or extrapolating the effects of this drug across ages. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 753-766, 2017. © 2016 Wiley Periodicals, Inc.

Minocycline Causes Widespread Cell Death and Increases Microglial Labeling in the Neonatal Mouse Brain

PubMed Central

Strahan, J. Alex; Walker, William H.; Montgomery, Taylor R.; Forger, Nancy G.

2016-01-01

Minocycline, an antibiotic of the tetracycline family, inhibits microglia in many paradigms, and is among the most commonly used tools for examining the role of microglia in physiological processes. Microglia may play an active role in triggering developmental neuronal cell death, although findings have been contradictory. To determine whether microglia influence developmental cell death, we treated perinatal mice with minocycline (45 mg/kg) and quantified effects on dying cells and microglial labeling using immunohistochemistry for activated caspase-3 (AC3) and ionized calcium-binding adapter molecule 1 (Iba1), respectively. Contrary to our expectations, minocycline treatment from embryonic day 18 to postnatal day (P)1 caused a >10-fold increase in cell death 8 h after the last injection in all brain regions examined, including the primary sensory cortex (S1), septum, hippocampus and hypothalamus. Iba1 labeling was also increased in most regions. Similar effects, although of smaller magnitude, were seen when treatment was delayed to P3-P5. Minocycline treatment from P3-P5 also decreased overall cell number in the septum at weaning, suggesting lasting effects of the neonatal exposure. When administered at lower doses (4.5 or 22.5 mg/kg), or at the same dose one week later (P10-P12), minocycline no longer increased microglial markers or cell death. Taken together, the most commonly used microglial “inhibitor” increases cell death and Iba1 labeling in the neonatal mouse brain. Minocycline is used clinically in infant and pediatric populations; caution is warrented when using minocycline in developing animals, or extrapolating the effects of this drug across ages. PMID:27706925

Antihelminthic Benzimidazoles Are Novel HIF Activators That Prevent Oxidative Neuronal Death via Binding to Tubulin

PubMed Central

Aleyasin, Hossein; Karuppagounder, Saravanan S.; Kumar, Amit; Sleiman, Sama; Basso, Manuela; Ma, Thong; Siddiq, Ambreena; Chinta, Shankar J.; Brochier, Camille; Langley, Brett; Haskew-Layton, Renee; Bane, Susan L.; Riggins, Gregory J.; Gazaryan, Irina; Starkov, Anatoly A.; Andersen, Julie K.

2015-01-01

Abstract Aims: Pharmacological activation of the adaptive response to hypoxia is a therapeutic strategy of growing interest for neurological conditions, including stroke, Huntington's disease, and Parkinson's disease. We screened a drug library with known safety in humans using a hippocampal neuroblast line expressing a reporter of hypoxia-inducible factor (HIF)-dependent transcription. Results: Our screen identified more than 40 compounds with the ability to induce hypoxia response element-driven luciferase activity as well or better than deferoxamine, a canonical activator of hypoxic adaptation. Among the chemical entities identified, the antihelminthic benzimidazoles represented one pharmacophore that appeared multiple times in our screen. Secondary assays confirmed that antihelminthics stabilized the transcriptional activator HIF-1α and induced expression of a known HIF target gene, p21cip1/waf1, in post-mitotic cortical neurons. The on-target effect of these agents in stimulating hypoxic signaling was binding to free tubulin. Moreover, antihelminthic benzimidazoles also abrogated oxidative stress-induced death in vitro, and this on-target effect also involves binding to free tubulin. Innovation and Conclusions: These studies demonstrate that tubulin-binding drugs can activate a component of the hypoxic adaptive response, specifically the stabilization of HIF-1α and its downstream targets. Tubulin-binding drugs, including antihelminthic benzimidazoles, also abrogate oxidative neuronal death in primary neurons. Given their safety in humans and known ability to penetrate into the central nervous system, antihelminthic benzimidazoles may be considered viable candidates for treating diseases associated with oxidative neuronal death, including stroke. Antioxid. Redox Signal. 22, 121–134. PMID:24766300

Death rates for acquired hypothyroidism and thyrotoxicosis in English populations (1979-2010): comparison of underlying cause and all certified causes.

PubMed

Goldacre, M J; Duncan, M E

2013-03-01

Overt hypothyroidism and thyrotoxicosis have widespread systemic effects and are associated with increased mortality. Most death certificates that include them do not have the thyroid disease coded as the underlying cause of death. To describe regional (1979-2010) and national (1995-2010) trends in mortality rates for acquired hypothyroidism and thyrotoxicosis, analysing all certified causes of death (termed 'mentions') and not just the underlying cause. Analysis of death registration data. Analysis of data for the Oxford region (mentions available from 1979) and English national data (mentions available from 1995). The data were grouped in periods defined by different national rules for selecting the underlying cause of death (1979-83, 1984-92, 1993-2000 and 2001-10) and were also analysed as single calendar years. Mentions mortality for acquired hypothyroidism in the Oxford region declined significantly from 1979 to 2010: the average annual percentage change (AAPC) was -2.6% (95% confidence intervals -3.5, -1.8). Most of the decrease occurred during the 1980s. The AAPC in rates for later years in England (1995-2010) was non-significant at 0.2% (-0.7, 1.0). Mortality rates for thyrotoxicosis decreased significantly: the AAPC was -2.8% (-4.1, -1.5) in the Oxford region and -3.8% (-4.7, -3.0) in England. In England, between 2001 and 2010, hypothyroidism or thyrotoxicosis was coded as the underlying cause of death on, respectively, 17 and 24% of death certificates that included them. Mortality rates for hypothyroidism and thyrotoxicosis have fallen substantially. The fall is probably wholly or mainly a result of improved care.

How nurses cope with patient death: A systematic review and qualitative meta-synthesis.

PubMed

Zheng, Ruishuang; Lee, Susan Fiona; Bloomer, Melissa Jane

2018-01-01

To review literature on nurses' coping strategies with patient death. Dealing with the loss of a patient was viewed as one of the most demanding and challenging encounters in clinical practice. Those nurses who are not competent in coping with patient death may be inadequate in supporting dying patients and their family members, and minimise the quality of end-of-life care. To get a broader understanding of how nurses cope with patient death and to develop meaningful and effective interventions, a systematic review which would help underpin the multidimensional approaches is needed. A systematic review. Exhaustive searching in ten databases: CINAHL Plus, EMBASE, MEDLINE, AMED, PsycINFO, ProQuest Health & Medical Complete, ProQuest Dissertations & Theses Global, Google Scholar, EThOS and CareSearch. Meta-aggregation was used to synthesise the findings of the included studies. This systematic review aggregated ten categories from the sixteen qualitative studies included, and then two synthesised findings were derived: intrinsic resources and extrinsic resources. The intrinsic resources consisted of setting boundaries, reflection, crying, death beliefs, life and work experience, and daily routines and activity. The extrinsic resources were comprised of talking and being heard, spiritual practices, education and programmes, and debriefing. This systematic review synthesised the findings about what resources nurses use when coping with patient death and made recommendations on future directions. Areas which could be developed to improve deficiencies that nurses had when faced with the losses of their patients were identified. Nurses need more support resources, which better assist them in coping with patient death. The results of this systematic review could provide evidence for nurses' coping strategies when dealing with patient death, and the recommendations could be employed by nurses to cope with the losses of patients. © 2017 John Wiley & Sons Ltd.

Mortality from Musculoskeletal Disorders Including Rheumatoid Arthritis in Southern Sweden: A Multiple-cause-of-death Analysis, 1998-2014.

PubMed

Kiadaliri, Aliasghar A; Turkiewicz, Aleksandra; Englund, Martin

2017-05-01

To assess mortality related to musculoskeletal (MSK) disorders and rheumatoid arthritis (RA), specifically, among adults (aged ≥ 20 yrs) in southern Sweden using the multiple-cause-of-death approach. All death certificates (DC; n = 201,488) from 1998 to 2014 for adults in the region of Skåne were analyzed when mortality from MSK disorders and RA was listed as the underlying and nonunderlying cause of death (UCD/NUCD). Trends in age-standardized mortality rates (ASMR) were evaluated using joinpoint regression, and associated causes were identified by age- and sex-adjusted observed/expected ratios. MSK (RA) was mentioned on 2.8% (0.8%) of all DC and selected as UCD in 0.6% (0.2%), with higher values among women. Proportion of MSK disorder deaths from all deaths increased from 2.7% in 1998 to 3.1% in 2014, and declined from 0.9% to 0.5% for RA. The mean age at death was higher in DC with mention of MSK/RA than in DC without. The mean ASMR for MSK (RA) was 15.5 (4.3) per 100,000 person-years and declined by 1.1% (3.8%) per year during 1998-2014. When MSK/RA were UCD, pneumonia and heart failure were the main NUCD. When MSK/RA were NUCD, the leading UCD were ischemic heart disease and neoplasms. The greatest observed/expected ratios were seen for infectious diseases (including sepsis) and blood diseases. We observed significant reduction in MSK and RA mortality rates and increase in the mean age at death. Further analyses are required to investigate determinants of these improvements in MSK/RA survival and their potential effect on the Swedish healthcare systems.

Challenging patient deaths in pediatric oncology.

PubMed

Granek, Leeat; Bartels, Ute; Scheinemann, Katrin; Barrera, Maru

2015-08-01

Pediatric oncologists look after patients and their families for extended periods of time when they are diagnosed and treated for cancer. Twenty percent of these children will die while under their care. The purpose of this study was to explore what makes patient deaths challenging for pediatric oncologists. Twenty-one Canadian pediatric oncologists were interviewed about their experiences with patient death and were probed about the factors that make patient deaths particularly challenging. Data were analyzed using the grounded theory method. Challenging factors pertaining to patient death were categorized into three main domains. Relational factors included dealing with families perceived as challenging; identifying with parents; and having long-term relationships and special connections with patients and their caregivers. The second domain captured the process of death and dying and included death after curative treatment was stopped; death caused by complications; and unexpected deaths. The third domain encompassed patient factors that included suffering of the child, and the sense that no child should die. The types of relationships pediatric oncologists have with patients and caregivers, and the process by which children die affects pediatric oncologists' perceived level of difficulty in coping with the death. The findings point to the complexity of working with children where parents are included in the decision-making processes around a child's treatment. Implementation of structured review opportunities around patient death and associated decision-making within a multidisciplinary healthcare team may alleviate some of the emotional burden associated with patient deaths.

Comparison of Types of Cell Death: Apoptosis and Necrosis.

ERIC Educational Resources Information Center

Manning, Francis; Zuzel, Katherine

2003-01-01

Cell death is an essential factor in many biological processes including development. Discusses two types of cell death: (1) necrosis (induced by sodium azide); and (2) apoptosis (induced by sodium chromate). Illustrates key features that differ between these two types of cells death including loss of membrane integrity and internucleosomal DNA…

Advance Report of Final Mortality Statistics, 1985.

ERIC Educational Resources Information Center

Monthly Vital Statistics Report, 1987

1987-01-01

This document presents mortality statistics for 1985 for the entire United States. Data analysis and discussion of these factors is included: death and death rates; death rates by age, sex, and race; expectation of life at birth and at specified ages; causes of death; infant mortality; and maternal mortality. Highlights reported include: (1) the…

PMCA2 silencing potentiates MDA-MB-231 breast cancer cell death initiated with the Bcl-2 inhibitor ABT-263.

PubMed

Curry, Merril; Roberts-Thomson, Sarah J; Monteith, Gregory R

2016-09-30

PMCA2 overexpression in some breast cancers suggests that this calcium pump isoform may play a role in breast pathophysiology. To investigate PMCA2 as a potential drug target for breast cancer therapy, we assessed the functional consequence of PMCA2 silencing on cell death pathways and calcium signals in the basal-like MDA-MB-231 breast cancer cell line. Silencing PMCA2 expression alone has no effect on MDA-MB-231 cell viability, however, PMCA2 silencing promotes calcium-induced cell death initiated with the calcium ionophore ionomycin. Assessment of cytoplasmic calcium responses generated with various agents including ionomycin demonstrates that in MDA-MB-231 cells, PMCA2 does not play a major role in shaping global calcium signals. We also examined the ability of PMCA2 silencing to modulate caspase-dependent cell death triggered by a Bcl-2 inhibitor that is in clinical development for the treatment of various cancers, ABT-263 (Navitoclax). Despite the lack of effect on global calcium responses, PMCA2 silencing augmented Bcl-2 inhibitor (ABT-263)-mediated MDA-MB-231 breast cancer cell death. These studies provide evidence that PMCA2 inhibitors could sensitize PMCA2-positive breast cancers to cell death initiators that work through mechanisms involving the Bcl-2 survival pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Natural Compounds As Modulators of Non-apoptotic Cell Death in Cancer Cells

PubMed Central

Guamán-Ortiz, Luis Miguel; Orellana, Maria Isabel Ramirez; Ratovitski, Edward A.

2017-01-01

Cell death is an innate capability of cells to be removed from microenvironment, if and when they are damaged by multiple stresses. Cell death is often regulated by multiple molecular pathways and mechanism, including apoptosis, autophagy, and necroptosis. The molecular network underlying these processes is often intertwined and one pathway can dynamically shift to another one acquiring certain protein components, in particular upon treatment with various drugs. The strategy to treat human cancer ultimately relies on the ability of anticancer therapeutics to induce tumor-specific cell death, while leaving normal adjacent cells undamaged. However, tumor cells often develop the resistance to the drug-induced cell death, thus representing a great challenge for the anticancer approaches. Numerous compounds originated from the natural sources and biopharmaceutical industries are applied today in clinics showing advantageous results. However, some exhibit serious toxic side effects. Thus, novel effective therapeutic approaches in treating cancers are continued to be developed. Natural compounds with anticancer activity have gained a great interest among researchers and clinicians alike since they have shown more favorable safety and efficacy then the synthetic marketed drugs. Numerous studies in vitro and in vivo have found that several natural compounds display promising anticancer potentials. This review underlines certain information regarding the role of natural compounds from plants, microorganisms and sea life forms, which are able to induce non-apoptotic cell death in tumor cells, namely autophagy and necroptosis. PMID:28367073

Cytokine-induced release of ceramide-enriched exosomes as a mediator of cell death signaling in an oligodendroglioma cell line[S

PubMed Central

Podbielska, Maria; Szulc, Zdzisław M.; Kurowska, Ewa; Hogan, Edward L.; Bielawski, Jacek; Bielawska, Alicja; Bhat, Narayan R.

2016-01-01

Th1 pro-inflammatory cytokines, i.e., TNF-α and IFN-γ, in combination are known to induce cell death in several cell types, including oligodendrocytes, but the mechanism of their synergistic cytotoxicity is unclear. Although ceramide (Cer) has been implicated in cytokine- and stress-induced cell death, its intracellular levels alone cannot explain cytokine synergy. We considered the possibility that Cer released as part of extracellular vesicles may contribute to cytokine-induced synergistic cell death. Using a human oligodendroglioma (HOG) cell line as a model, here we show that exosomes derived from TNF-α-treated “donor” cells, while being mildly toxic to fresh cultures (similar to individual cytokines), induce enhanced cell death when added to IFN-γ-primed target cultures in a fashion resembling the effect of cytokine combination. Further, the sphingolipid profiles of secreted exosomes, as determined by HPLC-MS/MS, revealed that the treatment with the cytokines time-dependently induced the formation and exosomal release, in particular of C16-, C24-, and C24:1-Cer species; C16-, C24-, and C24:1-dihydroCer species; and C16-, C24-, and C24:1-SM species. Finally, exogenous C6-Cer or C16-Cer mimicked and enhanced the cytotoxic effects of the cytokines upon HOG cells, thereby supporting the cell death-signaling role of extracellular Cer. PMID:27623848

Modeling the effect of comprehensive interventions on Ebola virus transmission

NASA Astrophysics Data System (ADS)

Shen, Mingwang; Xiao, Yanni; Rong, Libin

2015-10-01

Since the re-emergence of Ebola in West Africa in 2014, comprehensive and stringent interventions have been implemented to decelerate the spread of the disease. The effectiveness of interventions still remains unclear. In this paper, we develop an epidemiological model that includes various controlling measures to systematically evaluate their effects on the disease transmission dynamics. By fitting the model to reported cumulative cases and deaths in Guinea, Sierra Leone and Liberia until March 22, 2015, we estimate the basic reproduction number in these countries as 1.2552, 1.6093 and 1.7994, respectively. Model analysis shows that there exists a threshold of the effectiveness of isolation, below which increasing the fraction of latent individuals diagnosed prior to symptoms onset or shortening the duration between symptoms onset and isolation may lead to more Ebola infection. This challenges an existing view. Media coverage plays a substantial role in reducing the final epidemic size. The response to reported cumulative infected cases and deaths may have a different effect on the epidemic spread in different countries. Among all the interventions, we find that shortening the duration between death and burial and improving the effectiveness of isolation are two effective interventions for controlling the outbreak of Ebola virus infection.

Modeling the effect of comprehensive interventions on Ebola virus transmission.

PubMed

Shen, Mingwang; Xiao, Yanni; Rong, Libin

2015-10-30

Since the re-emergence of Ebola in West Africa in 2014, comprehensive and stringent interventions have been implemented to decelerate the spread of the disease. The effectiveness of interventions still remains unclear. In this paper, we develop an epidemiological model that includes various controlling measures to systematically evaluate their effects on the disease transmission dynamics. By fitting the model to reported cumulative cases and deaths in Guinea, Sierra Leone and Liberia until March 22, 2015, we estimate the basic reproduction number in these countries as 1.2552, 1.6093 and 1.7994, respectively. Model analysis shows that there exists a threshold of the effectiveness of isolation, below which increasing the fraction of latent individuals diagnosed prior to symptoms onset or shortening the duration between symptoms onset and isolation may lead to more Ebola infection. This challenges an existing view. Media coverage plays a substantial role in reducing the final epidemic size. The response to reported cumulative infected cases and deaths may have a different effect on the epidemic spread in different countries. Among all the interventions, we find that shortening the duration between death and burial and improving the effectiveness of isolation are two effective interventions for controlling the outbreak of Ebola virus infection.

Oncologists' negative attitudes towards expressing emotion over patient death and burnout.

PubMed

Granek, Leeat; Ben-David, Merav; Nakash, Ora; Cohen, Michal; Barbera, Lisa; Ariad, Samuel; Krzyzanowska, Monika K

2017-05-01

The aims of this study were to examine the relationship between negative attitudes towards expressing emotion following patient death and burnout in oncologists and to explore oncologists' preferences for institutional interventions to deal with patient death. The participants included a convenience sample of 177 oncologists from Israel and Canada. Oncologists completed a questionnaire package that included a sociodemographic survey, a burnout measure, a survey assessing negative attitudes towards expressing emotion, and a survey assessing desired interventions to cope with patient death. To examine the association between burnout and negative attitudes while controlling for the effect of sociodemographic variables, a hierarchical linear regression was computed. Higher burnout scores were related to higher negative attitudes towards perceived expressed emotion (partial r = .25, p < .01) of those who viewed this affect as a weakness and as a sign of unprofessionalism. Approximately half of the oncologists found each of the five categories of institutional interventions (pedagogical strategies, emotional support, group/peer support, taking time off, and research and training) helpful in coping with patient death. Our findings suggest that high burnout scores are associated with negative attitudes towards expressing emotion and that there is a wide variation in oncologist preferences in coping with patient death. Institutions should promote interventions that are varied and that focus on the needs of oncologists in order to reduce burnout. Interventions that legitimize expression of emotion about patient death may be useful. Another way to reduce stigma would be to require oncologists to "opt out" rather than "opt in" to accessing a selection of social and/or individual interventions.

Simulation-based training in brain death determination.

PubMed

MacDougall, Benjamin J; Robinson, Jennifer D; Kappus, Liana; Sudikoff, Stephanie N; Greer, David M

2014-12-01

Despite straightforward guidelines on brain death determination by the American Academy of Neurology (AAN), substantial practice variability exists internationally, between states, and among institutions. We created a simulation-based training course on proper determination based on the AAN practice parameters to address and assess knowledge and practice gaps at our institution. Our intervention consisted of a didactic course and a simulation exercise, and was bookended by before and after multiple-choice tests. The 40-min didactic course, including a video demonstration, covered all aspects of the brain death examination. Simulation sessions utilized a SimMan 3G manikin and involved a complete examination, including an apnea test. Possible confounders and signs incompatible with brain death were embedded throughout. Facilitators evaluated performance with a 26-point checklist based on the most recent AAN guidelines. A senior neurologist conducted all aspects of the course, including the didactic session, simulation, and debriefing session. Ninety physicians from multiple specialties have participated in the didactic session, 38 of whom have completed the simulation. Pre-test scores were poor (41.4 %), with attendings scoring higher than residents (46.6 vs. 40.4 %, p = 0.07), and neurologists and neurosurgeons significantly outperforming other specialists (53.9 vs. 38.9 %, p = 0.003). Post-test scores (73.3 %) were notably higher than pre-test scores (45.4 %). Participant feedback has been uniformly positive. Baseline knowledge of brain death determination among providers was low but improved greatly after the course. Our intervention represents an effective model that can be replicated at other institutions to train clinicians in the determination of brain death according to evidence-based guidelines.

Maternal mortality in developing countries.

PubMed

Harrison, K A

1989-01-01

A commentary on the state of maternal mortality is developing countries is presented. Of the estimated half million maternal deaths worldwide yearly, 150,000 occur in Africa, 282,000 in Southern and South Eastern Asia, 26,000 in Western and East Asia, 34,000 in tropical South America, 1,000 in temperate South America, and 2,000 in Oceania. 494,000 maternal deaths occur in developing countries, with 6,000 in all developing countries. Maternal death rates are highest in developing countries due primarily to flaws in the social, economic, and political conditions of the countries involved, combined with a grossly inadequate quantity and quality of available health care services. Here, major causes of maternal death include abortion, anemia, eclampsia, infection, hemorrhage, and obstructed labor and its accompanying complications. Attempts at lowering maternal mortality should include health intervention policies on a global scale, utilizing the intervention of developing countries with their necessary financial and technological support. Universal formal education appears to be the most effective weapon against maternal death. This approach is an effort to modernize most developing societies. Still, a few obstacles remain. These include: discarding cherished traditional customs of health care in favor of modernized techniques, restricting existing health services, and providing faster and more efficient operative intervention procedures. Family planning is also stressed as an important initiative. The most contentious of all methods to lower maternal death rates is the retraining of illiterate traditional birth attendants (TBAs). Activities of TBAs should be viewed cautiously as results of the techniques - in areas such as the Sudan, Africa, and Asia, - have proven to be of little consequence in lowering maternal mortality. Attention to retraining TBAs should be replaced with sufficient training and proper utilization of midwives. The Royal College of Obstetricians and Gynecologists has undertaken pioneering efforts towards lowering global maternal mortality.

Black rice extract protected HepG2 cells from oxidative stress-induced cell death via ERK1/2 and Akt activation

PubMed Central

Yoon, Jaemin; Ham, Hyeonmi; Sung, Jeehye; Kim, Younghwa; Choi, Youngmin; Lee, Jeom-Sig; Jeong, Heon-Sang; Lee, Junsoo

2014-01-01

BACKGROUND/OBJECTIVES The objective of this study was to evaluate the protective effect of black rice extract (BRE) on tert-butyl hydroperoxide (TBHP)-induced oxidative injury in HepG2 cells. MATERIALS/METHODS Methanolic extract from black rice was evaluated for the protective effect on TBHP-induced oxidative injury in HepG2 cells. Several biomarkers that modulate cell survival and death including reactive oxygen species (ROS), caspase-3 activity, and related cellular kinases were determined. RESULTS TBHP induced cell death and apoptosis by a rapid increase in ROS generation and caspase-3 activity. Moreover, TBHP-induced oxidative stress resulted in a transient ERK1/2 activation and a sustained increase of JNK1/2 activation. While, BRE pretreatment protects the cells against oxidative stress by reducing cell death, caspase-3 activity, and ROS generation and also by preventing ERKs deactivation and the prolonged JNKs activation. Moreover, pretreatment of BRE increased the activation of ERKs and Akt which are pro-survival signal proteins. However, this effect was blunted in the presence of ERKs and Akt inhibitors. CONCLUSIONS These results suggest that activation of ERKs and Akt pathway might be involved in the cytoprotective effect of BRE against oxidative stress. Our findings provide new insights into the cytoprotective effects and its possible mechanism of black rice against oxidative stress. PMID:24741394

Investigation of the performance of fermentation processes using a mathematical model including effects of metabolic bottleneck and toxic product on cells.

PubMed

Sriyudthsak, Kansuporn; Shiraishi, Fumihide

2010-11-01

A number of recent research studies have focused on theoretical and experimental investigation of a bottleneck in a metabolic reaction network. However, there is no study on how the bottleneck affects the performance of a fermentation process when a product is highly toxic and remarkably influences the growth and death of cells. The present work therefore studies the effect of bottleneck on product concentrations under different product toxicity conditions. A generalized bottleneck model in a fed-batch fermentation is constructed including both the bottleneck and the product influences on cell growth and death. The simulation result reveals that when the toxic product strongly influences the cell growth and death, the final product concentration is hardly changed even if the bottleneck is removed, whereas it is markedly changed by the degree of product toxicity. The performance of an ethanol fermentation process is also discussed as a case example to validate this result. In conclusion, when the product is highly toxic, one cannot expect a significant increase in the final product concentration even if removing the bottleneck; rather, it may be more effective to somehow protect the cells so that they can continuously produce the product. Copyright © 2010 Elsevier Inc. All rights reserved.

Cell death pathways of particulate matter toxicity.

PubMed

Peixoto, Milena Simões; de Oliveira Galvão, Marcos Felipe; Batistuzzo de Medeiros, Silvia Regina

2017-12-01

Humans are exposed to various complex mixtures of particulate matter (PM) from different sources. Long-term exposure to high levels of these particulates has been linked to a diverse range of respiratory and cardiovascular diseases that have resulted in hospital admission. The evaluation of the effects of PM exposure on the mechanisms related to cell death has been a challenge for many researchers. Therefore, in this review, we have discussed the effects of airborne PM exposure on mechanisms related to cell death. For this purpose, we have compiled literature data on PM sources, the effects of exposure, and the assays and models used for evaluation, in order to establish comparisons between various studies. The analysis of this collected data suggested divergent responses to PM exposure that resulted in different cell death types (apoptosis, autophagy, and necrosis). In addition, PM induced oxidative stress within cells, which appeared to be an important factor in the determination of cell fate. When the levels of reactive oxygen species were overpowering, the cellular fate was directed toward cell death. This may be the underlying mechanism of the development or exacerbation of respiratory diseases, such as emphysema and chronic obstructive pulmonary diseases. In addition, PM was shown to cause DNA damage and the resulting mutations increased the risk of cancer. Furthermore, several conditions should be considered in the assessment of cell death in PM-exposed models, including the cell culture line, PM composition, and the interaction of the different cells types in in vivo models. Copyright © 2017 Elsevier Ltd. All rights reserved.

CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects.

PubMed

Dalvin, Lauren A; Shields, Carol L; Orloff, Marlana; Sato, Takami; Shields, Jerry A

2018-06-01

To review immune checkpoint inhibitor indications and ophthalmic side effects. A literature review was performed using a PubMed search for publications between 1990 and 2017. Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1-24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy. Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.

Neuroprotective effect against axonal damage-induced retinal ganglion cell death in apolipoprotein E-deficient mice through the suppression of kainate receptor signaling.

PubMed

Omodaka, Kazuko; Nishiguchi, Koji M; Yasuda, Masayuki; Tanaka, Yuji; Sato, Kota; Nakamura, Orie; Maruyama, Kazuichi; Nakazawa, Toru

2014-10-24

Apolipoprotein E (ApoE) plays important roles in the body, including a carrier of cholesterols, an anti-oxidant, and a ligand for the low-density lipoprotein receptors. In the nervous system, the presence of ApoE4 isoforms is associated with Alzheimer's disease. ApoE gene polymorphisms are also associated with glaucoma, but the function of ApoE in the retina remains unclear. In this study, we investigated the role of ApoE in axonal damage-induced RGC death. ApoE was detected in the astrocytes and Müller cells in the wild-type (WT) retina. RGC damage was induced in adult ApoE-deficient mice (male, 10-12 weeks old) through ocular hypertension (OH), optic nerve crush (NC), or by administering kainic acid (KA) intravitreally. The WT mice were treated with a glutamate receptor antagonist (MK801 or CNQX) 30 min before performing NC or left untreated. Seven days later, the retinas were flat mounted and Fluorogold-labeled RGCs were counted. We found that the RGCs in the ApoE-deficient mice were resistant to OH-induced RGC death and optic nerve degeneration 4 weeks after induction. In WT mice, NC effectively induced RGC death (control: 4085±331 cells/mm(2), NC: 1728±170 cells/mm(2)). CNQX, an inhibitor of KA receptors, suppressed this RGC death (3031±246 cells/mm(2)), but MK801, an inhibitor of NMDA receptors, did not (1769±212 cells/mm(2)). This indicated the involvement of KA receptor signaling in NC-induced RGC death. We found that NC- or KA-induced RGC death was significantly less in the ApoE-deficient mice than in the WT mice. These data suggest that the ApoE deficiency had a neuroprotective effect against axonal damage-induced RGC death by suppressing the KA receptor signaling. Copyright © 2014 Elsevier B.V. All rights reserved.

Aberrant expression and function of death receptor-3 and death decoy receptor-3 in human cancer.

PubMed

Ge, Zhicheng; Sanders, Andrew J; Ye, Lin; Jiang, Wen G

2011-03-01

Death receptor-3 (DR3) and death decoy receptor-3 (DcR3) are both members of the tumour necrosis factor receptor (TNFR) superfamily. The TNFR superfamily contains eight death domain-containing receptors, including TNFR1 (also called DR1), Fas (also called DR2), DR3, DR4, DR5, DR6, NGFR and EDAR. Upon the binding of these receptors with their corresponding ligands, the death domain recruits various proteins that mediate both the death and proliferation of cells. Receptor function is negatively regulated by decoy receptors (DcR1, DcR2, DcR3 and OPG). DR3/DcR3 are a pair of positive and negative players with which vascular endothelial growth inhibitor (VEGI) interacts. VEGI has been suggested to be a potential tumour suppressor. The inhibitory effects of VEGI on cancer are manifested in three main areas: a direct effect on cancer cells, an anti-angiogenic effect on endothelial cells, and the stimulation of dendritic cell maturation. A recent study indicated that DR3 may be a new receptor for E-selectin, which has been reported to be associated with cancer metastasis. DcR3 is a soluble receptor, highly expressed in various tumours, which lacks an apparent transmembrane segment, prevents cytokine response through ligand binding and neutralization, and is an inhibitor of apoptosis. DcR3 serves as a decoy receptor for FasL, LIGHT and VEGI. The cytokine LIGHT activates various anti-tumour functions and is expected to be a promising candidate for cancer therapy. Certain tumours may escape FasL-dependent immune-cytotoxic attack by expressing DcR3, which blocks FasL function. DR3/DcR3 play profound roles in regulating cell death and proliferation in cancer. The present review briefly discusses DR3/DcR3 and attempts to elucidate the role of these negative and positive players in cancer.

Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hemendinger, Richelle A., E-mail: richelle.hemendinger@carolinashealthcare.org; Armstrong, Edward J.; Brooks, Benjamin Rix

Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC{sub 50} (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolatemore » (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC{sub 50} (concentration at which 50% of maximal cell death is inhibited) of 0.6 {mu}M and 0.4 {mu}M, respectively. In contrast, MTHF (up to 10 {mu}M) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron-neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS.« less

The acute toxicity of the death camas (Zigadenus species) alkaloid zygacine in mice, including the effect of methyllycaconitine coadministration on zygacine toxicity.

PubMed

Welch, K D; Panter, K E; Gardner, D R; Stegelmeier, B L; Green, B T; Pfister, J A; Cook, D

2011-05-01

Death camas (Zigadenus spp.) is a common poisonous plant on foothill rangelands in western North America. The steroidal alkaloid zygacine is believed to be the primary toxic component in death camas. Poisonings on rangelands generally occur in the spring when death camas is abundant, whereas other more desirable forage species are limited in availability. In most cases where livestock are poisoned by plants in a range setting, there is more than one potential poisonous plant in that area. One common poisonous plant that is often found growing simultaneously in the same area as death camas is low larkspur (Delphinium nuttallianum). Consequently, the objectives of this study were to conduct acute toxicity studies in mice and to determine if coadministration of low larkspur will exacerbate the toxicity of death camas. We first characterized the acute toxicity of zygacine in mice. The LD(50) of zygacine administered intravenously (i.v.) and orally was 2.0 ± 0.2 and 132 ± 21 mg/kg, respectively. The rate of elimination of zygacine from whole blood was determined to be 0.06 ± 0.01/min, which corresponds to an elimination half-life of 13.0 ± 2.7 min. The i.v. LD(50) of total alkaloid extracts from a Utah and a Nevada collection were 2.8 ± 0.8 and 2.2 ± 0.3 mg/kg, respectively. The i.v. LD(50) of methyllycaconitine (MLA), a major toxic alkaloid in low larkspur, was 4.6 ± 0.5 mg/kg, whereas the i.v. LD(50) of a 1:1 mixture of MLA and zygacine was 2.9 ± 0.7 mg/kg. The clinical signs in mice treated with this mixture were very similar to those of mice treated with zygacine alone, including the time of onset and death. These results suggest that there is an additive effect of coadministering these 2 alkaloids i.v. in mice. The results from this study increase knowledge and understanding regarding the acute toxicity of death camas. As combined intoxications are most likely common, this information will be useful in further developing management recommendations for ranchers and in designing additional experiments to study the toxicity of death camas to livestock.

Novel oxindole derivatives prevent oxidative stress-induced cell death in mouse hippocampal HT22 cells.

PubMed

Hirata, Yoko; Yamada, Chika; Ito, Yuki; Yamamoto, Shotaro; Nagase, Haruna; Oh-Hashi, Kentaro; Kiuchi, Kazutoshi; Suzuki, Hiromi; Sawada, Makoto; Furuta, Kyoji

2018-03-15

The current medical and surgical therapies for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease offer symptomatic relief but do not provide a cure. Thus, small synthetic compounds that protect neuronal cells from degeneration are critically needed to prevent and treat these. Oxidative stress has been implicated in various pathophysiological conditions, including neurodegenerative diseases. In a search for neuroprotective agents against oxidative stress using the murine hippocampal HT22 cell line, we found a novel oxindole compound, GIF-0726-r, which prevented oxidative stress-induced cell death, including glutamate-induced oxytosis and erastin-induced ferroptosis. This compound also exerted a protective effect on tunicamycin-induced ER stress to a lesser extent but had no effect on campthothecin-, etoposide- or staurosporine-induced apoptosis. In addition, GIF-0726-r was also found to be effective after the occurrence of oxidative stress. GIF-0726-r was capable of inhibiting reactive oxygen species accumulation and Ca 2+ influx, a presumed executor in cell death, and was capable of activating the antioxidant response element, which is a cis-acting regulatory element in promoter regions of several genes encoding phase II detoxification enzymes and antioxidant proteins. These results suggest that GIF-0726-r is a low-molecular-weight compound that prevents neuronal cell death through attenuation of oxidative stress. Among the more than 200 derivatives of the GIF-0726-r synthesized, we identified the 11 most potent activators of the antioxidant response element and characterized their neuroprotective activity in HT22 cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analysis of the Future Effects of the Fuel Shortage and Increased Small Car Usage Upon Traffic Deaths and Injuries

DOT National Transportation Integrated Search

1976-01-01

The Automotive Energy Efficiency Project is concerned with the examination of technological options for improving the fuel efficiency of highway vehicles. This examination includes an analysis of the effects of existing and proposed mandated standard...

Debris ingestion by juvenile marine turtles: an underestimated problem.

PubMed

Santos, Robson Guimarães; Andrades, Ryan; Boldrini, Marcillo Altoé; Martins, Agnaldo Silva

2015-04-15

Marine turtles are an iconic group of endangered animals threatened by debris ingestion. However, key aspects related to debris ingestion are still poorly known, including its effects on mortality and the original use of the ingested debris. Therefore, we analysed the impact of debris ingestion in 265 green turtles (Chelonia mydas) over a large geographical area and different habitats along the Brazilian coast. We determined the death rate due to debris ingestion and quantified the amount of debris that is sufficient to cause the death of juvenile green turtles. Additionally, we investigated the original use of the ingested debris. We found that a surprisingly small amount of debris was sufficient to block the digestive tract and cause death. We suggested that debris ingestion has a high death potential that may be masked by other causes of death. An expressive part of the ingested debris come from disposable and short-lived products. Copyright © 2015 Elsevier Ltd. All rights reserved.

Deaths Associated With Brotizolam Poisoning From a Single Drug Overdose: Four Reported Cases.

PubMed

Sakai, Kentaro; Saito, Kazuyuki; Takada, Aya; Hikiji, Wakako; Kikuchi, Yosuke; Fukunaga, Tatsushige

2018-03-01

Brotizolam is a short-acting hypnotic in the benzodiazepine family, and fatal poisonings by an overdose of brotizolam are rare. This report describes 4 cases of deaths associated with brotizolam poisoning from a single drug overdose. The ages ranged from 51 to 90 years, and the postmortem interval between death and tissue sampling was 1.5 to 2.5 days. These deaths were classified as 1 homicide and 3 suicides. The concentration of the brotizolam ranged from 0.05 to 0.21 mg/L in the blood samples. Ethanol, which could cause mild alcohol intoxication, was detected in the blood samples from 2 cases. Postmortem examinations did not find any significant pathologic conditions, except for a case of death by drowning in a bathtub due to brotizolam poisoning. These 4 cases suggest that a brotizolam overdose should not be underestimated in terms of its fatal effects, particularly when situations involve alcohol intoxication, injury subsequent to the poisoning, or underlying medical conditions including aging.

Fatty acids trigger mitochondrion-dependent necrosis.

PubMed

Rockenfeller, Patrick; Ring, Julia; Muschett, Vera; Beranek, Andreas; Buettner, Sabrina; Carmona-Gutierrez, Didac; Eisenberg, Tobias; Khoury, Chamel; Rechberger, Gerald; Kohlwein, Sepp D; Kroemer, Guido; Madeo, Frank

2010-07-15

Obesity is characterised by lipid accumulation in non-adipose tissues, leading to organ degeneration and a wide range of diseases, including diabetes, heart attack and liver cirrhosis. Free fatty acids (FFA) are believed to be the principal toxic triggers mediating the adverse cellular effects of lipids. Here, we show that various cooking oils used in human nutrition cause cell death in yeast in the presence of a triacylglycerol lipase, mimicking the physiological microenvironment of the small intestine. Combining genetic and cell death assays, we demonstrate that elevated FFA concentrations lead to necrotic cell death, as evidenced by loss of membrane integrity and release of nuclear HMGB1. FFA-mediated necrosis depends on functional mitochondria and leads to the accumulation of reactive oxygen species. We conclude that lipotoxicity is executed via a mitochondrial necrotic pathway, challenging the dogma that the adverse effects of lipid stress are exclusively apoptotic.

Vaccines to prevent pneumonia in children - a developing country perspective.

PubMed

Oliwa, Jacquie N; Marais, Ben J

2017-03-01

Pneumonia accounted for 15% of the 6.3 million deaths among children younger than five years in 2013, a total of approximately 935,000 deaths worldwide. Routine vaccination against common childhood illnesses has been identified as one of the most cost-effective strategies to prevent death from pneumonia. Vaccine-preventable or potentially preventable diseases commonly linked with respiratory tract infections include Streptococcus pneumoniae, Haemophilus influenza type-b (Hib), pertussis, influenza, measles, and tuberculosis. Although here have been great strides in the development and administration of effective vaccines, the countries that carry the largest disease burdens still struggle to vaccinate their children and newer conjugated vaccines remain out of reach for many. The Global Vaccine Action Plan (GVAP) has identified priority areas for innovation in research in all aspects of immunisation development and delivery to ensure equitable access to vaccines for all. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of education and income on cardiovascular outcomes: A systematic review and meta-analysis.

PubMed

Khaing, Win; Vallibhakara, Sakda A; Attia, John; McEvoy, Mark; Thakkinstian, Ammarin

2017-07-01

Objective Previous studies have reported discrepancy effects of education and income on cardiovascular diseases. This systematic review and meta-analysis was therefore conducted which aimed to summarize effects of education and income on cardiovascular diseases. Methods Studies were identified from Medline and Scopus until July 2016. Cohorts were eligible if they assessed associations between education/income and cardiovascular diseases, had at least one outcome including coronary artery diseases, cardiovascular events, strokes and cardiovascular deaths. A multivariate meta-analysis was applied to pool risk effects of these social determinants. Results Among 72 included cohorts, 39, 19, and 14 were studied in Europe, USA, and Asia. Pooled risk ratios of low and medium versus high education were 1.36 (95% confidence interval: 1.11-1.66) and 1.21 (1.06-1.40) for coronary artery diseases, 1.50 (1.17-1.92) and 1.27 (1.09-1.48) for cardiovascular events, 1.23 (1.06-1.43) and 1.17 (1.01-1.35) for strokes, and 1.39 (1.26-1.54) and 1.21 (1.12-1.30) for cardiovascular deaths. The effects of education on all cardiovascular diseases were still present in US and Europe settings, except in Asia this was present only for cardiovascular deaths. Effects of low and medium income versus high on these corresponding cardiovascular diseases were 1.49 (1.16-1.91) and 1.27 (1.10-1.47) for coronary artery diseases, 1.17 (0.96-1.44) and 1.05 (0.98-1.13) for cardiovascular events, 1.30 (0.99-1.72) and 1.24 (1.00-1.53) for strokes, and 1.76 (1.45-2.14) and 1.34 (1.17-1.54) for cardiovascular deaths. Conclusion Social determinants are risk factors of cardiovascular diseases in developed countries, although high heterogeneity in pooling. Data in Asia countries are still needed to update pooling.

Cost-Effectiveness of Antivenoms for Snakebite Envenoming in 16 Countries in West Africa.

PubMed

Hamza, Muhammad; Idris, Maryam A; Maiyaki, Musa B; Lamorde, Mohammed; Chippaux, Jean-Philippe; Warrell, David A; Kuznik, Andreas; Habib, Abdulrazaq G

2016-03-01

Snakebite poisoning is a significant medical problem in agricultural societies in Sub Saharan Africa. Antivenom (AV) is the standard treatment, and we assessed the cost-effectiveness of making it available in 16 countries in West Africa. We determined the cost-effectiveness of AV based on a decision-tree model from a public payer perspective. Specific AVs included in the model were Antivipmyn, FAV Afrique, EchiTab-G and EchiTab-Plus. We derived inputs from the literature which included: type of snakes causing bites (carpet viper (Echis species)/non-carpet viper), AV effectiveness against death, mortality without AV, probability of Early Adverse Reactions (EAR), likelihood of death from EAR, average age at envenomation in years, anticipated remaining life span and likelihood of amputation. Costs incurred by the victims include: costs of confirming and evaluating envenomation, AV acquisition, routine care, AV transportation logistics, hospital admission and related transportation costs, management of AV EAR compared to the alternative of free snakebite care with ineffective or no AV. Incremental Cost Effectiveness Ratios (ICERs) were assessed as the cost per death averted and the cost per Disability-Adjusted-Life-Years (DALY) averted. Probabilistic Sensitivity Analyses (PSA) using Monte Carlo simulations were used to obtain 95% Confidence Intervals of ICERs. The cost/death averted for the 16 countries of interest ranged from $1,997 in Guinea Bissau to $6,205 for Liberia and Sierra Leone. The cost/DALY averted ranged from $83 (95% Confidence Interval: $36-$240) for Benin Republic to $281 ($159-457) for Sierra-Leone. In all cases, the base-case cost/DALY averted estimate fell below the commonly accepted threshold of one time per capita GDP, suggesting that AV is highly cost-effective for the treatment of snakebite in all 16 WA countries. The findings were consistent even with variations of inputs in 1-way sensitivity analyses. In addition, the PSA showed that in the majority of iterations ranging from 97.3% in Liberia to 100% in Cameroun, Guinea Bissau, Mali, Nigeria and Senegal, our model results yielded an ICER that fell below the threshold of one time per capita GDP, thus, indicating a high degree of confidence in our results. Therapy for SBE with AV in countries of WA is highly cost-effective at commonly accepted thresholds. Broadening access to effective AVs in rural communities in West Africa is a priority.

Death Adder Envenoming Causes Neurotoxicity Not Reversed by Antivenom - Australian Snakebite Project (ASP-16)

PubMed Central

Johnston, Christopher I.; O'Leary, Margaret A.; Brown, Simon G. A.; Currie, Bart J.; Halkidis, Lambros; Whitaker, Richard; Close, Benjamin; Isbister, Geoffrey K.

2012-01-01

Background Death adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment. Methodology/Principal Findings Definite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5–74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5–15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients, all receiving one vial initially. The median time for resolution of neurotoxicity post-antivenom was 21 hours (5–168). The median peak venom concentration in 13 envenomed patients with blood samples was 22 ng/mL (4.4–245 ng/mL). In eight patients where post-antivenom bloods were available, no venom was detected after one vial of antivenom. Conclusions/Significance Death adder envenoming is characterised by neurotoxicity, which is mild in most cases. One vial of death adder antivenom was sufficient to bind all circulating venom. The persistent neurological effects despite antivenom, suggests that neurotoxicity is not reversed by antivenom. PMID:23029595

Death adder envenoming causes neurotoxicity not reversed by antivenom--Australian Snakebite Project (ASP-16).

PubMed

Johnston, Christopher I; O'Leary, Margaret A; Brown, Simon G A; Currie, Bart J; Halkidis, Lambros; Whitaker, Richard; Close, Benjamin; Isbister, Geoffrey K

2012-01-01

Death adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment. Definite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5-74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5-15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients, all receiving one vial initially. The median time for resolution of neurotoxicity post-antivenom was 21 hours (5-168). The median peak venom concentration in 13 envenomed patients with blood samples was 22 ng/mL (4.4-245 ng/mL). In eight patients where post-antivenom bloods were available, no venom was detected after one vial of antivenom. Death adder envenoming is characterised by neurotoxicity, which is mild in most cases. One vial of death adder antivenom was sufficient to bind all circulating venom. The persistent neurological effects despite antivenom, suggests that neurotoxicity is not reversed by antivenom.

Epilepsy-associated long-term mortality after aneurysmal subarachnoid hemorrhage.

PubMed

Huttunen, Jukka; Lindgren, Antti; Kurki, Mitja I; Huttunen, Terhi; Frösen, Juhana; Koivisto, Timo; von Und Zu Fraunberg, Mikael; Immonen, Arto; Jääskeläinen, Juha E; Kälviäinen, Reetta

2017-07-18

To elucidate the epilepsy-associated causes of death and subsequent excess long-term mortality among 12-month survivors of subarachnoid hemorrhage from saccular intracranial aneurysm (SIA-SAH). The Kuopio SIA Database (kuopioneurosurgery.fi) includes all SIA-SAH patients admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland. The study cohort consists of 779 patients, admitted from 1995 to 2007, who were alive at 12 months after SIA-SAH. Their use of reimbursable antiepileptic drugs and the causes of death (ICD-10) were fused from the Finnish national registries from 1994 to 2014. The 779 12-month survivors were followed up until death (n = 197) or December 31, 2014, a median of 12.0 years after SIA-SAH. Epilepsy had been diagnosed in 121 (15%) patients after SIA-SAH, and 34/121 (28%) had died at the end of follow-up, with epilepsy as the immediate cause of death in 7/34 (21%). In the 779 patients alive at 12 months after SIA-SAH, epilepsy was an independent risk factor for mortality (hazard ratio 1.8, 95% confidence interval 1.1-3.0). Comorbid epilepsy in 12-month survivors of SIA-SAH is associated with increased risk of death in long-term follow-up. Survivors of SIA-SAH require long-term dedicated follow-up, including identification and effective treatment of comorbid epilepsy to prevent avoidable deaths. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Childhood family disruptions and adult well-being: the differential effects of divorce and parental death.

PubMed

Mack, K Y

2001-01-01

This study draws on attachment theory and social learning theory and uses data from the National Survey of Families and Households to examine the differential effects of childhood family disruptions on adult well-being. Comparisons are made between adults who experienced parental divorce, adults who experienced parental death, and adults who were raised in intact families (N = 4,341). The present study differs from previous research by making direct comparisons between different family disruption groups, assessing the effects of family disruptions that occur before age 19, and including multiple measures of adult well-being as dependent variables. Consistent with hypotheses and inferences made from comparisons with adults from intact families, adults who experienced parental divorce report lower levels of parent-child relationship quality, higher levels of self-confidence, and lower levels of depression than adults who experienced parental death during childhood. Therefore, studies that fail to take type of childhood family disruption into account will lead to inaccurate and misleading conclusions about the effects of these experiences on adult outcomes.

Stroke rehabilitation

PubMed Central

Bindawas, Saad M.; Vennu, Vishal S.

2016-01-01

Stroke is a major cause of death and other complications worldwide. In Saudi Arabia, stroke has become an emerging health issue leading to disability and death. However, stroke care including rehabilitation services, in Saudi Arabia lags behind developed countries. Stroke rehabilitation is an essential recovery option after stroke and should start as early as possible to avoid potential complications. The growing evidence on stroke rehabilitation effectiveness in different health care settings and outcome measures used widely are reviewed in this call to action paper. PMID:27744457

Causes of death of patients with lung cancer.

PubMed

Nichols, Larry; Saunders, Rachel; Knollmann, Friedrich D

2012-12-01

The causes of death for patients with lung cancer are inadequately described. To categorize the immediate and contributing causes of death for patients with lung cancer. The autopsies from 100 patients who died of lung cancer between 1990 and February 2011 were analyzed. Tumor burden was judged the immediate cause of death in 30 cases, including 26 cases of extensive metastases and 4 cases with wholly or primarily lung tumor burden (causing respiratory failure). Infection was the immediate cause of death for 20 patients, including 8 with sepsis and 12 with pneumonia. Complications of metastatic disease were the immediate causes of death in 18 cases, including 6 cases of hemopericardium from pericardial metastases, 3 from myocardial metastases, 3 from liver metastases, and 3 from brain metastases. Other immediate causes of death were pulmonary hemorrhage (12 cases), pulmonary embolism (10 cases, 2 tumor emboli), and pulmonary diffuse alveolar damage (7 cases). From a functional (pathophysiologic) perspective, respiratory failure could be regarded as the immediate cause of death (or mechanism of death) in 38 cases, usually because of a combination of lung conditions, including emphysema, airway obstruction, pneumonia, hemorrhage, embolism, resection, and lung injury in addition to the tumor. For 94 of the 100 patients, there were contributing causes of death, with an average of 2.5 contributing causes and up to 6 contributing causes of death. The numerous and complex ways lung cancer kills patients pose a challenge for efforts to extend and improve their lives.

The effects of the pollutant, sodium cyanide, on the morphology and physiology of oedogonium cardiacum

NASA Technical Reports Server (NTRS)

Sparks, E.

1977-01-01

OEDOGONIUM cardiacum exposed to varying concentrations of sodium cyanide for 15 day periods exhibited both morphological and physiological alterations. Organisms were exposed to the pollutant in concentrations of 1, 10, 25, 50, and 100 parts per million. Exposure period for organisms in each concentration was 15 days. As the concentration of the pollutant increased fragmentation also increased. Exposure also caused organisms to lose chlorophyll. The third morphological alteration was the incidence of rupture. Physiological effects altered by exposure included: reduced oxygen evolution, retardation of starch production and death. Death occurs when organisms are exposed to high concentrations over the total 15 day period.

Induction of cytosine arabinoside-resistant human myeloid leukemia cell death through autophagy regulation by hydroxychloroquine.

PubMed

Kim, Yundeok; Eom, Ju-In; Jeung, Hoi-Kyung; Jang, Ji Eun; Kim, Jin Seok; Cheong, June-Won; Kim, Young Sam; Min, Yoo Hong

2015-07-01

We investigated the effects of the autophagy inhibitor hydroxychloroquine (HCQ) on cell death of cytosine arabinoside (Ara-C)-resistant human acute myeloid leukemia (AML) cells. Ara-C-sensitive (U937, AML-2) and Ara-C-resistant (U937/AR, AML-2/AR) human AML cell lines were used to evaluate HCQ-regulated cytotoxicity, autophagy, and apoptosis as well as effects on cell death-related signaling pathways. We found that HCQ-induced dose- and time-dependent cell death in Ara-C-resistant cells compared to Ara-C-sensitive cell lines. The extent of cell death and features of HCQ-induced autophagic markers including increase in microtubule-associated protein light chain 3 (LC3) I conversion to LC3-II, beclin-1, ATG5, as well as green fluorescent protein-LC3 positive puncta and autophagosome were remarkably greater in U937/AR cells. Also, p62/SQSTM1 was increased in response to HCQ. p62/SQSTM1 protein interacts with both LC3-II and ubiquitin protein and is degraded in autophagosomes. Therefore, a reduction of p62/SQSTM1 indicates increased autophagic degradation, whereas an increase of p62/SQSTM1 by HCQ indicates inhibited autophagic degradation. Knock down of p62/SQSTM1 using siRNA were prevented the HCQ-induced LC3-II protein level as well as significantly reduced the HCQ-induced cell death in U937/AR cells. Also, apoptotic cell death and caspase activation in U937/AR cells were increased by HCQ, provided evidence that HCQ-induced autophagy blockade. Taken together, our data show that HCQ-induced apoptotic cell death in Ara-C-resistant AML cells through autophagy regulation. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Death Attitudes Among Middle-Aged Koreans: Role of End-of-Life Care Planning and Death Experiences

PubMed Central

Hong, Michin; Hong, Seunghye; Adamek, Margaret E.; Kim, Mee Hye

2017-01-01

The purpose of this study was to examine factors affecting death attitudes among middle-aged Koreans. In addition, the study explored the interaction effect between knowledge about end-of-life care planning and the experience of death of family or friends on death attitudes. The sample was obtained from a national survey with middle-aged adults in South Korea (n = 2,026). Multivariate regression analysis revealed significant main effects and an interaction effect between knowledge about end-of-life care planning and the experience of death on death attitudes. Greater knowledge of end-of-life care planning was associated with more positive attitudes toward death; however, the effect was stronger for those who had not experienced the death of family or friends. Being older and having greater life satisfaction were also associated with more positive attitudes toward death. This study suggests that end-of-life education can help middle-aged adults embrace the final stage of life and prepare for their own death. PMID:28105867

Death Attitudes Among Middle-Aged Koreans: Role of End-of-Life Care Planning and Death Experiences.

PubMed

Hong, Michin; Hong, Seunghye; Adamek, Margaret E; Kim, Mee Hye

2018-01-01

The purpose of this study was to examine factors affecting death attitudes among middle-aged Koreans. In addition, the study explored the interaction effect between knowledge about end-of-life care planning and the experience of death of family or friends on death attitudes. The sample was obtained from a national survey with middle-aged adults in South Korea ( n = 2,026). Multivariate regression analysis revealed significant main effects and an interaction effect between knowledge about end-of-life care planning and the experience of death on death attitudes. Greater knowledge of end-of-life care planning was associated with more positive attitudes toward death; however, the effect was stronger for those who had not experienced the death of family or friends. Being older and having greater life satisfaction were also associated with more positive attitudes toward death. This study suggests that end-of-life education can help middle-aged adults embrace the final stage of life and prepare for their own death.

Terminal-decline effects for select cognitive tasks after controlling for preclinical dementia.

PubMed

Laukka, Erika J; MacDonald, Stuart W S; Bäckman, Lars

2008-05-01

In a previous study, the authors found no accelerated decline in close proximity to death for a measure of global cognitive functioning, after excluding persons in a preclinical phase of dementia. However, specific cognitive tasks might be more sensitive to terminal-decline effects. The purpose of this study was to explore possible terminal-decline effects for a range of cognitive tasks after controlling for preclinical dementia. Community-based cohort study. The Kungsholmen district of Stockholm. A total of 585 persons (75+ years) were repeatedly assessed over an 11-year period. Level and change in cognitive performance were compared for three groups: persons in close proximity to death, persons in a preclinical phase of dementia, and persons who remained alive and nondemented throughout the study. Tasks assessing primary and episodic memory, verbal ability, and visuospatial skill. Compared with an analysis where all dead subjects were included in the impending-death group, removing the preclinical dementia cases resulted in markedly attenuated mortality-related effects. However, the impending-death group still declined at a faster rate relative to the comparison group on Digit Span-forward, word recognition, and category fluency. Notably, these were tasks for which the comparison group showed no significant decline. A considerable proportion of the terminal-decline effect is accounted for by the impact of preclinical dementia. However, for tasks that are relatively resistant to age-related change, such effects might be detected independently of preclinical dementia.

Lived Experiences of Iranian Nurses Caring for Brain Death Organ Donor Patients: Caring as “Halo of Ambiguity and Doubt”

PubMed Central

Keshtkaran, Zahra; Sharif, Farkhondeh; Navab, Elham; Gholamzadeh, Sakineh

2016-01-01

Background: Brain death is a concept in which its criteria have been expressed as documentations in Harvard Committee of Brain Death. The various perceptions of caregiver nurses for brain death patients may have effect on the chance of converting potential donors into actual organ donors. Objective: The present study has been conducted in order to perceive the experiences of nurses in care-giving to the brain death of organ donor patients. Methods: This qualitative study was carried out by means of Heidegger’s hermeneutic phenomenology. Eight nurses who have been working in ICU were interviewed. The semi-structured interviews were recorded by a tape-recorder and the given texts were transcribed and the analyses were done by Van-Mannen methodology and (thematic) analysis. Results: One of the foremost themes extracted from this study included ‘Halo of ambiguity and doubt’ that comprised of two sub-themes of ‘having unreasonable hope’ and ‘Conservative acceptance of brain death’. The unreasonable hope included lack of trust (uncertainty) in diagnosis and verification of brain death, passing through denial wall, and avoidance from explicit and direct disclosure of brain death in patients’ family. In this investigation, the nurses were involved in a type of ambiguity and doubt in care-giving to the potentially brain death of organ donor patients, which were also evident in their interaction with patients’ family and for this reason, they did not definitely announce the brain death and so far they hoped for treatment of the given patient. Such confusion and hesitance both caused annoyance of nurses and strengthening the denial of patients’ family to be exposed to death. Conclusion: The results of this study reveal the fundamental perceived care-giving of brain death in organ donor patients and led to developing some strategies to improve care-giving and achievement in donation of the given organ and necessity for presentation of educational and supportive services for nurses might become more evident than ever. PMID:26925919

Implication of limonene and linalyl acetate in cytotoxicity induced by bergamot essential oil in human neuroblastoma cells.

PubMed

Russo, Rossella; Ciociaro, Antonella; Berliocchi, Laura; Cassiano, Maria Gilda Valentina; Rombolà, Laura; Ragusa, Salvatore; Bagetta, Giacinto; Blandini, Fabio; Corasaniti, Maria Tiziana

2013-09-01

Bergamot (Citrus bergamia, Risso et Poiteau) essential oil (BEO) is a widely used plant extract showing anxiolytic, analgesic and neuroprotective effects in rodents; also, BEO activates multiple death pathways in cancer cells. Despite detailed knowledge of its chemical composition, the constituent/s responsible for these pharmacological activities remain largely unknown. Aim of the present study was to identify the components of BEO implicated in cell death. To this end, limonene, linalyl acetate, linalool, γ-terpinene, β-pinene and bergapten were individually tested in human SH-SY5Y neuroblastoma cultures at concentrations comparable with those found in cytotoxic dilutions of BEO. None of the tested compounds elicited cell death. However, significant cytotoxicity was observed when cells were cotreated with limonene and linalyl acetate whereas no other associations were effective. Only cotreatment, but not the single exposure to limonene and linalyl acetate, replicated distinctive morphological and biochemical changes induced by BEO, including caspase-3 activation, PARP cleavage, DNA fragmentation, cell shrinkage, cytoskeletal alterations, together with necrotic and apoptotic cell death. Collectively, our findings suggest a major role for a combined action of these monoterpenes in cancer cell death induced by BEO. Copyright © 2013 Elsevier B.V. All rights reserved.

Secreted calmodulin-like skin protein inhibits neuronal death in cell-based Alzheimer's disease models via the heterotrimeric Humanin receptor

PubMed Central

Hashimoto, Y; Nawa, M; Kurita, M; Tokizawa, M; Iwamatsu, A; Matsuoka, M

2013-01-01

Humanin is a secreted bioactive peptide that is protective in a variety of death models, including cell-based neuronal death models related to Alzheimer's disease (AD). To mediate the protective effect in AD-related death models, Humanin signals via a cell-surface receptor that is generally composed of three subunits: ciliary neurotrophic factor receptor α, WSX-1 and gp130 (heterotrimeric Humanin receptor; htHNR). However, the protective effect of Humanin via the htHNR is weak (EC50=1–10 μℳ); therefore, it is possible that another physiological agonist for this receptor exists in vivo. In the current study, calmodulin-like skin protein (CLSP), a calmodulin relative with an undefined function, was shown to be secreted and inhibit neuronal death via the htHNR with an EC50 of 10–100 pℳ. CLSP was highly expressed in the skin, and the concentration in circulating normal human blood was ∼5 nℳ. When administered intraperitoneally in mice, recombinant CLSP was transported across the blood-cerebrospinal fluid (CSF)-barrier and its concentration in the CSF reaches 1/100 of its serum concentration at 1 h after injection. These findings suggest that CLSP is a physiological htHNR agonist. PMID:23519124

Global cancer statistics, 2012.

PubMed

Torre, Lindsey A; Bray, Freddie; Siegel, Rebecca L; Ferlay, Jacques; Lortet-Tieulent, Joannie; Jemal, Ahmedin

2015-03-01

Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.

Easier said than done!: methodological challenges with conducting maternal death review research in Malawi.

PubMed

Combs Thorsen, Viva; Sundby, Johanne; Meguid, Tarek; Malata, Address

2014-02-21

Maternal death auditing is widely used to ascertain in-depth information on the clinical, social, cultural, and other contributing factors that result in a maternal death. As the 2015 deadline for Millennium Development Goal 5 of reducing maternal mortality by three quarters between 1990 and 2015 draws near, this information becomes even more critical for informing intensified maternal mortality reduction strategies. Studies using maternal death audit methodologies are widely available, but few discuss the challenges in their implementation. The purpose of this paper is to discuss the methodological issues that arose while conducting maternal death review research in Lilongwe, Malawi. Critical reflections were based on a recently conducted maternal mortality study in Lilongwe, Malawi in which a facility-based maternal death review approach was used. The five-step maternal mortality surveillance cycle provided the framework for discussion. The steps included: 1) identification of cases, 2) data collection, 3) data analysis, 4) recommendations, and 5) evaluation. Challenges experienced were related to the first three steps of the surveillance cycle. They included: 1) identification of cases: conflicting maternal death numbers, and missing medical charts, 2) data collection: poor record keeping, poor quality of documentation, difficulties in identifying and locating appropriate healthcare workers for interviews, the potential introduction of bias through the use of an interpreter, and difficulties with locating family and community members and recall bias; and 3) data analysis: determining the causes of death and clinical diagnoses. Conducting facility-based maternal death reviews for the purpose of research has several challenges. This paper illustrated that performing such an activity, particularly the data collection phase, was not as easy as conveyed in international guidelines and in published studies. However, these challenges are not insurmountable. If they are anticipated and proper steps are taken in advance, they can be avoided or their effects minimized.

Changing the "Normal Range" for Blood Pressure from 140/90 to 130/Any Improves Risk Assessment.

PubMed

Fulks, Michael; Stout, Robert L; Dolan, Vera F

2015-01-01

Objective .- Redefine the "normal" reference range for blood pressure from <140/90 to one that more effectively identifies individuals with increased mortality risk. Method .- Data from the recently published 2014 CRL blood pressure study was used. It includes 2,472,706 life insurance applicants tested by Clinical Reference Laboratory from 1993 to 2007 with follow-up for vital status using the September 2011 Social Security Death Master File. Various upper limits of blood pressure (BP in mm Hg) were evaluated to determine if any was superior to the current, commonly used limit of 140/90 in identifying individuals with increased mortality risk. Results .- An alternative reference range using a systolic BP (SBP) <130 with any diastolic BP (DBP) included 84% of life insurance applicants. It had a lower mortality rate and narrower range of relative risk than <140/90, including 89% as many applicants but only 68% as many deaths. This pattern of lives and deaths was consistent across age and sex. Conclusion .- Switching to a "normal" reference range of SBP <130 offers superior risk assessment relative to using BP <140/90 while still including a sufficient percentage of the population.

Intrathecal treatment in cancer patients unresponsive to multiple trials of systemic opioids.

PubMed

Mercadante, Sebastiano; Intravaia, Giuseppe; Villari, Patrizia; Ferrera, Patrizia; Riina, Salvatore; David, Fabrizio; Mangione, Salvatore

2007-01-01

The aim of this study was to evaluate the clinical response to a combination of intrathecal morphine and levobupivacaine in advanced cancer patients who were highly opioid-tolerant, being previously treated with multiple opioid trials unsuccessfully. Initial intrathecal morphine dose was calculated from the previous opioid consumption using a morphine oral-intrathecal ratio of 100:1. Then, doses of both drugs were modified during the treatment according to the clinical needs and balanced with adverse effects. Fifty-five patients were assessed during admission, before starting the intrathecal treatment, during the titration phase, and followed up to death, by frequent phone contacts or visits, as available. Pain and symptom intensities were recorded before starting the intrathecal treatment (T0), at time of hospital discharge (T dis), and then at 1 month (T1), 3 months (T3), 6 months (T6) intervals, and the last observation, at least 1 week before death (T death). Fifty-five patients were selected for starting an intrathecal treatment. Thirty-two patients were males. The mean age was 60 years (95% CI 57-63), and 65.4% of patients were under 65 years. The most frequent indication was the presence of adverse effects and poor pain control. Complete data with adequate follow-up until death were available in 45 patients. Statistical differences in pain intensity were found at the different time intervals examined until death. Statistical decreases in the intensity of drowsiness and confusion were found until 1 month after starting intrathecal therapy. Statistical differences were found in daily intrathecal morphine doses, with a 3-fold increase at time of hospital discharge. Subsequently, further increases in doses were not significant. Conversely, systemic opioids, expressed as oral morphine equivalents, significantly decreased at all the intervals examined until death. Early complications included mild bleeding in 2 patients, without consequences, headache in 4 patients, bladder catheterization in 6 patients, reoperation for bleeding or changes of catheter position in 4 patients, unrelated death in 1 patient, and stroke in another 1. Late complications included local infection in 2 patients, and discontinuation of intrathecal therapy due to spinal compression. In patients who had received multiple trial of opioids and routes of administration, the intrathecal treatment started with an oral-intrathecal morphine conversion ratio of 100:1, and local anesthetics at the most convenient clinical doses provided a long-term improvement of analgesia, with a decrease in adverse effects and opioid consumption until death.

Nursing Support of Home Hospice Caregivers on the Day of Patient Death.

PubMed

Clayton, Margaret F; Hulett, Jennifer; Kaur, Kirandeep; Reblin, Maija; Wilson, Andrew; Ellington, Lee

2017-07-01

To describe nurse-caregiver communication on the day of patient death.
. A descriptive secondary analysis of 44 audio-recorded home hospice nursing visits on day of death.
. Nine hospices in Utah, Oregon, and Massachusetts.
. 42 caregiver-patient dyads, 27 hospice nurses.
. Transcripts of audio recordings were coded for supportive nursing communication and relative time spent in physical, psychosocial, and spiritual discussion.
. Tangible, emotional, informational, esteem, and networking supportive communication; nurses' self-reported communication effectiveness; caregiver religious affiliation.
. Nurses reported that their communication skills were less effective when discussing difficult topics as compared to their overall communication effectiveness. Eleven patients died before the nursing visit, 3 died during the visit, and 30 died post-visit. Nurses primarily engaged in discussions facilitating caregiver emotional, tangible, and informational support. More informational support was observed when patient death occurred during the nursing visit. Time spent in general conversation showed that physical care conversations predominated (80% of the average overall amount of conversation time), compared to lifestyle/psychosocial discussions (14%) and spiritual discussions (6%). Spiritual discussions were observed in only 7 of 44 hospice visits. Spiritual discussions, although short and infrequent, were significantly longer, on average, for caregivers without a religious affiliation.
. Nurses support caregivers on the day of patient death using multiple supportive communication strategies. Spiritual discussions are minimal.
. Communication skills programs can potentially increase self-reported communication effectiveness. Emerging acute spiritual concerns, particularly for caregivers without a previous religious affiliation, should be anticipated. Spiritual support is included in the hospice model of holistic care.

The Effects on the Family of Life-Threatening Childhood Disease.

ERIC Educational Resources Information Center

Mann, Gary M.; And Others

1980-01-01

Presented at the National Conference of the Forum for Death Education and Counselling, Washington, 1978, this paper explores the effects of childhood malignancy on family dynamics. Problem areas include marital difficulties, forgotten siblings, and the necessity of alternating between a "sick" and "well" world. Constructive approaches are…

77 FR 3646 - Products Containing Imidazolines Equivalent to 0.08 Milligrams or More

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-25

... congestion and/or ophthalmic irritation. Products containing imidazolines can cause serious adverse reactions... unpredictable, idiosyncratic reaction (i.e., a drug effect that occurs in a small number of people due to age..., and death associated with cardiac reactions in adults. Other systemic side effects can include...

Patterns of civilian and child deaths due to war-related violence in Syria: a comparative analysis from the Violation Documentation Center dataset, 2011-16.

PubMed

Guha-Sapir, Debarati; Schlüter, Benjamin; Rodriguez-Llanes, Jose Manuel; Lillywhite, Louis; Hicks, Madelyn Hsiao-Rei

2018-01-01

Since March, 2011, the Syrian civil war has lowered life expectancy by as much as 20 years. We describe demographic, spatial, and temporal patterns of direct deaths of civilians and opposition combatants from conflict-related violence in 6 years of war. We analysed conflict-related violent deaths with complete information on date, place, and cause of death and demographic group occurring from March 18, 2011, to Dec 31, 2016, recorded by the Violation Documentation Center (VDC). We included civilian and combatant deaths in all Syrian governorates, excluding government-controlled areas. We did not include detainees and missing persons, nor deaths from siege conditions or insufficient medical care. We categorised deaths based on VDC weapon type. We used χ 2 testing to compare deaths from different weapons in civilian men, women, boys, and girls and adult and child combatants. We analysed deaths by governorate and over time. The VDC recorded 143 630 conflict-related violent deaths with complete information between March 18, 2011, and Dec 31, 2016. Syrian civilians constituted 101 453 (70·6%) of the deaths compared with 42 177 (29·4%) opposition combatants. Direct deaths were caused by wide-area weapons of shelling and air bombardments in 58 099 (57·3%) civilians, including 8285 (74·6%) civilian women and 13 810 (79·4%) civilian children, and in 4058 (9·6%) opposition combatants. Proportions of children among civilian deaths increased from 8·9% (388 of 4254 civilian deaths) in 2011 to 19·0% (4927 of 25 972) in 2013 and to 23·3% (2662 of 11 444) in 2016. Of 7566 deaths from barrel bombs, 7351 (97·2%) were civilians, of whom 2007 (27·3%) were children. Of 20 281 deaths by execution, 18 747 (92·4%) were civilians and 1534 (7·6%) were opposition combatants. Compared with opposition child soldiers who were male (n=333), deaths of civilian male children (n=11 730) were caused more often by air bombardments (39·2% vs 5·4%, p<0·0001) and shelling (37·3% vs 13·2%, p<0·0001) and less often by shooting (12·5% vs 76·0%, p<0·0001). Aerial bombing and shelling rapidly became primary causes of direct deaths of women and children and had disproportionate lethal effects on civilians, calling into question the use of wide-area explosive weapons in urban areas. Increased reliance on aerial bombing by the Syrian Government and international partners is likely to have contributed to findings that children were killed in increasing proportions over time, ultimately comprising a quarter of civilian deaths in 2016. The inordinate proportion of civilians among the executed is consistent with deliberate tactics to terrorise civilians. Deaths from barrel bombs were overwhelmingly civilian rather than opposition combatants, suggesting indiscriminate or targeted warfare contrary to international humanitarian law and possibly constituting a war crime. None. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study.

PubMed

Imai, E; Chan, J C N; Ito, S; Yamasaki, T; Kobayashi, F; Haneda, M; Makino, H

2011-12-01

The renal and cardiovascular protective effects of angiotensin receptor blocker (ARB) remain controversial in type 2 diabetic patients treated with a contemporary regimen including an angiotensin converting enzyme inhibitor (ACEI). We examined the effects of olmesartan, an ARB, on primary composite outcome of doubling of serum creatinine, endstage renal disease and death in type 2 diabetic patients with overt nephropathy. Secondary outcome included composite cardiovascular outcomes, changes in renal function and proteinuria. Randomisation and allocation to trial group were carried out by a central computer system. Participants, caregivers, the people carrying out examinations and people assessing the outcomes were blinded to group assignment. Five hundred and seventy-seven (377 Japanese, 200 Chinese) patients treated with antihypertensive therapy (73.5% [n = 424] received concomitant ACEI), were given either once-daily olmesartan (10-40 mg) (n = 288) or placebo (n = 289) over 3.2 ± 0.6 years (mean±SD). In the olmesartan group, 116 developed the primary outcome (41.1%) compared with 129 (45.4%) in the placebo group (HR 0.97, 95% CI 0.75, 1.24; p = 0.791). Olmesartan significantly decreased blood pressure, proteinuria and rate of change of reciprocal serum creatinine. Cardiovascular death was higher in the olmesartan group than the placebo group (ten vs three cases), whereas major adverse cardiovascular events (cardiovascular death plus non-fatal stroke and myocardial infarction) and all-cause death were similar between the two groups (major adverse cardiovascular events 18 vs 21 cases, all-cause deaths; 19 vs 20 cases). Hyperkalaemia was more frequent in the olmesartan group than the placebo group (9.2% vs 5.3%). Olmesartan was well tolerated but did not improve renal outcome on top of ACEI. ClinicalTrials.gov NCT00141453.

MPP+ induces necrostatin-1- and ferrostatin-1-sensitive necrotic death of neuronal SH-SY5Y cells.

PubMed

Ito, Keisuke; Eguchi, Yutaka; Imagawa, Yusuke; Akai, Shuji; Mochizuki, Hideki; Tsujimoto, Yoshihide

2017-01-01

Regulation of cell death is potentially a powerful treatment modality for intractable diseases such as neurodegenerative diseases. Although there have been many reports about the possible involvement of various types of cell death in neurodegenerative diseases, it is still unclear exactly how neurons die in patients with these diseases, thus treatment strategies based on cell death regulation have not been established yet. To obtain some insight into the mechanisms of cell death involved in neurodegenerative diseases, we studied the effect of 1-methyl-4-phenylpyridinium (MPP+) on the human neuroblastoma cell line SH-SY5Y (a widely used model of Parkinson's disease). We found that MPP+ predominantly induced non-apoptotic death of neuronally differentiated SH-SY5Y cells. This cell death was strongly inhibited by necrostatin-1 (Nec-1), a necroptosis inhibitor, and by an indole-containing compound (3,3'-diindolylmethane: DIM). However, it occurred independently of receptor-interacting serine/threonine-protein kinase 1/3 (RIP1/RIP3), indicating that this form of cell death was not necroptosis. MPP+-induced cell death was also inhibited by several inhibitors of ferroptosis, including ferrostatin-1 (Fer-1). Although MPP+-induced death and ferroptosis shared some features, such as occurrence of lipid peroxidation and inhibition by Fer-1, MPP+-induced death seemed to be distinct from ferroptosis because MPP+-induced death (but not ferroptosis) was inhibited by Nec-1, was independent of p53, and was accompanied by ATP depletion and mitochondrial swelling. Further investigation of MPP+-induced non-apoptotic cell death may be useful for understanding the mechanisms of neuronal loss and for treatment of neurodegenerative diseases such as Parkinson's disease.

MPP+ induces necrostatin-1- and ferrostatin-1-sensitive necrotic death of neuronal SH-SY5Y cells

PubMed Central

Ito, Keisuke; Eguchi, Yutaka; Imagawa, Yusuke; Akai, Shuji; Mochizuki, Hideki; Tsujimoto, Yoshihide

2017-01-01

Regulation of cell death is potentially a powerful treatment modality for intractable diseases such as neurodegenerative diseases. Although there have been many reports about the possible involvement of various types of cell death in neurodegenerative diseases, it is still unclear exactly how neurons die in patients with these diseases, thus treatment strategies based on cell death regulation have not been established yet. To obtain some insight into the mechanisms of cell death involved in neurodegenerative diseases, we studied the effect of 1-methyl-4-phenylpyridinium (MPP+) on the human neuroblastoma cell line SH-SY5Y (a widely used model of Parkinson’s disease). We found that MPP+ predominantly induced non-apoptotic death of neuronally differentiated SH-SY5Y cells. This cell death was strongly inhibited by necrostatin-1 (Nec-1), a necroptosis inhibitor, and by an indole-containing compound (3,3′-diindolylmethane: DIM). However, it occurred independently of receptor-interacting serine/threonine-protein kinase 1/3 (RIP1/RIP3), indicating that this form of cell death was not necroptosis. MPP+-induced cell death was also inhibited by several inhibitors of ferroptosis, including ferrostatin-1 (Fer-1). Although MPP+-induced death and ferroptosis shared some features, such as occurrence of lipid peroxidation and inhibition by Fer-1, MPP+-induced death seemed to be distinct from ferroptosis because MPP+-induced death (but not ferroptosis) was inhibited by Nec-1, was independent of p53, and was accompanied by ATP depletion and mitochondrial swelling. Further investigation of MPP+-induced non-apoptotic cell death may be useful for understanding the mechanisms of neuronal loss and for treatment of neurodegenerative diseases such as Parkinson’s disease. PMID:28250973

Depression and the Risk of Myocardial Infarction and Coronary Death: A Meta-Analysis of Prospective Cohort Studies.

PubMed

Wu, Qing; Kling, Juliana M

2016-02-01

Findings regarding the association between depression and risk of coronary heart disease are inconsistent. We aimed to assess the association between depression and risk of myocardial infarction (MI) and coronary death through a meta-analysis.We performed an electronic literature search of MEDLINE, EMBASE, PsycINFO, ISI Web of Science, and Scopus databases through August 1, 2015, and manual search of the references of the eligible papers and related review articles. Two investigators independently conducted study selection and data abstraction. Disagreement was resolved by consensus. Confounder-adjusted hazard ratios (HRs) were pooled using a random-effects model. Heterogeneity was evaluated using the Cochran Q statistic and Higgins index. Publication bias was assessed by funnel plot and Egger test. Study quality was appraised with the Newcastle-Ottawa Scale.Among 19 eligible cohort studies including 323,709 participants, 8447 cases of MI and coronary death were reported during follow-up ranging from 4 to 37 years. The pooled adjusted HRs for patients with depression (vs those without) were 1.22 (95% CI, 1.13-1.32) for combined MI and coronary death, 1.31 (95% CI, 1.09-1.57) for MI alone (9 studies), and 1.36 (95% CI, 1.14-1.63) for coronary death alone (8 studies). The increased risk of MI and coronary death associated with depression was consistent using modified inclusion criteria, across most subgroups, and after adjusting for possible publication bias.Depression is associated with a significantly increased risk of MI and coronary death. Effective prevention and treatment of depression may decrease such risk.

Cordycepin-induced apoptosis and autophagy in breast cancer cells are independent of the estrogen receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Sunga; Lim, Mi-Hee; Kim, Ki Mo

2011-12-15

Cordycepin (3-deoxyadenosine), found in Cordyceps spp., has been known to have many therapeutic effects including immunomodulatory, anti-inflammatory, antimicrobial, and anti-aging effects. Moreover, anti-tumor and anti-metastatic effects of cordycepin have been reported, but the mechanism causing cancer cell death is poorly characterized. The present study was designed to investigate whether the mechanisms of cordycepin-induced cell death were associated with estrogen receptor in breast cancer cells. Exposure of both MDA-MB-231 and MCF-7 human breast cancer cells to cordycepin resulted in dose-responsive inhibition of cell growth and reduction in cell viability. The cordycepin-induced cell death in MDA-MB-231 cells was associated with several specificmore » features of the mitochondria-mediated apoptotic pathway, which was confirmed by DNA fragmentation, TUNEL, and biochemical assays. Cordycepin also caused a dose-dependent increase in mitochondrial translocation of Bax, triggering cytosolic release of cytochrome c and activation of caspases-9 and -3. Interestingly, MCF-7 cells showed autophagy-associated cell death, as observed by the detection of an autophagosome-specific protein and large membranous vacuole ultrastructure morphology in the cytoplasm. Cordycepin-induced autophagic cell death has applications in treating MCF-7 cells with apoptotic defects, irrespective of the ER response. Although autophagy has a survival function in tumorigenesis of some cancer cells, autophagy may be important for cordycepin-induced MCF-7 cell death. In conclusion, the results of our study demonstrate that cordycepin effectively kills MDA-MB-231 and MCF-7 human breast cancer cell lines in culture. Hence, further studies should be conducted to determine whether cordycepin will be a clinically useful, ER-independent, chemotherapeutic agent for human breast cancer. -- Highlights: Black-Right-Pointing-Pointer We studied the mechanism which cordycepin-induced cell death association with estrogen receptor (ER) in breast cancer cells, MDA-MB-231 and MCF-7. Black-Right-Pointing-Pointer The cordycepin-induced cell death in MDA-MB-231 cells was associated with the mitochondria-mediated apoptotic pathway. Black-Right-Pointing-Pointer Cordycepin treatment also resulted in autophagy in MCF-7 cells, associated with induction of autophagosome formation. Black-Right-Pointing-Pointer The different cordycepin-mediated cell death pathways are irrespective of the ER response. Black-Right-Pointing-Pointer Cordycepin proves a clinically useful, ER-independent chemotherapeutic agent for human breast cancer cells.« less

Mortality Predictors in Patients with Severe Dengue in the State of Amazonas, Brazil

PubMed Central

Pinto, Rosemary Costa; de Castro, Daniel Barros; de Albuquerque, Bernardino Cláudio; Sampaio, Vanderson de Souza; dos Passos, Ricardo Augusto; da Costa, Cristiano Fernandes; Sadahiro, Megumi; Braga, José Ueleres

2016-01-01

Dengue is a major public health problem in tropical and subtropical areas worldwide. There is a lack of information on the risk factors for death due to severe dengue fever in developing countries, including Brazil where the state of Amazonas is located. This knowledge is important for decision making and the implementation of effective measures for patient care. This study aimed to identify factors associated with death among patients with severe dengue, in Amazonas from 2001 to 2013. We conducted a retrospective cohort study based on secondary data from the epidemiological surveillance of dengue provided by the Fundação de Vigilância em Saúde do Amazonas, FVS (Health Surveillance Foundation) of the Secretaria de Saúde do Amazonas, SUSAM (Health Secretariat of the State of Amazonas). Data on dengue cases were obtained from the SINAN (Notifiable Diseases Information System) and SIM (Mortality Information System) databases. We selected cases of severe dengue with laboratory confirmation, including dengue-related deaths of residents in the state of Amazonas from January 1, 2001, to December 31, 2013. The explanatory variables analyzed were sex, age, level of education, spontaneous hemorrhagic manifestations, plasma extravasation and platelet count. Patients who died due to severe dengue had more hematuria, gastrointestinal bleeding, and thrombocytopenia than the survivors. Considering the simultaneous effects of demographic and clinical characteristics with a multiple logistic regression model, it was observed that the factors associated with death were age >55 years (odds ratio [OR] 4.98), gastrointestinal bleeding (OR 10.26), hematuria (OR 5.07), and thrombocytopenia (OR 2.55). Gastrointestinal bleeding was the clinical sign most strongly associated with death, followed by hematuria and age >55 years. The study results showed that the best predictor of death from severe dengue is based on the characteristic of age >55 years, together with the clinical signs of gastrointestinal bleeding, hematuria, and low platelet count. PMID:27564084

New, previously unreported correlations between latent Toxoplasma gondii infection and excessive ethanol consumption.

PubMed

Samojłowicz, Dorota; Borowska-Solonynko, Aleksandra; Kruczyk, Marcin

2017-11-01

A number of world literature reports indicate that a latent Toxoplasma gondii infection leads to development of central nervous system disorders, which in turn may lead to altered behavior in the affected individuals. T. gondii infection has been observed to play the greatest role in drivers, suicides, and psychiatric patients. Studies conducted for this manuscript involve a different, never before really reported correlation between latent T. gondii infection and ethanol abuse. A total of 538 decedents with a known cause of death were included in the study. These individuals were divided into three groups: the risky behavior group, inconclusively risky behavior group, and control group. The criterion for this division was the likely effect of the individual's behavior on the mechanism and cause of his/her death. The material used for analyses were blood samples collected during routine medico-legal examinations in these cases. The blood samples were used to measure anti-T. gondii IgG antibodies with an enzyme-linked immunosorbent assay (ELISA). Moreover, the following data were recorded for each decedent: sex, age, circumstances of death, cause of death, time from death to autopsy, and (if provided) substance abuse status (alcohol, illicit drugs). In those cases where blood alcohol level or toxicology tests were requested by the Prosecutor's Office, their results were also included in our analysis. Test results demonstrated a strong correlation between latent T. gondii infection and engaging in risky behaviors leading to death. Moreover, analyses demonstrated a positive correlation between the presence of anti-T. gondii IgG antibodies and psychoactive substance (especially ethanol) abuse, however, the causal relationship remains unclear. Due to the fact that alcohol abuse constitutes a significant social problem, searching for eliminable risk factors for addiction is extremely important. Our analyses provided new important information on the possible effects of latent T. gondii infection in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

In-hospital death and adverse clinical events in elderly patients according to disease clustering: the REPOSI study.

PubMed

Marengoni, A; Bonometti, F; Nobili, A; Tettamanti, M; Salerno, F; Corrao, S; Iorio, A; Marcucci, M; Mannucci, P M

2010-08-01

The aim of the study was to recognize clusters of diseases among hospitalized elderly and to identify groups of patients at risk of in-hospital death and adverse clinical events according to disease clustering. This was a cross-sectional study conducted in 38 internal medicine and geriatric wards in Italy participating in the Registro Politerapie SIMI (REPOSI) study during 2008. The subjects were 1,332 inpatients aged 65 years or older. Clusters of diseases (i.e., two or more co-occurrent diseases) were identified using the odds ratios (OR) for the associations between pairs of conditions, followed by cluster analysis. Logistic regression models were used to evaluate the effect of disease clusters on in-hospital death and adverse clinical events. A total of 86.7% of the patients were discharged, 8.3% were transferred to another hospital unit, and 5.0% died during hospitalization; 36.4% of the patients had at least one adverse clinical event. Patients affected by the clusters, including heart failure (HF) and either chronic renal failure (CRF) or chronic obstructive pulmonary disease, had a significant association with in-hospital death (OR, 4.3;95% confidence interval [CI], 1.6-11.5; OR, 2.9; 95% CI, 1.1-8.3, respectively), as well as patients affected by CRF and anemia (OR, 6.1; 95% CI, 2.3-16.2). The cluster including HF and CRF was also associated with adverse clinical events (OR, 3.5; 95% CI, 1.5-7.8). The effect of both HF and CRF and anemia and CRF on in-hospital death was additive. Several groups of older patients at risk of in-hospital death and adverse clinical events were identified according to disease clustering. Knowledge of the relationship among co-occurring diseases may help developing strategies to improve clinical practice and preventative interventions.

Mortality Predictors in Patients with Severe Dengue in the State of Amazonas, Brazil.

PubMed

Pinto, Rosemary Costa; Castro, Daniel Barros de; Albuquerque, Bernardino Cláudio de; Sampaio, Vanderson de Souza; Passos, Ricardo Augusto Dos; Costa, Cristiano Fernandes da; Sadahiro, Megumi; Braga, José Ueleres

2016-01-01

Dengue is a major public health problem in tropical and subtropical areas worldwide. There is a lack of information on the risk factors for death due to severe dengue fever in developing countries, including Brazil where the state of Amazonas is located. This knowledge is important for decision making and the implementation of effective measures for patient care. This study aimed to identify factors associated with death among patients with severe dengue, in Amazonas from 2001 to 2013. We conducted a retrospective cohort study based on secondary data from the epidemiological surveillance of dengue provided by the Fundação de Vigilância em Saúde do Amazonas, FVS (Health Surveillance Foundation) of the Secretaria de Saúde do Amazonas, SUSAM (Health Secretariat of the State of Amazonas). Data on dengue cases were obtained from the SINAN (Notifiable Diseases Information System) and SIM (Mortality Information System) databases. We selected cases of severe dengue with laboratory confirmation, including dengue-related deaths of residents in the state of Amazonas from January 1, 2001, to December 31, 2013. The explanatory variables analyzed were sex, age, level of education, spontaneous hemorrhagic manifestations, plasma extravasation and platelet count. Patients who died due to severe dengue had more hematuria, gastrointestinal bleeding, and thrombocytopenia than the survivors. Considering the simultaneous effects of demographic and clinical characteristics with a multiple logistic regression model, it was observed that the factors associated with death were age >55 years (odds ratio [OR] 4.98), gastrointestinal bleeding (OR 10.26), hematuria (OR 5.07), and thrombocytopenia (OR 2.55). Gastrointestinal bleeding was the clinical sign most strongly associated with death, followed by hematuria and age >55 years. The study results showed that the best predictor of death from severe dengue is based on the characteristic of age >55 years, together with the clinical signs of gastrointestinal bleeding, hematuria, and low platelet count.

26 CFR 20.2055-3 - Effect of death taxes and administration expenses.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Effect of death taxes and administration... § 20.2055-3 Effect of death taxes and administration expenses. (a) Death taxes—(1) If under the terms... uses, that is, the amount of the fund remaining after the payment of all death taxes. Thus, if $50,000...

26 CFR 20.2055-3 - Effect of death taxes and administration expenses.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 14 2012-04-01 2012-04-01 false Effect of death taxes and administration... § 20.2055-3 Effect of death taxes and administration expenses. (a) Death taxes—(1) If under the terms... uses, that is, the amount of the fund remaining after the payment of all death taxes. Thus, if $50,000...

26 CFR 20.2055-3 - Effect of death taxes and administration expenses.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 14 2011-04-01 2010-04-01 true Effect of death taxes and administration... § 20.2055-3 Effect of death taxes and administration expenses. (a) Death taxes—(1) If under the terms... uses, that is, the amount of the fund remaining after the payment of all death taxes. Thus, if $50,000...

Risk of death among children of atomic bomb survivors after 62 years of follow-up: a cohort study.

PubMed

Grant, Eric J; Furukawa, Kyoji; Sakata, Ritsu; Sugiyama, Hiromi; Sadakane, Atsuko; Takahashi, Ikuno; Utada, Mai; Shimizu, Yukiko; Ozasa, Kotaro

2015-10-01

No clear epidemiological hereditary effects of radiation exposure in human beings have been reported. However, no previous studies have investigated mortality into middle age in a population whose parents were exposed to substantial amounts of radiation before conception. We assessed mortality in children of the atomic bomb survivors after 62 years of follow-up. In this prospective cohort study, we assessed 75 327 singleton children of atomic bomb survivors in Hiroshima and Nagasaki and unexposed controls, born between 1946 and 1984, and followed up to Dec 31, 2009. Parental gonadal doses of radiation from the atomic bombings were the primary exposures. The primary endpoint was death due to cancer or non-cancer disease, based on death certificates. Median follow-up was 54·3 years (IQR 45·4-59·3). 5183 participants died from disease. The mean age of the 68 689 surviving children at the end of follow-up was 53·1 years (SD 7·9) with 15 623 (23%) older than age 60 years. For parents who were exposed to a non-zero gonadal dose of radiation, the mean dose was 264 mGy (SD 463). We detected no association between maternal gonadal radiation exposure and risk of death caused by cancer (hazard ratio [HR] for 1 Gy change in exposure 0·891 [95% CI 0·693-1·145]; p=0·36) or risk of death caused by non-cancer diseases (0·973 [0·849-1·115]; p=0·69). Likewise, paternal exposure had no effect on deaths caused by cancer (0·815 [0·614-1·083]; p=0·14) or deaths caused by non-cancer disease (1·103 [0·979-1·241]; p=0·12). Age or time between parental exposure and delivery had no effect on risk of death. Late effects of ionising radiation exposure include increased mortality risks, and models of the transgenerational effects of radiation exposure predict more genetic disease in the children of people exposed to radiation. However, children of people exposed to the atomic bombs in Hiroshima and Nagasaki had no indications of deleterious health effects after 62 years. Epidemiological studies complemented by sensitive molecular techniques are needed to understand the overall effects of preconception exposure to ionising radiation on human beings. Copyright © 2015 Elsevier Ltd. All rights reserved.

Discussion of death and dying in surgical textbooks.

PubMed

Easson, A M; Crosby, J A; Librach, S L

2001-07-01

Quality end-of-life care is an increasing concern for the public and the medical profession. Surgical textbooks could serve as an important educational and reference resource to improve this care. Four general surgical textbooks were scored for helpful information on death and dying for eight surgical diseases. For each disease, nine content domains related to care of the dying patient were evaluated. Three texts included a chapter on cancer that was evaluated separately. Disease epidemiology, prognosis/prevention, progression, and medical interventions were generally well discussed in all textbooks. However, little helpful information was provided with regards to breaking bad news/advanced care planning, mode of death, treatment decision-making, effect on family/surgeon, and symptom management. Cancer chapters also addressed only a few of these concerns. Death and the dying patient are sufficiently frequent in surgical practice that it would be appropriate to increase the amount of information provided.

Liver Disease in the HIV-Infected Individual

PubMed Central

Price, Jennifer C.; Thio, Chloe L.

2010-01-01

Since the advent of effective antiretroviral therapy (ART) for human immunodeficiency virus-1 (HIV), there has been a substantial decrease in deaths related to acquired immunodeficiency syndrome (AIDS). However, in the ART-era liver disease is now the most common non-AIDS related cause of death among HIV-infected patients, accounting for 14-18% of all deaths in this population and almost half of deaths among hospitalized HIV-infected patients. Just as the burden of non-AIDS morbidity and mortality has changed in the ART-era, the types of liver disease the clinician is likely to encounter among these patients have changed as well. This review will discuss the causes of liver disease in the HIV-infected population in the ART-era, including chronic hepatitis C virus, chronic hepatitis B virus, medication-related hepatotoxicity, alcohol abuse, nonalcoholic fatty liver disease, and AIDS-related liver diseases. PMID:20851211

Ebola Virus Disease in Children, Sierra Leone, 2014–2015

PubMed Central

Naveed, Asad; Wing, Kevin; Gbessay, Musa; Ross, J.C.G.; Checchi, Francesco; Youkee, Daniel; Jalloh, Mohammed Boie; Baion, David; Mustapha, Ayeshatu; Jah, Hawanatu; Lako, Sandra; Oza, Shefali; Boufkhed, Sabah; Feury, Reynold; Bielicki, Julia A.; Gibb, Diana M.; Klein, Nigel; Sahr, Foday; Yeung, Shunmay

2016-01-01

Little is known about potentially modifiable factors in Ebola virus disease in children. We undertook a retrospective cohort study of children <13 years old admitted to 11 Ebola holding units in the Western Area, Sierra Leone, during 2014–2015 to identify factors affecting outcome. Primary outcome was death or discharge after transfer to Ebola treatment centers. All 309 Ebola virus–positive children 2 days–12 years old were included; outcomes were available for 282 (91%). Case-fatality was 57%, and 55% of deaths occurred in Ebola holding units. Blood test results showed hypoglycemia and hepatic/renal dysfunction. Death occurred swiftly (median 3 days after admission) and was associated with younger age and diarrhea. Despite triangulation of information from multiple sources, data availability was limited, and we identified no modifiable factors substantially affecting death. In future Ebola virus disease epidemics, robust, rapid data collection is vital to determine effectiveness of interventions for children. PMID:27649367

Causes of death and demographic characteristics of victims of meteorological disasters in Korea from 1990 to 2008

PubMed Central

2011-01-01

Background Meteorological disasters are an important component when considering climate change issues that impact morbidity and mortality rates. However, there are few epidemiological studies assessing the causes and characteristics of deaths from meteorological disasters. The present study aimed to analyze the causes of death associated with meteorological disasters in Korea, as well as demographic and geographic vulnerabilities and their changing trends, to establish effective measures for the adaptation to meteorological disasters. Methods Deaths associated with meteorological disasters were examined from 2,045 cases in Victim Survey Reports prepared by 16 local governments from 1990 to 2008. Specific causes of death were categorized as drowning, structural collapse, electrocution, lightning, fall, collision, landslide, avalanche, deterioration of disease by disaster, and others. Death rates were analyzed according to the meteorological type, specific causes of death, and demographic and geographic characteristics. Results Drowning (60.3%) caused the greatest number of deaths in total, followed by landslide (19.7%) and structural collapse (10.1%). However, the causes of deaths differed between disaster types. The meteorological disaster associated with the greatest number of deaths has changed from flood to typhoon. Factors that raised vulnerability included living in coastal provinces (11.3 times higher than inland metropolitan), male gender (1.9 times higher than female), and older age. Conclusions Epidemiological analyses of the causes of death and vulnerability associated with meteorological disasters can provide the necessary information for establishing future adaptation measures against climate change. A more comprehensive system for assessing disaster epidemiology needs to be established. PMID:21943038

The pro-apoptotic protein Bmf co-operates with Bim and Puma in neuron death induced by β-amyloid or NGF deprivation.

PubMed

Akhter, Rumana; Saleem, Suraiya; Saha, Akash; Biswas, Subhas Chandra

2018-04-01

The pro-apoptotic Bcl-2 homology 3 domain only (BH3-only) proteins are central regulators of cell death in various physiological and pathological conditions, including Alzheimer's disease (AD). Bcl-2 modifying factor (Bmf) is one such BH3-only protein that is implicated in various death paradigms such as anoikis, seizures, cancer and autoimmunity. It also co-operates with other BH3-only proteins such as Bim in various death paradigms. However, its role in neurodegeneration is under-investigated. Here, we report for the first time the essential role of Bmf and its co-operativity with direct activator BH3-only proteins Bim and Puma in neuron death induced by beta-amyloid (Aβ) toxicity or NGF deprivation. Oligomeric Aβ is main pathologic species in AD and NGF deprivation is relevant for both developmental as well as pathologic neuron death. We find that Bmf over-expression causes cell death and Bmf knockdown protects neurons against death evoked by Aβ or NGF deprivation. We also find that Bmf co-operates with other important BH3-only proteins such as Bim and Puma in neuron death induced by Aβ or NGF deprivation. Simultaneous knocking down of these molecules by their respective shRNAs provide enhanced protection against Aβ. Taken together, our results elucidate the essential role of Bmf and its co-operative effects with already known neuron death inducers, Bim and Puma, in neuron death evoked by Aβ treatment or NGF deprivation. Copyright © 2018 Elsevier Inc. All rights reserved.

Thanatophobia (Death Anxiety) in the Elderly: The Problem of the Child's Inability to Assess Their Own Parent's Death Anxiety State.

PubMed

Sinoff, Gary

2017-01-01

Thanatophobia is omnipresent in our lives. Research has shown separate but connected constructs: fear of death or fear of the dying process. The influences on death anxiety are varied including religiosity, gender, psychological state, and age. It is often assumed by the children of the elderly that the fear of death is prevalent in their parents. Daily the medical staff encounters the presence of death anxiety: from family members or the staff itself. In order to understand this phenomenon, a three-tier study was conducted on non-terminal elderly inpatients in an acute geriatric care ward. The study showed that the elderly had low levels of anxiety (scoring 4/15 on Templer's Death Anxiety Scale) but their children scored higher for themselves (6.9/15) and for their parents (8.9/15). A regression model showed that only the presence of generalized anxiety and religiosity of parent had an effect explaining 33.6% of the variance. Death anxiety of death is usually absent in the elderly but rather they fear the dying process. On the other hand, their children do fear death, which they extrapolate onto their parents. This causes conflicts since the children prevent disclosure of relevant medical information to their parents. This has to be addressed by the staff when dealing with family members, to allow open and honest communication with their patients. The staff need to explain to the family that the elderly are not afraid of death but of the suffering from the dying process.

Association of extremely high levels of high-density lipoprotein cholesterol with cardiovascular mortality in a pooled analysis of 9 cohort studies including 43,407 individuals: The EPOCH-JAPAN study.

PubMed

Hirata, Aya; Sugiyama, Daisuke; Watanabe, Makoto; Tamakoshi, Akiko; Iso, Hiroyasu; Kotani, Kazuhiko; Kiyama, Masahiko; Yamada, Michiko; Ishikawa, Shizukiyo; Murakami, Yoshitaka; Miura, Katsuyuki; Ueshima, Hirotsugu; Okamura, Tomonori

2018-02-08

The effect of very high or extremely high levels of high-density lipoprotein cholesterol (HDL-C) on cardiovascular disease (CVD) is not well described. Although a few recent studies have reported the adverse effects of extremely high levels of HDL-C on CVD events, these did not show a statistically significant association between extremely high levels of HDL-C and cause-specific CVD mortality. In addition, Asian populations have not been studied. We examine the impact of extremely high levels of HDL-C on cause-specific CVD mortality using pooled data of Japanese cohort studies. We performed a large-scale pooled analysis of 9 Japanese cohorts including 43,407 participants aged 40-89 years, dividing the participants into 5 groups by HDL-C levels, including extremely high levels of HDL-C ≥2.33 mmol/L (≥90 mg/dL). We estimated the adjusted hazard ratio of each HDL-C category for all-cause death and cause-specific deaths compared with HDL-C 1.04-1.55 mmol/L (40-59 mg/dL) using a cohort-stratified Cox proportional hazards model. During a 12.1-year follow-up, 4995 all-cause deaths and 1280 deaths due to overall CVD were identified. Extremely high levels of HDL-C were significantly associated with increased risk of atherosclerotic CVD mortality (hazard ratio = 2.37, 95% confidence interval: 1.37-4.09 for total) and increased risk for coronary heart disease and ischemic stroke. In addition, the risk for extremely high HDL-C was more evident among current drinkers. We showed extremely high levels of HDL-C had an adverse effect on atherosclerotic CVD mortality in a pooled analysis of Japanese cohorts. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Maternal and child health services and an integrated, life-cycle approach to the prevention of non-communicable diseases

PubMed Central

Brumana, Luisa; Arroyo, Alvaro; Schwalbe, Nina R; Lehtimaki, Susanna

2017-01-01

Described as the ‘invisible epidemic’, non-communicable diseases (NCDs) are the world’s leading cause of death. Most are caused by preventable factors, including poor diet, tobacco use, harmful use of alcohol and physical inactivity. Diabetes, cancer and cardiovascular and chronic lung diseases were responsible for 38 million (68%) of global deaths in 2012. Since 1990, proportionate NCD mortality has increased substantially as populations have aged and communicable diseases decline. The majority of NCD deaths, especially premature NCD deaths (<70 years, 82%), occur in low-income and middle-income countries, and among poor communities within them. Addressing NCDs is recognised as central to the post-2015 agenda; accordingly, NCDs have a specific objective and target in the Sustainable Development Goals. While deaths from NCDs occur mainly in adulthood, many have their origins in early life, including through epigenetic mechanisms operating before conception. Good nutrition before conception and interventions aimed at preventing NCDs during the first 1000 days (from conception to age 2 years), childhood and adolescence may be more cost-effective than managing established NCDs in later life with costly tests and drugs. Following a life-course approach, maternal and child health interventions, before delivery and during childhood and adolescence, can prevent NCDs and should influence global health and socioeconomic development. This paper describes how such an approach may be pursued, including through the engagement of non-health sectors. It also emphasises evaluating and documenting related initiatives to underwrite systematic and evidence-based cross-sectoral engagement on NCD prevention in the future. PMID:29082005

Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review.

PubMed

Warren-Gash, Charlotte; Smeeth, Liam; Hayward, Andrew C

2009-10-01

Cardiac complications of influenza infection, such as myocarditis, are well recognised, but the role of influenza as a trigger of acute myocardial infarction is less clear. We did a systematic review of the evidence that influenza (including influenza-like illness and acute respiratory infection) triggers acute myocardial infarction or cardiovascular death. We examined the effectiveness of influenza vaccines at protecting against cardiac events and did a meta-analysis of data from randomised controlled trials. 42 publications describing 39 studies were identified. Many observational studies in different settings with a range of methods reported consistent associations between influenza and acute myocardial infarction. There was weaker evidence of an association with cardiovascular death. Two small randomised trials assessed the protection provided by influenza vaccine against cardiac events in people with existing cardiovascular disease. Whereas one trial found that influenza vaccination gave significant protection against cardiovascular death, the other trial was inconclusive. A pooled estimate from a random-effects model suggests a protective, though non-significant, effect (relative risk 0.51, 95% CI 0.15-1.76). We believe influenza vaccination should be encouraged wherever indicated, especially in people with existing cardiovascular disease, among whom there is often suboptimum vaccine uptake. Further evidence is needed on the effectiveness of influenza vaccines to reduce the risk of cardiac events in people without established vascular disease.

Surveillance for violent deaths - National Violent Death Reporting System, 16 states, 2010.

PubMed

Parks, Sharyn E; Johnson, Linda L; McDaniel, Dawn D; Gladden, Matthew

2014-01-17

An estimated 55,000 persons die annually in the United States as a result of violence-related injuries. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) regarding violent deaths from 16 U.S. states for 2010. Results are reported by sex, age group, race/ethnicity, marital status, location of injury, method of injury, circumstances of injury, and other selected characteristics. 2010. NVDRS collects data regarding violent deaths obtained from death certificates, coroner/medical examiner reports, law enforcement reports, and secondary sources (e.g., child fatality review team data, supplementary homicide reports, hospital data, and crime laboratory data). NVDRS data collection began in 2003 with seven states (Alaska, Maryland, Massachusetts, New Jersey, Oregon, South Carolina, and Virginia) participating; six states (Colorado, Georgia, North Carolina, Oklahoma, Rhode Island, and Wisconsin) joined in 2004, four (California, Kentucky, New Mexico, and Utah) in 2005, and two in 2010 (Ohio and Michigan), for a total of 19 states. This report includes data from 16 states that collected statewide data in 2010; data from California are not included in this report because data were not collected after 2009. Ohio and Michigan were excluded because data collection, which began in 2010, did not occur statewide until 2011. For 2010, a total of 15,781 fatal incidents involving 16,186 deaths were captured by NVDRS in the 16 states included in this report. The majority (62.8%) of deaths were suicides, followed by homicides and deaths involving legal intervention (i.e., deaths caused by law enforcement and other persons with legal authority to use deadly force, excluding legal executions) (24.4%), deaths of undetermined intent (12.2%), and unintentional firearm deaths (0.7%). Suicides occurred at higher rates among males, non-Hispanic whites, American Indians/Alaska Natives, and persons aged 45-54 years. Suicides most often occurred in a house or apartment and involved the use of firearms. Suicides were preceded primarily by a mental health or intimate partner problem, a crisis during the previous 2 weeks, or a physical health problem. Homicides occurred at higher rates among males and persons aged 20-24 years; rates were highest among non-Hispanic black males. The majority of homicides involved the use of a firearm and occurred in a house or apartment or on a street/highway. Homicides were precipitated primarily by arguments and interpersonal conflicts or in conjunction with another crime. This report provides a detailed summary of data from NVDRS for 2010. The results indicate that violent deaths resulting from self-inflicted or interpersonal violence disproportionately affected persons aged <55 years, males, and certain minority populations. For homicides and suicides, relationship problems, interpersonal conflicts, mental health problems, and recent crises were among the primary precipitating factors. Because additional information might be reported subsequently as participating states update their findings, the data provided in this report are preliminary. For the occurrence of violent deaths in the United States to be better understood and ultimately prevented, accurate, timely, and comprehensive surveillance data are necessary. NVDRS data can be used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in the development, implementation, and evaluation of programs and policies to reduce and prevent violent deaths at the national, state, and local levels. NVDRS data have been used to enhance prevention programs. Examples include use of linked NVDRS data and adult protective service data to better target elder maltreatment prevention programs and improve staff training to identify violent death risks for older adults in North Carolina, use of Oklahoma VDRS homicide data to help evaluate the effectiveness of a new police and advocate intervention at domestic violence incident scenes, and data-informed changes in primary care practice in Oregon to more effectively address older adult suicide prevention. The continued development and expansion of NVDRS is essential to CDC's efforts to reduce the personal, familial, and societal impacts of violence. Further efforts are needed to increase the number of states participating in NVDRS, with an ultimate goal of full national representation.

Traditional birth attendant training for improving health behaviours and pregnancy outcomes

PubMed Central

Sibley, Lynn M; Sipe, Theresa Ann; Barry, Danika

2014-01-01

Background Between the 1970s and 1990s, the World Health Organization promoted traditional birth attendant (TBA) training as one strategy to reduce maternal and neonatal mortality. To date, evidence in support of TBA training is limited but promising for some mortality outcomes. Objectives To assess the effects of TBA training on health behaviours and pregnancy outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (18 June 2012), citation alerts from our work and reference lists of studies identified in the search. Selection criteria Published and unpublished randomised controlled trials (RCT), comparing trained versus untrained TBAs, additionally trained versus trained TBAs, or women cared for/living in areas served by TBAs. Data collection and analysis Three authors independently assessed study quality and extracted data in the original and first update review. Three authors and one external reviewer independently assessed study quality and two extracted data in this second update. Main results Six studies involving over 1345 TBAs, more than 32,000 women and approximately 57,000 births that examined the effects of TBA training for trained versus untrained TBAs (one study) and additionally trained TBA training versus trained TBAs (five studies) are included in this review. These studies consist of individual randomised trials (two studies) and cluster-randomised trials (four studies). The primary outcomes across the sample of studies were perinatal deaths, stillbirths and neonatal deaths (early, late and overall). Trained TBAs versus untrained TBAs: one cluster-randomised trial found a significantly lower perinatal death rate in the trained versus untrained TBA clusters (adjusted odds ratio (OR) 0.70, 95% confidence interval (CI) 0.59 to 0.83), lower stillbirth rate (adjusted OR 0.69, 95% CI 0.57 to 0.83) and lower neonatal death rate (adjusted OR 0.71, 95% CI 0.61 to 0.82). This study also found the maternal death rate was lower but not significant (adjusted OR 0.74, 95% CI 0.45 to 1.22). Additionally trained TBAs versus trained TBAs: three large cluster-randomised trials compared TBAs who received additional training in initial steps of resuscitation, including bag-valve-mask ventilation, with TBAs who had received basic training in safe, clean delivery and immediate newborn care. Basic training included mouth-to-mouth resuscitation (two studies) or bag-valve-mask resuscitation (one study). There was no significant difference in the perinatal death rate between the intervention and control clusters (one study, adjusted OR 0.79, 95% CI 0.61 to 1.02) and no significant difference in late neonatal death rate between intervention and control clusters (one study, adjusted risk ratio (RR) 0.47, 95% CI 0.20 to 1.11). The neonatal death rate, however, was 45% lower in intervention compared with the control clusters (one study, 22.8% versus 40.2%, adjusted RR 0.54, 95% CI 0.32 to 0.92). We conducted a meta-analysis on two outcomes: stillbirths and early neonatal death. There was no significant difference between the additionally trained TBAs versus trained TBAs for stillbirths (two studies, mean weighted adjusted RR 0.99, 95% CI 0.76 to 1.28) or early neonatal death rate (three studies, mean weighted adjusted RR 0.83, 95% CI 0.68 to 1.01). Authors’ conclusions The results are promising for some outcomes (perinatal death, stillbirth and neonatal death). However, most outcomes are reported in only one study. A lack of contrast in training in the intervention and control clusters may have contributed to the null result for stillbirths and an insufficient number of studies may have contributed to the failure to achieve significance for early neonatal deaths. Despite the additional studies included in this updated systematic review, there remains insufficient evidence to establish the potential of TBA training to improve peri-neonatal mortality. PMID:22895949

The Effects of Evacuation on Nursing Home Residents With Dementia

PubMed Central

Brown, Lisa M.; Dosa, David M.; Thomas, Kali; Hyer, Kathryn; Feng, Zhanlian; Mor, Vincent

2013-01-01

Background In response to the hurricane-related deaths of nursing home residents, there has been a steady increase in the number of facilities that evacuate under storm threat. This study examined the effects of evacuation during Hurricane Gustav on residents who were cognitively impaired. Methods Nursing homes in counties located in the path of Hurricane Gustav were identified. The Minimum Data Set resident assessment files were merged with the Centers for Medicare enrollment file to determine date of death for residents in identified facilities. Difference-in-differences analyses were conducted adjusting for residents’ demographic characteristics and acuity. Results The dataset included 21,255 residents living in 119 at risk nursing homes over three years of observation. Relative to the two years before the storm, there was a 2.8 percent increase in death at 30 days and a 3.9 percent increase in death at 90 days for residents with severe dementia who evacuated for Hurricane Gustav, controlling for resident demographics and acuity. Conclusions The findings of this research reveal the deleterious effects of evacuation on residents with severe dementia. Interventions need to be developed and tested to determine the best methods for protecting this at risk population when there are no other options than to evacuate the facility. PMID:22930698

Protective effect of T-type calcium channel blocker flunarizine on cisplatin-induced death of auditory cells.

PubMed

So, Hong-Seob; Park, Channy; Kim, Hyung-Jin; Lee, Jung-Han; Park, Sung-Yeol; Lee, Jai-Hyung; Lee, Zee-Won; Kim, Hyung-Min; Kalinec, Federico; Lim, David J; Park, Raekil

2005-06-01

Changes in intracellular Ca2+ level are involved in a number of intracellular events, including triggering of apoptosis. The role of intracellular calcium mobilization in cisplatin-induced hair cell death, however, is still unknown. In this study, the effect of calcium channel blocker flunarizine (Sibelium), which is used to prescribe for vertigo and tinnitus, on cisplatin-induced hair cell death was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1, and the neonatal (P2) rat organ of Corti explant. Cisplatin induced apoptotic cell death showing nuclear fragmentation, DNA ladder, and TUNEL positive in both HEI-OC1 and primary organ of Corti explant. Flunarizine significantly inhibited the cisplatin-induced apoptosis. Unexpectedly, flunarizine increased the intracellular calcium ([Ca2+]i) levels of HEI-OC1. However, the protective effect of flunarizine against cisplatin was not mediated by modulation of intracellular calcium level. Treatment of cisplatin resulted in ROS generation and lipid peroxidation in HEI-OC1. Flunarizine did not attenuate ROS production but inhibited lipid peroxidation and mitochondrial permeability transition in cisplatin-treated cells. This result suggests that the protective mechanism of flunarizine on cisplatin-induced cytotoxicity is associated with direct inhibition of lipid peroxidation and mitochondrial permeability transition.

The Relationship Between Index Hospitalizations, Sepsis, and Death or Transition to Hospice Care During 30-Day Hospital Readmissions.

PubMed

Dietz, Brett W; Jones, Tiffanie K; Small, Dylan S; Gaieski, David F; Mikkelsen, Mark E

2017-04-01

Hospital readmissions are common, expensive, and increasingly used as a metric for assessing quality of care. The relationship between index hospitalizations and specific outcomes among those readmitted remains largely unknown. Identify risk factors present during the index hospitalization associated with death or transition to hospice care during 30-day readmissions and examine the contribution of infection in readmissions resulting in death. Retrospective cohort study. A total of 17,716 30-day readmissions in an academic health system. We used mixed-effects multivariable logistic regression models to identify risk factors associated with the primary outcome, in-hospital death, or transition to hospice during 30-day readmissions. Of 17,716 30-day readmissions, 1144 readmissions resulted in death or transition to hospice care (6.5%). Risk factors identified included: age, burden, and type of comorbid conditions, recent hospitalizations, nonelective index admission type, outside hospital transfer, low discharge hemoglobin, low discharge sodium, high discharge red blood cell distribution width, and disposition to a setting other than home. Sepsis (OR=1.33; 95% CI, 1.02-1.72; P=0.03) and shock (OR=1.78; 95% CI, 1.22-2.58; P=0.002) during the index admission were associated with the primary outcome, and in-hospital mortality specifically. In patients who died, infection was the primary cause for readmission in 51.6% of readmissions after sepsis and 28.6% of readmissions after a nonsepsis hospitalization (P=0.009). We identified factors, including sepsis and shock during the index hospitalization, associated with death or transition to hospice care during readmission. Infection was frequently implicated as the cause of a readmission that ended in death.

Screen of FDA-approved drug library reveals compounds that protect hair cells from aminoglycosides and cisplatin

PubMed Central

Vlasits, Anna L.; Simon, Julian A.; Raible, David W.; Rubel, Edwin W; Owens, Kelly N.

2012-01-01

Loss of mechanosensory hair cells in the inner ear accounts for many hearing loss and balance disorders. Several beneficial pharmaceutical drugs cause hair cell death as a side effect. These include aminoglycoside antibiotics, such as neomycin, kanamycin and gentamicin, and several cancer chemotherapy drugs, such as cisplatin. Discovering new compounds that protect mammalian hair cells from toxic insults is experimentally difficult because of the inaccessibility of the inner ear. We used the zebrafish lateral line sensory system as an in vivo screening platform to survey a library of FDA-approved pharmaceuticals for compounds that protect hair cells from neomycin, gentamicin, kanamycin and cisplatin. Ten compounds were identified that provide protection from at least two of the four toxins. The resulting compounds fall into several drug classes, including serotonin and dopamine-modulating drugs, adrenergic receptor ligands, and estrogen receptor modulators. The protective compounds show different effects against the different toxins, supporting the idea that each toxin causes hair cell death by distinct, but partially overlapping, mechanisms. Furthermore, some compounds from the same drug classes had different protective properties, suggesting that they might not prevent hair cell death by their known target mechanisms. Some protective compounds blocked gentamicin uptake into hair cells, suggesting that they may block mechanotransduction or other routes of entry. The protective compounds identified in our screen will provide a starting point for studies in mammals as well as further research discovering the cellular signaling pathways that trigger hair cell death. PMID:22967486

The Effect of Maternal Death on the Health of the Husband and Children in a Rural Area of China: A Prospective Cohort Study.

PubMed

Zhou, Hong; Zhang, Long; Ye, Fang; Wang, Hai-Jun; Huntington, Dale; Huang, Yanjie; Wang, Anqi; Liu, Shuiqing; Wang, Yan

2016-01-01

To examine the effects of maternal death on the health of the index child, the health and educational attainment of the older children, and the mental health and quality of life of the surviving husband. A cohort study including 183 households that experienced a maternal death matched to 346 households that experienced childbirth but not a maternal death was conducted prospectively between June 2009 and October 2011 in rural China. Data on household sociodemographic characteristics, physical and mental health were collected using a quantitative questionnaire and medical examination at baseline and follow-up surveys. Multivariate linear regression, logistic regression models and difference-in-difference (DID) were used to compare differences of outcomes between two groups. The index children who experienced the loss of a mother had a significantly higher likelihood of dying, abandonment and malnutrition compared to children whose mothers survived at the follow-up survey. The risk of not attending school on time and dropping out of school among older children in the affected group was higher than those in the control group during the follow-up. Husbands whose wife died had significantly lower EQ-5D index and EQ-VAS both at baseline and at follow-up surveys compared to those without experiencing a wife's death, suggesting an immediate and sustained poorer mental health quality of life among the surviving husbands. Also the prevalence of posttraumatic stress disorder (PTSD) was 72.6% at baseline and 56.2% at follow-up among husbands whose wife died. Maternal death has multifaceted and spillover effects on the physical and mental health of family members that are sustained over time. Programmes that reduce maternal mortality will mitigate repercussions on surviving family members are critical and needed.

Análisis de Costo Efectividad de Estrategias de Tratamiento Antimicótico en Pacientes con Neutropenia Febril Persistente y Tratamiento Antibiótico de Amplio Espectro.

PubMed

Gamboa Garay, Oscar Andrés; Fuentes Pachón, Juan Camilo; Cuervo Maldonado, Sonia Isabel; Gómez Rincón, Julio Cesar; Castillo Londoño, Juan Sebastian

2012-12-01

To assess cost-effectiveness of antifungal treatment on patients with persistent fever neutropenia: empiric antifungal therapy (EAT) vs. anticipated antifungal therapy (AAT). A decision model was performed to evaluate the cost-effectiveness of antifungal treatment strategies in patients with febrile neutropenia not responding to a broad spectrum antibiotic treatment. The strategies included were: 1) EAT with amphotericin B deoxycholate; 2) EAT with liposomal amphotericin B; 3) EAT with caspofungin; and 4) AAT with voriconazole and amphotericin B deoxycholate or liposomal amphotericin B or caspofungin in patients who initiate treatment despite having negative CT scan and galactomannan or fail to voriconazole. Effectiveness was measured as the number of deaths averted. Cost-effectiveness and incremental cost-effectiveness ratios were calculated. Deterministic and probabilistic sensitivity analyzes were performed. EAT with Amphotericin B deoxycholate was the least expensive and least effective strategy. The EAT with caspofungin was the most effective. The cost per death averted for caspofungin when compared with amphotericin B deoxycholate was $17,011,073.83, which would indicate that this strategy would be cost-effective for the country if the willingness to pay per death averted is equal to or greater than this value. EAT with liposomal amphotericin B and AAT with voriconazole were dominated by AET with caspofungin, which is less costly and more effective. EAT with caspofungin would be cost-effective for Colombia if the threshold per death averted is greater to $18.000.000. If the threshold is lesser the EAT with amphotericin B deoxycholate would be the election. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Retrospective economic evaluation of childhood 7-valent pneumococcal conjugate vaccination in Australia: Uncertain herd impact on pneumonia critical.

PubMed

Newall, A T; Reyes, J F; McIntyre, P; Menzies, R; Beutels, P; Wood, J G

2016-01-12

Retrospective cost-effectiveness analyses of vaccination programs using routinely collected post-implementation data are sparse by comparison with pre-program analyses. We performed a retrospective economic evaluation of the childhood 7-valent pneumococcal conjugate vaccine (PCV7) program in Australia. We developed a deterministic multi-compartment model that describes health states related to invasive and non-invasive pneumococcal disease. Costs (Australian dollars, A$) and health effects (quality-adjusted life years, QALYs) were attached to model states. The perspective for costs was that of the healthcare system and government. Where possible, we used observed changes in the disease rates from national surveillance and healthcare databases to estimate the impact of the PCV7 program (2005-2010). We stratified our cost-effectiveness results into alternative scenarios which differed by the outcome states included. Parameter uncertainty was explored using probabilistic sensitivity analysis. The PCV7 program was estimated to have prevented ∼5900 hospitalisations and ∼160 deaths from invasive pneumococcal disease (IPD). Approximately half of these were prevented in adults via herd protection. The incremental cost-effectiveness ratio was ∼A$161,000 per QALY gained when including only IPD-related outcomes. The cost-effectiveness of PCV7 remained in the range A$88,000-$122,000 when changes in various non-invasive disease states were included. The inclusion of observed changes in adult non-invasive pneumonia deaths substantially improved cost-effectiveness (∼A$9000 per QALY gained). Using the initial vaccine price negotiated for Australia, the PCV7 program was unlikely to have been cost-effective (at conventional thresholds) unless observed reductions in non-invasive pneumonia deaths in the elderly are attributed to it. Further analyses are required to explore this finding, which has significant implications for the incremental benefit achievable by adult PCV programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cost-effectiveness of percutaneous coronary intervention with drug-eluting stents in patients with multivessel coronary artery disease compared to coronary artery bypass surgery five-years after intervention

PubMed Central

Krenn, Lisa; Kopp, Christoph; Glogar, Dietmar; Lang, Irene M; Delle-Karth, Georg; Neunteufl, Thomas; Kreiner, Gerhard; Kaider, Alexandra; Bergler-Klein, Jutta; Khorsand, Aliasghar; Nikfardjam, Mariam; Laufer, Günther; Maurer, Gerald; Gyöngyösi, Mariann

2014-01-01

Objectives Cost-effectiveness of percutaneous coronary intervention (PCI) using drug-eluting stents (DES), and coronary artery bypass surgery (CABG) was analyzed in patients with multivessel coronary artery disease over a 5-year follow-up. Background DES implantation reducing revascularization rate and associated costs might be attractive for health economics as compared to CABG. Methods Consecutive patients with multivessel DES-PCI (n = 114, 3.3 ± 1.2 DES/patient) or CABG (n = 85, 2.7 ± 0.9 grafts/patient) were included prospectively. Primary endpoint was cost-benefit of multivessel DES-PCI over CABG, and the incremental cost-effectiveness ratio (ICER) was calculated. Secondary endpoint was the incidence of major adverse cardiac and cerebrovascular events (MACCE), including acute myocardial infarction (AMI), all-cause death, revascularization, and stroke. Results Despite multiple uses for DES, in-hospital costs were significantly less for PCI than CABG, with 4551 €/patient difference between the groups. At 5-years, the overall costs remained higher for CABG patients (mean difference 5400 € between groups). Cost-effectiveness planes including all patients or subgroups of elderly patients, diabetic patients, or Syntax score >32 indicated that CABG is a more effective, more costly treatment mode for multivessel disease. At the 5-year follow-up, a higher incidence of MACCE (37.7% vs. 25.8%; log rank P = 0.048) and a trend towards more AMI/death/stroke (25.4% vs. 21.2%, log rank P = 0.359) was observed in PCI as compared to CABG. ICER indicated 45615 € or 126683 € to prevent one MACCE or AMI/death/stroke if CABG is performed. Conclusions Cost-effectiveness analysis of DES-PCI vs. CABG demonstrated that CABG is the most effective, but most costly, treatment for preventing MACCE in patients with multivessel disease. © 2014 Wiley Periodicals, Inc. PMID:24403120

The Effect of Widowhood on Mental Health - an Analysis of Anticipation Patterns Surrounding the Death of a Spouse.

PubMed

Siflinger, Bettina

2017-12-01

This study explores the effects of widowhood on mental health by taking into account the anticipation and adaptation to the partner's death. The empirical analysis uses representative panel data from the USA that are linked to administrative death records of the National Death Index. I estimate static and dynamic specifications of the panel probit model in which unobserved heterogeneity is modeled with correlated random effects. I find strong anticipation effects of the partner's death on the probability of depression, implying that the partner's death event cannot be assumed to be exogenous in econometric models. In the absence of any anticipation effects, the partner's death has long-lasting mental health consequences, leading to a significantly slower adaptation to widowhood. The results suggest that both anticipation effects and adaptation effects can be attributed to a caregiver burden and to the cause of death. The findings of this study have important implications for designing adequate social policies for the elderly US population that alleviate the negative consequences of bereavement. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Dietary and supplemental calcium intake and cardiovascular disease mortality: the National Institutes of Health-AARP diet and health study.

PubMed

Xiao, Qian; Murphy, Rachel A; Houston, Denise K; Harris, Tamara B; Chow, Wong-Ho; Park, Yikyung

2013-04-22

Calcium intake has been promoted because of its proposed benefit on bone health, particularly among the older population. However, concerns have been raised about the potential adverse effect of high calcium intake on cardiovascular health. To investigate whether intake of dietary and supplemental calcium is associated with mortality from total cardiovascular disease (CVD), heart disease, and cerebrovascular diseases. Prospective study from 1995 through 1996 in California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania and the 2 metropolitan areas of Atlanta, Georgia, and Detroit, Michigan. A total of 388 229 men and women aged 50 to 71 years from the National Institutes of Health-AARP Diet and Health Study. Dietary and supplemental calcium intake was assessed at baseline (1995-1996). Supplemental calcium intake included calcium from multivitamins and individual calcium supplements. Cardiovascular disease deaths were ascertained using the National Death Index. Multivariate Cox proportional hazards regression models adjusted for demographic, lifestyle, and dietary variables were used to estimate relative risks (RRs) and 95% CIs. During a mean of 12 years of follow-up, 7904 and 3874 CVD deaths in men and women, respectively, were identified. Supplements containing calcium were used by 51% of men and 70% of women. In men, supplemental calcium intake was associated with an elevated risk of CVD death (RR>1000 vs 0 mg/d, 1.20; 95% CI, 1.05-1.36), more specifically with heart disease death (RR, 1.19; 95% CI, 1.03-1.37) but not significantly with cerebrovascular disease death (RR, 1.14; 95% CI, 0.81-1.61). In women, supplemental calcium intake was not associated with CVD death (RR, 1.06; 95% CI, 0.96-1.18), heart disease death (1.05; 0.93-1.18), or cerebrovascular disease death (1.08; 0.87-1.33). Dietary calcium intake was unrelated to CVD death in either men or women. Our findings suggest that high intake of supplemental calcium is associated with an excess risk of CVD death in men but not in women. Additional studies are needed to investigate the effect of supplemental calcium use beyond bone health.

20 CFR 702.201 - Reports from employers of employee's injury or death.

Code of Federal Regulations, 2010 CFR

2010-04-01

... or death. 702.201 Section 702.201 Employees' Benefits EMPLOYMENT STANDARDS ADMINISTRATION, DEPARTMENT... death. (a) Within 10 days from the date of an employee's injury or death, or 10 days from the date an employer has knowledge of an employee's injury or death, including any disease or death proximately caused...

Acute stress cardiomyopathy and deaths associated with electronic weapons.

PubMed

Cevik, Cihan; Otahbachi, Mohammad; Miller, Elizabeth; Bagdure, Satish; Nugent, Kenneth M

2009-03-06

Deaths associated with the use of electronic weapons almost always occur in young men involved in either civil disturbances or criminal activity. These situations are associated with high levels of circulating catecholamines and frequently associated with drug intoxication. The mechanism for these deaths is unclear. Clinical studies indicate that these high voltage electrical pulses do not cause cardiac arrhythmia. Acute stress cardiomyopathy provides an alternative explanation for deaths associated with electronic weapons and may provide a better explanation for the usual time course associated with taser deaths. Patients with acute stress cardiomyopathy usually have had an emotional or physical stress, have high circulating levels of catecholamines, present with an acute coronary syndrome but have normal coronary vessels without significant thrombus formation. They have unusual left ventricular dysfunction with so-called apical ballooning. This presentation has been attributed to the direct effects of catecholamines on myocardial cell function. Alternative explanations include vasospasm in the coronary microcirculation and/or acute thrombosis followed by rapid thrombolysis. Similar events could occur during the high stress situations associated with the use of electronic weapons. These events also likely explain restraint-related deaths which occur in independent of any use of electronic weapons. Forensic pathologists have the opportunity to provide important details about the pathogenesis of these deaths through histological studies and careful evaluation of coronary vessels.

Disenfranchised grief and nonfinite loss as experienced by the families of death row inmates.

PubMed

Jones, Sandra J; Beck, Elizabeth

The families of death row inmates experience grief and loss issues that have been neglected by scholars and clinicians alike. The issues found in this population are unique and require our understanding. The present study uses the concepts of disenfranchised grief and nonfinite loss to uncover the pain experienced by the children and other family members who have a loved one on death row. Kenneth Doka's (1989) concept of disenfranchised grief is utilized to bring attention to the ways in which the circumstances surrounding an execution leave the family members of those condemned to death outside of the "grieving rules" that exist in the United States. Family members are disenfranchised from their grief, as society does not socially validate their pain. The loss that they feel is also nonfinite (Bruce & Schultz, 2001) in that it is continuous and denies the families all of the hopes, dreams, and expectations that they had for their loved one who now sits on death row. The qualitative interview method was utilized by the authors of this study to gather data from 26 family members of death row inmates who are incarcerated along the East Coast of the United States. The reactions of this group of family members are varied and complex, yet they include the following common responses: social isolation due to stigma and their own feelings of criminalization, intensified family conflict between family members who grieve differently from one another, diminished self-esteem, shame, diffused and specific feelings of guilt, and a chronic state of despair. This study explores virtually untapped terrain. An examination of the microlevel effects of the death penalty on families provides insight in to the area of death and dying, especially as it is related to disenfranchised loss and nonfinite grief. In addition, this study provides insight into the death penalty and its effects.

Sudden death in eating disorders

PubMed Central

Jáuregui-Garrido, Beatriz; Jáuregui-Lobera, Ignacio

2012-01-01

Eating disorders are usually associated with an increased risk of premature death with a wide range of rates and causes of mortality. “Sudden death” has been defined as the abrupt and unexpected occurrence of fatality for which no satisfactory explanation of the cause can be ascertained. In many cases of sudden death, autopsies do not clarify the main cause. Cardiovascular complications are usually involved in these deaths. The purpose of this review was to report an update of the existing literature data on the main findings with respect to sudden death in eating disorders by means of a search conducted in PubMed. The most relevant conclusion of this review seems to be that the main causes of sudden death in eating disorders are those related to cardiovascular complications. The predictive value of the increased QT interval dispersion as a marker of sudden acute ventricular arrhythmia and death has been demonstrated. Eating disorder patients with severe cardiovascular symptoms should be hospitalized. In general, with respect to sudden death in eating disorders, some findings (eg, long-term eating disorders, chronic hypokalemia, chronically low plasma albumin, and QT intervals >600 milliseconds) must be taken into account, and it must be highlighted that during refeeding, the adverse effects of hypophosphatemia include cardiac failure. Monitoring vital signs and performing electrocardiograms and serial measurements of plasma potassium are relevant during the treatment of eating disorder patients. PMID:22393299

Comparison of the injury severity and medical history of disease-related versus trauma-related bicyclist fatalities.

PubMed

Hitosugi, Masahito; Koseki, Takeshi; Miyama, Genta; Furukawa, Satoshi; Morita, Satomu

2016-01-01

The objective of this study was to clarify the relationship between injury severity and mechanism of death in bicycle fatalities resulting from trauma compared with those resulting from disease, to propose effective measures to prevent fatal bicyclist accidents. Autopsy and accident records were reviewed for bicyclist fatalities who had undergone forensic autopsy at the Dokkyo Medical University School of Medicine between September 1999 and March 2014. Victims' health histories, blood alcohol levels, causes of death, mechanisms of injury, Abbreviated Injury Scale (AIS) scores and Injury Severity Scores (ISSs) were determined. Fifty-five bicyclists (43 male and 12 female) with a mean age of 62.5±17.3 years were included in this study. Sixteen victims had driven under the influence of alcohol (mean blood concentration of 1.8±0.7 mg/ml). Mean ISS was 32.4 and the chest had the highest mean AIS score (2.6), followed by the head (2.1) and the neck (1.8). Thirty-nine victims (70.9%) had died of trauma and 16 had died of disease. The disease-death victims had significantly higher prevalence of having diabetes mellitus, hyperlipidemia, hypertension, heart disease or cerebrovascular diseases (50.0% vs. 22.2%, p=0.03) and a lower rate of drunk driving (6.3% vs. 41.0%, p=0.01) than the trauma-death group. All victims who were affected by disease, and 33.3% of trauma-death victims, had fallen on the road without a vehicle collision (p<0.001). The mean ISS of the trauma-death group was significantly higher than that of the disease-death group (44.0 vs. 4.2, p<0.001). Except for facial injuries, the AIS scores were significantly higher in trauma-death victims than in the disease-death group (p<0.005). To effectively reduce bicyclist fatalities, the authors strongly advocate efforts that will increase compliance with drunk driving prohibitions. For victims of fatal bicycle accidents with a medical history of diseases, a forensic autopsy should be performed to establish a disease-related death while bicycle riding. We must also put into effect preventative safety measures, which take into consideration the physical condition of bicyclists, to reduce the incidence of these types of accidents. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Can Intoxication Status Be Used as a Prediction Tool for Manner of Death?: A Comparison of the Intoxication Status in Violent Suicides and Homicides.

PubMed

Molina, D Kimberley; Hargrove, Veronica M

2017-03-01

Determining the manner of death in medicolegal death investigations can be difficult. The investigator relies on many facets of death investigation, including the circumstances of death and autopsy examination. A study was designed to analyze whether the intoxication status of the decedent could be used as another tool in death investigations. The intoxication status of violent (nonoverdose or poisoning) suicides and homicides was retrospectively reviewed and compared. A total of 625 deaths were identified, including 366 suicides and 259 homicides. Age, sex, cause of death, and intoxication status, including the specific drugs present, were analyzed. Gunshot wounds were the most common cause of death in both groups, with hanging being the second most common cause in suicides and sharp force injuries in homicides. Analysis found that although the overall intoxication status for suicides versus homicides did not differ significantly, certain drugs were more prevalent in one group over the other. Specifically, illicit drugs, that is, heroin, cocaine, and methamphetamine, were more likely to be present in homicides, whereas antidepressants or antipsychotics, benzodiazepines, and zolpidem were more common in suicides.

Daytime napping and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis of prospective cohort studies.

PubMed

Zhong, Guochao; Wang, Yi; Tao, TieHong; Ying, Jun; Zhao, Yong

2015-07-01

The association between daytime napping and mortality remains controversial. We conducted a meta-analysis to examine the associations between daytime napping and the risks of death from all causes, cardiovascular disease (CVD), and cancer. PubMed and Embase databases were searched through 19 September 2014. Prospective cohort studies that provided risk estimates of daytime napping and mortality were eligible for our meta-analysis. Two investigators independently performed study screening and data extraction. A random-effects model was used to estimate the combined effect size. Subgroup analyses were conducted to identify potential effect modifiers. Twelve studies, involving 130,068 subjects, 49,791 nappers, and 19,059 deaths, were included. Our meta-analysis showed that daytime napping was associated with an increased risk of death from all causes [n = 9 studies; hazard ratio (HR), 1.22; 95% confidence interval (CI), 1.14-1.31; I(2) = 42.5%]. No significant associations between daytime napping and the risks of death from CVD (n = 6 studies; HR, 1.20; 95% CI, 0.96-1.50; I(2) = 75.0%) and cancer (n = 4 studies; HR, 1.07; 95% CI, 0.99-1.15; I(2) = 8.9%) were found. There were no significant differences in risks of all-cause and CVD mortality between subgroups stratified by the prevalence of napping, follow-up duration, outcome assessment, age, and sex. Daytime napping is a predictor of increased all-cause mortality but not of CVD and cancer mortality. However, our findings should be treated with caution because of limited numbers of included studies and potential biases. Copyright © 2015. Published by Elsevier B.V.

STAT1 Activation is Enhanced by Cisplatin and Variably Affected by EGFR Inhibition in HNSCC Cells

PubMed Central

Schmitt, Nicole C.; Trivedi, Sumita; Ferris, Robert L.

2015-01-01

Cisplatin is a cytotoxic chemotherapeutic drug frequently used to treat many solid tumors, including head and neck squamous cell carcinoma (HNSCC). EGFR inhibitors have also shown efficacy as alternatives to cisplatin in some situations. However, large clinical trials have shown no added survival benefit from the use of these two drugs in combination. Possible explanations for this include overlapping downstream signaling cascades. Using in vitro studies, we tested the hypothesis that cisplatin and EGFR inhibitors rely on the activation of the tumor suppressor STAT1, characterized by its phosphorylation at serine (S727) or tyrosine (Y701) residues. Cisplatin consistently increased the levels of p-S727-STAT1, and STAT1 siRNA knockdown attenuated cisplatin-induced cell death. EGFR stimulation also activated p-S727-STAT1 and p-Y701-STAT1 in a subset of cell lines, whereas EGFR inhibitors alone decreased levels of p-S727-STAT1 and p-Y701-STAT1 in these cells. Contrary to our hypothesis, EGFR inhibitors added to cisplatin treatment caused variable effects among cell lines, with attenuation of p-S727-STAT1 and enhancement of cisplatin-induced cell death in some cells and minimal effect in other cells. Using HNSCC tumor specimens from a clinical trial of adjuvant cisplatin plus the anti-EGFR antibody panitumumab, higher intratumoral p-S727-STAT1 appeared to correlate with worse survival. Together, these results suggest that cisplatin-induced cell death is associated with STAT1 phosphorylation, and the addition of anti-EGFR therapy to cisplatin has variable effects on STAT1 and cell death in HNSCC. PMID:26141950

When a desired home death does not occur: the consequences of broken promises.

PubMed

Topf, Lorrianne; Robinson, Carole A; Bottorff, Joan L

2013-08-01

Evidence shows that most people prefer to die at home; however, the majority of expected deaths occur away from home. Although home deaths require family caregiver (FCG) commitment and care, we understand very little about their experiences in this context. The study's aim was to gain a better understanding of the experiences of FCGs when circumstances prevented a desired home death for a family member with advanced cancer. An interpretive description approach was used. Data collection involved semistructured interviews. Field notes and reflective journaling aided interpretive and analytical processes. The study was conducted in western Canada and included 18 bereaved FCGs. FCGs were committed to the promises made to care for their family member at home until death. These promises were challenged by a lack of preparedness for caregiving, difficulty accessing professional support and information, and frustration with the inadequate help they received. The events that precipitated dying family members leaving their home for hospital or hospice were unexpected and often influenced by FCGs' lack of situation-specific knowledge and ability to cope with complex caregiving responsibilities. FCGs found it extremely challenging to reconcile with breaking their promise to care at home until death and many were unable to do so. FCGs' despair about not being able to keep their promise for a home death was related to complicated bereavement. Prospective studies of the experiences of FCGs who are aiming for home deaths are needed to identify both short- and long-term interventions to effectively support death at home.

Cost-effectiveness of polysaccharide pneumococcal vaccination in people aged 65 and above in Poland

PubMed Central

Grzesiowski, Pawel; Aguiar-Ibáñez, Raquel; Kobryń, Aleksandra; Durand, Laure; Puig, Pierre-Emmanuel

2012-01-01

Introduction: Invasive pneumococcal disease is associated with substantial morbidity, mortality and cost implications, which could be reduced by vaccination. Aim: To assess the cost-effectiveness of a 23-valent pneumococcal vaccine in the elderly (65 and older) in Poland. Methods: A Markov model with a 1-year cycle length was developed, allowing up to 10 cohorts to enter the model over the lifetime horizon (35 years). In the base case, costs and benefits were assessed using the public health care payer (NFZ) perspective. The analysis included routine vaccination of all elderly and high-risk (HR) elderly versus no vaccination. The analysis assumed that the government would reimburse 50% of the vaccine price. Costs and benefits were discounted 5%, with costs expressed in 2009 Polish Zloty (PLN). Extensive sensitivity analyses were carried out. Results: PPV23 vaccination targeting all elderly and HR elderly in Poland would avoid 8,935 pneumococcal infections, 2,542 hospitalisations, 671 deaths and 5,886 infections, 1,673 hospitalisations and 441 deaths respectively. The incremental cost per QALY gained would be PLN 3,382 in all elderly and PLN2,148 in HR elderly. Conclusion: Vaccinating adults 65 and older regardless of risk status with a 23-valent pneumococcal vaccine, is cost-effective, resulting in clinical and economic benefits including a non-negligible reduction of ambulatory doctor visits, hospitalizations and, deaths in Poland. PMID:23095867

Nitrosothiol signaling and protein nitrosation in cell death.

PubMed

Iyer, Anand Krishnan V; Rojanasakul, Yon; Azad, Neelam

2014-11-15

Nitric oxide, a reactive free radical, is an important signaling molecule that can lead to a plethora of cellular effects affecting homeostasis. A well-established mechanism by which NO manifests its effect on cellular functions is the post-translational chemical modification of cysteine thiols in substrate proteins by a process known as S-nitrosation. Studies that investigate regulation of cellular functions through NO have increasingly established S-nitrosation as the primary modulatory mechanism in their respective systems. There has been a substantial increase in the number of reports citing various candidate proteins undergoing S-nitrosation, which affects cell-death and -survival pathways in a number of tissues including heart, lung, brain and blood. With an exponentially growing list of proteins being identified as substrates for S-nitrosation, it is important to assimilate this information in different cell/tissue systems in order to gain an overall view of protein regulation of both individual proteins and a class of protein substrates. This will allow for broad mapping of proteins as a function of S-nitrosation, and help delineate their global effects on pathophysiological responses including cell death and survival. This information will not only provide a much better understanding of overall functional relevance of NO in the context of various disease states, it will also facilitate the generation of novel therapeutics to combat specific diseases that are driven by NO-mediated S-nitrosation. Copyright © 2014 Elsevier Inc. All rights reserved.

Interaction between digoxin and dronedarone in the PALLAS trial.

PubMed

Hohnloser, Stefan H; Halperin, Jonathan L; Camm, A John; Gao, Peggy; Radzik, David; Connolly, Stuart J

2014-12-01

Elevated serum digoxin concentration can cause toxicity, including death. Dronedarone increases digoxin concentration by P-glycoprotein interaction. In Permanent Atrial Fibrillation Outcome Study Using Dronedarone On Top Of Standard Therapy Trial (PALLAS), dronedarone was associated with both increased cardiovascular death and heart failure in patients with permanent atrial fibrillation. The present analysis examines whether the dronedarone-digoxin interaction might explain these adverse outcomes. Subgroup analysis was performed to compare outcomes of patients on digoxin at baseline or not. In PALLAS, 1619 patients were randomized to dronedarone and 1617 to placebo, of whom 544 (33.6%) and 526 (32.5%) were receiving digoxin, respectively. Median (Q1,Q3) digoxin serum concentration on day 7 was 1.1 (0.7,1.5) ng/mL on dronedarone and 0.7 (0.5,1.1) ng/mL on placebo (P<0.001). Among patients on digoxin, there were 15 (8.6%/year) cardiovascular deaths on dronedarone and 2 (1.2%/year) on placebo (adjusted hazard ratio, 7.31; 95% confidence interval, 1.66-32.20; P=0.009). Among patients not on digoxin, there were 6 cardiovascular deaths on dronedarone (1.7%/year) and 8 on placebo (2.2%/year; adjusted hazard ratio, 0.67; 95% confidence interval, 0.23-1.95; P=0.46; interaction P value 0.01). In patients on digoxin, there were 11 arrhythmic deaths on dronedarone and none on placebo; and in patients not on digoxin, there were 2 arrhythmic deaths on dronedarone and 4 on placebo (P value for interaction 0.002). There was no interaction between baseline digoxin use and the adverse effect of dronedarone on heart failure events. In PALLAS, there was a strong effect of concurrent digoxin use on the adverse effect of dronedarone on cardiovascular death, but not on occurrence of heart failure. http://www.clinicaltrials.gov. Unique identifier: NCT01151137. © 2014 American Heart Association, Inc.

Multiple neurotoxic effects of haloperidol resulting in neuronal death.

PubMed

Nasrallah, Henry A; Chen, Alexander T

2017-08-01

Several published studies have reported an association between antipsychotic medications, especially first-generation agents, and a decline in gray matter volume. This prompted us to review the possible neurotoxic mechanisms of first-generation antipsychotics (FGAs), especially haloperidol, which has been widely used over the past several decades. A PubMed search was conducted using the keywords haloperidol, antipsychotic, neurotoxicity, apoptosis, oxidative stress, and neuroplasticity. No restrictions were placed on the date of the articles or language. Studies with a clearly described methodology were included. Animal, cell culture, and human tissue studies were identified. Thirty reports met the criteria for the search. All studies included haloperidol; a few also included other FGAs (fluphenazine and perphenazine) and/or second-generation agents (SGAs) (aripiprazole, paliperidone, and risperidone). A neurotoxic effect of haloperidol and other FGAs was a common theme across all studies. Minimal (mainly at high doses) or no neurotoxic effects were noted in SGAs. A review of the literature suggests that haloperidol exerts measurable neurotoxic effects at all doses via many molecular mechanisms that lead to neuronal death. A similar effect was observed in 2 other FGAs, but the effect in SGAs was much smaller and occurred mainly at high doses. A stronger binding to serotonin 5HT-2A receptors than to dopamine D2 receptors may have a neuroprotective effect among SGAs. Further studies are warranted to confirm these findings.

Cardiomyopathy from 1,1-Difluoroethane Inhalation.

PubMed

Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

2016-10-01

Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.

Die another way – non-apoptotic mechanisms of cell death

PubMed Central

Tait, Stephen W. G.; Ichim, Gabriel; Green, Douglas R.

2014-01-01

ABSTRACT Regulated, programmed cell death is crucial for all multicellular organisms. Cell death is essential in many processes, including tissue sculpting during embryogenesis, development of the immune system and destruction of damaged cells. The best-studied form of programmed cell death is apoptosis, a process that requires activation of caspase proteases. Recently it has been appreciated that various non-apoptotic forms of cell death also exist, such as necroptosis and pyroptosis. These non-apoptotic cell death modalities can be either triggered independently of apoptosis or are engaged should apoptosis fail to execute. In this Commentary, we discuss several regulated non-apoptotic forms of cell death including necroptosis, autophagic cell death, pyroptosis and caspase-independent cell death. We outline what we know about their mechanism, potential roles in vivo and define outstanding questions. Finally, we review data arguing that the means by which a cell dies actually matters, focusing our discussion on inflammatory aspects of cell death. PMID:24833670

Problem-Based Learning and Use of Higher-Order Thinking by Emergency Medical Technicians

ERIC Educational Resources Information Center

Rosenberger, Paul

2013-01-01

Emergency Medical Technicians (EMTs) often handle chaotic life-and-death situations that require higher-order thinking skills. Improving the pass rate of EMT students depends on many factors, including the use of proven and effective teaching methods. Results from recent research about effective teaching have suggested that the instructional…

Myocardial uptake of cocaine and effects of cocaine on myocardial substrate utilization and perfusion in hypertensive rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Som, P.; Wang, G.J.; Oster, Z.H.

Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal failure, which are major problems confronting emergency facilities. While the studies of cocaine effects on the brain have been given the most attention, it is clear that the effects of cocaine on the cardiovascular system are of great importance, given the increasing number of reports on sudden death and myocardial infarctions in young adults related to cocaine use. The precise mechanisms of cardiotoxic actions of cocaine are unclear.more » We investigated the whole-body distribution of C-14-labeled cocaine to determine the cocaine-binding sites, including blocking experiments to determine the nature of regional binding sites, and differential response of the normal vs. diseased heart (hypertensive cardiomyopathy) in an animal model to mimic a potentially high risk population. We investigated the acute effects of cocaine on myocardial metabolism using two myocardial energy substrate analogs, fatty acid and glucose with comparison with regional perfusion.« less

76 FR 60132 - Proposed Information Collection (Application for Dependency and Indemnity Compensation by Parent...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-28

... (Application for Dependency and Indemnity Compensation by Parent(s), (Including Accrued Benefits and Death... eligibility for dependency and indemnity compensation, death compensation, and/or accrued benefits. DATES...: Application for Dependency and Indemnity Compensation by Parent(s), (Including Accrued Benefits and Death...

Effects of synthetic sphingosine-1-phosphate analogs on cytosolic phospholipase A2alpha-independent release of arachidonic acid and cell toxicity in L929 fibrosarcoma cells: the structure-activity relationship.

PubMed

Shimizu, Masaya; Muramatsu, Yuki; Tada, Eiko; Kurosawa, Takeshi; Yamaura, Erika; Nakamura, Hiroyuki; Fujino, Hiromichi; Houjyo, Yuuya; Miyasaka, Yuri; Koide, Yuuki; Nishida, Atsushi; Murayama, Toshihiko

2009-03-01

Sphingolipid metabolites including ceramide, sphingosine, and their phosphorylated products [sphingosine-1-phosphate (S1P) and ceramide-1-phosphate] regulate cell functions including arachidonic acid (AA) metabolism and cell death. The development of analogs of S1P may be useful for regulating these mediator-induced cellular responses. We synthesized new analogs of S1P and examined their effects on the release of AA and cell death in L929 mouse fibrosarcoma cells. Among the analogs tested, several compounds including DMB-mC11S [dimethyl (2S,3R)-2-tert-butoxycarbonylamino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate] and DMB-mC9S [dimethyl (2S,3R)-2-tert-butoxycarbonylamino-3-hydroxy-3-(3'-nonyl)phenylpropyl phosphate] released AA within 1 h and caused cell death 6 h after treatment. The release of AA was observed in C12 cells [a L929 variant lacking a type alpha cytosolic phospholipase A(2) (cPLA(2)alpha)] and L929-cPLAalpha-siRNA cells (L929 cells treated with small interference RNA for cPLA(2)alpha). Treatment with pharmacological inhibitors of secretory and Ca(2+)-independent PLA(2)s decreased the DMB-mC11S-induced release of AA. The effect of the S1P analogs tested on the release of AA was comparable to that on cell death in L929 cells, and a high correlation coefficient was observed. Two analogs lacking a butoxycarbonyl moiety [DMAc-mC11S (dimethyl (2S,3R)-2-acetamino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate] and DMAm-mC11S [dimethyl (2S,3R)-2-amino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate)] had inhibitory effects on the release of AA and cell toxicity induced by DMB-mC11S. Synthetic phosphorylated lipid analogs may be useful for studying PLA(2) activity and its toxicity in cells. [Supplementary Fig. 1: available only at http://dx.doi.org/10.1254/jphs.08284FP].

Death or Neurodevelopmental Impairment at 18 To 22 Months in a Randomized Trial of Early Dexamethasone to Prevent Death or Chronic Lung Disease in Extremely Low Birth Weight Infants

PubMed Central

Stark, Ann R.; Carlo, Waldemar A.; Vohr, Betty R; Papile, Lu Ann; Saha, Shampa; Bauer, Charles R.; Donovan, Edward F.; Oh, William; Shankaran, Seetha; Tyson, Jon E.; Wright, Linda L.; Poole, W. Kenneth; Das, Abhik; Stoll, Barbara J.; Fanaroff, Avroy A.; Korones, Sheldon B.; Ehrenkranz, Richard A.; Stevenson, David K.; Peralta-Carcelen, Myriam; Adams-Chapman, Ira; Wilson-Costello, Deanne E.; Bada, Henrietta S.; Heyne, Roy J.; Johnson, Yvette R.; Lee, Kimberly Gronsman; Steichen, Jean J.; Hintz, Susan R.

2014-01-01

Objective To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18 to 22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants. Methods Evaluation of infants at 18 to 22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI). NDI was defined as moderate or severe cerebral palsy, MDI or PDI less than 70, blindness, or hearing impairment. Results Death or NDI at 18 to 22 months corrected age was similar in the dexamethasone and placebo groups (65 vs 66 percent, p= 0.99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50 vs 41 percent, p=0.42 for weight less than 10th percentile). Forty nine percent of infants in the placebo group received treatment with corticosteroid compared to 32% in the dexamethasone group (p=0.02). Conclusion The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group. PMID:23992673

Treatment-related Death in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

PubMed

Abdel-Rahman, O; Helbling, D; Schmidt, J; Petrausch, U; Giryes, A; Mehrabi, A; Schöb, O; Mannhart, M; Oweira, H

2017-04-01

We carried out a meta-analysis to determine the risk of treatment-related death associated with immune checkpoint inhibitor use in cancer patients. We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, pembrolizumab; nivolumab; tremelimumab and atezolizumab. The authors extracted relevant information on participants, characteristics, treatment-related death and information on the methodology of the studies. After exclusion of ineligible records, 18 clinical trials were included in the analysis. The odds ratio for treatment-related death for CTLA-4 inhibitors (ipilimumab and tremelimumab) was 1.80 (95% confidence interval 1.25, 2.59; P=0.002) and for PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and atezolizumab) was 0.63 (95% confidence interval 0.31, 1.30; P=0.22). Treated cancer seems to have no effect on the risk of treatment-related death. Analysis of our data showed that CTLA-4 inhibitors (ipilimumab and tremelimumab) in a higher dose (10 mg/kg) seem to be associated with a higher risk of treatment-related death compared with control regimens, whereas PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and atezolizumab) do not cause the same risk. Clinicians have to be fully aware of these differential risks and council their patients appropriately. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

John F. Kennedy's back: chronic pain, failed surgeries, and the story of its effects on his life and death.

PubMed

Pait, T Glenn; Dowdy, Justin T

2017-09-01

The 35th president of the United States, John F. Kennedy (JFK), experienced chronic back pain beginning in his early 20s. He underwent a total of 4 back operations, including a discectomy, an instrumentation and fusion, and 2 relatively minor surgeries that failed to significantly improve his pain. The authors examined the nature and etiology of JFK's back pain and performed a detailed investigation into the former president's numerous medical evaluations and treatment modalities. This information may lead to a better understanding of the profound effects that JFK's chronic back pain and its treatment had on his life and presidency, and even his death.

Alternative strategies to reduce maternal mortality in India: a cost-effectiveness analysis.

PubMed

Goldie, Sue J; Sweet, Steve; Carvalho, Natalie; Natchu, Uma Chandra Mouli; Hu, Delphine

2010-04-20

Approximately one-quarter of all pregnancy- and delivery-related maternal deaths worldwide occur in India. Taking into account the costs, feasibility, and operational complexity of alternative interventions, we estimate the clinical and population-level benefits associated with strategies to improve the safety of pregnancy and childbirth in India. Country- and region-specific data were synthesized using a computer-based model that simulates the natural history of pregnancy (both planned and unintended) and pregnancy- and childbirth-associated complications in individual women; and considers delivery location, attendant, and facility level. Model outcomes included clinical events, population measures, costs, and cost-effectiveness ratios. Separate models were adapted to urban and rural India using survey-based data (e.g., unmet need for birth spacing/limiting, facility births, skilled birth attendants). Model validation compared projected maternal indicators with empiric data. Strategies consisted of improving coverage of effective interventions that could be provided individually or packaged as integrated services, could reduce the incidence of a complication or its case fatality rate, and could include improved logistics such as reliable transport to an appropriate referral facility as well as recognition of referral need and quality of care. Increasing family planning was the most effective individual intervention to reduce pregnancy-related mortality. If over the next 5 y the unmet need for spacing and limiting births was met, more than 150,000 maternal deaths would be prevented; more than US$1 billion saved; and at least one of every two abortion-related deaths averted. Still, reductions in maternal mortality reached a threshold ( approximately 23%-35%) without including strategies that ensured reliable access to intrapartum and emergency obstetrical care (EmOC). An integrated and stepwise approach was identified that would ultimately prevent four of five maternal deaths; this approach coupled stepwise improvements in family planning and safe abortion with consecutively implemented strategies that incrementally increased skilled attendants, improved antenatal/postpartum care, shifted births away from home, and improved recognition of referral need, transport, and availability/quality of EmOC. The strategies in this approach ranged from being cost-saving to having incremental cost-effectiveness ratios less than US$500 per year of life saved (YLS), well below India's per capita gross domestic product (GDP), a common benchmark for cost-effectiveness. Early intensive efforts to improve family planning and control of fertility choices and to provide safe abortion, accompanied by a paced systematic and stepwise effort to scale up capacity for integrated maternal health services over several years, is as cost-effective as childhood immunization or treatment of malaria, tuberculosis, or HIV. In just 5 y, more than 150,000 maternal deaths would be averted through increasing contraception rates to meet women's needs for spacing and limiting births; nearly US$1.5 billion would be saved by coupling safe abortion to aggressive family planning efforts; and with stepwise investments to improve access to pregnancy-related health services and to high-quality facility-based intrapartum care, more than 75% of maternal deaths could be prevented. If accomplished over the next decade, the lives of more than one million women would be saved.

The effect of oral rehydration solution and recommended home fluids on diarrhoea mortality

PubMed Central

Munos, Melinda K.; Walker, Christa L Fischer; Black, Robert E

2010-01-01

Background Most diarrhoeal deaths can be prevented through the prevention and treatment of dehydration. Oral rehydration solution (ORS) and recommended home fluids (RHFs) have been recommended since 1970s and 1980s to prevent and treat diarrhoeal dehydration. We sought to estimate the effects of these interventions on diarrhoea mortality in children aged <5 years. Methods We conducted a systematic review to identify studies evaluating the efficacy and effectiveness of ORS and RHFs and abstracted study characteristics and outcome measures into standardized tables. We categorized the evidence by intervention and outcome, conducted meta-analyses for all outcomes with two or more data points and graded the quality of the evidence supporting each outcome. The CHERG Rules for Evidence Review were used to estimate the effectiveness of ORS and RHFs against diarrhoea mortality. Results We identified 205 papers for abstraction, of which 157 were included in the meta-analyses of ORS outcomes and 12 were included in the meta-analyses of RHF outcomes. We estimated that ORS may prevent 93% of diarrhoea deaths. Conclusions ORS is effective against diarrhoea mortality in home, community and facility settings; however, there is insufficient evidence to estimate the effectiveness of RHFs against diarrhoea mortality. PMID:20348131

Aerobic exercise conditioning: a nonpharmacological antiarrhythmic intervention.

PubMed

Billman, George E

2002-02-01

Sudden, unexpected cardiac death due to ventricular fibrillation is the leading cause of death in most industrially developed countries. Yet, despite the enormity of this problem, the development of safe and effective antiarrhythmic therapies has proven to be an elusive goal. In fact, many initially promising antiarrhythmic medications were subsequently found to increase rather than to decrease cardiac mortality. It is now known that cardiac disease alters cardiac autonomic balance and that the patients with the greatest changes in this cardiac neural regulation (i.e., decreased parasympathetic coupled with increased sympathetic activity) are also the patients at the greatest risk for sudden death. A growing body of experimental and epidemiological data demonstrates that aerobic exercise conditioning can dramatically reduce cardiac mortality, even in patients with preexisting cardiac disease. Conversely, the lack of exercise is strongly associated with an increased incidence of many chronic debilitating diseases, including coronary heart disease. Because it is well established that aerobic exercise conditioning can alter autonomic balance (increasing parasympathetic tone and decreasing sympathetic activity), a prudently designed exercise program could prove to be an effective and nonpharmacological way to enhance cardiac electrical stability, thereby protecting against sudden cardiac death.

An important date in rabies history.

PubMed

Dodet, Betty

2007-12-17

Rabies is estimated to cause 31,000 human deaths in Asia annually. Several recent events, including World Rabies Day have brought this neglected disease to the attention of the scientific community, governmental authorities, the media and the public. It is hoped that this will result in an increased collaboration between veterinary and human health authorities, and an involvement at all levels necessary for the control and elimination of rabies in dogs, the main reservoir and vector of rabies in Asia. Dog rabies elimination is considered as the most cost-effective solution to prevent rabies deaths in humans. Asian countries such as India and the Philippines have recently adopted the objective of eliminating rabies by 2020. To support World Rabies Day, the Asian Rabies Expert Bureau (AREB) had its 4th annual meeting from 5 to 7 September 2007, with the objective of debating strategies for lowering the human rabies toll. Human rabies deaths can already be prevented by improving the compliance to WHO post-exposure prophylaxis recommendations. In addition, in regions with a high incidence of canine rabies and where rabies control in dogs is not yet achieved or not effective, systematic pre-exposure vaccination of children who are the main victims of rabies, may prevent their premature deaths.

Keys to successful organ procurement: An experience-based review of clinical practices at a high-performing health-care organization

PubMed Central

Wojda, Thomas R.; Stawicki, Stanislaw P.; Yandle, Kathy P.; Bleil, Maria; Axelband, Jennifer; Wilde-Onia, Rebecca; Thomas, Peter G.; Cipolla, James; Hoff, William S.; Shultz, Jill

2017-01-01

Organ procurement (OP) from donors after brain death and circulatory death represents the primary source of transplanted organs. Despite favorable laws and regulations, OP continues to face challenges for a number of reasons, including institutional, personal, and societal barriers. This focused review presents some of the key components of a successful OP program at a large, high-performing regional health network. This review focuses on effective team approaches, aggressive resuscitative strategies, optimal communication, family support, and community outreach efforts. PMID:28660162

Practice Safe Driving.

PubMed

2017-07-01

More than 30,000 people die in motor vehicle collisions each year in the United States. Distracted, drowsy, and drunk driving cause most motor vehicle collision injuries and deaths. An editorial published in the October 2016 issue of JOSPT identified the global need for effective strategies to reduce, if not eliminate, preventable injuries, including whiplash-associated disorders and deaths from distracted driving. This is a call to action for everyone who gets behind the wheel of a car. J Orthop Sports Phys Ther 2017;47(7):449. doi:10.2519/jospt.2017.0506.

SIDS and Other Sleep-Related Infant Deaths: Evidence Base for 2016 Updated Recommendations for a Safe Infant Sleeping Environment.

PubMed

Moon, Rachel Y

2016-11-01

Approximately 3500 infants die annually in the United States from sleep-related infant deaths, including sudden infant death syndrome (SIDS), ill-defined deaths, and accidental suffocation and strangulation in bed. After an initial decrease in the 1990s, the overall sleep-related infant death rate has not declined in more recent years. Many of the modifiable and nonmodifiable risk factors for SIDS and other sleep-related infant deaths are strikingly similar. The American Academy of Pediatrics recommends a safe sleep environment that can reduce the risk of all sleep-related infant deaths. Recommendations for a safe sleep environment include supine positioning, use of a firm sleep surface, room-sharing without bed-sharing, and avoidance of soft bedding and overheating. Additional recommendations for SIDS risk reduction include avoidance of exposure to smoke, alcohol, and illicit drugs; breastfeeding; routine immunization; and use of a pacifier. New evidence and rationale for recommendations are presented for skin-to-skin care for newborn infants, bedside and in-bed sleepers, sleeping on couches/armchairs and in sitting devices, and use of soft bedding after 4 months of age. In addition, expanded recommendations for infant sleep location are included. The recommendations and strength of evidence for each recommendation are published in the accompanying policy statement, "SIDS and Other Sleep-Related Infant Deaths: Updated 2016 Recommendations for a Safe Infant Sleeping Environment," which is included in this issue. Copyright © 2016 by the American Academy of Pediatrics.

Effect of serostatus for hepatitis C virus on mortality among antiretrovirally naive HIV-positive patients.

PubMed

Braitstein, Paula; Yip, Benita; Montessori, Valentina; Moore, David; Montaner, Julio S G; Hogg, Robert S

2005-07-19

We examined the effect of hepatitis C virus (HCV) seropositivity on risk of death among people receiving their first antiretroviral treatment (ART) for HIV infection. In British Columbia, the HIV/ AIDS Drug Treatment Program is the only source of free ART. Patients who initiated a triple-drug ART regimen between July 31, 1996, and July 31, 2000, were included if they were ART-naive and had baseline HCV serological data. Outcomes of interest for survival analysis were deaths from natural and HIV-related causes, with a data cutoff of June 30, 2003. Of 1186 eligible subjects, 606 (51%) were HCV positive and 580, negative. Fewer HCV-positive people were male (78% v. 93%, p < 0.001) and had an AIDS diagnosis at baseline (11% v. 15%, p = 0.028). Their CD4 fraction was significantly higher at baseline (19% v. 16% of T lymphocytes, p < 0.001) but their absolute CD4 counts, log HIV viral load and the type of ART initiated were similar to those of HCV negative people. Of 163 deaths (from natural causes only) during the study period, 118 (19%) were in HCV positive and 45 (8%) in HCV negative patients (p < 0.001); of the 114 deaths attributed to HIV infection, these proportions were 79 (13%) versus 35 (6%; p < 0.001). After adjustment for potential confounders, HCV seropositivity remained predictive of death (adjusted hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.50- 3.21, p < 0.001), especially HIV-related death (adjusted HR 1.75, 95% CI 1.13- 2.72, p = 0.012). In this population-based HIV treatment program, we found HCV seropositivity to be an independent predictor of mortality, especially death related to HIV infection.

Effect of serostatus for hepatitis C virus on mortality among antiretrovirally naive HIV-positive patients

PubMed Central

Braitstein, Paula; Yip, Benita; Montessori, Valentina; Moore, David; Montaner, Julio S.G.; Hogg, Robert S.

2005-01-01

Background We examined the effect of hepatitis C virus (HCV) seropositivity on risk of death among people receiving their first antiretroviral treatment (ART) for HIV infection. Methods In British Columbia, the HIV/ AIDS Drug Treatment Program is the only source of free ART. Patients who initiated a triple-drug ART regimen between July 31, 1996, and July 31, 2000, were included if they were ART-naive and had baseline HCV serological data. Outcomes of interest for survival analysis were deaths from natural and HIV-related causes, with a data cutoff of June 30, 2003. Results Of 1186 eligible subjects, 606 (51%) were HCV positive and 580, negative. Fewer HCV-positive people were male (78% v. 93%, p < 0.001) and had an AIDS diagnosis at baseline (11% v. 15%, p = 0.028). Their CD4 fraction was significantly higher at baseline (19% v. 16% of T lymphocytes, p < 0.001) but their absolute CD4 counts, log HIV viral load and the type of ART initiated were similar to those of HCV negative people. Of 163 deaths (from natural causes only) during the study period, 118 (19%) were in HCV positive and 45 (8%) in HCV negative patients (p < 0.001); of the 114 deaths attributed to HIV infection, these proportions were 79 (13%) versus 35 (6%; p < 0.001). After adjustment for potential confounders, HCV seropositivity remained predictive of death (adjusted hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.50– 3.21, p < 0.001), especially HIV-related death (adjusted HR 1.75, 95% CI 1.13– 2.72, p = 0.012). Interpretation In this population-based HIV treatment program, we found HCV seropositivity to be an independent predictor of mortality, especially death related to HIV infection. PMID:16027432

Anticancer Effect of Ginger Extract against Pancreatic Cancer Cells Mainly through Reactive Oxygen Species-Mediated Autotic Cell Death

PubMed Central

Akimoto, Miho; Iizuka, Mari; Kanematsu, Rie; Yoshida, Masato; Takenaga, Keizo

2015-01-01

The extract of ginger (Zingiber officinale Roscoe) and its major pungent components, [6]-shogaol and [6]-gingerol, have been shown to have an anti-proliferative effect on several tumor cell lines. However, the anticancer activity of the ginger extract in pancreatic cancer is poorly understood. Here, we demonstrate that the ethanol-extracted materials of ginger suppressed cell cycle progression and consequently induced the death of human pancreatic cancer cell lines, including Panc-1 cells. The underlying mechanism entailed autosis, a recently characterized form of cell death, but not apoptosis or necroptosis. The extract markedly increased the LC3-II/LC3-I ratio, decreased SQSTM1/p62 protein, and enhanced vacuolization of the cytoplasm in Panc-1 cells. It activated AMPK, a positive regulator of autophagy, and inhibited mTOR, a negative autophagic regulator. The autophagy inhibitors 3-methyladenine and chloroquine partially prevented cell death. Morphologically, however, focal membrane rupture, nuclear shrinkage, focal swelling of the perinuclear space and electron dense mitochondria, which are unique morphological features of autosis, were observed. The extract enhanced reactive oxygen species (ROS) generation, and the antioxidant N-acetylcystein attenuated cell death. Our study revealed that daily intraperitoneal administration of the extract significantly prolonged survival (P = 0.0069) in a peritoneal dissemination model and suppressed tumor growth in an orthotopic model of pancreatic cancer (P < 0.01) without serious adverse effects. Although [6]-shogaol but not [6]-gingerol showed similar effects, chromatographic analyses suggested the presence of other constituent(s) as active substances. Together, these results show that ginger extract has potent anticancer activity against pancreatic cancer cells by inducing ROS-mediated autosis and warrants further investigation in order to develop an efficacious candidate drug. PMID:25961833

Servo-control for maintaining abdominal skin temperature at 36C in low birth weight infants.

PubMed

Sinclair, J C

2000-01-01

Randomized trials have shown that the neonatal mortality rate of low birth-weight babies can be reduced by keeping them warm. For low birth-weight babies nursed in incubators, warm conditions may be achieved either by heating the air to a desired temperature, or by servo-controlling the baby's body temperature at a desired set-point. In low birth weight infants, to determine the effect on death and other important clinical outcomes of targeting body temperature rather than air temperature as the end-point of control of incubator heating. Standard search strategy of the Cochrane Neonatal Collaborative Review Group. Randomized or quasi-randomized trials which test the effects of having the heat output of the incubator servo-controlled from body temperature compared with setting a constant incubator air temperature. Trial methodologic quality was systematically assessed. Outcome measures included death, timing of death, cause of death, and other clinical outcomes. Categorical outcomes were analyzed using relative risk and risk difference. Meta-analysis assumed a fixed effect model. Compared to setting a constant incubator air temperature of 31.8C, servo-control of abdominal skin temperature at 36C reduces the neonatal death rate among low birth weight infants: relative risk 0.72 (95% CI 0.54, 0.97); risk difference -12.7% (95% CI -1.6, -23.9). This effect is even greater among VLBW infants. During at least the first week after birth, low birth weight babies should be provided with a carefully regulated thermal environment that is near the thermoneutral point. For LBW babies in incubators, this can be achieved by adjusting incubator temperature to maintain an anterior abdominal skin temperature of at least 36C, using either servo-control or frequent manual adjustment of incubator air temperature.

The Role of Public Policies in Reducing Smoking Prevalence: Results from the Michigan SimSmoke Tobacco Policy Simulation Model

PubMed Central

Levy, David T.; Huang, An-Tsun; Havumaki, Joshua S.; Meza, Rafael

2016-01-01

Introduction Michigan has implemented several of the tobacco control policies recommended by the World Health Organization MPOWER goals. We consider the effect of those policies and additional policies consistent with MPOWER goals on smoking prevalence and smoking-attributable deaths (SADs). Methods The SimSmoke tobacco control policy simulation model is used to examine the effect of past policies and a set of additional policies to meet the MPOWER goals. The model is adapted to Michigan using state population, smoking and policy data starting in 1993. SADs are estimated using standard attribution methods. Upon validating the model, SimSmoke is used to distinguish the effect of policies implemented since 1993 against a counterfactual with policies kept at their 1993 levels. The model is then used to project the effect of implementing stronger policies beginning in 2014. Results SimSmoke predicts smoking prevalence accurately between 1993 and 2010. Since 1993, a relative reduction in smoking rates of 22% by 2013 and of 30% by 2054 can be attributed to tobacco control policies. Of the 22% reduction, 44% is due to taxes, 28% to smoke-free air laws, 26% to cessation treatment policies, and 2% to youth access. Moreover, 234,000 smoking-attributable deaths are projected to be averted by 2054. With additional policies consistent with MPOWER goals, the model projects that, by 2054, smoking prevalence can be further reduced by 17% with 80,000 deaths averted relative to the absence of those policies. Conclusions Michigan SimSmoke shows that tobacco control policies, including cigarette taxes, smoke-free air laws and cessation treatment policies, have substantially reduced smoking and smoking-attributable deaths. Higher taxes, strong mass media campaigns and cessation treatment policies would further reduce smoking prevalence and smoking-attributable deaths. PMID:26983616

Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes.

PubMed

Nissen, Steven E; Wolski, Kathy

2007-06-14

Rosiglitazone is widely used to treat patients with type 2 diabetes mellitus, but its effect on cardiovascular morbidity and mortality has not been determined. We conducted searches of the published literature, the Web site of the Food and Drug Administration, and a clinical-trials registry maintained by the drug manufacturer (GlaxoSmithKline). Criteria for inclusion in our meta-analysis included a study duration of more than 24 weeks, the use of a randomized control group not receiving rosiglitazone, and the availability of outcome data for myocardial infarction and death from cardiovascular causes. Of 116 potentially relevant studies, 42 trials met the inclusion criteria. We tabulated all occurrences of myocardial infarction and death from cardiovascular causes. Data were combined by means of a fixed-effects model. In the 42 trials, the mean age of the subjects was approximately 56 years, and the mean baseline glycated hemoglobin level was approximately 8.2%. In the rosiglitazone group, as compared with the control group, the odds ratio for myocardial infarction was 1.43 (95% confidence interval [CI], 1.03 to 1.98; P=0.03), and the odds ratio for death from cardiovascular causes was 1.64 (95% CI, 0.98 to 2.74; P=0.06). Rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance. Our study was limited by a lack of access to original source data, which would have enabled time-to-event analysis. Despite these limitations, patients and providers should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes. Copyright 2007 Massachusetts Medical Society.

Banking crises and mortality during the Great Depression: evidence from US urban populations, 1929-1937.

PubMed

Stuckler, David; Meissner, Christopher; Fishback, Price; Basu, Sanjay; McKee, Martin

2012-05-01

Previous research suggests that the Great Depression led to improvements in public health. However, these studies rely on highly aggregated national data (using fewer than 25 data points) and potentially biased measures of the Great Depression. The authors assess the effects of the Great Depression using city-level estimates of US mortality and an underlying measure of economic crisis, bank suspensions, at the state level. Cause-specific mortalities covering 114 US cities in 36 states between 1929 and 1937 were regressed against bank suspensions and income data from the Federal Deposit Insurance Corporation Database, using dynamic fixed-effects models and adjustments for potential confounding variables. Reductions in all-cause mortalities were mainly attributable to declines in death rates owing to pneumonia (26.4% of total), flu (13.1% of total) and respiratory tuberculosis (11.2% of total), while death rates increased from heart disease (19.4% of total), cancer (8.1% of total) and diabetes (2.9%). Only heart disease can plausibly relate to the contemporaneous economic shocks. The authors found that a higher rate of bank suspensions was significantly associated with higher suicide rates (β=0.32, 95% CI 0.24 to 0.41) but lower death rates from motor-vehicle accidents (β=-0.18, 95% CI -0.29 to -0.07); no significant effects were observed for 30 other causes of death or with a time lag. In contrast with existing research, the authors find that many of the changes in deaths from different causes during the Great Depression were unrelated to economic shocks. Further research is needed to understand the causes of the marked variations in mortality change across cities and states, including the effects of the New Deal and Prohibition.

20 CFR 10.2 - What do these regulations contain?

Code of Federal Regulations, 2014 CFR

2014-04-01

... records, and a description of rights and penalties under the FECA, including convictions for fraud. (b... payment of monetary compensation benefits for disability, impairment and death. It includes the provisions... of medical providers. (j) Subpart J. Death Gratuity. The rules relating to the payment of the death...

8 CFR 208.18 - Implementation of the Convention Against Torture.

Code of Federal Regulations, 2010 CFR

2010-01-01

... actions authorized by law, including the death penalty, but do not include sanctions that defeat the... procedures calculated to disrupt profoundly the senses or the personality; (iii) The threat of imminent death; or (iv) The threat that another person will imminently be subjected to death, severe physical pain or...

8 CFR 208.18 - Implementation of the Convention Against Torture.

Code of Federal Regulations, 2012 CFR

2012-01-01

... actions authorized by law, including the death penalty, but do not include sanctions that defeat the... procedures calculated to disrupt profoundly the senses or the personality; (iii) The threat of imminent death; or (iv) The threat that another person will imminently be subjected to death, severe physical pain or...

20 CFR 10.2 - What do these regulations contain?

Code of Federal Regulations, 2013 CFR

2013-04-01

... records, and a description of rights and penalties under the FECA, including convictions for fraud. (b... payment of monetary compensation benefits for disability, impairment and death. It includes the provisions... of medical providers. (j) Subpart J. Death Gratuity. The rules relating to the payment of the death...

8 CFR 208.18 - Implementation of the Convention Against Torture.

Code of Federal Regulations, 2013 CFR

2013-01-01

... actions authorized by law, including the death penalty, but do not include sanctions that defeat the... procedures calculated to disrupt profoundly the senses or the personality; (iii) The threat of imminent death; or (iv) The threat that another person will imminently be subjected to death, severe physical pain or...

20 CFR 10.2 - What do these regulations contain?

Code of Federal Regulations, 2012 CFR

2012-04-01

... records, and a description of rights and penalties under the FECA, including convictions for fraud. (b... payment of monetary compensation benefits for disability, impairment and death. It includes the provisions... of medical providers. (j) Subpart J. Death Gratuity. The rules relating to the payment of the death...

8 CFR 208.18 - Implementation of the Convention Against Torture.

Code of Federal Regulations, 2014 CFR

2014-01-01

... actions authorized by law, including the death penalty, but do not include sanctions that defeat the... procedures calculated to disrupt profoundly the senses or the personality; (iii) The threat of imminent death; or (iv) The threat that another person will imminently be subjected to death, severe physical pain or...

8 CFR 208.18 - Implementation of the Convention Against Torture.

Code of Federal Regulations, 2011 CFR

2011-01-01

... actions authorized by law, including the death penalty, but do not include sanctions that defeat the... procedures calculated to disrupt profoundly the senses or the personality; (iii) The threat of imminent death; or (iv) The threat that another person will imminently be subjected to death, severe physical pain or...

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment.

PubMed

2014-08-01

High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. UK Medical Research Council, US National Institutes of Health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Place of death of pediatric cancer patients in a single institute during 7 years.

PubMed

Yanai, Tomoko; Hirase, Satoshi; Matsunoshita, Natsuki; Yamamoto, Nobuyuki; Ninchoji, Takeshi; Kubokawa, Ikuko; Mori, Takeshi; Hayakawa, Akira; Takeshima, Yasuhiro; Iijima, Kazumoto; Matsuo, Masafumi

2012-06-27

Place of death is an important issue at the end-of-life. It is poorly understood in pediatric cancer patients in Japan. This study aimed to clarify place of death of children with cancer as well as variables associated with place of death. Study population was pediatric cancer patients who died in the Department of Pediatrics at Kobe University Hospital during the last 7 years. The medical records were retrospectively reviewed regardless of cause of death to derive data relating to patients' characteristics and disease. 18 patients were included. Median age at death was 12.2 years old. 6 patients including 5 children in complete remission had hematological disease and 12 patients suffered from solid tumors. 4 patients (22.2%) died at home, whereas 14 patients (77.8%) died in the hospital including 6 ICU deaths. No one died in hospices. Preference of patients was unavailable due to the lack of inquiry. Factors influencing place of death (home, ICU, non-ICU) were disease (hematological disease vs. solid tumor, p=0.010, brain tumor vs. non-brain tumor, p=0.023), disease status (complete remission vs. non-complete remission, p=0.0014) and preference of families (p=0.029). Among 6 families who expressed preference, no disparity was observed between actual and preferred place of death. This is the first English publication of place of death of pediatric cancer patients in Japan. The low percentage of home death, factors influencing place of death and the lack of disparity between actual and preferred place of death were indicated. Further studies are required to better understand place of death.

Necroptosis in cancer: An angel or a demon?

PubMed

Wang, Tianzhen; Jin, Yinji; Yang, Weiwei; Zhang, Lei; Jin, Xiaoming; Liu, Xi; He, Yan; Li, Xiaobo

2017-06-01

In the past few decades, apoptosis has been regarded as the only form of programmed cell death. However, the traditional view has been challenged by the identification of several forms of regulated necrosis, including necroptosis. Necroptosis is typified by a necrotic cell death morphology and is controlled by RIP1, RIP3, and mixed lineage kinase domain-like protein. The physiological role of necroptosis is to serve as a "fail-safe" form of cell death for cells that fail to undergo apoptosis during embryonic development and disease defense. Currently, established studies have indicated that necroptosis is involved in cancer initiation and progression. Although elevated necroptosis contributes to cancer cell death, extensive cell death also increases the risk of proliferation and metastasis of the surviving cells by inducing the generation reactive oxygen species, activation of inflammation, and suppression of the immune response. Thus, questions regarding the overall impact of necroptosis on cancer remain open. In this review, we introduce the basic knowledge regarding necroptosis, summarize its dual effects on cancer progression, and analyze its advantages and disadvantages in clinical applications.

Discrimination and instructional comprehension: guided discretion, racial bias, and the death penalty.

PubMed

Lynch, M; Haney, C

2000-06-01

This study links two previously unrelated lines of research: the lack of comprehension of capital penalty-phase jury instructions and discriminatory death sentencing. Jury-eligible subjects were randomly assigned to view one of four versions of a simulated capital penalty trial in which the race of defendant (Black or White) and the race of victim (Black or White) were varied orthogonally. Dependent measures included a sentencing verdict (life without the possibility of parole or the death penalty), ratings of penalty phase evidence, and a test of instructional comprehension. Results indicated that instructional comprehension was poor overall and that, although Black defendants were treated only slightly more punitively than White defendants in general, discriminatory effects were concentrated among participants whose comprehension was poorest. In addition, the use of penalty phase evidence differed as a function of race of defendant and whether the participant sentenced the defendant to life or death. The study suggest that racially biased and capricious death sentencing may be in part caused or exacerbated by the inability to comprehend penalty phase instructions.

Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation?

NASA Technical Reports Server (NTRS)

Morgan, William F.

2003-01-01

A number of nontargeted and delayed effects associated with radiation exposure have now been described. These include radiation-induced genomic instability, death-inducing and bystander effects, clastogenic factors and transgenerational effects. It is unlikely that these nontargeted effects are directly induced by cellular irradiation. Instead, it is proposed that some as yet to be identified secreted factor can be produced by irradiated cells that can stimulate effects in nonirradiated cells (death-inducing and bystander effects, clastogenic factors) and perpetuate genomic instability in the clonally expanded progeny of an irradiated cell. The proposed factor must be soluble and capable of being transported between cells by cell-to-cell gap junction communication channels. Furthermore, it must have the potential to stimulate cellular cytokines and/or reactive oxygen species. While it is difficult to imagine a role for such a secreted factor in contributing to transgenerational effects, the other nontargeted effects of radiation may all share a common mechanism.

Human radiation tolerance

NASA Technical Reports Server (NTRS)

Lushbaugh, C. C.

1974-01-01

The acute radiation syndrome in man is clinically bounded by death at high dose levels and by the prodromal syndrome of untoward physiological effects at minimal levels of clinically effective exposure. As in lower animals, man experiences principally three acute modes of death from radiation exposure (Bond et al., 1965). These are known collectively as the lethal radiation syndromes: central nervous system death, gastrointestinal death, and hematopoietic death. The effect of multiple exposure on lethality, the effect of multiple exposure on hematopoietic recovery, and quantitative aspects of cell and tissue repair are discussed.

Modeling decay rates of dead wood in a neotropical forest.

PubMed

Hérault, Bruno; Beauchêne, Jacques; Muller, Félix; Wagner, Fabien; Baraloto, Christopher; Blanc, Lilian; Martin, Jean-Michel

2010-09-01

Variation of dead wood decay rates among tropical trees remains one source of uncertainty in global models of the carbon cycle. Taking advantage of a broad forest plot network surveyed for tree mortality over a 23-year period, we measured the remaining fraction of boles from 367 dead trees from 26 neotropical species widely varying in wood density (0.23-1.24 g cm(-3)) and tree circumference at death time (31.5-272.0 cm). We modeled decay rates within a Bayesian framework assuming a first order differential equation to model the decomposition process and tested for the effects of forest management (selective logging vs. unexploited), of mode of death (standing vs. downed) and of topographical levels (bottomlands vs. hillsides vs. hilltops) on wood decay rates. The general decay model predicts the observed remaining fraction of dead wood (R2 = 60%) with only two biological predictors: tree circumference at death time and wood specific density. Neither selective logging nor local topography had a differential effect on wood decay rates. Including the mode of death into the model revealed that standing dead trees decomposed faster than downed dead trees, but the gain of model accuracy remains rather marginal. Overall, these results suggest that the release of carbon from tropical dead trees to the atmosphere can be simply estimated using tree circumference at death time and wood density.

Ursodeoxycholic acid effectively kills drug-resistant gastric cancer cells through induction of autophagic death.

PubMed

Lim, Sung-Chul; Han, Song Iy

2015-09-01

Carcinoma cells that have acquired drug resistance often exhibit cross-resistance to various other cytotoxic stimuli. Here, we investigated the effects of ursodeoxycholic acid (UDCA), a gastrointestinal tumor-suppressor, on a cisplatin‑resistant SNU601 gastric cancer subline (SNU601/R). While other anticancer drugs, including L-OHP, etoposide, and death ligand TRAIL, had minimal effects on the viability of these resistant cells, they were sensitive to UDCA. The UDCA‑induced reduction in the viability of the SNU601/R cells was accomplished through autophagy while the primary means of cell death in the parental SNU601 cells (SNU601/WT) was apoptosis. Previously, we demonstrated that the UDCA-triggered apoptosis of gastric cancer cells was regulated by a cell surface death receptor, TRAIL-R2/DR5, which was upregulated and re-distributed on lipid rafts. The UDCA stimulation of TRAIL-R2/DR5 also occurred in the SNU601/R cells despite the lack of apoptosis. In the present study, we found that CD95/Fas, another cell surface death receptor, was also translocated into lipid rafts in response to UDCA although it was not involved in the decrease in cell viability. Specifically, raft relocalization of CD95/Fas was triggered by UDCA in the SNU601/WT cells in which apoptosis occurred, but not in the SNU601/R cells where autophagic death occurred. Notably, UDCA reduced ATG5 levels, an essential component of autophagy, in the SNU601/WT, but not in the SNU601/R cell line. Moreover, in CD95/Fas-silenced SNU601/WT cells, UDCA did not decrease ATG5 levels and induced autophagic cell death rather than apoptosis. These results imply that raft‑distributed CD95/Fas may support UDCA-induced apoptosis via downregulation of ATG5 levels, preventing the autophagic pathway. Taken together, these results suggest that UDCA induces both apoptotic and autophagic cell death depending on the intracellular signaling environment, thereby conferring the advantage to overcome drug resistance through apoptotic defects.

SIDS and other sleep-related infant deaths: expansion of recommendations for a safe infant sleeping environment.

PubMed

Moon, Rachel Y

2011-11-01

Despite a major decrease in the incidence of sudden infant death syndrome (SIDS) since the American Academy of Pediatrics (AAP) released its recommendation in 1992 that infants be placed for sleep in a nonprone position, this decline has plateaued in recent years. Concurrently, other causes of sudden unexpected infant death occurring during sleep (sleep-related deaths), including suffocation, asphyxia, and entrapment, and ill-defined or unspecified causes of death have increased in incidence, particularly since the AAP published its last statement on SIDS in 2005. It has become increasingly important to address these other causes of sleep-related infant death. Many of the modifiable and nonmodifiable risk factors for SIDS and suffocation are strikingly similar. The AAP, therefore, is expanding its recommendations from being only SIDS-focused to focusing on a safe sleep environment that can reduce the risk of all sleep-related infant deaths including SIDS. The recommendations described in this report include supine positioning, use of a firm sleep surface, breastfeeding, room-sharing without bed-sharing, routine immunization, consideration of a pacifier, and avoidance of soft bedding, overheating, and exposure to tobacco smoke, alcohol, and illicit drugs. The rationale for these recommendations is discussed in detail in this technical report. The recommendations are published in the accompanying "Policy Statement--Sudden Infant Death Syndrome and Other Sleep-Related Infant Deaths: Expansion of Recommendations for a Safe Infant Sleeping Environment," which is included in this issue (www.pediatrics.org/cgi/doi/10.1542/peds.2011-2220).

A Sociocultural Approach to Children's Perceptions of Death and Loss.

PubMed

Yang, Sungeun; Park, Soyeon

2017-11-01

By employing the phenomenographic approach, the present study explored children's cognitive understanding of and emotional responses to death and bereavement. Participants included 52 Korean, 16 Chinese, and 16 Chinese American children ages 5-6. Thematic analysis of children's drawings and open-ended interviews revealed that most children associated death with negative emotions such as fear, anxiety, and sadness. The majority of children used realistic expressions to narrate death. The core themes from their drawings included causes for death, attempts to stop the dying, and situations after death. This study contributes to the literature by targeting young children who have been relatively excluded in death studies and provides evidence in the usefulness of drawings as a developmentally appropriate data collection tool. The findings also enrich our knowledge about children's understanding of death and bereavement, rooted in the inductive analysis of empirical data with children from culturally diverse backgrounds.

Ethics in Public Health Research

PubMed Central

Kunitz, Stephen J.

2008-01-01

Mortality rates for American Indians (including Alaska Natives) declined for much of the 20th century, but data published by the Indian Health Service indicate that since the mid-1980s, age-adjusted deaths for this population have increased both in absolute terms and compared with rates for the White American population. This increase appears to be primarily because of the direct and indirect effects of type 2 diabetes. Despite increasing appropriations for the Special Diabetes Program for Indians, per capita expenditures for Indian health, including third-party reimbursements, remain substantially lower than those for other Americans and, when adjusted for inflation, have been essentially unchanged since the early 1990s. I argue that inadequate funding for health services has contributed significantly to the increased death rate. PMID:18235064

Extreme umbilical cord lengths, cord knot and entanglement: Risk factors and risk of adverse outcomes, a population-based study

PubMed Central

Kessler, Jörg

2018-01-01

Objectives To determine risk factors for short and long umbilical cord, entanglement and knot. Explore their associated risks of adverse maternal and perinatal outcome, including risk of recurrence in a subsequent pregnancy. To provide population based gestational age and sex and parity specific reference ranges for cord length. Design Population based registry study. Setting Medical Birth Registry of Norway 1999–2013. Population All singleton births (gestational age>22weeks<45 weeks) (n = 856 300). Methods Descriptive statistics and odds ratios of risk factors for extreme cord length and adverse outcomes based on logistic regression adjusted for confounders. Main outcome measures Short or long cord (<10th or >90th percentile), cord knot and entanglement, adverse pregnancy outcomes including perinatal and intrauterine death. Results Increasing parity, maternal height and body mass index, and diabetes were associated with increased risk of a long cord. Large placental and birth weight, and fetal male sex were factors for a long cord, which again was associated with a doubled risk of intrauterine and perinatal death, and increased risk of adverse neonatal outcome. Anomalous cord insertion, female sex, and a small placenta were associated with a short cord, which was associated with increased risk of fetal malformations, placental complications, caesarean delivery, non-cephalic presentation, perinatal and intrauterine death. At term, cord knot was associated with a quadrupled risk of perinatal death. The combination of a cord knot and entanglement had a more than additive effect to the association to perinatal death. There was a more than doubled risk of recurrence of a long or short cord, knot and entanglement in a subsequent pregnancy of the same woman. Conclusion Cord length is influenced both by maternal and fetal factors, and there is increased risk of recurrence. Extreme cord length, entanglement and cord knot are associated with increased risk of adverse outcomes including perinatal death. We provide population based reference ranges for umbilical cord length. PMID:29584790

The Study of Personal Constructs of Death and Fear of Death among Taiwanese Adolescents

ERIC Educational Resources Information Center

Yang, Shu Ching; Chen, Shih-Fen

2009-01-01

This study administered an open-ended questionnaire about death and the Multidimensional Fear of Death Scale (MODS) to explore the relationships between personal constructs about death and fears of death among Taiwanese adolescents. The sample included 329 adolescents in junior and senior high school grades 7 to 12. A coding manual was used to…

The synthetic purine reversine selectively induces cell death of cancer cells.

PubMed

Piccoli, Marco; Palazzolo, Giacomo; Conforti, Erika; Lamorte, Giuseppe; Papini, Nadia; Creo, Pasquale; Fania, Chiara; Scaringi, Raffaella; Bergante, Sonia; Tringali, Cristina; Roncoroni, Leda; Mazzoleni, Stefania; Doneda, Luisa; Galli, Rossella; Venerando, Bruno; Tettamanti, Guido; Gelfi, Cecilia; Anastasia, Luigi

2012-10-01

The synthetic purine reversine has been shown to possess a dual activity as it promotes the de-differentiation of adult cells, including fibroblasts, into stem-cell-like progenitors, but it also induces cell growth arrest and ultimately cell death of cancer cells, suggesting its possible application as an anti-cancer agent. Aim of this study was to investigate the mechanism underneath reversine selectivity in inducing cell death of cancer cells by a comparative analysis of its effects on several tumor cells and normal dermal fibroblasts. We found that reversine is lethal for all cancer cells studied as it induces cell endoreplication, a process that malignant cells cannot effectively oppose due to aberrations in cell cycle checkpoints. On the other hand, normal cells, like dermal fibroblasts, can control reversine activity by blocking the cell cycle, entering a reversible quiescent state. However, they can be induced to become sensitive to the molecule when key cell cycle proteins, e.g., p53, are silenced. Copyright © 2012 Wiley Periodicals, Inc.

Research on Near Roadway and Other Near Source Air Pollution

EPA Pesticide Factsheets

Research has shown that living and working near sources of air pollution can lead to higher exposures to air contaminants many of which contribute to adverse health effects including reduced lung function, asthma, cardiovascular disease and premature death

Medicolegal Death Scene Investigations After Natural Disaster- and Weather-Related Events: A Review of the Literature

PubMed Central

Rocha, Luciana A.; Fromknecht, Catharine Q.; Redman, Sarah Davis; Brady, Joanne E.; Hodge, Sarah E.; Noe, Rebecca S.

2017-01-01

Background The number of disaster-related deaths recorded by vital statistics departments often differs from that reported by other agencies, including the National Oceanic and Atmospheric Administration-National Weather Service storm database and the American Red Cross. The Centers for Disease Control and Prevention (CDC) has launched an effort to improve disaster-related death scene investigation reporting practices to make data more comparable across jurisdictions, improve accuracy of reporting disaster-related deaths, and enhance identification of risk and protective factors. We conducted a literature review to examine how death scene data are collected and how such data are used to determine disaster relatedness. Methods Two analysts conducted a parallel search using Google and Google Scholar. We reviewed published peer-reviewed articles and unpublished documents including relevant forms, protocols, and worksheets from coroners, medical examiners, and death scene investigators. Results We identified 177 documents: 32 published peer-reviewed articles and 145 other documents (grey literature). Published articles suggested no consistent approach for attributing deaths to a disaster. Researchers generally depended on death certificates to identify disaster-related deaths; several studies also drew on supplemental sources, including medical examiner, coroner, and active surveillance reports. Conclusions These results highlight the critical importance of consistent, accurate data collection during a death investigation. Review of the grey literature found variation in use of death scene data collection tools, indicating the potential for widespread inconsistency in data captured for routine reporting and public health surveillance. Findings from this review will be used to develop guidelines and tools for capturing disaster-related death investigation data. PMID:28845205

Correlates of a good death and the impact of hospice involvement: findings from the national survey of households affected by cancer.

PubMed

Cagle, John G; Pek, Jolynn; Clifford, Maggie; Guralnik, Jack; Zimmerman, Sheryl

2015-03-01

Knowing how to improve the dying experience for patients with end-stage cancer is essential for cancer professionals. However, there is little evidence on the relationship between clinically relevant factors and quality of death. Also, while hospice has been linked with improved outcomes, our understanding of factors that contribute to a "good death" when hospice is involved remains limited. This study (1) identified correlates of a good death and (2) provided evidence on the impact of hospice on quality of death. Using data from a survey of US households affected by cancer (N = 930, response rate 51 %), we fit regression models with a subsample of 158 respondents who had experienced the death of a family member with cancer. Measures included quality of death (good/bad) and clinically relevant factors including: hospice involvement, symptoms during treatment, whether wishes were followed, provider knowledge/expertise, and compassion. Respondents were 60 % female, 89 % White, and averaged 57 years old. Decedents were most often a respondent's spouse (46 %). While 73 % of respondents reported a good death, Hispanics were less likely to experience good death (p = 0.007). Clinically relevant factors, including hospice, were associated with good death (p < 0.05)--an exception being whether the physician said the cancer was curable/fatal. With adjustments, perceptions of provider knowledge/expertise was the only clinical factor that remained associated with good death. Enhanced provider training/communication, referrals to hospice and greater attention to symptom management may facilitate improved quality of dying. Additionally, the cultural relevance of the concept of a "good death" warrants further research.

Cost-Effectiveness of Antivenoms for Snakebite Envenoming in 16 Countries in West Africa

PubMed Central

Hamza, Muhammad; Idris, Maryam A.; Maiyaki, Musa B.; Lamorde, Mohammed; Chippaux, Jean-Philippe; Warrell, David A.; Kuznik, Andreas; Habib, Abdulrazaq G.

2016-01-01

Background Snakebite poisoning is a significant medical problem in agricultural societies in Sub Saharan Africa. Antivenom (AV) is the standard treatment, and we assessed the cost-effectiveness of making it available in 16 countries in West Africa. Methods We determined the cost-effectiveness of AV based on a decision-tree model from a public payer perspective. Specific AVs included in the model were Antivipmyn, FAV Afrique, EchiTab-G and EchiTab-Plus. We derived inputs from the literature which included: type of snakes causing bites (carpet viper (Echis species)/non-carpet viper), AV effectiveness against death, mortality without AV, probability of Early Adverse Reactions (EAR), likelihood of death from EAR, average age at envenomation in years, anticipated remaining life span and likelihood of amputation. Costs incurred by the victims include: costs of confirming and evaluating envenomation, AV acquisition, routine care, AV transportation logistics, hospital admission and related transportation costs, management of AV EAR compared to the alternative of free snakebite care with ineffective or no AV. Incremental Cost Effectiveness Ratios (ICERs) were assessed as the cost per death averted and the cost per Disability-Adjusted-Life-Years (DALY) averted. Probabilistic Sensitivity Analyses (PSA) using Monte Carlo simulations were used to obtain 95% Confidence Intervals of ICERs. Results The cost/death averted for the 16 countries of interest ranged from $1,997 in Guinea Bissau to $6,205 for Liberia and Sierra Leone. The cost/DALY averted ranged from $83 (95% Confidence Interval: $36-$240) for Benin Republic to $281 ($159–457) for Sierra-Leone. In all cases, the base-case cost/DALY averted estimate fell below the commonly accepted threshold of one time per capita GDP, suggesting that AV is highly cost-effective for the treatment of snakebite in all 16 WA countries. The findings were consistent even with variations of inputs in 1—way sensitivity analyses. In addition, the PSA showed that in the majority of iterations ranging from 97.3% in Liberia to 100% in Cameroun, Guinea Bissau, Mali, Nigeria and Senegal, our model results yielded an ICER that fell below the threshold of one time per capita GDP, thus, indicating a high degree of confidence in our results. Conclusions Therapy for SBE with AV in countries of WA is highly cost-effective at commonly accepted thresholds. Broadening access to effective AVs in rural communities in West Africa is a priority. PMID:27027633

Comparing effectiveness of mass media campaigns with price reductions targeting fruit and vegetable intake on US cardiovascular disease mortality and race disparities.

PubMed

Pearson-Stuttard, Jonathan; Bandosz, Piotr; Rehm, Colin D; Afshin, Ashkan; Peñalvo, Jose L; Whitsel, Laurie; Danaei, Goodarz; Micha, Renata; Gaziano, Tom; Lloyd-Williams, Ffion; Capewell, Simon; Mozaffarian, Dariush; O'Flaherty, Martin

2017-07-01

Background: A low intake of fruits and vegetables (F&Vs) is a major risk factor for cardiovascular disease (CVD) in the United States. Both mass media campaigns (MMCs) and economic incentives may increase F&V consumption. Few data exist on their comparative effectiveness. Objective: We estimated CVD mortality reductions potentially achievable by price reductions and MMC interventions targeting F&V intake in the US population. Design: We developed a US IMPACT Food Policy Model to compare 3 policies targeting F&V intake across US adults from 2015 to 2030: national MMCs and national F&V price reductions of 10% and 30%. We accounted for differences in baseline diets, CVD rates, MMC coverage, MMC duration, and declining effects over time. Outcomes included cumulative CVD (coronary heart disease and stroke) deaths prevented or postponed and life-years gained (LYGs) over the study period, stratified by age, sex, and race. Results: A 1-y MMC in 2015 would increase the average national F&V consumption by 7% for 1 y and prevent ∼18,600 CVD deaths (95% CI: 17,600, 19,500), gaining ∼280,100 LYGs by 2030. With a 15-y MMC, increased F&V consumption would be sustained, yielding a 3-fold larger reduction (56,100; 95% CI: 52,400, 57,700) in CVD deaths. In comparison, a 10% decrease in F&V prices would increase F&V consumption by ∼14%. This would prevent ∼153,300 deaths (95% CI: 146,400, 159,200), gaining ∼2.51 million LYGs. For a 30% price decrease, resulting in a 42% increase in F&V consumption, corresponding values would be 451,900 CVD deaths prevented or postponed (95% CI: 433,100, 467,500) and 7.3 million LYGs gained. Effects were similar by sex, with a smaller proportional effect and larger absolute effects at older ages. A 1-y MMC would be 35% less effective in preventing CVD deaths in non-Hispanic blacks than in whites. In comparison, price-reduction policies would have equitable proportional effects. Conclusion: Both national MMCs and price-reduction policies could reduce US CVD mortality, with price reduction being more powerful and sustainable. © 2017 American Society for Nutrition.

Cell-based optical assay for amyloid β-induced neuronal cell dysfunction using femtosecond-pulsed laser

NASA Astrophysics Data System (ADS)

Lee, Seunghee; Yoon, Jonghee; Choi, Chulhee

2015-03-01

Amyloid β-protein (Aβ) is known as a key molecule related to the pathogenesis of Alzheimer's disease (AD). Over time, the amyloid cascade disrupts essential function of mitochondria including Ca2+ homeostasis and reactive oxygen species (ROS) regulation, and eventually leads to neuronal cell death. However, there have been no methods that analyze and measure neuronal dysfuction in pathologic conditions quantitatively. Here, we suggest a cell-based optical assay to investigate neuronal function in AD using femtosecond-pulsed laser stimulation. We observed that laser stimulation on primary rat hippocampal neurons for a few microseconds induced intracellular Ca2+ level increases or produced intracellular ROS which was a primary cause of neuronal cell death depending on delivered energy. Although Aβ treatment alone had little effect on the neuronal morphologies and networks in a few hours, Aβ-treated neurons showed delayed Ca2+ increasing pattern and were more vulnerable to laser-induced cell death compared to normal neurons. Our results collectively indicate that femtosecond laser stimulation can be a useful tool to study neuronal dysfuction related to AD pathologies. We anticipate this optical method to enable studies in the early progression of neuronal impairments and the quantitative evaluation of drug effects on neurons in neurodegenerative diseases, including AD and Parkinson's disease in a preclinical study.

20 CFR 410.410 - Total disability due to pneumoconiosis, including statutory presumption.

Code of Federal Regulations, 2011 CFR

2011-04-01

... FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969, TITLE IV-BLACK LUNG BENEFITS (1969- ) Total Disability or Death Due to Pneumoconiosis § 410.410 Total disability due to pneumoconiosis, including statutory... their death. (For benefits to the eligible survivors of miners whose deaths are determined to have been...

20 CFR 410.410 - Total disability due to pneumoconiosis, including statutory presumption.

Code of Federal Regulations, 2010 CFR

2010-04-01

... FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969, TITLE IV-BLACK LUNG BENEFITS (1969- ) Total Disability or Death Due to Pneumoconiosis § 410.410 Total disability due to pneumoconiosis, including statutory... their death. (For benefits to the eligible survivors of miners whose deaths are determined to have been...

Effect of Dysphagia Screening Strategies on Clinical Outcomes After Stroke: A Systematic Review for the 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke.

PubMed

Smith, Eric E; Kent, David M; Bulsara, Ketan R; Leung, Lester Y; Lichtman, Judith H; Reeves, Mathew J; Towfighi, Amytis; Whiteley, William N; Zahuranec, Darin B

2018-03-01

Dysphagia screening protocols have been recommended to identify patients at risk for aspiration. The American Heart Association convened an evidence review committee to systematically review evidence for the effectiveness of dysphagia screening protocols to reduce the risk of pneumonia, death, or dependency after stroke. The Medline, Embase, and Cochrane databases were searched on November 1, 2016, to identify randomized controlled trials (RCTs) comparing dysphagia screening protocols or quality interventions with increased dysphagia screening rates and reporting outcomes of pneumonia, death, or dependency. Three RCTs were identified. One RCT found that a combined nursing quality improvement intervention targeting fever and glucose management and dysphagia screening reduced death and dependency but without reducing the pneumonia rate. Another RCT failed to find evidence that pneumonia rates were reduced by adding the cough reflex to routine dysphagia screening. A smaller RCT randomly assigned 2 hospital wards to a stroke care pathway including dysphagia screening or regular care and found that patients on the stroke care pathway were less likely to require intubation and mechanical ventilation; however, the study was small and at risk for bias. There were insufficient RCT data to determine the effect of dysphagia screening protocols on reducing the rates of pneumonia, death, or dependency after stroke. Additional trials are needed to compare the validity, feasibility, and clinical effectiveness of different screening methods for dysphagia. © 2018 American Heart Association, Inc.

Cost-Effectiveness Evaluation of a Novel Integrated Bite Case Management Program for the Control of Human Rabies, Haiti 2014–2015

PubMed Central

Undurraga, Eduardo A.; Meltzer, Martin I.; Tran, Cuc H.; Atkins, Charisma Y.; Etheart, Melissa D.; Millien, Max F.; Adrien, Paul; Wallace, Ryan M.

2017-01-01

Haiti has the highest burden of rabies in the Western hemisphere, with 130 estimated annual deaths. We present the cost-effectiveness evaluation of an integrated bite case management program combining community bite investigations and passive animal rabies surveillance, using a governmental perspective. The Haiti Animal Rabies Surveillance Program (HARSP) was first implemented in three communes of the West Department, Haiti. Our evaluation encompassed all individuals exposed to rabies in the study area (N = 2,289) in 2014–2015. Costs (2014 U.S. dollars) included diagnostic laboratory development, training of surveillance officers, operational costs, and postexposure prophylaxis (PEP). We used estimated deaths averted and years of life gained (YLG) from prevented rabies as health outcomes. HARSP had higher overall costs (range: $39,568–$80,290) than the no-bite-case-management (NBCM) scenario ($15,988–$26,976), partly from an increased number of bite victims receiving PEP. But HARSP had better health outcomes than NBCM, with estimated 11 additional annual averted deaths in 2014 and nine in 2015, and 654 additional YLG in 2014 and 535 in 2015. Overall, HARSP was more cost-effective (US$ per death averted) than NBCM (2014, HARSP: $2,891–$4,735, NBCM: $5,980–$8,453; 2015, HARSP: $3,534–$7,171, NBCM: $7,298–$12,284). HARSP offers an effective human rabies prevention solution for countries transitioning from reactive to preventive strategies, such as comprehensive dog vaccination. PMID:28719253

Cost-Effectiveness Evaluation of a Novel Integrated Bite Case Management Program for the Control of Human Rabies, Haiti 2014-2015.

PubMed

Undurraga, Eduardo A; Meltzer, Martin I; Tran, Cuc H; Atkins, Charisma Y; Etheart, Melissa D; Millien, Max F; Adrien, Paul; Wallace, Ryan M

2017-06-01

AbstractHaiti has the highest burden of rabies in the Western hemisphere, with 130 estimated annual deaths. We present the cost-effectiveness evaluation of an integrated bite case management program combining community bite investigations and passive animal rabies surveillance, using a governmental perspective. The Haiti Animal Rabies Surveillance Program (HARSP) was first implemented in three communes of the West Department, Haiti. Our evaluation encompassed all individuals exposed to rabies in the study area ( N = 2,289) in 2014-2015. Costs (2014 U.S. dollars) included diagnostic laboratory development, training of surveillance officers, operational costs, and postexposure prophylaxis (PEP). We used estimated deaths averted and years of life gained (YLG) from prevented rabies as health outcomes. HARSP had higher overall costs (range: $39,568-$80,290) than the no-bite-case-management (NBCM) scenario ($15,988-$26,976), partly from an increased number of bite victims receiving PEP. But HARSP had better health outcomes than NBCM, with estimated 11 additional annual averted deaths in 2014 and nine in 2015, and 654 additional YLG in 2014 and 535 in 2015. Overall, HARSP was more cost-effective (US$ per death averted) than NBCM (2014, HARSP: $2,891-$4,735, NBCM: $5,980-$8,453; 2015, HARSP: $3,534-$7,171, NBCM: $7,298-$12,284). HARSP offers an effective human rabies prevention solution for countries transitioning from reactive to preventive strategies, such as comprehensive dog vaccination.

Radiobiological basis of SBRT and SRS.

PubMed

Song, Chang W; Kim, Mi-Sook; Cho, L Chinsoo; Dusenbery, Kathryn; Sperduto, Paul W

2014-08-01

Stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) have been demonstrated to be highly effective for a variety of tumors. However, the radiobiological principles of SBRT and SRS have not yet been clearly defined. It is well known that newly formed tumor blood vessels are fragile and extremely sensitive to ionizing radiation. Various lines of evidence indicate that irradiation of tumors with high dose per fraction, i.e. >10 Gy per fraction, not only kills tumor cells but also causes significant damage in tumor vasculatures. Such vascular damage and ensuing deterioration of the intratumor environment then cause ischemic or indirect/secondary tumor cell death within a few days after radiation exposure, indicating that vascular damage plays an important role in the response of tumors to SBRT and SRS. Indications are that the extensive tumor cell death due to the direct effect of radiation on tumor cells and the secondary effect through vascular damage may lead to massive release of tumor-associated antigens and various pro-inflammatory cytokines, thereby triggering an anti-tumor immune response. However, the precise role of immune assault on tumor cells in SBRT and SRS has not yet been clearly defined. The "4 Rs" for conventional fractionated radiotherapy do not include indirect cell death and thus 4 Rs cannot account for the effective tumor control by SBRT and SRS. The linear-quadratic model is for cell death caused by DNA breaks and thus the usefulness of this model for ablative high-dose SBRT and SRS is limited.

The Concept of Death and Loss Education.

ERIC Educational Resources Information Center

Wrenn, Robert L.

1982-01-01

Presents an overview of topics and concepts appropriate for a secondary course on death and dying including stress, environments within which death occurs, those models explaining the emotional impact of death, treatment of dying patients, and concepts for students. (DC)

Causes of death in Vanuatu.

PubMed

Carter, Karen; Tovu, Viran; Langati, Jeffrey Tila; Buttsworth, Michael; Dingley, Lester; Calo, Andy; Harrison, Griffith; Rao, Chalapati; Lopez, Alan D; Taylor, Richard

2016-01-01

The population of the Pacific Melanesian country of Vanuatu was 234,000 at the 2009 census. Apart from subsistence activities, economic activity includes tourism and agriculture. Current completeness of vital registration is considered too low to be usable for national statistics; mortality and life expectancy (LE) are derived from indirect demographic estimates from censuses/surveys. Some cause of death (CoD) data are available to provide information on major causes of premature death. Deaths 2001-2007 were coded for cause (ICDv10) for ages 0-59 years from: hospital separations (HS) (n = 636), hospital medical certificates (MC) of death (n = 1,169), and monthly reports from community health facilities (CHF) (n = 1,212). Ill-defined causes were 3 % for hospital deaths and 20 % from CHF. Proportional mortality was calculated by cause (excluding ill-defined) and age group (0-4, 5-14 years), and also by sex for 15-59 years. From total deaths by broad age group and sex from 1999 and 2009 census analyses, community deaths were estimated by deduction of hospital deaths MC. National proportional mortality by cause was estimated by a weighted average of MC and CHF deaths. National estimates indicate main causes of deaths <5 years were: perinatal disorders (45 %) and malaria, diarrhea, and pneumonia (27 %). For 15-59 years, main causes of male deaths were: circulatory disease 27 %, neoplasms 13 %, injury 13 %, liver disease 10 %, infection 10 %, diabetes 7 %, and chronic respiratory disease 7 %; and for females: neoplasms 29 %, circulatory disease 15 %, diabetes 10 %, infection 9 %, and maternal deaths 8 %. Infection included tuberculosis, malaria, and viral hepatitis. Liver disease (including hepatitis and cancer) accounted for 18 % of deaths in adult males and 9 % in females. Non-communicable disease (NCD), including circulatory disease, diabetes, neoplasm, and chronic respiratory disease, accounted for 52 % of premature deaths in adult males and 60 % in females. Injuries accounted for 13 % in adult males and 6 % in females. Maternal deaths translate into an annual maternal mortality ratio of 130/100,000 for the period. Vanuatu manifests a double burden of disease with significant proportional mortality from perinatal disorders and infection/pneumonia <5 years and maternal mortality, coupled with significant proportional mortality in adults (15-59 years) from cardiovascular disease (CVD), neoplasms, and diabetes.

Separation from Loved Ones in the Fear of Death

ERIC Educational Resources Information Center

Bath, Debra M.

2010-01-01

Individuals' death anxiety or fear of death has been extensively investigated, and there are numerous conceptualizations used in the literature, including a distinction between the dimensions of death and dying of self, and death and dying of others. This article addresses a gap in the literature and re-examines the relationship between these two…

Preparing Classroom Teachers for the Impending Death of a Student with Terminal Illness.

ERIC Educational Resources Information Center

Rice, Craig J.; Gourley, Junean Krajewski

2003-01-01

This article discusses students with terminal illnesses and the challenges teachers face in dealing with the issue of death. Classroom strategies for dealing with death are described and include using children's literature that explores death, using deaths of pets as teachable moments, and using children's films. (Contains references.) (CR)

[Effectiveness of special stroke units in treatment of acute stroke].

PubMed

Nikolaus, T; Jamour, M

2000-04-01

In Germany the implementation of specialized wards for the care of stroke patients is proposed. However, which type of organized inpatient stroke unit care is most effective and which group of patients will benefit most remains unclear. Based on the analyses of the Stroke Unit Trialists' Collaboration this paper reports results of randomized and quasi-randomized trials that compared organized inpatient (stroke unit) care with contemporary conventional care. The primary analyses examined death, dependency and institutionalization. Secondary outcome measures included patient quality of life, patient and carer satisfaction and length of stay in hospital and/or institution. The analysis of twenty trails with 3864 patients showed a reduction in the rate of deaths in the stroke unit group as compared with the control group (OR 0.83, 95% CI 0.71-0.97). The odds of death or institutionalized care were lower (OR 0.76, 95% CI 0.65-0.90) as were death or dependency (OR 0.75, 95% CI 0.65-0.87). The results were independent of patient age, sex, stroke severity, and type of stroke unit organization. Organized care in stroke units resulted in benefits for stroke patients with regard to survival, independence, and probability of living at home. However, these results refer exclusively to Anglo-American and Scandinavian trials. German stroke unit services are organized in a different way. No data about the effectiveness of the German model is yet available.

Demographic, social, and economic effects on Mexican causes of death in 1990.

PubMed

Pick, J B; Butler, E W

1998-01-01

This study examined spatial geographic patterns of cause of death and 28 demographic and socioeconomic influences on causes of death for 31 Mexican states plus the Federal District for 1990. Mortality data were obtained from the state death registration system and are age standardized. The 28 socioeconomic variables were obtained from Census records. Analysis included 2 submodels: one with all 28 socioeconomic variables in a stepwise regression, and one with each of the 4 groups of factors. The conceptual model is based on epidemiological transition theory and empirical findings. There are 4 stages in mortality decline. Effects are grouped as demographic, sociocultural, economic prosperity, and housing, health, and crime factors. Findings indicate that cancer and cardiovascular disease were strongly correlated and consistently high in border areas as well as the Federal District and Jalisco. Respiratory mortality had higher values in the Federal District, Puebla, and surrounding states, as well as Jalisco. The standardized total mortality rate was only in simple correlations associated inversely with underemployment. All cause specific mortality was associated with individual factors. Respiratory mortality was linked with manufacturing work force. Cardiovascular and cancer mortality were associated with socioeconomic factors. In submodel I, cause specific mortality was predicted by crowding, housing characteristics, marriage and divorce, and manufacturing work force. In submodel II, economic group factors had the strongest model fits explaining 33-60% of the "r" square. Hypothesized effects were only partially validated.

Dandelion root extract affects colorectal cancer proliferation and survival through the activation of multiple death signalling pathways

PubMed Central

Ovadje, Pamela; Ammar, Saleem; Guerrero, Jose-Antonio; Arnason, John Thor; Pandey, Siyaram

2016-01-01

Dandelion extracts have been studied extensively in recent years for its anti-depressant and anti-inflammatory activity. Recent work from our lab, with in-vitro systems, shows the anti-cancer potential of an aqueous dandelion root extract (DRE) in several cancer cell models, with no toxicity to non-cancer cells. In this study, we examined the cancer cell-killing effectiveness of an aqueous DRE in colon cancer cell models. Aqueous DRE induced programmed cell death (PCD) selectively in > 95% of colon cancer cells, irrespective of their p53 status, by 48 hours of treatment. The anti-cancer efficacy of this extract was confirmed in in-vivo studies, as the oral administration of DRE retarded the growth of human colon xenograft models by more than 90%. We found the activation of multiple death pathways in cancer cells by DRE treatment, as revealed by gene expression analyses showing the expression of genes implicated in programmed cell death. Phytochemical analyses of the extract showed complex multi-component composition of the DRE, including some known bioactive phytochemicals such as α-amyrin, β-amyrin, lupeol and taraxasterol. This suggested that this natural extract could engage and effectively target multiple vulnerabilities of cancer cells. Therefore, DRE could be a non-toxic and effective anti-cancer alternative, instrumental for reducing the occurrence of cancer cells drug-resistance. PMID:27564258

Mortality, Causes of Death and Associated Factors Relate to a Large HIV Population-Based Cohort.

PubMed

Garriga, César; García de Olalla, Patricia; Miró, Josep M; Ocaña, Inma; Knobel, Hernando; Barberá, Maria Jesús; Humet, Victoria; Domingo, Pere; Gatell, Josep M; Ribera, Esteve; Gurguí, Mercè; Marco, Andrés; Caylà, Joan A

2015-01-01

Antiretroviral therapy has led to a decrease in HIV-related mortality and to the emergence of non-AIDS defining diseases as competing causes of death. This study estimates the HIV mortality rate and their risk factors with regard to different causes in a large city from January 2001 to June 2013. We followed-up 3137 newly diagnosed HIV non-AIDS cases. Causes of death were classified as HIV-related, non-HIV-related and external. We examined the effect of risk factors on survival using mortality rates, Kaplan-Meier plots and Cox models. Finally, we estimated survival for each main cause of death groups through Fine and Gray models. 182 deaths were found [14.0/1000 person-years of follow-up (py); 95% confidence interval (CI):12.0-16.1/1000 py], 81.3% of them had a known cause of death. Mortality rate by HIV-related causes and non-HIV-related causes was the same (4.9/1000 py; CI:3.7-6.1/1000 py), external was lower [1.7/1000 py; (1.0-2.4/1000 py)]. Kaplan-Meier estimate showed worse survival in intravenous drug user (IDU) and heterosexuals than in men having sex with men (MSM). Factors associated with HIV-related causes of death include: IDU male (subHazard Ratio (sHR):3.2; CI:1.5-7.0) and <200 CD4 at diagnosis (sHR:2.7; CI:1.3-5.7) versus ≥500 CD4. Factors associated with non-HIV-related causes of death include: ageing (sHR:1.5; CI:1.4-1.7) and heterosexual female (sHR:2.8; CI:1.1-7.3) versus MSM. Factors associated with external causes of death were IDU male (sHR:28.7; CI:6.7-123.2) and heterosexual male (sHR:11.8; CI:2.5-56.4) versus MSM. There are important differences in survival among transmission groups. Improved treatment is especially necessary in IDUs and heterosexual males.

The potential impacts of climate variability and change on temperature-related morbidity and mortality in the United States.

PubMed

McGeehin, M A; Mirabelli, M

2001-05-01

Heat and heat waves are projected to increase in severity and frequency with increasing global mean temperatures. Studies in urban areas show an association between increases in mortality and increases in heat, measured by maximum or minimum temperature, heat index, and sometimes, other weather conditions. Health effects associated with exposure to extreme and prolonged heat appear to be related to environmental temperatures above those to which the population is accustomed. Models of weather-mortality relationships indicate that populations in northeastern and midwestern U.S. cities are likely to experience the greatest number of illnesses and deaths in response to changes in summer temperature. Physiologic and behavioral adaptations may reduce morbidity and mortality. Within heat-sensitive regions, urban populations are the most vulnerable to adverse heat-related health outcomes. The elderly, young children, the poor, and people who are bedridden or are on certain medications are at particular risk. Heat-related illnesses and deaths are largely preventable through behavioral adaptations, including the use of air conditioning and increased fluid intake. Overall death rates are higher in winter than in summer, and it is possible that milder winters could reduce deaths in winter months. However, the relationship between winter weather and mortality is difficult to interpret. Other adaptation measures include heat emergency plans, warning systems, and illness management plans. Research is needed to identify critical weather parameters, the associations between heat and nonfatal illnesses, the evaluation of implemented heat response plans, and the effectiveness of urban design in reducing heat retention.

Protection against death and renal failure by renin-angiotensin system blockers in patients with diabetes and kidney disease.

PubMed

Shen, Jian; Huang, Yan-Mei; Song, Xin-Nan; Hong, Xue-Zhi; Wang, Min; Ling, Wei; Zhang, Xiao-Xi; Zhao, Hai-Lu

2016-07-01

Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used to block the renin-angiotensin system (RAS). Yet it remains uncertain whether these drugs are equally effective and safe. Systematic reviews and meta-analyses of ACEis/ARBs in diabetes and kidney disease published in PubMed, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for clinical outcomes including all-cause mortality, end-stage renal disease (ESRD), hyperkalemia and cough. Eight meta-analyses included 2177-61,264 patients with follow-up of 6-108 months. RAS blockers reduced mortality (relative risk ratio (RR), 0.90, 95% confidence interval (CI), 0.86-0.95) without heterogeneity. The death protection was significant specifically with ACEis (RR, 0.85, 95% CI, 0.79-0.91), but not with ARBs. Protection against ESRD was homogenously evident by ARBs (RR, 0.79, 95% CI, 0.73-0.87), ACEis (RR, 0.79, 95% , 0.64-0.94), and both (RR, 0.79, 95% CI, 0.73-0.87). Significant side effects were hyperkalemia by ARBs (RR, 2.44, 95% CI, 1.13-5.26), and cough by ACEis (RR, 2.38, 95% CI, 1.75-3.22) CONCLUSIONS: In patients with diabetes and kidney disease, ACEis and ARBs are consistently protective for the development of ESRD. Use of ACEis alone additionally reduces deaths and increases the risk for cough. Use of ARBs alone increases the risk for hyperkalemia without additional benefit of death protection. © The Author(s) 2016.

Diabetes, hepatocellular carcinoma, and mortality in hepatitis C-infected patients: A population-based cohort study.

PubMed

Huang, Ting-Shuo; Lin, Chih-Lang; Lu, Mu-Jie; Yeh, Chau-Ting; Liang, Kung-Hao; Sun, Chi-Chin; Shyu, Yu-Chiau; Chien, Rong-Nan

2017-07-01

The effect of diabetes mellitus (DM) on the development of hepatocellular carcinoma (HCC) and all-cause mortality after HCC development in chronic hepatitis C virus (HCV)-infected patients remains inconclusive. This cohort study aimed to investigate these issues using the Taiwanese National Health Insurance Research Database. We retrieved and enrolled newly diagnosed DM patients with HCV from the Longitudinal Cohort of Diabetes Patients database. Propensity score matching-including age, sex, alcohol-related liver disease, and baseline liver cirrhosis-was used to identify and enroll HCV patients without DM from the Longitudinal Health Insurance Database (n = 1686). A multi-state model was used to investigate transitions from "start-to-HCC," "start-to-death," and "HCC-to-death." The multi-state model showed higher cumulative hazards for "start-to-HCC," "start-to-death," and "HCC-to-death" transitions in the DM (vs non-DM) cohort. The cumulative probability of death with or without HCC after 10 years of follow-up was higher in the DM cohort than in the non-DM cohort. Multivariable transition-specific Cox models demonstrated that DM significantly increased the risk for transition from "start-to-HCC" (adjusted hazard ratio [aHR] 1.36; 95% confidence interval [CI] 1.16-1.59; P < 0.001), "start-to-death" (aHR 2.61; 95% CI: 2.05-3.33; P < 0.001), and "HCC-to-death" (aHR 1.36; 95% CI 1.10-1.68; P = 0.005). The effect of liver cirrhosis on "start-to-HCC" and "start-to-death" transitions decreased over time, particularly within 2 years. Diabetes mellitus increased the risk of HCC development in HCV-infected patients and the risk of all-cause mortality in patients with or without HCC. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Histopathological study of cardiac lesions in methamphetamine poisoning-related deaths.

PubMed

Akhgari, Maryam; Mobaraki, Homeira; Etemadi-Aleagha, Afshar

2017-02-17

Methamphetamine abuse is a worldwide health concern. Methamphetamine causes health hazards in many vital organs. It can cause damage to cardiac tissue via catecholamines release. Methamphetamine related deaths are becoming one of the most important problems in Iran. The purpose of the present study was to determine cardiac pathology in methamphetamine poisoning-related deaths. The study included 100 cases of methamphetamine poisoning-related deaths and 100 cases as control group. Toxicology analysis of liver, gastric content, bile, urine, blood and vitreous humor were conducted to detect drugs, poisons and alcohols using thin layer chromatography, gas chromatography/mass spectrometry, and high performance liquid chromatography. Positive toxicology analysis results except for amphetamine and methamphetamine were excluded from the study in order to omit interfering factors. The most striking features of cardiac damage were observed by light microscopy. Methamphetamine and amphetamine were detected in either urine or gastric content samples. In all of the cases methamphetamine toxicity was determined to be a direct cause of death by forensic medicine practitioner. Cardiovascular pathology was noted in 68% of studied cases. The most common histopathologic features were myocardial fiber hypertrophy, mild, moderate to severe atherosclerosis and focal degeneration/necrosis. The results of the present study indicate that cardiotoxicity is one of the major contributing factors in methamphetamine poisoning related deaths. Overall, the current study highlights the fact that cardiotoxic effects of methamphetamine can explain increasing reports of heart failure and consequently death in young abusers. Not applicable. Histopathological study of cardiac lesions in methamphetamine poisoning-related deaths.

Temporal trends in the leading causes of death among a large national cohort of patients with colorectal cancer from 1975 to 2009 in the United States.

PubMed

Tong, Liyue; Ahn, Chul; Symanski, Elaine; Lai, Dejian; Du, Xianglin L

2014-06-01

To assess the distribution of proportion of deaths from causes other than colorectal cancer (CRC) over time and temporal trends of cause-specific cumulative incidence of death due to six leading causes in patients with CRC. Overall, 375,462 patients with CRC in nine Surveillance, Epidemiology, and End Results registries from 1975 to 2009 were included. Competing risks proportional hazards regression was used to examine the effect of diagnostic periods on the risk of cause-specific death. From 1975 to 2009 by 5-year interval, the proportion of deaths from causes other than CRC increased significantly with diagnostic periods according to the lengths of follow-up (P < .0001). The 5-year risk of death significantly decreased with diagnostic periods for all-cause, CRC, and circulation diseases among all age groups (<65, 65-74, and ≥75 years) but increased for chronic obstructive pulmonary disease, diabetes, and Alzheimer disease among patients aged 65 years or older. Deaths due to causes other than CRC increased significantly over time regardless of tumor stage and site but more sharply in those with early-stage and distal colon cancer. The increasing leading causes of death are chronic obstructive pulmonary disease, diabetes, and Alzheimer disease, which may be prevented or delayed substantially by modification or intervention in lifestyle or other factors. Copyright © 2014 Elsevier Inc. All rights reserved.

Morbidity and mortality in type B Niemann-Pick disease.

PubMed

McGovern, Margaret M; Lippa, Natalie; Bagiella, Emilia; Schuchman, Edward H; Desnick, Robert J; Wasserstein, Melissa P

2013-08-01

The purpose of this study was to perform a systematic evaluation of morbidity and mortality in type B Niemann-Pick disease. A total of 103 patients with Niemann-Pick disease (49 males, 54 females, age range: 1-72 years) participated in natural history studies through Mount Sinai's International Center for Types A and B Niemann-Pick Disease between 1992 and 2012. Serious morbidities included significant neurological, hepatic, and cardiac disease. Thirteen patients had some degree of neurological impairment. Nine patients had cirrhosis or liver failure requiring transplantation. Coronary artery and valvular heart disease were present in nine patients. Of note, only four patients were oxygen dependent, although progressive pulmonary disease is a well-described feature of Niemann-Pick disease. During the follow-up period, 18 deaths occurred. The median age of death was 15.5 years (range 1-72). Causes of death included pneumonia, liver failure, and hemorrhage. The majority of deaths (12 of 18) occurred in patients <21 years, yielding a mortality rate of 19% in the pediatric population. This study demonstrates that Niemann-Pick disease is a life-threatening disorder with significant morbidity and mortality, especially in the pediatric population. The information collected in this series highlights the need for safe, effective therapy for Niemann-Pick disease.

2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptotic cell death and cytochrome P4501A expression in developing Fundulus heteroclitus embryos

USGS Publications Warehouse

Toomey, B.H.; Bello, S.; Hahn, M.E.; Cantrell, S.; Wright, P.; Tillitt, D.E.; Di Giulio, R.T.

2001-01-01

Fundulus heteroclitus embryos were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during early development using nanoinjection or water bath exposure. TCDD caused developmental abnormalities that included hemorrhaging, loss of vascular integrity, edema, stunted development and death. The LC50 and LD50 of TCDD for Fundulus embryos were ???19.7??9.5 pg TCDD/??l (water bath) and 0.25??0.09 ng TCDD/g embryo (nanoinjection). To identify a possible cause for these developmental abnormalities we analyzed the effects of TCDD on apoptotic cell death and cytochrome P4501A (CYP1A) expression in the embryos. TCDD exposure increased apoptotic cell death in several tissues including brain, eye, gill, kidney, tail, intestine, heart, and vascular tissue. CYP1A expression was also increased in the TCDD-exposed embryos predominantly in liver, kidney, gill, heart, intestine, and in vascular tissues throughout the embryo. There was co-occurrence of TCDD-induced apoptosis and CYP1A expression in some, but not all, cell types. In addition the dose response relationships for apoptosis and mortality were similar, while CYP1A expression appeared more sensitive to TCDD induction. Copyright ?? 2001 Elsevier Science B.V.

Grief symptoms and difficult patient loss for oncologists in response to patient death.

PubMed

Granek, Leeat; Ben-David, Merav; Shapira, Shahar; Bar-Sela, Gil; Ariad, Samuel

2017-07-01

The study aimed to explore oncologist's grief symptoms over patient death and to identify why and which losses are particularly challenging when patients die. The grounded theory method was used to collect and analyze the data. Twenty-two oncologists were interviewed between March 2013 and June 2014 from three adult oncology centers in the north, center, and south of Israel. Oncologists were at different stages of their careers and varied in their sub-specialties, gender, and personal and professional backgrounds. Grief begun when the patient died, in anticipation of the patient's death, many days after the death, or when the patient received a poor prognosis. The phenomenological experience of grief for oncologists included behavioral, cognitive, physical, and emotional symptoms in response to patient death. Behavioral symptoms included crying and difficulties sleeping. Cognitive symptoms included self-doubt and rumination about the patient and the care the patient had received before death. Physical symptoms included chest pain, fatigue, and general physical discomfort. Emotional symptoms included sadness, anxiety, helplessness, guilt, relief, irritability, and loss. Difficult patient loss was caused by patient-related factors, family-related factors, and disease-related factors. Patient deaths result in behavioral, cognitive, physical, and emotional symptoms of grief in oncologists. These symptoms become particularly intense in the context of patient, family, and disease-related factors. Educational and supportive interventions for managing grief related to patient death are needed in order to support oncologists in their emotionally and mentally taxing work. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Lead Levels in Landfill Areas and Childhood Exposure: An Integrative Review.

PubMed

Kim, M Angela; Williams, Kimberly A

2017-01-01

Landfills are high-risk areas for environmental lead exposure for children living in poverty stricken areas in many countries. This review examines landfills and lead toxicity in children. The review discusses the effects of lead toxicity, provides evidenced based recommendations to reduce lead exposure, and identify gaps in the evidence. A database search was conducted of articles in English from 1985 to 2014. Ten articles met the inclusion criteria. The Whittemore and Knafl framework and the John Hopkins Research Evidence Appraisal Tool © were used for reviewing the data. Elevated blood lead levels (BLLs) of children living near landfills were related to increased soil lead levels. Toxic effects of lead included adverse outcomes such as encephalopathy or death for children. Different approaches to decrease lead level include environmental surveillance, BLL screening, and soil abatement which are costly. Increased BLL through environmental exposure is connected with poor health outcomes and death among children. Evidence-based prevention included monitoring and screening and costly soil abatement. It is recommended that future studies focus on community education for exposure avoidance for children living near landfill areas. © 2016 Wiley Periodicals, Inc.

Reliability of postmortem fentanyl concentrations in determining the cause of death.

PubMed

Gill, James R; Lin, Peter T; Nelson, Lewis

2013-03-01

Transdermal fentanyl, an opioid used for management of marked pain, also is abused and may cause death. We reviewed medical examiner reports of 92 decedents who had one or more fentanyl transdermal patches on their body and had fentanyl detected in their postmortem toxicology analysis. The manners of death included 40 accidents, 36 natural, 8 suicides, 5 therapeutic complications, and 3 undetermined deaths. Among the accidental fentanyl intoxication deaths, 32 of 37 involved substance abuse. The majority (95 %) of the 37 accidental deaths involving fentanyl were multi-drug intoxications. The substance abuse deaths had a mean fentanyl blood concentration (26.4 ng/ml or μg/L) that was over twice that of the natural group (11.8 ng/ml). Our analysis suggests a relationship between total patch dosage and mean postmortem fentanyl concentration up to the 100-μg/h dose. The very wide and overlapping ranges of postmortem fentanyl concentrations effectively nullify the utility of correlating the dose and expected postmortem concentration for any particular death. Based on the variable relationship between dose and blood concentration, the antemortem dose cannot be reliably predicted based on the postmortem concentration. This does not, however, render the medical examiner/coroner unable to determine the cause and manner of death because the toxicology results are only one datum point among several that are considered. Although there was a weakly positive relationship between body mass index and fentanyl concentration, further research is needed to determine whether adipose tissue represents a significant depot for postmortem release of fentanyl.

Causes of death in U.S. Special Operations Forces in the global war on terrorism: 2001-2004.

PubMed

Holcomb, John B; McMullin, Neil R; Pearse, Lisa; Caruso, Jim; Wade, Charles E; Oetjen-Gerdes, Lynne; Champion, Howard R; Lawnick, Mimi; Farr, Warner; Rodriguez, Sam; Butler, Frank K

2007-06-01

Effective combat trauma management strategies depend upon an understanding of the epidemiology of death on the battlefield. A panel of military medical experts reviewed photographs and autopsy and treatment records for all Special Operations Forces (SOF) who died between October 2001 and November 2004 (n = 82). Fatal wounds were classified as nonsurvivable or potentially survivable. Training and equipment available at the time of injury were taken into consideration. A structured analysis was conducted to identify equipment, training, or research requirements for improved future outcomes. Five (6%) of 82 casualties had died in an aircraft crash, and their bodies were lost at sea; autopsies had been performed on all other 77 soldiers. Nineteen deaths, including the deaths at sea were noncombat; all others were combat related. Deaths were caused by explosions (43%), gunshot wounds (28%), aircraft accidents (23%), and blunt trauma (6%). Seventy of 82 deaths (85%) were classified as nonsurvivable; 12 deaths (15%) were classified as potentially survivable. Of those with potentially survivable injuries, 16 causes of death were identified: 8 (50%) truncal hemorrhage, 3 (19%) compressible hemorrhage, 2 (13%) hemorrhage amenable to tourniquet, and 1 (6%) each from tension pneumothorax, airway obstruction, and sepsis. The population with nonsurvivable injuries was more severely injured than the population with potentially survivable injuries. Structured analysis identified improved methods of truncal hemorrhage control as a principal research requirement. The majority of deaths on the modern battlefield are nonsurvivable. Improved methods of intravenous or intracavitary, noncompressible hemostasis combined with rapid evacuation to surgery may increase survival.

Causes of Death in U.S. Special Operations Forces in the Global War on Terrorism

PubMed Central

Holcomb, John B.; McMullin, Neil R.; Pearse, Lisa; Caruso, Jim; Wade, Charles E.; Oetjen-Gerdes, Lynne; Champion, Howard R.; Lawnick, Mimi; Farr, Warner; Rodriguez, Sam; Butler, Frank K.

2007-01-01

Background: Effective combat trauma management strategies depend upon an understanding of the epidemiology of death on the battlefield. Methods: A panel of military medical experts reviewed photographs and autopsy and treatment records for all Special Operations Forces (SOF) who died between October 2001 and November 2004 (n = 82). Fatal wounds were classified as nonsurvivable or potentially survivable. Training and equipment available at the time of injury were taken into consideration. A structured analysis was conducted to identify equipment, training, or research requirements for improved future outcomes. Results: Five (6%) of 82 casualties had died in an aircraft crash, and their bodies were lost at sea; autopsies had been performed on all other 77 soldiers. Nineteen deaths, including the deaths at sea were noncombat; all others were combat related. Deaths were caused by explosions (43%), gunshot wounds (28%), aircraft accidents (23%), and blunt trauma (6%). Seventy of 82 deaths (85%) were classified as nonsurvivable; 12 deaths (15%) were classified as potentially survivable. Of those with potentially survivable injuries, 16 causes of death were identified: 8 (50%) truncal hemorrhage, 3 (19%) compressible hemorrhage, 2 (13%) hemorrhage amenable to tourniquet, and 1 (6%) each from tension pneumothorax, airway obstruction, and sepsis. The population with nonsurvivable injuries was more severely injured than the population with potentially survivable injuries. Structured analysis identified improved methods of truncal hemorrhage control as a principal research requirement. Conclusions: The majority of deaths on the modern battlefield are nonsurvivable. Improved methods of intravenous or intracavitary, noncompressible hemostasis combined with rapid evacuation to surgery may increase survival. PMID:17522526

The "AMA-Brazil" cooperative project: a nation-wide assessment of the clinical and epidemiological profile of AIDS-related deaths in Brazil in the antiretroviral treatment era.

PubMed

Veras, Maria Amelia de Sousa Mascena; Ribeiro, Manoel C A; Jamal, Leda Fátima; McFarland, Willi; Bastos, Francisco Inácio; Ribeiro, Karina Braga; Barata, Rita Barradas; Moraes, José Cassio de; Reingold, Arthur L

2011-01-01

The objective of this study was to assess the profile of AIDS-related deaths in the post antiretroviral therapy (ART) scale up period in Brazil. A case-control study was conducted including a nationally probabilistic sample of AIDS deaths and living controls. Data were abstracted from medical records and nation-wide databases of AIDS cases, mortality, ART care, and laboratory testing. Interrupted (adjusted odds ratio--AOR 4.35, 95%CI: 3.15-6.00) or no use of ART (AOR 2.39, 95%CI: 1.57-3.65) was the strongest predictor of death, followed by late diagnosis (AOR 3.95, 95%CI: 2.68-5.82). Criterion other than CD4 < 350 had a higher likelihood of death (AOR 1.65, 95%CI: 1.14-2.40). Not receiving recommended vaccines (AOR, 1.76, 95%CI: 1.21-2.56), presenting AIDS-related diseases (AOR 2.19, 95%CI: 1.22-3.93) and tuberculosis (AOR 1.50, 95%CI: 1.14-1.97) had higher odds of death. Being an injecting drug user (IDU) had a borderline association with higher odds of death, while homo/bisexual exposure showed a protective effect. Despite remarkable successes, Brazilians continue to die of AIDS in the post-ART scale up period. Many factors contributing to continued mortality are preventable.

Increased Serum Alkaline Phosphatase and Serum Phosphate as Predictors of Mortality after Stroke

PubMed Central

S, Pratibha; JB, Agadi

2014-01-01

Context: Serum Alkaline phosphatase (ALP) & phosphate are considered to be indicators of vascular calcification. Link between bone metabolism, vascular calcification, cardiovascular events have been well studied in chronic kidney disease and ischemic heart disease. Aims: To determine that increased serum phosphate and alkaline phosphatase are predictors of mortality rates and recurrent vascular events in stroke. Materials and Methods: Sixty patients admitted with acute stroke (ischemic & haemorrhagic) were included in the study. Their baseline clinical characteristics and biochemical parameters including serum ALP and phosphate were noted. All patients were followed up for a period of one year. The all- cause mortality, the mortality due to cardiovascular events and recurrent vascular events without death were noted during the follow up. Statistical analyses were done to look for any correlation between mortality and baseline levels of serum ALP and phosphate. Results: Of the 60 patients, 8 (13.3%) patients were lost for follow up. Fourteen (26.9%) patients died; of which 12 deaths were due to vascular causes and 2 deaths were due to non vascular causes. Increasing levels of serum ALP and phosphate correlated with all cause mortality and recurrent vascular events without death Conclusion: Serum ALP and phosphate prove to be cost effective prognostic indicator of mortality and recurrent vascular events in stroke. This finding has to be confirmed with studies including larger population. Further research on ALP inhibitors, Vitamin D analogues and phosphate binders to improve mortality in stroke population can be encouraged. PMID:25300293

Increased serum alkaline phosphatase and serum phosphate as predictors of mortality after stroke.

PubMed

S, Pratibha; S, Praveen-Kumar; Jb, Agadi

2014-08-01

Serum Alkaline phosphatase (ALP) & phosphate are considered to be indicators of vascular calcification. Link between bone metabolism, vascular calcification, cardiovascular events have been well studied in chronic kidney disease and ischemic heart disease. To determine that increased serum phosphate and alkaline phosphatase are predictors of mortality rates and recurrent vascular events in stroke. Sixty patients admitted with acute stroke (ischemic & haemorrhagic) were included in the study. Their baseline clinical characteristics and biochemical parameters including serum ALP and phosphate were noted. All patients were followed up for a period of one year. The all- cause mortality, the mortality due to cardiovascular events and recurrent vascular events without death were noted during the follow up. Statistical analyses were done to look for any correlation between mortality and baseline levels of serum ALP and phosphate. Of the 60 patients, 8 (13.3%) patients were lost for follow up. Fourteen (26.9%) patients died; of which 12 deaths were due to vascular causes and 2 deaths were due to non vascular causes. Increasing levels of serum ALP and phosphate correlated with all cause mortality and recurrent vascular events without death Conclusion: Serum ALP and phosphate prove to be cost effective prognostic indicator of mortality and recurrent vascular events in stroke. This finding has to be confirmed with studies including larger population. Further research on ALP inhibitors, Vitamin D analogues and phosphate binders to improve mortality in stroke population can be encouraged.

Crocetin shifts autophagic cell survival to death of breast cancer cells in chemotherapy.

PubMed

Zhang, Ailian; Li, Jincheng

2017-03-01

The chemotherapy with fluorouracil is not always effective, in which some breast cancer cells may survive the fluorouracil treatment through enhanced autophagy. Crocetin is the major constituent of saffron, a Chinese traditional herb, which has recently found to have multiple pharmacological effects, including anticancer. However, the effects of Crocetin on the outcome of fluorouracil therapy for breast cancer have not been studied. Here, we showed that fluorouracil treatment inhibited the growth of breast cancer cells, in either a Cell Counting Kit-8 assay or an MTT assay. Inhibition of autophagy further suppressed breast cancer cell growth, suggesting that the breast cancer cells increased autophagic cell survival during fluorouracil treatment. However, Crocetin significantly increased the suppressive effects of fluorouracil on breast cancer cell growth, without affecting either cell apoptosis or autophagy. Inhibition of autophagy at the presence of Crocetin partially abolished the suppressive effects on breast cancer cell growth, suggesting that Crocetin may increase autophagic cell death in fluorouracil-treated breast cancer cells. Furthermore, Crocetin decreased Beclin-1 levels but increased ATG1 levels in fluorouracil-treated breast cancer cells. Together, these data suggest that Crocetin may shift autophagic cell survival to autophagic cell death in fluorouracil-treated breast cancer cells, possibly through modulation of the expression of ATG1 and Beclin-1.

High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death.

PubMed

Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Hall, Kathi; Stein, C Michael

2017-02-01

Studies demonstrating that higher doses of citalopram (> 40 mg) and escitalopram (> 20 mg) prolong the corrected QT interval prompted regulatory agency warnings, which are controversial, given the absence of confirmatory clinical outcome studies. We compared the risk of potential arrhythmia-related deaths for high doses of these selective serotonin reuptake inhibitors (SSRIs) to that for equivalent doses of fluoxetine, paroxetine, and sertraline. The Tennessee Medicaid retrospective cohort study included 54,220 persons 30-74 years of age without cancer or other life-threatening illness who were prescribed high-dose SSRIs from 1998 through 2011. The mean age was 47 years, and 76% were female. Demographic characteristics and comorbidity for individual SSRIs were comparable. Because arrhythmia-related deaths are typically sudden and occur outside the hospital, we analyzed out-of-hospital sudden unexpected death as well as sudden cardiac deaths, a more specific indicator of proarrhythmic effects. The adjusted risk of sudden unexpected death for citalopram did not differ significantly from that for the other SSRIs. The respective hazard ratios (HRs) for citalopram versus escitalopram, fluoxetine, paroxetine, and sertraline were 0.84 (95% CI, 0.40-1.75), 1.24 (95% CI, 0.75-2.05), 0.75 (95% CI, 0.45-1.24), and 1.53 (95% CI, 0.91-2.55). There were no significant differences for sudden cardiac death or all study deaths, nor were there significant differences among high-risk patients (≥ 60 years of age, upper quartile baseline cardiovascular risk). Escitalopram users had no significantly increased risk for any study end point. We found no evidence that risk of sudden unexpected death, sudden cardiac death, or total mortality for high-dose citalopram and escitalopram differed significantly from that for comparable doses of fluoxetine, paroxetine, and sertraline. © Copyright 2016 Physicians Postgraduate Press, Inc.

High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death

PubMed Central

Ray, Wayne A.; Chung, Cecilia P.; Murray, Katherine T.; Hall, Kathi; Stein, C. Michael

2018-01-01

Objective Studies demonstrating higher doses of citalopram (>40mg) and escitalopram (>20mg) prolong the QTc interval prompted regulatory agency warnings, which are controversial, given the absence of confirmatory clinical outcome studies. We compared the risk of potential arrhythmia-related deaths for high doses of these SSRIs to that for equivalent doses of fluoxetine, paroxetine, and sertraline. Method The Tennessee Medicaid retrospective cohort study included 54,220 persons 30–74 years of age without cancer or other life-threatening illness prescribed high-dose SSRIs. The mean age was 47 years and 76% were female. Demographic characteristics and comorbidity for individual SSRIs were comparable. Because arrhythmia-related deaths are typically sudden and occur outside the hospital, we analyzed out-of-hospital sudden unexpected death as well as sudden cardiac deaths, a more specific indicator of pro-arrhythmic effects. Results The adjusted risk of sudden unexpected death for citalopram did not differ significantly from that for the other SSRIs. The respective hazard ratios (HRs) for citalopram versus escitalopram, fluoxetine, paroxetine, and sertraline were 0.84 (95% confidence interval [CI], 0.40–1.75), 1.24 (0.75–2.05), 0.75 (0.45–1.24), and 1.53 (0.91–2.55). There were no significant differences for sudden cardiac death or all study deaths, nor were there significant differences among high-risk patients (≥60 years of age, upper quartile baseline cardiovascular risk). Escitalopram users had no significantly increased risk for any study endpoint. Conclusions We found no evidence that risk of sudden unexpected death, sudden cardiac death, or total mortality for high-dose citalopram and escitalopram differed significantly from that for comparable doses of fluoxetine, paroxetine, and sertraline. PMID:27736049

Pregnancy associated death in record linkage studies relative to delivery, termination of pregnancy, and natural losses: A systematic review with a narrative synthesis and meta-analysis

PubMed Central

Reardon, David C; Thorp, John M

2017-01-01

Objectives: Measures of pregnancy associated deaths provide important guidance for public health initiatives. Record linkage studies have significantly improved identification of deaths associated with childbirth but relatively few have also examined deaths associated with pregnancy loss even though higher rates of maternal death have been associated with the latter. Following PRISMA guidelines we undertook a systematic review of record linkage studies examining the relative mortality risks associated with pregnancy loss to develop a narrative synthesis, a meta-analysis, and to identify research opportunities. Methods: MEDLINE and SCOPUS were searched in July 2015 using combinations of: mortality, maternal death, record linkage, linked records, pregnancy associated mortality, and pregnancy associated death to identify papers using linkage of death certificates to independent records identifying pregnancy outcomes. Additional studies were identified by examining all citations for relevant studies. Results: Of 989 studies, 11 studies from three countries reported mortality rates associated with termination of pregnancy, miscarriage or failed pregnancy. Within a year of their pregnancy outcomes, women experiencing a pregnancy loss are over twice as likely to die compared to women giving birth. The heightened risk is apparent within 180 days and remains elevated for many years. There is a dose effect, with exposure to each pregnancy loss associated with increasing risk of death. Higher rates of death from suicide, accidents, homicide and some natural causes, such as circulatory diseases, may be from elevated stress and risk taking behaviors. Conclusions: Both miscarriage and termination of pregnancy are markers for reduced life expectancy. This association should inform research and new public health initiatives including screening and interventions for patients exhibiting known risk factors. PMID:29163945

Leading Causes of Cancer Mortality - Caribbean Region, 2003-2013.

PubMed

Razzaghi, Hilda; Quesnel-Crooks, Sarah; Sherman, Recinda; Joseph, Rachael; Kohler, Betsy; Andall-Brereton, Glennis; Ivey, Marsha A; Edwards, Brenda K; Mery, Les; Gawryszewski, Vilma; Saraiya, Mona

2016-12-16

Cancer is one of the leading causes of deaths worldwide (1); in 2012, an estimated 65% of all cancer deaths occurred in the less developed regions of the world (2). In the Caribbean region, cancer is the second leading cause of mortality, with an estimated 87,430 cancer-related deaths reported in 2012 (3). The Pan American Health Organization defines the Caribbean region as a group of 27 countries that vary in size, geography, resources, and surveillance systems.* CDC calculated site- and sex-specific proportions of cancer deaths and age-standardized mortality rates (ASMR) for 21 English- and Dutch-speaking Caribbean countries, the United States, and two U.S. territories (Puerto Rico and the U.S. Virgin Islands [USVI]), using the most recent 5 years of mortality data available from each jurisdiction during 2003-2013. The selection of years varied by availability of the data from the countries and territories in 2015. ASMR for all cancers combined ranged from 46.1 to 139.3 per 100,000. Among males, prostate cancers were the leading cause of cancer deaths, followed by lung cancers; the percentage of cancer deaths attributable to prostate cancer ranged from 18.4% in Suriname to 47.4% in Dominica, and the percentage of cancer deaths attributable to lung cancer ranged from 5.6% in Barbados to 24.4% in Bermuda. Among females, breast cancer was the most common cause of cancer deaths, ranging from 14.0% of cancer deaths in Belize to 29.7% in the Cayman Islands, followed by cervical cancer. Several of the leading causes of cancer deaths in the Caribbean can be reduced through primary and secondary preventions, including prevention of exposure to risk factors, screening, early detection, and timely and effective treatment.

Lights out: Impact of the August 2003 power outage on mortality in New York, NY

PubMed Central

Anderson, G. Brooke; Bell, Michelle L.

2012-01-01

Background Little is known about how power outages affect health. We investigated mortality effects of the largest US blackout to date, August 14–15, 2003 in New York, NY. Methods We estimated mortality risk in New York, NY, using a generalized linear model with data from 1987–2005. We incorporated possible confounders, including weather and long-term and seasonal mortality trends. Results During the blackout, mortality increased for accidental deaths (122% [95% confidence interval = 28%–287%]) and non-accidental (i.e., disease-related) deaths (25% [12%–41%]), resulting in approximately 90 excess deaths. Increased mortality was not from deaths being advanced by a few days; rather, mortality risk remained slightly elevated through August 2003. Discussion To our knowledge, this is the first analysis of power outages and non-accidental mortality. Understanding the impact of power outages on human health is relevant, given that increased energy demand and climate change are likely to put added strain on power grids. PMID:22252408

Factors Affecting the Occurrence of Spinal Reflexes in Brain Dead Cases.

PubMed

Hosseini, Mahsa Sadat; Ghorbani, Fariba; Ghobadi, Omid; Najafizadeh, Katayoun

2015-08-01

Brain death is defined as the permanent absence of all cortical and brain stem reflexes. A wide range of spontaneous or reflex movements that are considered medullary reflexes are observed in heart beating cases that appear brain dead, which may create uncertainty about the diagnosis of brain death and cause delays in deceased-donor organ donation process. We determined the frequency and type of medullary reflexes and factors affecting their occurrence in brain dead cases. During 1 year, 122 cases who fulfilled the criteria for brain death were admitted to the special intensive care unit for organ procurement of Masih Daneshvari Hospital. Presence of spinal reflexes was evaluated by trained coordinators and was recorded in a form in addition to other information including demographic characteristics, cause of brain death, time from detection of brain death, history of craniotomy, vital signs, serum electrolyte levels, and parameters of arterial blood gas determination. Most cases (63%) included in this study were male, and mean age was 33 ± 15 y. There was > 1 spinal reflex observed in 40 cases (33%). The most frequent reflex was plantar response (17%) following by myoclonus (10%), triple flexion reflex (9%), pronator extension reflex (8%), and undulating toe reflex (7%). Mean systolic blood pressure was significantly higher in cases who exhibited medullary reflexes than other cases (126 ± 19 mm Hg vs 116 ± 17 mm Hg; P = .007). Spinal reflexes occur frequently in brain dead cases, especially when they become hemodynamically stable after treatment in the organ procurement unit. Observing these movements by caregivers and family members has a negative effect on obtaining family consent and organ donation. Increasing awareness about spinal reflexes is necessary to avoid suspicion about the brain death diagnosis and delays in organ donation.

Hospital Versus Home Death: Results from the Mexican Health and Aging Study

PubMed Central

Cárdenas-Turanzas, Marylou; Torres-Vigil, Isabel; Tovalín-Ahumada, Horacio; Nates, Joseph L.

2013-01-01

Context Characterizing where people die is needed to inform palliative care programs in Mexico. Objectives To determine whether access to health care influences the place of death of older Mexicans and examine the modifying effects of demographic and clinical characteristics. Methods We analyzed 2001 baseline and 2003 follow-up data from the Mexican Health and Aging Study. Cases included adults who completed the baseline interview and died before the follow-up interview and for whom a proxy interview was obtained in 2003. The main outcome variable was the place of death (hospital vs. home). The predictors of the place of death were identified using logistic regression analysis. Results The study group included 473 deceased patients; 52.9% died at home. Factors associated with hospital death were having spent at least one night in a hospital during the last year of life (odds ratio [OR]: 6.73; 95% confidence interval [CI]: 3.29, 13.78) and dying in a city other than the city of usual residence (OR: 4.68, 95% CI: 2.56, 8.57). Factors associated with home death were not having health care coverage (OR: 2.78, 95% CI: 1.34, 5.88), living in a city of less than 100,000 residents (OR: 2.44, 95% CI: 1.43, 4.17), and older age (OR: 1.03, 95% CI: 1.01, 1.05). Conclusion Older Mexicans with access to health care services were more likely to die in the hospital even after controlling for important clinical and demographic characteristics. Findings from the study may be used to plan the provision of accessible end-of-life hospital and home-based services. PMID:21146354

Projected health impact and cost-effectiveness of rotavirus vaccination among children <5 years of age in China.

PubMed

Liu, Na; Yen, Catherine; Fang, Zhao-yin; Tate, Jacqueline E; Jiang, Baoming; Parashar, Umesh D; Zeng, Guang; Duan, Zhao-jun

2012-11-06

Two rotavirus vaccines have been licensed globally since 2006. In China, only a lamb rotavirus vaccine is licensed and several new rotavirus vaccines are in development. Data regarding the projected health impact and cost-effectiveness of vaccination of children in China against rotavirus will assist policy makers in developing recommendations for vaccination. Using a Microsoft Excel model, we compared the national health and economic burden of rotavirus disease in China with and without a vaccination program. Model inputs included 2007 data on burden and cost of rotavirus outcomes (deaths, hospitalizations, outpatient visits), projected vaccine efficacy, coverage, and cost. Cost-effectiveness was measured in US dollars per disability-adjusted life-year (DALY) and US dollars per life saved. A 2-dose rotavirus vaccination program could annually avert 3013 (62%) deaths, 194,794 (59%) hospitalizations and 1,333,356 (51%) outpatient visits associated with rotavirus disease in China. The medical break-even price of the vaccine is $1.19 per dose. From a societal perspective, a vaccination program would be highly cost-effective in China at the vaccine price of $2.50 to $5 per dose, and be cost-effective at the price of $10 to $20 per dose. A national rotavirus vaccination program could be a cost-effective measure to effectively reduce deaths, hospitalizations, and outpatient visits due to rotavirus disease in China. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia.

PubMed

Panickar, Kiran S; Jang, Saebyeol

2013-08-01

Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, energy failure, free radical production, excitotoxicity, altered calcium homeostasis, and activation of proteases all of which affect brain functioning and also contribute to longterm disabilities including cognitive decline. Inflammation, mitochondrial dysfunction, increased oxidative/nitrosative stress, and intracellular calcium overload contribute to brain injury including cell death and brain edema. However, there is a paucity of agents that can effectively reduce cerebral damage and hence considerable attention has focused on developing newer agents with more efficacy and fewer side-effects. Polyphenols are natural compounds with variable phenolic structures and are rich in vegetables, fruits, grains, bark, roots, tea, and wine. Most polyphenols have antioxidant, anti-inflammatory, and anti-apoptotic properties and their protective effects on mitochondrial functioning, glutamate uptake, and regulating intracellular calcium levels in ischemic injury in vitro have been demonstrated. This review will assess the current status of the potential effects of polyphenols in reducing cerebral injury and improving cognitive function in ischemia in animal and human studies. In addition, the review will also examine available patents in nutrition and agriculture that relates to cerebral ischemic injury with an emphasis on plant polyphenols.

Sudden infant death syndrome caused by poliomyelitis.

PubMed

Dunne, J W; Harper, C G; Hilton, J M

1984-07-01

Most seemingly well infants who die suddenly and unexpectedly have no adequate cause of death found on thorough postmortem examination. Respiratory and enteric viruses are often present, especially in the upper respiratory tract, but the infective process seems, of itself, insufficient to cause death. In the remainder of the cases, a variety of lesions will be discovered, including viral myocarditis, bronchiolitis, and sepsis. We report a case of sudden and unexpected death in a 5-week-old male infant due to acute anterior poliomyelitis. This case illustrates the importance of a thorough postmortem examination, including histologic studies of the brain stem and spinal cord in cases of sudden infant death syndrome.

Leveraging Google Trends, Twitter, and Wikipedia to Investigate the Impact of a Celebrity's Death From Rheumatoid Arthritis.

PubMed

Mahroum, Naim; Bragazzi, Nicola Luigi; Sharif, Kassem; Gianfredi, Vincenza; Nucci, Daniele; Rosselli, Roberto; Brigo, Francesco; Adawi, Mohammad; Amital, Howard; Watad, Abdulla

2018-06-01

Technological advancements, such as patient-centered smartphone applications, have enabled to support self-management of the disease. Further, the accessibility to health information through the Internet has grown tremendously. This article aimed to investigate how big data can be useful to assess the impact of a celebrity's rheumatic disease on the public opinion. Variable tools and statistical/computational approaches have been used, including massive data mining of Google Trends, Wikipedia, Twitter, and big data analytics. These tools were mined using an in-house script, which facilitated the process of data collection, parsing, handling, processing, and normalization. From Google Trends, the temporal correlation between "Anna Marchesini" and rheumatoid arthritis (RA) queries resulted 0.66 before Anna Marchesini's death and 0.90 after Anna Marchesini's death. The geospatial correlation between "Anna Marchesini" and RA queries resulted 0.45 before Anna Marchesini's death and 0.52 after Anna Marchesini's death. From Wikitrends, after Anna Marchesini's death, the number of accesses to Wikipedia page for RA has increased 5770%. From Twitter, 1979 tweets have been retrieved. Numbers of likes, retweets, and hashtags have increased throughout time. Novel data streams and big data analytics are effective to assess the impact of a disease in a famous person on the laypeople.

Review of Canine Deaths While in Service in US Civilian Law Enforcement (2002-2012).

PubMed

Stojsih, Sarah E; Baker, Janice L; Les, Clifford M; Bir, Cynthia A

2014-01-01

Working dogs have been proven effective in multiple military and law enforcement applications. Similar to their human counterparts, understanding mortality while still in service can help improve treatment of injuries, and improve equipment and training, to potentially reduce deaths. This is a retrospective study to characterize mortality of working dogs used in civilian law enforcement. Reported causes of death were gathered from two working dog and law enforcement officer memorial websites. Of the 867 civilian law enforcement dogs reported to these memorial websites from 2002 to 2012 with reported causes of death while in service, the deaths of 318 were categorized as traumatic. The leading reported causes of traumatic death or euthanasia include trauma as a result of a vehicle strike, 25.8% (n=82); heatstroke, 24.8% (n=79); and penetrating ballistic trauma, 23.0% (n=73). Although the information gathered was from online sources, this study casts some light on the risks that civilian law enforcement dogs undergo as part of the tasks to which they are assigned. These data underscore the need for a comprehensive database for this specialized population of working dogs to provide the robust, reliable data needed to develop prevention and treatment strategies for this valuable resource. 2014.

Death Education and Attitudes of Counselors-in-Training toward Death: An Exploratory Study

ERIC Educational Resources Information Center

Harrawood, Laura K.; Doughty, Elizabeth A.; Wilde, Brandon

2011-01-01

This study reviewed how attitudes of counselors-in-training toward death develop after completing a course on death education. Participants included 11 graduate counseling students enrolled in a 2-credit-hour course addressing death and dying, and grief and loss. Qualitative results from a content analysis of free-response narratives suggest the…

Disasters and youth: a meta-analytic examination of posttraumatic stress.

PubMed

Furr, Jami M; Comer, Jonathan S; Edmunds, Julie M; Kendall, Philip C

2010-12-01

Meta-analyze the literature on posttraumatic stress (PTS) symptoms in youths post-disaster. Meta-analytic synthesis of the literature (k = 96 studies; Ntotal = 74,154) summarizing the magnitude of associations between disasters and youth PTS, and key factors associated with variations in the magnitude of these associations. We included peer-reviewed studies published prior to 1/1/2009 that quantitatively examined youth PTS (≤ 18 years at event) after a distinct and identifiable disaster. Despite variability across studies, disasters had a significant effect on youth PTS (small-to-medium magnitude; rpooled = .19, SEr = .03; d = 0.4). Female gender (rpooled = .14), higher death toll (disasters of death toll ≤ 25: rpooled = .09; vs. disasters with ≥ 1,000 deaths: rpooled = .22), child proximity (rpooled = .33), personal loss (rpooled = .16), perceived threat (rpooled = .34), and distress (rpooled = .38) at time of event were each associated with increased PTS. Studies conducted within 1 year post-disaster, studies that used established measures, and studies that relied on child-report data identified a significant effect. Youths are vulnerable to appreciable PTS after disaster, with pre-existing child characteristics, aspects of the disaster experience, and study methodology each associated with variations in the effect magnitude. Findings underscore the importance of measurement considerations in post-disaster research. Areas in need of research include the long-term impact of disasters, disaster-related media exposure, prior trauma and psychopathology, social support, ethnicity/race, prejudice, parental psychopathology, and the effects of disasters in developing regions of the world. Policy and clinical implications are discussed. (c) 2010 APA, all rights reserved.

Vaccination and 30-Day Mortality Risk in Children, Adolescents, and Young Adults.

PubMed

McCarthy, Natalie L; Gee, Julianne; Sukumaran, Lakshmi; Weintraub, Eric; Duffy, Jonathan; Kharbanda, Elyse O; Baxter, Roger; Irving, Stephanie; King, Jennifer; Daley, Matthew F; Hechter, Rulin; McNeil, Michael M

2016-03-01

This study evaluates the potential association of vaccination and death in the Vaccine Safety Datalink (VSD). The study cohort included individuals ages 9 to 26 years with deaths between January 1, 2005, and December 31, 2011. We implemented a case-centered method to estimate a relative risk (RR) for death in days 0 to 30 after vaccination.Deaths due to external causes (accidents, homicides, and suicides) were excluded from the primary analysis. In a secondary analysis, we included all deaths regardless of cause. A team of physicians reviewed available medical records and coroner's reports to confirm cause of death and assess the causal relationship between death and vaccination. Of the 1100 deaths identified during the study period, 76 (7%) occurred 0 to 30 days after vaccination. The relative risks for deaths after any vaccination and influenza vaccination were significantly lower for deaths due to nonexternal causes (RR 0.57, 95% confidence interval [CI] 0.38-0.83, and RR 0.44, 95% CI 0.24-0.80, respectively) and deaths due to all causes (RR 0.72, 95% CI 0.56-0.91, and RR 0.44, 95% CI 0.28-0.65). No other individual vaccines were significantly associated with death. Among deaths reviewed, 1 cause of death was unknown, 25 deaths were due to nonexternal causes, and 34 deaths were due to external causes. The causality assessment found no evidence of a causal association between vaccination and death. Risk of death was not increased during the 30 days after vaccination, and no deaths were found to be causally associated with vaccination. Copyright © 2016 by the American Academy of Pediatrics.

Effects of CCR5-delta32 and CCR2-64I alleles on disease progression of perinatally HIV-1-infected children: an international meta-analysis.

PubMed

Ioannidis, John P A; Contopoulos-Ioannidis, Despina G; Rosenberg, Philip S; Goedert, James J; De Rossi, Anita; Espanol, Teresa; Frenkel, Lisa; Mayaux, Marie-Jeanne; Newell, Marie-Louise; Pahwa, Savita G; Rousseau, Christine; Scarlatti, Gabriella; Sei, Shizuko; Sen, Luisa; O'Brien, Thomas R

2003-07-25

Among perinatally infected children, the effects of certain alleles of the CCR5 and CCR2 genes on the rate of disease progression remain unclear. We addressed the effects of CCR5-delta32 and CCR2-64I in an international meta-analysis. Genotype data were contributed from 10 studies with 1317 HIV-1-infected children (7263 person-years of follow-up). Time-to-event analyses were performed stratified by study and racial group. Endpoints included progression to clinical AIDS, death, and death after the diagnosis of clinical AIDS. The time-dependence of the genetic effects was specifically investigated. There was large heterogeneity in the observed rates of disease progression between different cohorts. For progression to clinical AIDS, both CCR5-delta32 and CCR2-64I showed overall non-significant trends for protection [hazard ratios 0.84, 95% confidence interval (CI) 0.58-1.23; and 0.87, 95% CI 0.67-1.14, respectively]. However, analyses of survival showed statistically significant time-dependence. No deaths occurred among CCR5-delta32 carriers in the first 3 years of life, whereas there was no protective effect (hazard ratio 0.95; 95% CI 0.43-2.10) in later years (P=0.01 for the time-dependent model). For CCR2-64I, the hazard ratio for death was 0.69 (95% CI 0.39-1.21) in the first 6 years of life and 2.56 (95% CI 1.26-5.20) in subsequent years (P<0.01 for the time-dependent model). CCR5-delta32 and CCR2-64I offered no clear protection after clinical AIDS had developed. The CCR5-delta32 and CCR2-64I alleles are associated with a decreased risk of death among perinatally infected children, but only for the first years of life.

Effectiveness of statins for secondary prevention in elderly patients after acute myocardial infarction: an evaluation of class effect

PubMed Central

Zhou, Zheng; Rahme, Elham; Abrahamowicz, Michal; Tu, Jack V.; Eisenberg, Mark J.; Humphries, Karin; Austin, Peter C.; Pilote, Louise

2005-01-01

Background Clinical trials have shown the benefits of statins after acute myocardial infarction (AMI). However, it is unclear whether different statins exert a similar effect in reducing the incidence of recurrent AMI and death when used in clinical practice. Methods We conducted a retrospective cohort study (1997–2002) to compare 5 statins using data from medical administrative databases in 3 provinces (Quebec, Ontario and British Columbia). We included patients aged 65 years and over who were discharged alive after their first AMI-related hospital stay and who began statin treatment within 90 days after discharge. The primary end point was the combined outcome of recurrent AMI or death from any cause. The secondary end point was death from any cause. Adjusted hazard ratios (HRs) for each statin compared with atorvastatin as the reference drug were estimated using Cox proportional hazards regression analysis. Results A total of 18 637 patients were prescribed atorvastatin (n = 6420), pravastatin (n = 4480), simvastatin (n = 5518), lovastatin (n = 1736) or fluvastatin (n = 483). Users of different statins showed similar baseline characteristics and patterns of statin use. The adjusted HRs (and 95% confidence intervals) for the combined outcome of AMI or death showed that each statin had similar effects when compared with atorvastatin: pravastatin 1.00 (0.90–1.11), simvastatin 1.01 (0.91– 1.12), lovastatin 1.09 (0.95–1.24) and fluvastatin 1.01 (0.80– 1.27). The results did not change when death alone was the end point, nor did they change after adjustment for initial daily dose or after censoring of patients who switched or stopped the initial statin treatment. Interpretation Our results suggest that, under current usage, statins are equally effective for secocondary prevention in elderly patients after AMI. PMID:15851712

Epidural therapy for the treatment of severe pre-eclampsia in non labouring women.

PubMed

Ray, Amita; Ray, Sujoy

2017-11-28

Pre-eclampsia is a pregnancy-specific multi-organ disorder, which is characterised by hypertension and multisystem organ involvement and which has significant maternal and fetal morbidity and mortality. Failure of the placental vascular remodelling and reduced uteroplacental flow form the etiopathological basis of pre-eclampsia. There are several established therapies for pre-eclampsia including antihypertensives and anticonvulsants. Most of these therapies aim at controlling the blood pressure or preventing complications of elevated blood pressure, or both. Epidural therapy aims at blocking the vasomotor tone of the arteries, thereby increasing uteroplacental blood flow. This review was aimed at evaluating the available evidence about the possible benefits and risks of epidural therapy in the management of severe pre-eclampsia, to define the current evidence level of this therapy, and to determine what (if any) further evidence is required. To assess the effectiveness, safety and cost of the extended use of epidural therapy for treating severe pre-eclampsia in non-labouring women. This review aims to compare the use of extended epidural therapy with other methods, which include intravenous magnesium sulphate, anticonvulsants other than magnesium sulphate, with or without use of the antihypertensive drugs and adjuncts in the treatment of severe pre-eclampsia.This review only considered the use of epidural anaesthesia in the management of severe pre-eclampsia in the antepartum period and not as pain relief in labour. We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (13 July 2017) and reference lists of retrieved studies. Randomised controlled trials (RCTs) or quasi-RCTs comparing epidural therapy versus traditional therapy for pre-eclampsia in the form of antihypertensives, anticonvulsants, magnesium sulphate, low-dose dopamine, corticosteroids or a combination of these, were eligible for inclusion. Trials using a cluster design, and studies published in abstract form only are also eligible for inclusion in this review. Cross-over trials were not eligible for inclusion in this review. The two review authors independently assessed trials for inclusion and trial quality. There were no relevant data available for extraction. We included one small study (involving 24 women). The study was a single-centre randomised trial conducted in Mexico. This study compared a control group who received antihypertensive therapy, anticonvulsant therapy, plasma expanders, corticosteroids and dypyridamole with an intervention group that received epidural block instead of the antihypertensives, as well as all the other four drugs. Lumbar epidural block was given using 0.25% bupivacaine, 10 mg bolus and 5 mg each hour on continuous epidural infusion for six hours. This study was at low risk of bias in three domains but was assessed to be high risk of bias in two domains due to lack of allocation concealment and blinding of women and staff, and unclear for random sequence generation and outcome assessor blinding.The included study did not report on any of this review's important outcomes. Meta-analysis was not possible.For the mother, these were: maternal death (death during pregnancy or up to 42 days after the end of the pregnancy, or death more than 42 days after the end of the pregnancy); development of eclampsia or recurrence of seizures; stroke; any serious morbidity: defined as at least one of stroke, kidney failure, liver failure, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), disseminated intravascular coagulation, pulmonary oedema.For the baby, these were: death: stillbirths (death in utero at or after 20 weeks' gestation), perinatal deaths (stillbirths plus deaths in the first week of life), death before discharge from the hospital, neonatal deaths (death within the first 28 days after birth), deaths after the first 28 days; preterm birth (defined as the birth before 37 completed weeks' gestation); and side effects of the intervention. Reported outcomesThe included study only reported on a single secondary outcome of interest to this review: the Apgar score of the baby at birth and after five minutes and there was no clear difference between the intervention and control groups.The included study also reported a reduction in maternal diastolic arterial pressure. However, the change in maternal mean arterial pressure and systolic arterial pressure, which were the other reported outcomes of this trial, were not significantly different between the two groups. Currently, there is insufficient evidence from randomised controlled trials to evaluate the effectiveness, safety or cost of using epidural therapy for treating severe pre-eclampsia in non-labouring women.High-quality randomised controlled trials are needed to evaluate the use of epidural agents as therapy for treatment of severe pre-eclampsia. The rationale for the use of epidural is well-founded. However there is insufficient evidence from randomised controlled trials to show that the effect of epidural translates into improved maternal and fetal outcomes. Thus, there is a need for larger, well-designed studies to come to an evidence-based conclusion as to whether the lowering of vasomotor tone by epidural therapy results in better maternal and fetal outcomes and for how long that could be maintained. Another important question that needs to be answered is how long should extended epidural be used to ensure any potential clinical benefits and what could be the associated side effects and costs. Interactions with other modalities of treatment and women's satisfaction could represent other avenues of research.

The direct and indirect effects of corruption on motor vehicle crash deaths.

PubMed

Hua, Law Teik; Noland, Robert B; Evans, Andrew W

2010-11-01

Recent empirical research has found that there is an inverted U-shaped or Kuznets relationship between income and motor vehicle crash (MVC) deaths, such that MVC deaths increase as national income increases and decrease after reaching a critical level. Corruption has been identified as one of the underlying factors that could affect this relationship, primarily by undermining institutional development and effective enforcement schemes. The total effect of corruption can be decomposed into two components, a direct and an indirect effect. The direct effect measures the immediate impact of corruption on MVC deaths by undermining effective enforcement and regulations, while the indirect effect captures the impact of corruption on hindering increases in per capita income and the consequent impact of reduced income on MVC deaths. By influencing economic growth, corruption can lead to an increase or decrease in MVC deaths depending on the income level. Using data from 60 countries between 1982 and 2003, these effects are estimated using linear panel and fixed effects negative binomial models. The estimation results suggest that corruption has different direct effects for less developed and highly developed countries. It has a negative (decreasing) effect on MVC deaths for less developed countries and a positive (increasing) effect on MVC deaths for highly developed countries. For highly developed countries, the total effect is positive at lower per capita income levels, but decreases with per capita income and becomes negative at per capita income levels of about US$ 38,248. For less developed countries, the total effect is negative within the sample range and decreases with increased per capita income. In summary, the results of this study suggest that reduction of corruption is likely a necessary condition to effectively tackle road safety problems. 2010 Elsevier Ltd. All rights reserved.

SIDS and other sleep-related infant deaths: expansion of recommendations for a safe infant sleeping environment.

PubMed

Moon, Rachel Y

2011-11-01

Despite a major decrease in the incidence of sudden infant death syndrome (SIDS) since the American Academy of Pediatrics (AAP) released its recommendation in 1992 that infants be placed for sleep in a nonprone position, this decline has plateaued in recent years. Concurrently, other causes of sudden unexpected infant death that occur during sleep (sleep-related deaths), including suffocation, asphyxia, and entrapment, and ill-defined or unspecified causes of death have increased in incidence, particularly since the AAP published its last statement on SIDS in 2005. It has become increasingly important to address these other causes of sleep-related infant death. Many of the modifiable and nonmodifiable risk factors for SIDS and suffocation are strikingly similar. The AAP, therefore, is expanding its recommendations from focusing only on SIDS to focusing on a safe sleep environment that can reduce the risk of all sleep-related infant deaths, including SIDS. The recommendations described in this policy statement include supine positioning, use of a firm sleep surface, breastfeeding, room-sharing without bed-sharing, routine immunizations, consideration of using a pacifier, and avoidance of soft bedding, overheating, and exposure to tobacco smoke, alcohol, and illicit drugs. The rationale for these recommendations is discussed in detail in the accompanying "Technical Report--SIDS and Other Sleep-Related Infant Deaths: Expansion of Recommendations for a Safe Infant Sleeping Environment," which is included in this issue of Pediatrics (www.pediatrics.org/cgi/content/full/128/5/e1341).

Timing and causes of death in septic shock.

PubMed

Daviaud, Fabrice; Grimaldi, David; Dechartres, Agnès; Charpentier, Julien; Geri, Guillaume; Marin, Nathalie; Chiche, Jean-Daniel; Cariou, Alain; Mira, Jean-Paul; Pène, Frédéric

2015-12-01

Most studies about septic shock report a crude mortality rate that neither distinguishes between early and late deaths nor addresses the direct causes of death. We herein aimed to determine the modalities of death in septic shock. This was a 6-year (2008-2013) monocenter retrospective study. All consecutive patients diagnosed for septic shock within the first 48 h of intensive care unit (ICU) admission were included. Early and late deaths were defined as occurring within or after 3 days following ICU admission, respectively. The main cause of death in the ICU was determined from medical files. A multinomial logistic regression analysis using the status alive as the reference category was performed to identify the prognostic factors associated with early and late deaths. Five hundred forty-three patients were included, with a mean age of 66 ± 15 years and a high proportion (67 %) of comorbidities. The in-ICU and in-hospital mortality rates were 37.2 and 45 %, respectively. Deaths occurred early for 78 (32 %) and later on for 166 (68 %) patients in the ICU (n = 124) or in the hospital (n = 42). Early deaths were mainly attributable to intractable multiple organ failure related to the primary infection (82 %) and to mesenteric ischemia (6.4 %). In-ICU late deaths were directly related to end-of-life decisions in 29 % of patients and otherwise mostly related to ICU-acquired complications, including nosocomial infections (20.4 %) and mesenteric ischemia (16.6 %). Independent determinants of early death were age, malignancy, diabetes mellitus, no pathogen identification, and initial severity. Among 3-day survivors, independent risk factors for late death were age, cirrhosis, no pathogen identification, and previous corticosteroid treatment. Our study provides a comprehensive assessment of septic shock-related deaths. Identification of risk factors of early and late deaths may determine differential prognostic patterns.

Age, education and dementia related deaths. The Norwegian Counties Study and The Cohort of Norway.

PubMed

Strand, Bjørn Heine; Langballe, Ellen Melbye; Rosness, Tor A; Bergem, Astrid Liv Mina; Engedal, Knut; Nafstad, Per; Tell, Grethe S; Ormstad, Heidi; Tambs, Kristian; Bjertness, Espen

2014-10-15

An inverse relationship between educational level and dementia has been reported in several studies. In this study we investigated the relationship between educational level and dementia related deaths for cohorts of people all born during 1915-39. The cohorts were followed up from adulthood or old age, taking into account possible confounders and mediating paths. Our study population comprised participants in Norwegian health examination studies in the period 1974-2002; The Counties Study and Cohort of Norway (CONOR). Dementia related deaths were defined as deaths with a dementia diagnosis on the death certificate and linked using the Cause of Death Registry to year 2012. The study included 90,843 participants, 2.06 million person years and 2440 dementia related deaths. Cox regression was used to assess the association between education and dementia related deaths. Both high and middle educational levels were associated with lower dementia related death risk compared to those with low education when follow-up started in adulthood (35-49 years, high versus low education: HR=0.68, 95% confidence interval (CI) 0.50-0.93; 50-69 years, high versus low education: HR=0.52, 95% CI 0.34-0.80). However, when follow-up started at old age (70-80 years) there was no significant association between education and dementia related death. Restricting the study population to those born during a five-year period 1925-29 (the birth cohort overlapping all three age groups), gave similar main findings. The protective effects found for both high and middle educational level compared to low education were robust to adjustment for cardiovascular health and life style factors, suggesting education to be a protective factor for dementia related death. Both high and middle educational levels were associated with decreased dementia related death risk compared with low educational level when follow-up started in adulthood, but no association was observed when follow-up started at old age. Copyright © 2014 Elsevier B.V. All rights reserved.

Grief following pet and human loss: Closeness is key.

PubMed

Eckerd, Lizabeth M; Barnett, James E; Jett-Dias, Latishia

2016-01-01

The authors compared grief severity and its predictors in two equivalent college student samples who had experienced the death of a pet (n = 211) or a person (n = 146) within the past 2 years. The human death sample reported higher grief severity, p < .01, but effect sizes were small (ds = .28-.30). For both samples, closeness to the deceased was overwhelmingly the strongest predictor of grief severity; other predictors generally dropped out with closeness added to the model. Results highlight the importance of including closeness to deceased in grief research, and its centrality in understanding grief counseling clients.

What proportion of cancer deaths in the contemporary United States is attributable to cigarette smoking?

PubMed

Jacobs, Eric J; Newton, Christina C; Carter, Brian D; Feskanich, Diane; Freedman, Neal D; Prentice, Ross L; Flanders, W Dana

2015-03-01

The proportion of cancer deaths in the contemporary United States caused by cigarette smoking (the population attributable fraction [PAF]) is not well documented. The PAF of all cancer deaths due to active cigarette smoking among adults 35 years and older in the United States in 2010 was calculated using age- and sex-specific smoking prevalence from the National Health Interview Survey (NHIS) and age- and sex-specific relative risks from the Cancer Prevention Study-II (for ages 35-54 years) and from the Pooled Contemporary Cohort data set (for ages 55 years and older). The PAF for active cigarette smoking was 28.7% when estimated conservatively, including only deaths from the 12 cancers currently formally established as caused by smoking by the US Surgeon General. The PAF was 31.7% when estimated more comprehensively, including excess deaths from all cancers. These estimates do not include additional potential cancer deaths from environmental tobacco smoke or other type of tobacco use such as cigars, pipes, or smokeless tobacco. Cigarette smoking causes a large proportion of cancer deaths in the contemporary United States. Reducing smoking prevalence as rapidly as possible should be a top priority for the US public health efforts to prevent cancer deaths. Copyright © 2015 Elsevier Inc. All rights reserved.

Alternative Strategies to Reduce Maternal Mortality in India: A Cost-Effectiveness Analysis

PubMed Central

Goldie, Sue J.; Sweet, Steve; Carvalho, Natalie; Natchu, Uma Chandra Mouli; Hu, Delphine

2010-01-01

Background Approximately one-quarter of all pregnancy- and delivery-related maternal deaths worldwide occur in India. Taking into account the costs, feasibility, and operational complexity of alternative interventions, we estimate the clinical and population-level benefits associated with strategies to improve the safety of pregnancy and childbirth in India. Methods and Findings Country- and region-specific data were synthesized using a computer-based model that simulates the natural history of pregnancy (both planned and unintended) and pregnancy- and childbirth-associated complications in individual women; and considers delivery location, attendant, and facility level. Model outcomes included clinical events, population measures, costs, and cost-effectiveness ratios. Separate models were adapted to urban and rural India using survey-based data (e.g., unmet need for birth spacing/limiting, facility births, skilled birth attendants). Model validation compared projected maternal indicators with empiric data. Strategies consisted of improving coverage of effective interventions that could be provided individually or packaged as integrated services, could reduce the incidence of a complication or its case fatality rate, and could include improved logistics such as reliable transport to an appropriate referral facility as well as recognition of referral need and quality of care. Increasing family planning was the most effective individual intervention to reduce pregnancy-related mortality. If over the next 5 y the unmet need for spacing and limiting births was met, more than 150,000 maternal deaths would be prevented; more than US$1 billion saved; and at least one of every two abortion-related deaths averted. Still, reductions in maternal mortality reached a threshold (∼23%–35%) without including strategies that ensured reliable access to intrapartum and emergency obstetrical care (EmOC). An integrated and stepwise approach was identified that would ultimately prevent four of five maternal deaths; this approach coupled stepwise improvements in family planning and safe abortion with consecutively implemented strategies that incrementally increased skilled attendants, improved antenatal/postpartum care, shifted births away from home, and improved recognition of referral need, transport, and availability/quality of EmOC. The strategies in this approach ranged from being cost-saving to having incremental cost-effectiveness ratios less than US$500 per year of life saved (YLS), well below India's per capita gross domestic product (GDP), a common benchmark for cost-effectiveness. Conclusions Early intensive efforts to improve family planning and control of fertility choices and to provide safe abortion, accompanied by a paced systematic and stepwise effort to scale up capacity for integrated maternal health services over several years, is as cost-effective as childhood immunization or treatment of malaria, tuberculosis, or HIV. In just 5 y, more than 150,000 maternal deaths would be averted through increasing contraception rates to meet women's needs for spacing and limiting births; nearly US$1.5 billion would be saved by coupling safe abortion to aggressive family planning efforts; and with stepwise investments to improve access to pregnancy-related health services and to high-quality facility-based intrapartum care, more than 75% of maternal deaths could be prevented. If accomplished over the next decade, the lives of more than one million women would be saved. Please see later in the article for the Editors' Summary PMID:20421922

Fatal anaphylaxis registries data support changes in the who anaphylaxis mortality coding rules.

PubMed

Tanno, Luciana Kase; Simons, F Estelle R; Annesi-Maesano, Isabella; Calderon, Moises A; Aymé, Ségolène; Demoly, Pascal

2017-01-13

Anaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction. The difficulty of coding anaphylaxis fatalities under the World Health Organization (WHO) International Classification of Diseases (ICD) system is recognized as an important reason for under-notification of anaphylaxis deaths. On current death certificates, a limited number of ICD codes are valid as underlying causes of death, and death certificates do not include the word anaphylaxis per se. In this review, we provide evidences supporting the need for changes in WHO mortality coding rules and call for addition of anaphylaxis as an underlying cause of death on international death certificates. This publication will be included in support of a formal request to the WHO as a formal request for this move taking the 11 th ICD revision.

Age- and Sex-Specific Trends in Lung Cancer Mortality over 62 Years in a Nation with a Low Effort in Cancer Prevention

PubMed Central

John, Ulrich; Hanke, Monika

2016-01-01

Background: A decrease in lung cancer mortality among females below 50 years of age has been reported for countries with significant tobacco control efforts. The aim of this study was to describe the lung cancer deaths, including the mortality rates and proportions among total deaths, for females and males by age at death in a country with a high smoking prevalence (Germany) over a time period of 62 years. Methods: The vital statistics data were analyzed using a joinpoint regression analysis stratified by age and sex. An age-period-cohort analysis was used to estimate the potential effects of sex and school education on mortality. Results: After an increase, lung cancer mortality among women aged 35–44 years remained stable from 1989 to 2009 and decreased by 10.8% per year from 2009 to 2013. Conclusions: Lung cancer mortality among females aged 35–44 years has decreased. The potential reasons include an increase in the number of never smokers, following significant increases in school education since 1950, particularly among females. PMID:27023582

The Effect of Augmenting OPTN Data With External Death Data on Calculating Patient Survival Rates After Organ Transplantation.

PubMed

Wilk, Amber R; Edwards, Leah B; Edwards, Erick B

2017-04-01

Although the Organ Procurement and Transplantation Network (OPTN) database contains a rich set of data on United States transplant recipients, follow-up data may be incomplete. It was of interest to determine if augmenting OPTN data with external death data altered patient survival estimates. Solitary kidney, liver, heart, and lung transplants performed between January 1, 2011, and January 31, 2013, were queried from the OPTN database. Unadjusted Kaplan-Meier 3-year patient survival rates were computed using 4 nonmutually exclusive augmented datasets: OPTN only, OPTN + verified external deaths, OPTN + verified + unverified external deaths (OPTN + all), and an additional source extending recipient survival time if no death was found in OPTN + all (OPTN + all [Assumed Alive]). Pairwise comparisons were made using unadjusted Cox Proportional Hazards analyses applying Bonferroni adjustments. Although differences in patient survival rates across data sources were small (≤1 percentage point), OPTN only data often yielded slightly higher patient survival rates than sources including external death data. No significant differences were found, including comparing OPTN + verified (hazard ratio [HR], 1.05; 95% confidence interval [95% CI], 1.00-1.10); P = 0.0356), OPTN + all (HR, 1.06; 95% CI, 1.01-1.11; P = 0.0243), and OPTN + all (Assumed Alive) (HR, 1.00; 95% CI, 0.96-1.05; P = 0.8587) versus OPTN only, or OPTN + verified (HR, 1.05; 95% CI, 1.00-1.10; P = 0.0511), and OPTN + all (HR, 1.05; 95% CI, 1.00-1.10; P = 0.0353) versus OPTN + all (Assumed Alive). Patient survival rates varied minimally with augmented data sources, although using external death data without extending the survival time of recipients not identified in these sources results in a biased estimate. It remains important for transplant centers to maintain contact with transplant recipients and obtain necessary follow-up information, because this information can improve the transplantation process for future recipients.

Epidemiology, neurobiology and pharmacological interventions related to suicide deaths and suicide attempts in bipolar disorder: Part I of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder.

PubMed

Schaffer, Ayal; Isometsä, Erkki T; Tondo, Leonardo; Moreno, Doris H; Sinyor, Mark; Kessing, Lars Vedel; Turecki, Gustavo; Weizman, Abraham; Azorin, Jean-Michel; Ha, Kyooseob; Reis, Catherine; Cassidy, Frederick; Goldstein, Tina; Rihmer, Zoltán; Beautrais, Annette; Chou, Yuan-Hwa; Diazgranados, Nancy; Levitt, Anthony J; Zarate, Carlos A; Yatham, Lakshmi

2015-09-01

Bipolar disorder is associated with elevated risk of suicide attempts and deaths. Key aims of the International Society for Bipolar Disorders Task Force on Suicide included examining the extant literature on epidemiology, neurobiology and pharmacotherapy related to suicide attempts and deaths in bipolar disorder. Systematic review of studies from 1 January 1980 to 30 May 2014 examining suicide attempts or deaths in bipolar disorder, with a specific focus on the incidence and characterization of suicide attempts and deaths, genetic and non-genetic biological studies and pharmacotherapy studies specific to bipolar disorder. We conducted pooled, weighted analyses of suicide rates. The pooled suicide rate in bipolar disorder is 164 per 100,000 person-years (95% confidence interval = [5, 324]). Sex-specific data on suicide rates identified a 1.7:1 ratio in men compared to women. People with bipolar disorder account for 3.4-14% of all suicide deaths, with self-poisoning and hanging being the most common methods. Epidemiological studies report that 23-26% of people with bipolar disorder attempt suicide, with higher rates in clinical samples. There are numerous genetic associations with suicide attempts and deaths in bipolar disorder, but few replication studies. Data on treatment with lithium or anticonvulsants are strongly suggestive for prevention of suicide attempts and deaths, but additional data are required before relative anti-suicide effects can be confirmed. There were limited data on potential anti-suicide effects of treatment with antipsychotics or antidepressants. This analysis identified a lower estimated suicide rate in bipolar disorder than what was previously published. Understanding the overall risk of suicide deaths and attempts, and the most common methods, are important building blocks to greater awareness and improved interventions for suicide prevention in bipolar disorder. Replication of genetic findings and stronger prospective data on treatment options are required before more decisive conclusions can be made regarding the neurobiology and specific treatment of suicide risk in bipolar disorder. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Epidemiology, neurobiology and pharmacological interventions related to suicide deaths and suicide attempts in bipolar disorder: Part I of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder

PubMed Central

Schaffer, Ayal; Isometsä, Erkki T; Tondo, Leonardo; Moreno, Doris H; Sinyor, Mark; Kessing, Lars Vedel; Turecki, Gustavo; Weizman, Abraham; Azorin, Jean-Michel; Ha, Kyooseob; Reis, Catherine; Cassidy, Frederick; Goldstein, Tina; Rihmer, Zoltán; Beautrais, Annette; Chou, Yuan-Hwa; Diazgranados, Nancy; Levitt, Anthony J; Zarate, Carlos A; Yatham, Lakshmi

2016-01-01

Objectives Bipolar disorder is associated with elevated risk of suicide attempts and deaths. Key aims of the International Society for Bipolar Disorders Task Force on Suicide included examining the extant literature on epidemiology, neurobiology and pharmacotherapy related to suicide attempts and deaths in bipolar disorder. Methods Systematic review of studies from 1 January 1980 to 30 May 2014 examining suicide attempts or deaths in bipolar disorder, with a specific focus on the incidence and characterization of suicide attempts and deaths, genetic and non-genetic biological studies and pharmacotherapy studies specific to bipolar disorder. We conducted pooled, weighted analyses of suicide rates. Results The pooled suicide rate in bipolar disorder is 164 per 100,000 person-years (95% confidence interval = [5, 324]). Sex-specific data on suicide rates identified a 1.7:1 ratio in men compared to women. People with bipolar disorder account for 3.4–14% of all suicide deaths, with self-poisoning and hanging being the most common methods. Epidemiological studies report that 23–26% of people with bipolar disorder attempt suicide, with higher rates in clinical samples. There are numerous genetic associations with suicide attempts and deaths in bipolar disorder, but few replication studies. Data on treatment with lithium or anticonvulsants are strongly suggestive for prevention of suicide attempts and deaths, but additional data are required before relative anti-suicide effects can be confirmed. There were limited data on potential anti-suicide effects of treatment with antipsychotics or antidepressants. Conclusion This analysis identified a lower estimated suicide rate in bipolar disorder than what was previously published. Understanding the overall risk of suicide deaths and attempts, and the most common methods, are important building blocks to greater awareness and improved interventions for suicide prevention in bipolar disorder. Replication of genetic findings and stronger prospective data on treatment options are required before more decisive conclusions can be made regarding the neurobiology and specific treatment of suicide risk in bipolar disorder. PMID:26185269

Cooking with Fire: The Mutagenicity- and PAH-Emission Factors of Solid-Fuel Cookstoves

EPA Science Inventory

Emissions from solid fuels used for cooking cause ~4 million premature deaths per year. Advanced solid-fuel cookstoves are a potential solution, but they should be assessed by appropriate performance indicators, including biological effects. We evaluated two categories of solid...

Identifying Monoclonal Antibodies that Potently Inhibit MERS-CoV | Center for Cancer Research

Cancer.gov

The Middle East respiratory syndrome coronavirus (MERS-CoV), first isolated in September 2012, infects cells lining the human airway, causing severe flu-like symptoms that, in some cases, lead to death. As of July 2, 2014, 824 confirmed cases of MERS-CoV infection, including at least 286 related deaths, have been reported to the World Health Organization. While there are currently no effective therapies against the virus, monoclonal antibodies (MAbs) may be a promising candidate. Having previously developed MAbs against other viruses, including the related severe acute respiratory syndrome coronavirus or SARS-CoV, Dimiter Dimitrov, Ph.D., of CCR’s Laboratory of Experimental Immunology (LEI), and his colleagues decided to pan a library of antigen binding fragments (Fab) for activity against MERS-CoV.

Use and misuse of motor-vehicle crash death rates in assessing highway-safety performance.

PubMed

O'Neill, Brian; Kyrychenko, Sergey Y

2006-12-01

The objectives of the article are to assess the extent to which comparisons of motor-vehicle crash death rates can be used to determine the effectiveness of highway-safety policies over time in a country or to compare policy effectiveness across countries. Motor-vehicle crash death rates per mile traveled in the 50 U.S. states from 1980 to 2003 are used to show the influence on these rates of factors independent of highway-safety interventions. Multiple regression models relating state death rates to various measures related to urbanization and demographics are used. The analyses demonstrate strong relationships between state death rates and urbanization and demographics. Almost 60% of the variability among the state death rates can be explained by the independent variables in the multiple regression models. When the death rates for passenger vehicle occupants (i.e., excluding motorcycle, pedestrian, and other deaths) are used in the regression models, almost 70% of the variability in the rates can be explained by urbanization and demographics. The analyses presented in the article demonstrate that motor-vehicle crash death rates are strongly influenced by factors unrelated to highway-safety countermeasures. Overall death rates should not be used as a basis for judging the effectiveness (or ineffectiveness) of specific highway-safety countermeasures or to assess overall highway-safety policies, especially across jurisdictions. There can be no substitute for the use of carefully designed scientific evaluations of highway-safety interventions that use outcome measures directly related to the intervention; e.g., motorcyclist deaths should be used to assess the effectiveness of motorcycle helmet laws. While this may seem obvious, there are numerous examples in the literature of death rates from all crashes being used to assess the effectiveness of interventions aimed at specific subsets of crashes.

Portrayal of Brain Death in Film and Television.

PubMed

Lewis, A; Weaver, J; Caplan, A

2017-03-01

We sought to evaluate whether television and cinematic coverage of brain death is educational or misleading. We identified 24 accessible productions that addressed brain death using the archives of the Paley Center for Media (160 000 titles) and the Internet Movie Database (3.7 million titles). Productions were reviewed by two board-certified neurologists. Although 19 characters were pronounced brain dead, no productions demonstrated a complete examination to assess for brain death (6 included an assessment for coma, 9 included an evaluation of at least 1 brainstem reflex, but none included an assessment of every brainstem reflex, and 2 included an apnea test). Subjectively, both authors believed only a small fraction of productions (13% A.L., 13% J.W.) provided the public a complete and accurate understanding of brain death. Organ donation was addressed in 17 productions (71%), but both reviewers felt that the discussions about organ donation were professional in a paucity of productions (9% for A.L., 27% for J.W.). Because television and movies serve as a key source for public education, the quality of productions that feature brain death must be improved. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Protection against RAGE-mediated neuronal cell death by sRAGE-secreting human mesenchymal stem cells in 5xFAD transgenic mouse model.

PubMed

Son, Myeongjoo; Oh, Seyeon; Park, Hyunjin; Ahn, Hyosang; Choi, Junwon; Kim, Hyungho; Lee, Hye Sun; Lee, Sojung; Park, Hye-Jeong; Kim, Seung U; Lee, Bonghee; Byun, Kyunghee

2017-11-01

Alzheimer's disease (AD), which is the most commonly encountered neurodegenerative disease, causes synaptic dysfunction and neuronal loss due to various pathological processes that include tau abnormality and amyloid beta (Aβ) accumulation. Aβ stimulates the secretion and the synthesis of Receptor for Advanced Glycation End products (RAGE) ligand by activating microglial cells, and has been reported to cause neuronal cell death in Aβ 1-42 treated rats and in mice with neurotoxin-induced Parkinson's disease. The soluble form of RAGE (sRAGE) is known to reduce inflammation, and to decrease microglial cell activation and Aβ deposition, and thus, it protects from neuronal cell death in AD. However, sRAGE protein has too a short half-life for therapeutic purposes. We developed sRAGE-secreting umbilical cord derived mesenchymal stem cells (sRAGE-MSCs) to enhance the inhibitory effects of sRAGE on Aβ deposition and to reduce the secretion and synthesis of RAGE ligands in 5xFAD mice. In addition, these cells improved the viability of injected MSCs, and enhanced the protective effects of sRAGE by inhibiting the binding of RAGE and RAGE ligands in 5xFAD mice. These findings suggest sRAGE protein from sRAGE-MSCs has better protection against neuronal cell death than sRAGE protein or single MSC treatment by inhibiting the RAGE cell death cascade and RAGE-induce inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Immortalization-Upregulated Protein-2 (IMUP-2) on Cell Death of Trophoblast

PubMed Central

Jung, Ran; Choi, Jong Ho; Lee, Hyun Jung; Kim, Jin Kyeoung; Kim, Gi Jin

2013-01-01

Trophoblasts, in the placenta, play a role for placental development as well as implantation in the early pregnancy. The characteristics and functions of trophoblast are identified by their localization and potency for proliferation, differentiation, and invasion. Thus, inadequate trophoblast cell death induces trophoblast dysfunction resulting in abnormal placental development and several gynecological diseases. Recently, it was reported that increased immortalization-upregulated protein-2 (IMUP-2) by hypoxia influences trophoblast apoptosis. However, IMUP-2 function on autophagy, which is type II programmed cell death remains unclear. In this study, we analyzed IMUP-2 expression in trophoblast cells (HTR8-SVneo) and compared IMUP-2 effects on cell death including apoptosis and autophagy in trophoblast regardless of IMUP-2 expression. Increased IMUP-2 in trophoblast by IMUP-2 gene transfection induces cell death, especially, apoptosis increases more than autophagy (p<0.05). However, the decreased IMUP-2 in trophoblasts after siRNA treatment decreased apoptosis with the decreased activities of caspase 3 and 7. The expressions of LC3 and MDC as an autophagosome makers and phosphorylated mTOR, which is a negative regulator for autophagy, increased. In addition, the S phase of cell cycle increased in trophoblasts when IMUP-2 expression decreased. Taken together, the alteration of IMUP-2 can control the balance between apoptosis and autophagy of trophoblasts resulting in functional involvement in placental development and in gynecological diseases by regulating the function of trophoblasts. PMID:25949126

Human GAPDH Is a Target of Aspirin’s Primary Metabolite Salicylic Acid and Its Derivatives

PubMed Central

Manohar, Murli; Harraz, Maged M.; Park, Sang-Wook; Schroeder, Frank C.; Snyder, Solomon H.; Klessig, Daniel F.

2015-01-01

The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA’s multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH) also binds SA. In addition to its central role in glycolysis, HsGAPDH participates in several pathological processes, including viral replication and neuronal cell death. The anti-Parkinson’s drug deprenyl has been shown to suppress nuclear translocation of HsGAPDH, an early step in cell death and the resulting cell death induced by the DNA alkylating agent N-methyl-N’-nitro-N-nitrosoguanidine. Here, we demonstrate that SA, which is the primary metabolite of aspirin (acetyl SA) and is likely responsible for many of its pharmacological effects, also suppresses nuclear translocation of HsGAPDH and cell death. Analysis of two synthetic SA derivatives and two classes of compounds from the Chinese medicinal herb Glycyrrhiza foetida (licorice), glycyrrhizin and the SA-derivatives amorfrutins, revealed that they not only appear to bind HsGAPDH more tightly than SA, but also exhibit a greater ability to suppress translocation of HsGAPDH to the nucleus and cell death. PMID:26606248

A Death in the Family: Death as a Zen Concept

ERIC Educational Resources Information Center

Black, Helen K.; Rubinstein, Robert L.

2013-01-01

This study is based on original research that explored family reaction to the death of an elderly husband and father. We interviewed 34 families (a family included a widow and two adult biological children) approximately 6 to 10 months after the death. In one-on-one interviews, we discussed family members' initial reaction to the death, how the…

Causes of death among full term stillbirths and early neonatal deaths in the Region of Southern Denmark.

PubMed

Basu, Millie Nguyen; Johnsen, Iben Birgit Gade; Wehberg, Sonja; Sørensen, Rikke Guldberg; Barington, Torben; Nørgård, Bente Mertz

2018-02-23

We examined the causes of death amongst full term stillbirths and early neonatal deaths. Our cohort includes women in the Region of Southern Denmark, who gave birth at full term to a stillborn infant or a neonate who died within the first 7 days from 2010 through 2014. Demographic, biometric and clinical variables were analyzed to assess the causes of death using two classification systems: causes of death and associated conditions (CODAC) and a Danish system based on initial causes of fetal death (INCODE). A total of 95 maternal-infant cases were included. Using the CODAC and INCODE classification systems, we found that the causes of death were unknown in 59/95 (62.1%). The second most common cause of death in CODAC was congenital anomalies in 10/95 (10.5%), similar to INCODE with fetal, genetic, structural and karyotypic anomalies in 11/95 (11.6%). The majority of the mothers were healthy, primiparous, non-smokers, aged 20-34 years and with a normal body mass index (BMI). Based on an unselected cohort from an entire region in Denmark, the cause of stillbirth and early neonatal deaths among full term infants remained unknown for the vast majority.

Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury.

PubMed

Jeong, Hoon Jae; Kim, Dae Won; Kim, Mi Jin; Woo, Su Jung; Kim, Hye Ri; Kim, So Mi; Jo, Hyo Sang; Hwang, Hyun Sook; Kim, Duk Soo; Cho, Sung Woo; Won, Moo Ho; Han, Kyu Hyung; Park, Jin Seu; Eum, Won Sik; Choi, Soo Young

2012-10-31

Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a doseand time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.

Adverse events, including death, associated with the use of 1,4-butanediol.

PubMed

Zvosec, D L; Smith, S W; McCutcheon, J R; Spillane, J; Hall, B J; Peacock, E A

2001-01-11

1,4-Butanediol is an industrial solvent that, when ingested, is converted to gamma-hydroxybutyrate, a drug of abuse with depressant effects, primarily on the central nervous system. After reports of toxic effects of gamma-hydroxybutyrate and its resultant regulation by the federal government, 1,4-butanediol and gamma-butyrolactone, another precursor of gamma-hydroxybutyrate and an industrial solvent, began to be marketed as dietary supplements. We investigated reports of toxic effects due to the ingestion of 1,4-butanediol and reviewed the related health risks. From June 1999 through December 1999, we identified cases of toxic effects of 1,4-butanediol involving patients who presented to our emergency departments with a clinical syndrome suggesting toxic effects of gamma-hydroxybutyrate and a history of ingesting 1,4-butanediol and patients discovered through public health officials and family members. We used gas chromatography-mass spectrometry to measure 1,4-butanediol or its metabolite, gamma-hydroxybutyrate, in urine, serum, or blood. We identified nine episodes of toxic effects in eight patients who had ingested 1,4-butanediol recreationally, to enhance bodybuilding, or to treat depression or insomnia. One patient presented twice with toxic effects and had withdrawal symptoms after her second presentation. Clinical findings and adverse events included vomiting, urinary and fecal incontinence, agitation, combativeness, a labile level of consciousness, respiratory depression, and death. No additional intoxicants were identified in six patients, including the two who died. The doses of 1,4-butanediol ingested ranged from 5.4 to 20 g in the patients who died and ranged from 1 to 14 g in the nonfatal cases. The health risks of 1,4-butanediol are similar to those of its counterparts, gamma-hydroxybutyrate and gamma-butyrolactone. These include acute toxic effects, which may be fatal, and addiction and withdrawal.

The pharmacoeconomics of peri-operative beta-blocker therapy.

PubMed

Biccard, B M; Sear, J W; Foëx, P

2006-01-01

It is widely recommended that beta-blockade be used peri-operatively as it may reduce the incidence of postoperative cardiovascular complications including death. However, there are few data concerning the cost-effectiveness of such strategies. We have analysed the pharmacoeconomics of acute beta-blockade using data from eight prospective peri-operative studies in which patients underwent elective non-cardiac surgery, and in which the incidence of adverse side-effects of treatment, as well as clinical outcomes, have been reported. The costs of treatment were based on the NHS reference costs for 2004. From these data, the number-needed-to-treat (NNT) to prevent a major cardiovascular complication (including cardiovascular death) in high-risk patients was 18.5. This is comparable to the NNT for peri-operative statin therapy. The incremental cost of peri-operative beta-blockade (costs of drug acquisition and of treating associated adverse drug events) was 67.80 pounds sterling per patient. This results in a total cost of 1254.30 pounds sterling per peri-operative cardiovascular complication prevented. However, there is evidence that in patients at lower cardiovascular risk, beta-blockers may be potentially harmful, since their adverse effects (hypotension, bradycardia) may outweigh their potential cardioprotective effects.

Methanolic extract of white asparagus shoots activates TRAIL apoptotic death pathway in human cancer cells and inhibits colon carcinogenesis in a preclinical model

PubMed Central

BOUSSEROUEL, SOUAD; LE GRANDOIS, JULIE; GOSSÉ, FRANCINE; WERNER, DALAL; BARTH, STEPHAN W.; MARCHIONI, ERIC; MARESCAUX, JACQUES; RAUL, FRANCIS

2013-01-01

Shoots of white asparagus are a popular vegetable dish, known to be rich in many bioactive phytochemicals reported to possess antioxidant, and anti-inflammatory and antitumor activities. We evaluated the anticancer mechanisms of a methanolic extract of Asparagus officinalis L. shoots (Asp) on human colon carcinoma cells (SW480) and their derived metastatic cells (SW620), and Asp chemopreventive properties were also assessed in a model of colon carcinogenesis. SW480 and SW620 cell proliferation was inhibited by 80% after exposure to Asp (80 μg/ml). We demonstrated that Asp induced cell death through the activation of TRAIL DR4/DR5 death receptors leading to the activation of caspase-8 and caspase-3 and to cell apoptosis. By specific blocking agents of DR4/DR5 receptors we were able to prevent Asp-triggered cell death confirming the key role of DR4/DR5 receptors. We found also that Asp (80 μg/ml) was able to potentiate the effects of the cytokine TRAIL on cell death even in the TRAIL-resistant metastatic SW620 cells. Colon carcinogenesis was initiated in Wistar rats by intraperitoneal injections of azoxymethane (AOM), once a week for two weeks. One week after (post-initiation) rats received daily Asp (0.01%, 14 mg/kg body weight) in drinking water. After 7 weeks of Asp-treatment the colon of rats exhibited a 50% reduction of the number of preneoplastic lesions (aberrant crypt foci). In addition Asp induced inhibition of several pro-inflammatory mediators, in association with an increased expression of host-defense mediators. In the colonic mucosa of Asp-treated rats we also confirmed the pro-apoptotic effects observed in vitro including the activation of the TRAIL death-receptor signaling pathway. Taken together, our data highlight the chemopreventive effects of Asp on colon carcinogenesis and its ability to promote normal cellular homeostasis. PMID:23754197

Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jo, Miran; Park, Mi Hee; Kollipara, Pushpa Saranya

We investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1–5 μg/ml) and melittin (0.5–2 μg/ml) inhibited the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, 8, andmore » Bax was concomitantly increased, but the phosphorylation of JAK2 and STAT3 and the expression of Bcl-2 were inhibited by treatment with bee venom and melittin in SKOV3 and PA-1 cells. Expression of cleaved caspase-3 was increased in SKOV3, but cleaved caspase-8 was increased in PA-1 cells. Moreover, deletion of DR3, DR4, and DR6 by small interfering RNA significantly reversed bee venom and melittin-induced cell growth inhibitory effect as well as down regulation of STAT3 by bee venom and melittin in SKOV3 and PA-1 ovarian cancer cell. These results suggest that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway. -- Highlights: ► Some studies have showed that bee venom and/or melittin have anti-cancer effects. ► We found that bee venom and melittin inhibited cell growth in ovarian cancer cells. ► Bee venom and melittin induce apoptosis in SKOV3 and PA-1.« less

Road trauma among young Australians: Implementing policy to reduce road deaths and serious injury.

PubMed

Walker, Clara; Thompson, Jason; Stevenson, Mark

2017-05-19

The objective of this study was to estimate the likely reduction in road trauma associated with the implementation of effective interventions to reduce road trauma among young Australians. A desktop evaluation was conducted to model the likely reduction in road trauma (deaths and serious injuries resulting in hospitalization) among young people aged 17-24 years residing in Queensland, New South Wales, and Victoria. Potential interventions were identified using a rapid literature review and assigned a score based on evidence of effectiveness and implementation feasibility with the 3 highest scoring interventions included in the modeling. Likely reduction in road trauma was estimated by applying the average risk reduction effect sizes for each intervention to baseline risk (passenger or driver death or serious injury per 100,000 population) of road trauma for young Australians. Point estimates were calculated for the potential number of deaths and serious injuries averted in each state and per 100,000 population, with a one-way sensitivity analysis conducted using uncertainty ranges identified. Peer passenger and night driving restrictions as well as improved vehicle safety measures had the greatest potential to reduce road trauma. Peer passenger restrictions could avert 14 (range: 5-24) and 24 (range: 8-41) hospitalizations per year in Queensland and New South Wales, respectively, and night driving restrictions could avert 17 (range: 7-26), 28 (range: 12-45), and 13 (range: 6-21) hospitalizations annually in Queensland, New South Wales, and Victoria. These interventions reduced fatalities by less than 1 death annually in each state. Improved vehicle safety measures could avert 0-3, 0-4, and 0-3 deaths and 3-91, 4-156, and 2-75 hospitalizations in Queensland, New South Wales, and Victoria. Key elements of graduated licensing (peer passenger and night driving restrictions) along with vehicle safety interventions offer modest but practically significant reductions in road trauma for young Australians. State governments need to revise current legislation to ensure that these reductions in road trauma can be realized.

76 FR 71890 - Federal Travel Regulation (FTR); Payment of Expenses Connected With the Death of Certain Employees

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-21

... Connected With the Death of Certain Employees AGENCY: Office of Governmentwide Policy, General Services..., household goods, personal effects, and one privately owned vehicle of a covered employee whose death... dependents and the household effects of a ``covered employee'' whose death occurred as a result of personal...

38 CFR 3.904 - Effect of forfeiture after veteran's death.

Code of Federal Regulations, 2012 CFR

2012-07-01

... after veteran's death. 3.904 Section 3.904 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... § 3.904 Effect of forfeiture after veteran's death. (a) Fraud. Whenever a veteran has forfeited his or...)) (b) Treasonable acts. Death benefits may be paid as provided in paragraph (a) of this section where...

38 CFR 3.904 - Effect of forfeiture after veteran's death.

Code of Federal Regulations, 2014 CFR

2014-07-01

... after veteran's death. 3.904 Section 3.904 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... § 3.904 Effect of forfeiture after veteran's death. (a) Fraud. Whenever a veteran has forfeited his or...)) (b) Treasonable acts. Death benefits may be paid as provided in paragraph (a) of this section where...

38 CFR 3.904 - Effect of forfeiture after veteran's death.

Code of Federal Regulations, 2013 CFR

2013-07-01

... after veteran's death. 3.904 Section 3.904 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... § 3.904 Effect of forfeiture after veteran's death. (a) Fraud. Whenever a veteran has forfeited his or...)) (b) Treasonable acts. Death benefits may be paid as provided in paragraph (a) of this section where...

Effects of a didactic and guided-imagery intervention regarding horrendous death by nuclear war upon fear of death, health locus of control, and social responsibility in health education college students

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campanelli, L.C.

1987-01-01

This investigation studied the effects of a videotaped lecture explaining horrendous death theory, with a guided imagery component describing horrendous death of a beloved other, upon action toward anti-nuclearism and three individual difference variables. The primary purpose of this study was to determine the effects of a videotaped lecture on college students' fear of death, health locus of control, and social responsibility. A second purpose was to determine whether participants who viewed the videotape were likely to sign a petition against nuclear war, in support of the Physicians for Social Responsibility's position against nuclearism. One hundred fifty-two (152) college studentsmore » participated in this study; approximately 55% were female and 50% were seniors. No significant differences were found regarding individual difference variables, except concerning fear of death of self between death education and non-death education experimental groups. Although an interaction effect was found, the hypothesis that experimental groups would be more likely to sign the petition against nuclear was not confirmed.« less

Ruta graveolens L. induces death of glioblastoma cells and neural progenitors, but not of neurons, via ERK 1/2 and AKT activation.

PubMed

Gentile, Maria Teresa; Ciniglia, Claudia; Reccia, Mafalda G; Volpicelli, Floriana; Gatti, Monica; Thellung, Stefano; Florio, Tullio; Melone, Mariarosa A B; Colucci-D'Amato, Luca

2015-01-01

Glioblastoma multiforme is a highly aggressive brain tumor whose prognosis is very poor. Due to early invasion of brain parenchyma, its complete surgical removal is nearly impossible, and even after aggressive combined treatment (association of surgery and chemo- and radio-therapy) five-year survival is only about 10%. Natural products are sources of novel compounds endowed with therapeutic properties in many human diseases, including cancer. Here, we report that the water extract of Ruta graveolens L., commonly known as rue, induces death in different glioblastoma cell lines (U87MG, C6 and U138) widely used to test novel drugs in preclinical studies. Ruta graveolens' effect was mediated by ERK1/2 and AKT activation, and the inhibition of these pathways, via PD98058 and wortmannin, reverted its antiproliferative activity. Rue extract also affects survival of neural precursor cells (A1) obtained from embryonic mouse CNS. As in the case of glioma cells, rue stimulates the activation of ERK1/2 and AKT in A1 cells, whereas their blockade by pharmacological inhibitors prevents cell death. Interestingly, upon induction of differentiation and cell cycle exit, A1 cells become resistant to rue's noxious effects but not to those of temozolomide and cisplatin, two alkylating agents widely used in glioblastoma therapy. Finally, rutin, a major component of the Ruta graveolens water extract, failed to cause cell death, suggesting that rutin by itself is not responsible for the observed effects. In conclusion, we report that rue extracts induce glioma cell death, discriminating between proliferating/undifferentiated and non-proliferating/differentiated neurons. Thus, it can be a promising tool to isolate novel drugs and also to discover targets for therapeutic intervention.

Comorbidities contribute to the risk of cancer death among Aboriginal and non-Aboriginal South Australians: Analysis of a matched cohort study.

PubMed

Banham, David; Roder, David; Brown, Alex

2018-02-01

Aboriginal Australians have poorer cancer survival than other Australians. Diagnoses at later stages and correlates of remote area living influence, but do not fully explain, these disparities. Little is known of the prevalence and influence of comorbid conditions experienced by Aboriginal people, including their effect on cancer survival. This study quantifies hospital recorded comorbidities using the Elixhauser Comorbidity Index (ECI), examines their influence on risk of cancer death, then considers effect variation by Aboriginality. Cancers diagnosed among Aboriginal South Australians in 1990-2010 (N = 777) were matched with randomly selected non-Aboriginal cases by birth year, diagnostic year, sex, and primary site, then linked to administrative hospital records to the time of diagnosis. Competing risk regression summarised associations of Aboriginal status, stage, geographic attributes and comorbidities with risk of cancer death. A threshold of four or more ECI conditions was associated with increased risk of cancer death (sub-hazard ratio SHR 1.66, 95%CI 1.11-2.46). Alternatively, the presence of any one of a subset of ECI conditions was associated with similarly increased risk (SHR = 1.62, 95%CI 1.23-2.14). The observed effects did not differ between Aboriginal and matched non-Aboriginal cases. However, Aboriginal cases experienced three times higher exposure than non-Aboriginal to four or more ECI conditions (14.2% versus 4.5%) and greater exposure to the subset of ECI conditions (20.7% versus 8.0%). Comorbidities at diagnosis increased the risk of cancer death in addition to risks associated with Aboriginality, remoteness of residence and disease stage at diagnosis. The Aboriginal cohort experienced comparatively greater exposure to comorbidities which adds to disparities in cancer outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Screening for Lung Cancer

PubMed Central

Mazzone, Peter J.; Naidich, David P.; Bach, Peter B.

2013-01-01

Background: Lung cancer is by far the major cause of cancer deaths largely because in the majority of patients it is at an advanced stage at the time it is discovered, when curative treatment is no longer feasible. This article examines the data regarding the ability of screening to decrease the number of lung cancer deaths. Methods: A systematic review was conducted of controlled studies that address the effectiveness of methods of screening for lung cancer. Results: Several large randomized controlled trials (RCTs), including a recent one, have demonstrated that screening for lung cancer using a chest radiograph does not reduce the number of deaths from lung cancer. One large RCT involving low-dose CT (LDCT) screening demonstrated a significant reduction in lung cancer deaths, with few harms to individuals at elevated risk when done in the context of a structured program of selection, screening, evaluation, and management of the relatively high number of benign abnormalities. Whether other RCTs involving LDCT screening are consistent is unclear because data are limited or not yet mature. Conclusions: Screening is a complex interplay of selection (a population with sufficient risk and few serious comorbidities), the value of the screening test, the interval between screening tests, the availability of effective treatment, the risk of complications or harms as a result of screening, and the degree with which the screened individuals comply with screening and treatment recommendations. Screening with LDCT of appropriate individuals in the context of a structured process is associated with a significant reduction in the number of lung cancer deaths in the screened population. Given the complex interplay of factors inherent in screening, many questions remain on how to effectively implement screening on a broader scale. PMID:23649455

A preliminary investigation of asthma mortality in schools.

PubMed

Greiling, Andrea K; Boss, Leslie P; Wheeler, Lani S

2005-10-01

Although asthma deaths in children are rare, most asthma deaths should be preventable. No information has been identified in the professional literature addressing the occurrence of asthma deaths in schools. This investigation identified asthma deaths that occurred in US schools between 1990 and 2003 and the circumstances surrounding those deaths. Data were obtained through newspaper articles in the LexisNexis database and death certificates. Between 1990 and 2003, 38 asthma school deaths were reported. Eighteen (47%) identified deaths occurred among black children and 12 (31%) among white. Twenty-seven (72%) of the deaths occurred among teens. Of the fatal asthma attacks, 16 (42%) occurred while the children were participating in a physically active event. Twelve (31%) children died while waiting for medical assistance. Due to the nature of these data, inferences may be subject to source bias. For the identified asthma deaths, key findings include the following: (1) most deaths occurred in teens and high school students; (2) frequently, the precipitating event was related in time to exercise; and (3) a delayed response or hesitancy of school staff to provide medical assistance may have contributed to some of the deaths. Although few school-related asthma deaths are reported each year, the true number is unknown. Key factors in managing the disease and preventing asthma deaths and exacerbations in schools include identification of students with diagnosed asthma, communication with parents and health care providers, removal of triggers in the immediate school environment, and maximizing access to needed medications.

Causes of death in patients with chronic sarcoidosis.

PubMed

Hu, Xiaowen; Carmona, Eva M; Yi, Eunhee S; Pellikka, Patricia A; Ryu, Jay

2016-10-07

Sarcoidosis is a multi-system, granulomatous disorder of unknown etiology that is associated with a variable prognosis and sometimes results in death. There are conflicting reports regarding the causes of death in patients with sarcoidosis. Forty-four consecutive patients with sarcoidosis who underwent an autopsy (35 patients) or died at Mayo Clinic (Rochester, MN, USA) over a 20-yr period, from January 1, 1994 to December 31, 2013 were analyzed. The median age at death was 63 years (range, 33-94 years) and there were 22 (50%) women. Sarcoidosis had not been clinically diagnosed in 16 (36%) patients before death. Fifteen deaths (34%) were related to sarcoidosis and included seven deaths (16%) from cardiac sarcoidosis and four deaths (9%) from progressive pulmonary sarcoidosis. Other sarcoidosis-related causes of death included advanced hepatic sarcoidosis (5%) and opportunistic infections (5%) related to immunosuppressive therapy for treating sarcoidosis. Among seven patients dying from cardiac sarcoidosis, three had been diagnosed with sarcoidosis during life and cardiac involvement was known in two of them. Six of seven deaths from cardiac sarcoidosis occurred in the autopsied cohort while all four deaths from pulmonary sarcoidosis occurred in those not autopsied. In the majority of patients dying with sarcoidosis the cause of death is unrelated to sarcoidosis. Cardiac involvement is the most common cause of sarcoidosis-related deaths in patients subjected to postmortem examination and was usually undiagnosed during life. The cause distribution of death in patients with sarcoidosis differed depending on whether autopsy was performed.

Implementing Suicide Prevention Programs: Costs and Potential Life Years Saved in Canada.

PubMed

Vasiliadis, Helen-Maria; Lesage, Alain; Latimer, Eric; Seguin, Monique

2015-09-01

Little is known about the costs and effects of suicide prevention programs at the population level. We aimed to determine (i) the costs associated with a suicide death and using prospective values (ii) the costs and effects of transferring, into a Canadian context, the results of the European Nuremberg Alliance against Depression (NAD) trial with the addition of 4 community-based suicide prevention strategies. These included the training of family physicians in the detection and treatment of depression, population campaigns aimed at increasing awareness about depression, the training of community leaders among first responders and follow-up of individuals who attempted suicide. This study includes a prospective value implementation study design. Using published data and information from interviews with Canadian decision makers, we assessed the costs of a suicide death in the province of Quebec and the costs of potentially implementing the NAD multi-modal suicide prevention programs, and the incremental cost-effectiveness ratio (ICER), from a health care system and societal perspective, associated with the NAD program while considering the friction cost method (FCM) and human capital approach (HCA) (discounted at 3%.) The costs considered included those incurred for the suicide prevention program and direct medical and non-medical costs as well as those related to a police investigation and funeral costs. Indirect costs associated with loss of productivity and short term disability were also considered. Sensitivity analyses were also carried out. Costs presented were in 2010 dollars. The annual total cost of implementing the suicide prevention programs in Quebec reached CAD23,982,293. The most expensive components of the program included the follow-up of individuals who had attempted suicide and psychotherapy for bereaved individuals. These accounted for 39% and 34% of total costs. The ICER associated with the implementation of the programs reached on average CAD3,979 per life year saved. Suicide prevention programs such as the NAD trial are cost-effective and can result in important potential cost-savings due to averted suicide deaths and reduced life years lost. Implementation of suicide prevention programs at the population level in Canada is cost-effective. Community mental health programs aimed at increasing awareness and the treatment of depression and better follow-up of high risk individuals for suicide are associated with a minimal per capita investment. These programs can result in important potential cost-savings due to averted suicide deaths and decreased disability due to depression. Additional research should focus on whether the outcomes of multi-modal suicide programs are specific or synergistic and most effective for which population subgroups. This may help inform how best to invest resources for the highest return.

Time to Death after Terminal Withdrawal of Mechanical Ventilation: Specific Respiratory and Physiologic Parameters May Inform Physician Predictions.

PubMed

Long, Ann C; Muni, Sarah; Treece, Patsy D; Engelberg, Ruth A; Nielsen, Elizabeth L; Fitzpatrick, Annette L; Curtis, J Randall

2015-12-01

Discussions about withdrawal of life-sustaining therapies often include family members of critically ill patients. These conversations should address essential components of the dying process, including expected time to death after withdrawal. The study objective was to aid physician communication about the dying process by identifying predictors of time to death after terminal withdrawal of mechanical ventilation. We conducted an observational analysis from a single-center, before-after evaluation of an intervention to improve palliative care. We studied 330 patients who died after terminal withdrawal of mechanical ventilation. Predictors included patient demographics, laboratory, respiratory, and physiologic variables, and medication use. The median time to death for the entire cohort was 0.58 hours (interquartile range (IQR) 0.22-2.25 hours) after withdrawal of mechanical ventilation. Using Cox regression, independent predictors of shorter time to death included higher positive end-expiratory pressure (per 1 cm H2O hazard ratio [HR], 1.07; 95% CI 1.04-1.11); higher static pressure (per 1 cm H2O HR, 1.03; 95% CI 1.01-1.04); extubation prior to death (HR, 1.41; 95% CI 1.06-1.86); and presence of diabetes (HR, 1.75; 95% CI 1.25-2.44). Higher noninvasive mean arterial pressure predicted longer time to death (per 1 mmHg HR, 0.98; 95% CI 0.97-0.99). Comorbid illness and key respiratory and physiologic parameters may inform physician predictions of time to death after withdrawal of mechanical ventilation. An understanding of the predictors of time to death may facilitate discussions with family members of dying patients and improve communication about end-of-life care.

Time to Death after Terminal Withdrawal of Mechanical Ventilation: Specific Respiratory and Physiologic Parameters May Inform Physician Predictions

PubMed Central

Muni, Sarah; Treece, Patsy D.; Engelberg, Ruth A.; Nielsen, Elizabeth L.; Fitzpatrick, Annette L.; Curtis, J. Randall

2015-01-01

Abstract Background: Discussions about withdrawal of life-sustaining therapies often include family members of critically ill patients. These conversations should address essential components of the dying process, including expected time to death after withdrawal. Objectives: The study objective was to aid physician communication about the dying process by identifying predictors of time to death after terminal withdrawal of mechanical ventilation. Methods: We conducted an observational analysis from a single-center, before–after evaluation of an intervention to improve palliative care. We studied 330 patients who died after terminal withdrawal of mechanical ventilation. Predictors included patient demographics, laboratory, respiratory, and physiologic variables, and medication use. Results: The median time to death for the entire cohort was 0.58 hours (interquartile range (IQR) 0.22–2.25 hours) after withdrawal of mechanical ventilation. Using Cox regression, independent predictors of shorter time to death included higher positive end-expiratory pressure (per 1 cm H2O hazard ratio [HR], 1.07; 95% CI 1.04–1.11); higher static pressure (per 1 cm H2O HR, 1.03; 95% CI 1.01–1.04); extubation prior to death (HR, 1.41; 95% CI 1.06–1.86); and presence of diabetes (HR, 1.75; 95% CI 1.25–2.44). Higher noninvasive mean arterial pressure predicted longer time to death (per 1 mmHg HR, 0.98; 95% CI 0.97–0.99). Conclusions: Comorbid illness and key respiratory and physiologic parameters may inform physician predictions of time to death after withdrawal of mechanical ventilation. An understanding of the predictors of time to death may facilitate discussions with family members of dying patients and improve communication about end-of-life care. PMID:26555010

Judging the quality of mercy: drawing a line between palliation and euthanasia.

PubMed

Morrison, Wynne; Kang, Tammy

2014-02-01

Clinicians frequently worry that medications used to treat pain and suffering at the end of life might also hasten death. Intentionally hastening death, or euthanasia, is neither legal nor ethically appropriate in children. In this article, we explore some of the historical and legal background regarding appropriate end-of-life care and outline what distinguishes it from euthanasia. Good principles include clarity of goals and assessments, titration of medications to effect, and open communication. When used appropriately, medications to treat symptoms should rarely hasten death significantly. Medications and interventions that are not justifiable are also discussed, as are the implications of palliative sedation and withholding fluids or nutrition. It is imperative that clinicians know how to justify and use such medications to adequately treat suffering at the end of life within a relevant clinical and legal framework.

The antineoplastic agent α-bisabolol promotes cell death by inducing pores in mitochondria and lysosomes.

PubMed

Rigo, Antonella; Vinante, Fabrizio

2016-08-01

The sesquiterpene α-bisabolol (α-BSB) has been shown to be an effective cytotoxic agent for a variety of human cancer cells in culture and animal models. However, much of its intracellular action remains elusive. We evaluated the cytotoxic action of α-BSB against CML-T1, Jurkat and HeLa cell lines, as preclinical models for myeloid, lymphoid and epithelial neoplasias. The approach included single cell analysis (flow cytometry, immunocytology) combined with cytotoxicity and proliferation assays to characterize organelle damage, autophagy, cytostatic effect, and apoptosis. The study focuses on the relevant steps in the cytotoxic cascade triggered by α-BSB: (1) the lipid rafts through which α-BSB enters the cells, (2) the opening of pores in the mitochondria and lysosomes, (3) the activation of both caspase-dependent and caspase-independent cell death pathways, (4) the induction of autophagy and (5) apoptosis. The effectiveness of α-BSB as an agent against tumor cells is grounded on its capability to act on different layers of cell regulation to elicit different concurrent death signals, thereby neutralizing a variety of aberrant survival mechanisms leading to treatment resistance in neoplastic cell.

Synergistic effects on dopamine cell death in a Drosophila model of chronic toxin exposure

PubMed Central

Martin, Ciara A.; Barajas, Angel; Lawless, George; Lawal, Hakeem O.; Assani, Khadij; Lumintang, Yosephine P.; Nunez, Vanessa; Krantz, David E.

2014-01-01

The neurodegenerative effects of Parkinson’s disease (PD) are marked by a selective loss of dopaminergic (DA) neurons. Epidemiological studies suggest that chronic exposure to the pesticide paraquat may increase the risk for PD and DA cell loss. However, combined exposure with additional fungicide(s) including maneb and/or ziram may be required for pathogenesis. To explore potential pathogenic mechanisms, we have developed a Drosophila model of chronic paraquat exposure. We find that while chronic paraquat exposure alone decreased organismal survival and motor function, combined chronic exposure to both paraquat and maneb was required for DA cell death in the fly. To initiate mechanistic studies of this interaction, we used additional genetic reagents to target the ubiquitin proteasome system, implicated in some rare familial forms of PD and the toxic effects of ziram. Genetic inhibition of E1 ubiquitin ligase, but not the proteasome itself, increased DA cell death in combination with maneb but not paraquat. These studies establish a model for long-term exposure to multiple pesticides, and support the idea that pesticide interactions relevant to PD may involve inhibition of protein ubiquitination. PMID:25160001

Fallout risk following a major nuclear attack on the United States.

PubMed

Harvey, T F; Shapiro, C S; Wittler, R F

1992-01-01

Fallout distributions are calculated for nuclear attacks on the contiguous United States. Four attack scenarios are treated, including counterforce and counterforce-countervalue attacks, for meteorological conditions associated with a typical day in summer and one in winter. The countervalue attacks contain mostly airbursts. To determine fallout effects, the population surviving the prompt effects is first calculated. For the prompt effects, a "conflagration-type" model is used. The counterforce attack produces about 8 million prompt deaths, and the counterforce-countervalue case projects 98 million prompt deaths. Partial relocation before attack to low-risk fallout areas at least 15 km from potential strategic targets would result in a decrease in projections of deaths by tens of millions. For fallout risk calculations, only the dose received in the first 48 h (the early or local fallout) is considered. Populations are assumed to be sheltered, with a shelter protection factor profile that varies for a large urban area, a small urban area, or a rural area. With these profiles, without relocation, the fallout fatalities for all four attack scenarios are calculated to be less than one million people. This can be compared to fallout fatalities of about 10 million for a hypothetical unsheltered "phantom" population.

Factors associated with maternal death in an intensive care unit

PubMed Central

Saintrain, Suzanne Vieira; de Oliveira, Juliana Gomes Ramalho; Saintrain, Maria Vieira de Lima; Bruno, Zenilda Vieira; Borges, Juliana Lima Nogueira; Daher, Elizabeth De Francesco; da Silva Jr, Geraldo Bezerra

2016-01-01

Objective To identify factors associated with maternal death in patients admitted to an intensive care unit. Methods A cross-sectional study was conducted in a maternal intensive care unit. All medical records of patients admitted from January 2012 to December 2014 were reviewed. Pregnant and puerperal women were included; those with diagnoses of hydatidiform mole, ectopic pregnancy, or anembryonic pregnancy were excluded, as were patients admitted for non-obstetrical reasons. Death and hospital discharge were the outcomes subjected to comparative analysis. Results A total of 373 patients aged 13 to 45 years were included. The causes for admission to the intensive care unit were hypertensive disorders of pregnancy, followed by heart disease, respiratory failure, and sepsis; complications included acute kidney injury (24.1%), hypotension (15.5%), bleeding (10.2%), and sepsis (6.7%). A total of 28 patients died (7.5%). Causes of death were hemorrhagic shock, multiple organ failure, respiratory failure, and sepsis. The independent risk factors associated with death were acute kidney injury (odds ratio [OR] = 6.77), hypotension (OR = 15.08), and respiratory failure (OR = 3.65). Conclusion The frequency of deaths was low. Acute kidney injury, hypotension, and respiratory insufficiency were independent risk factors for maternal death. PMID:28099637

Why cachexia kills: examining the causality of poor outcomes in wasting conditions.

PubMed

Kalantar-Zadeh, Kamyar; Rhee, Connie; Sim, John J; Stenvinkel, Peter; Anker, Stefan D; Kovesdy, Csaba P

2013-06-01

Weight loss is the hallmark of any progressive acute or chronic disease state. In its extreme form of significant lean body mass (including skeletal muscle) and fat loss, it is referred to as cachexia. It has been known for millennia that muscle and fat wasting leads to poor outcomes including death. On one hand, conditions and risk factors that lead to cachexia and inadequate nutrition may independently lead to increased mortality. Additionaly, cachexia per se, withdrawal of nutritional support in progressive cachexia, and advanced age may lead to death via cachexia-specific pathways. Despite the strong and consistent association of cachexia with mortality, no unifying mechanism has yet been suggested as to why wasting conditions are associated with an exceptionally high mortality risk. Hence, the causality of the cachexia-death association, even though it is biologically plausible, is widely unknown. This century-long uncertainty may have played a role as to why the field of cachexia treatment development has not shown major advances over the past decades. We suggest that cachexia-associated relative thrombocytosis and platelet activation may play a causal role in cachexia-related death, while other mechanisms may also contribute including arrhythmia-associated sudden deaths, endocrine disorders such as hypothyroidism, and immune system compromise leading to infectious events and deaths. Multidimensional research including examining biologically plausible models is urgently needed to investigate the causality of the cachexia-death association.

CKD and Sudden Cardiac Death: Epidemiology, Mechanisms, and Therapeutic Approaches

PubMed Central

Whitman, Isaac R.; Feldman, Harold I.

2012-01-01

Multiple studies demonstrate a strong independent association between CKD and cardiovascular events including death, heart failure, and myocardial infarction. This review focuses on recent clinical studies that expand this spectrum of adverse cardiovascular events to include ventricular arrhythmias and sudden cardiac death. In addition, experimental models suggest structural remodeling of the heart and electrophysiologic changes in this population. These processes may explain the increased arrhythmic risk in kidney disease and aid in identifying patients who are at higher risk for sudden cardiac death. Finally, we review here the data to support the use of pharmacologic and device-based therapies for both the primary and secondary prevention of sudden cardiac death. PMID:23100219

76 FR 61779 - Agency Information Collection (Application for Dependency and Indemnity Compensation, Death...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... (Application for Dependency and Indemnity Compensation, Death Pension and Accrued Benefits by a Surviving... Dependency and Indemnity Compensation, Death Pension and Accrued Benefits by a Surviving Spouse or Child (Including Death Compensation if Applicable), VA Form 21-534. b. Application for Dependency and Indemnity...

Proceedings of the Sudden Oak Death Fourth Science Symposium

Treesearch

Susan J. Frankel; John T. Kliejunas; Katharine M. Palmieri

2010-01-01

The Sudden Oak Death Fourth Science Symposium provided a forum for current research on sudden oak death, caused by the exotic, quarantine pathogen, Phytophthora ramorum. Ninety submissions describing papers or posters on the following sudden oak death/P. ramorum topics are included: biology, genetics, nursery and wildland...

Proceedings of the sudden oak death third science symposium

Treesearch

Susan J. Frankel; John T. Kliejunas; Katharine M. Palmieri

2008-01-01

The Sudden Oak Death Third Science Symposium provided a forum for current research on sudden oak death, caused by the exotic, quarantine pathogen, Phytophthora ramorum. One hundred and seventeen submissions describing papers and posters on the following sudden oak death/ P. ramorum topics are included: biology, genetics, nursery,...

Proceedings of the sudden oak death sixth science symposium

Treesearch

Susan J. Frankel; Katharine M. Harrell

2017-01-01

The Sudden Oak Death Sixth Science Symposium provided a forum for current research on sudden oak death, caused by the exotic quarantine pathogen Phytophthora ramorum. More than 50 submissions describing papers or posters on the following sudden oak death/P. ramorum topics are included: biology, genetics, nursery and wildland...

Resources for Helping Young Children Deal with Death.

ERIC Educational Resources Information Center

Wass, Hannelore

This bibliography contains selected resources (1965-1983) to help parents and teachers assist young children with death-related concerns. Included are materials for adults: an annotated list of books on death (13 citations); a bibliography of articles about children and death from recent literature (50 citations); and an annotated list of…

[Efficacy of glycopyrronium bromide and scopolamine hydrobromide in patients with death rattle: a randomized controlled study].

PubMed

Likar, Rudolf; Rupacher, Ernst; Kager, Hans; Molnar, Mario; Pipam, Wofgang; Sittl, Reinhard

2008-01-01

Death rattle is an extremely distressing symptom for the dying patient and for his environment. The aim of this study was to assess the efficacy of glycopyrronium bromide as compared with scopolamine hydrobromide in alleviating death rattle in terminal cancer patients with cognitive impairment. In a randomized, controlled study design patients were allocated in two groups. Group A received scopolamine hydrobromide in a dose of 0.5 mg intravenously every 6 hours for a period of 12 hours, group B received glycopyrronium bromide 0.4 mg every 6 hours for a period of 12 hours. In addition, standardized sedatives were administered as required and the analgesic therapy continued either orally or, if necessary, subcutaneously or intravenously in equipotent doses. Every 2 hours death rattle was assessed and rated on a scale of 1 to 5 (1 = audible breathing noises, 5 = very severe rattling noises). In addition, restlessness and expressions of pain were assessed and rated on a scale of 1 to 3 (1 = mild, 2 = moderate, 3 = severe). 13 patients were included in the study, 7 patients were allocated to group A and 6 patients to group B. There were no significant differences in demographic data, age, weight and diagnosis distribution between the two groups. Group B demonstrated a significant reduction of death rattle in the first 12 hours (p = 0.029) in comparison to group A. There were no significant differences concerning the side effects (restlessness, expressions of pain) in both groups. Glycopyrronium bromide given in a dose of 0,4 mg every six hours demonstrated a significant reduction of death rattle compared to scopolamine hydrobromide. Concerning side effects (restlessness, expressions of pain) there was no difference between both substances.

Alpha-crystallin-mediated protection of lens cells against heat and oxidative stress-induced cell death.

PubMed

Christopher, Karen L; Pedler, Michelle G; Shieh, Biehuoy; Ammar, David A; Petrash, J Mark; Mueller, Niklaus H

2014-02-01

In addition to their key role as structural lens proteins, α-crystallins also appear to confer protection against many eye diseases, including cataract, retinitis pigmentosa, and macular degeneration. Exogenous recombinant α-crystallin proteins were examined for their ability to prevent cell death induced by heat or oxidative stress in a human lens epithelial cell line (HLE-B3). Wild type αA- or αB-crystallin (WT-αA and WT-αB) and αA- or αB-crystallins, modified by the addition of a cell penetration peptide (CPP) designed to enhance the uptake of proteins into cells (gC-αB, TAT-αB, gC-αA), were produced by recombinant methods. In vitro chaperone-like assays were used to assay the ability of α-crystallins to protect client proteins from chemical or heat induced aggregation. In vivo viability assays were performed in HLE-B3 to determine whether pre-treatment with α-crystallins reduced death after exposure to oxidative or heat stress. Most of the five recombinant α-crystallin proteins tested conferred some in vitro protection from protein aggregation, with the greatest effect seen with WT-αB and gC-αB. All α-crystallins displayed significant protection to oxidative stress induced cell death, while only the αB-crystallins reduced cell death induced by thermal stress. Our findings indicate that the addition of the gC tag enhanced the protective effect of αB-crystallin against oxidative but not thermally-induced cell death. In conclusion, modifications that increase the uptake of α-crystallin proteins into cells, without destroying their chaperone-like activity and anti-apoptotic functions, create the potential to use these proteins therapeutically. Copyright © 2013 Elsevier B.V. All rights reserved.

Likely effect of adding flexible sigmoidoscopy to the English NHS Bowel Cancer Screening Programme: impact on colorectal cancer cases and deaths

PubMed Central

Geurts, S M E; Massat, N J; Duffy, S W

2015-01-01

Background: From 2013, once-only flexible sigmoidoscopy (FS) at age 55 is being phased into the England National Health Service Bowel Cancer Screening Programme (NHSBCSP), augmenting biennial guaiac faecal occult blood testing (gFOBT) at ages 60–74. Here, we project the impact of this change on colorectal cancer (CRC) cases and deaths prevented in England by mid-2030. Methods: We simulated the life-course of English residents reaching age 55 from 2013 onwards. Model inputs included population numbers, invitation rates and CRC incidence and mortality rates. The impact of gFOBT and FS alone on CRC incidence and mortality were derived from published trials, assuming an uptake of 50% for FS and 57% for gFOBT. For FS plus gFOBT, we assumed the gFOBT effect to be 75% of the gFOBT alone impact. Results: By mid-2030, 8.5 million individuals will have been invited for once-only FS screening. Adding FS to gFOBT screening is estimated to prevent an extra 9627 (−10%) cases and 2207 (−12%) deaths by mid-2030. If FS uptake is 38% or 71%, respectively, an extra 7379 (−8%) or 13 689 (−15%) cases and 1691 (−9%) or 3154 (−17%) deaths will be prevented by mid-2030. Conclusions: Adding once-only FS at age 55 to the NHSBCSP will prevent ∼10 000 CRC cases and ∼2000 CRC deaths by mid-2030 if FS uptake is 50%. In 2030, one cancer was estimated to be prevented per 150 FS screening episodes, and one death prevented per 900 FS screening episodes. The actual reductions will depend on the FS invitation schedule and uptake rates. PMID:26110973

Risk factors for mortality before age 18 years in cystic fibrosis.

PubMed

McColley, Susanna A; Schechter, Michael S; Morgan, Wayne J; Pasta, David J; Craib, Marcia L; Konstan, Michael W

2017-07-01

Understanding early-life risk factors for childhood death in cystic fibrosis (CF) is important for clinical care, including the identification of effective interventions. Data from the Epidemiologic Study of Cystic Fibrosis (ESCF) collected 1994-2005 were linked with the Cystic Fibrosis Foundation Patient Registry (CFFPR) demographic and mortality data from 2013. Inclusion criteria were ≥1 visit annually at age 3-5 years and ≥1 FEV 1 measurement at age 6-8 years. Demographic data, nutritional parameters, pulmonary signs and symptoms, microbiology, and FEV 1 were evaluated as risk factors for death before age 18 years. Multivariable Cox proportional hazards regression was used to model the simultaneous effects of risk factors associated with death before age 18 years. Among 5365 patients enrolled in ESCF who met inclusion criteria, 3880 (72%) were linked to the CFFPR. Among these, 191 (5.7%) died before age 18 years; median age at death was 13.4 ± 3.1 years. Multivariable regression showed clubbing, crackles, female sex, unknown CFTR genotype, minority race or ethnicity, Medicaid insurance (a proxy of low socioeconomic status), Pseudomonas aeruginosa on 2 or more cultures, and weight-for-age <50th percentile were significant risk factors for death regardless of inclusion of FEV 1 at age 6-8 years in the model. We identified multiple risk factors for childhood death of patients with CF, all of which remained important after incorporating FEV 1 at age 6-8 years. Among the factors identified were the presence of clubbing or crackles at age 3-5 years, signs which are not routinely collected in registries. © 2017 Wiley Periodicals, Inc.

Combined effect of blood pressure and total cholesterol levels on long-term risks of subtypes of cardiovascular death: Evidence for Cardiovascular Prevention from Observational Cohorts in Japan.

PubMed

Satoh, Michihiro; Ohkubo, Takayoshi; Asayama, Kei; Murakami, Yoshitaka; Sakurai, Masaru; Nakagawa, Hideaki; Iso, Hiroyasu; Okayama, Akira; Miura, Katsuyuki; Imai, Yutaka; Ueshima, Hirotsugu; Okamura, Tomonori

2015-03-01

No large-scale, longitudinal studies have examined the combined effects of blood pressure (BP) and total cholesterol levels on long-term risks for subtypes of cardiovascular death in an Asian population. To investigate these relationships, a meta-analysis of individual participant data, which included 73 916 Japanese subjects (age, 57.7 years; men, 41.1%) from 11 cohorts, was conducted. During a mean follow-up of 15.0 years, deaths from coronary heart disease, ischemic stroke, and intraparenchymal hemorrhage occurred in 770, 724, and 345 cases, respectively. Cohort-stratified Cox proportional hazard models were used. After stratifying the participants by 4 systolic BP ×4 total cholesterol categories, the group with systolic BP ≥160 mm Hg with total cholesterol ≥5.7 mmol/L had the greatest risk for coronary heart disease death (adjusted hazard ratio, 4.39; P<0.0001 versus group with systolic BP <120 mm Hg and total cholesterol <4.7 mmol/L). The adjusted hazard ratios of systolic BP (per 20 mm Hg) increased with increases in total cholesterol categories (hazard ratio, 1.52; P<0.0001 in group with total cholesterol ≥5.7 mmol/L). Similarly, the adjusted hazard ratios of total cholesterol increased with increases in systolic BP categories (P for interaction ≤0.04). Systolic BP was positively associated with ischemic stroke and intraparenchymal hemorrhage death, and total cholesterol was inversely associated with intraparenchymal hemorrhage, but no significant interactions between BP and total cholesterol were observed for stroke. High BP and high total cholesterol can synergistically increase the risk for coronary heart disease death but not for stroke in the Asian population. © 2015 American Heart Association, Inc.

Questionnaire on Brain Death and Organ Procurement.

PubMed

Hammad, Saleh; Alnammourah, Manal; Almahmoud, Farah; Fawzi, Mais; Breizat, Abdel-Hadi

2017-02-01

The subject of organs for transplant after brain death raises many concerns, including definition and timing of death, how to permit human organ transplant, and the idea of paying for organs. Many ethical concerns are raised regarding regulations and procedures for organ transplant in developing countries. These include where and how to obtain organs and the concept of justice in organ distribution. We administered 2682 questionnaires to 628 men and 2054 women over 24 months (range, 18 to 70 years old). We included people from universities, colleges, and the general public and asked questions on the circumstances of death, the conditions of conversations around organ donation, and reasons for acceptance or refusal of donation. The identical questionnaire, consisting of 8 questions, was administered twice: before and after a teaching session on brain death and organ procurement. The study was approved by our Ethical Review Committee and in accordance with the ethical guidelines of the 1975 Helsinki Declaration. Written informed consent was obtained from all participants. We found that 72.1% understood brain death in the prequestionnaire and 88% understood brain death in the postquestionnaire, with 63.8% versus 68% accepting the concept of brain death, 50.6% versus 58.3% thinking that their religion is against brain death, 11.3% versus 11.3% carrying a donor card, 50.7% versus 58.9% wanting to carry a donor card, 46.4% versus 56.4% agreeing to give consent for organ donation if a relative was diagnosed with brain death, 28.3% versus 50% aware of the laws and regulations concerning brain death and organ donation and transplant in Jordan, and 35.4% versus 40% in agreement with the Presumed Consent Law, respectively. In Jordan, along with legal requirements concerning brain death and organ donation and transplant, there is a lack of acceptance of organ donation after brain death, necessitating further work and activities to achieve self-sufficiency from donated organs.

In Vitro Induction of Erythrocyte Phosphatidylserine Translocation by the Natural Naphthoquinone Shikonin

PubMed Central

Lupescu, Adrian; Bissinger, Rosi; Jilani, Kashif; Lang, Florian

2014-01-01

Shikonin, the most important component of Lithospermum erythrorhizon, has previously been shown to exert antioxidant, anti-inflammatory, antithrombotic, antiviral, antimicrobial and anticancer effects. The anticancer effect has been attributed to the stimulation of suicidal cell death or apoptosis. Similar to the apoptosis of nucleated cells, erythrocytes may experience eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and by phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include the increase of cytosolic Ca2+-activity ([Ca2+]i) and ceramide formation. The present study explored whether Shikonin stimulates eryptosis. To this end, Fluo 3 fluorescence was measured to quantify [Ca2+]i, forward scatter to estimate cell volume, annexin V binding to identify phosphatidylserine-exposing erythrocytes, hemoglobin release to determine hemolysis and antibodies to quantify ceramide abundance. As a result, a 48 h exposure of human erythrocytes to Shikonin (1 µM) significantly increased [Ca2+]i, increased ceramide abundance, decreased forward scatter and increased annexin V binding. The effect of Shikonin (1 µM) on annexin V binding was significantly blunted, but not abolished by the removal of extracellular Ca2+. In conclusion, Shikonin stimulates suicidal erythrocyte death or eryptosis, an effect at least partially due to the stimulation of Ca2+ entry and ceramide formation. PMID:24828755

Advanced Electrocardiographic Predictors of Sudden Death in Familial Dysautonomia

NASA Technical Reports Server (NTRS)

Solaimanzadeh, I.; Schlegel, T. T.; Greco, E. C.; DePalma, J. L.; Starc, V.; Marthol, H.; Tutaj, M.; Buechner, S.; Axelrod, F. B.; Hilz, M. J.

2007-01-01

To identify accurate predictors for the risk of sudden death in patients with familial dysautonomia (FD). Ten-minute resting high-fidelity 12-lead ECGs were obtained from 14 FD patients and 14 age/gender-matched healthy subjects. Multiple conventional and advanced ECG parameters were studied for their ability to predict sudden death in FD over a subsequent 4.5-year period, including multiple indices of linear and non-linear heart rate variability (HRV); QT variability; waveform complexity; high frequency QRS; and derived Frank-lead parameters. Four of the 14 FD patients died suddenly during the follow-up period, usually with concomitant pulmonary disorder. The presence of low vagally-mediated HRV was the ECG finding most predictive of sudden death. Concomitant left ventricular hypertrophy and other ECG abnormalities such as increased QTc and JTc intervals, spatial QRS-T angles, T-wave complexity, and QT variability were also present in FD patients, suggesting that structural heart disease is fairly common in FD. Although excessive or unopposed cardiac vagal (relative to sympathetic) activity has been postulated as a contributor to sudden death in FD, the presence of low vagally-mediated HRV was paradoxically the best predictor of sudden death. However, we suggest that low vagally-mediated HRV be construed not as a direct cause of sudden death in FD, but rather as an effect of concurrent pathological processes, especially hypoxia due to pulmonary disorders and sleep apnea, that themselves increase the risk of sudden death in FD and simultaneously diminish HRV. We speculate that adenosine may play a role in sudden death in FD, possibly independently of vagal activity, and that adenosine inhibitors such as theophylline might therefore be useful as prophylaxis in this disorder.

The effects of sacubitril/valsartan on coronary outcomes in PARADIGM-HF.

PubMed

Mogensen, Ulrik M; Køber, Lars; Kristensen, Søren L; Jhund, Pardeep S; Gong, Jianjian; Lefkowitz, Martin P; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Swedberg, Karl; Zile, Michael R; Solomon, Scott D; Packer, Milton; McMurray, John J V

2017-06-01

Angiotensin converting enzyme inhibitors (ACE-I), are beneficial both in heart failure with reduced ejection fraction (HF-REF) and after myocardial infarction (MI). We examined the effects of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan, compared with the ACE-I enalapril, on coronary outcomes in PARADIGM-HF. We examined the effect of sacubitril/valsartan compared with enalapril on the following outcomes: i) the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, ii) a pre-defined broader composite including, in addition, MI, stroke, and resuscitated sudden death, and iii) a post hoc coronary composite of CV-death, non-fatal MI, angina hospitalization or coronary revascularization. At baseline, of 8399 patients, 3634 (43.3%) had a prior MI and 4796 (57.1%) had a history of any coronary artery disease. Among all patients, compared with enalapril, sacubitril/valsartan reduced the risk of the primary outcome (HR 0.80 [0.73-0.87], P<.001), the broader composite (HR 0.83 [0.76-0.90], P<.001) and the coronary composite (HR 0.83 [0.75-0.92], P<.001). Although each of the components of the coronary composite occurred less frequently in the sacubitril/valsartan group, compared with the enalapril group, only CV death was reduced significantly. Compared with enalapril, sacubitril/valsartan reduced the risk of both the primary endpoint and a coronary composite outcome in PARADIGM-HF. Additional studies on the effect of sacubitril/valsartan on atherothrombotic outcomes in high-risk patients are merited. Copyright © 2017 Elsevier Inc. All rights reserved.

Bayesian regression analyses of radiation modality effects on pericardial and pleural effusion and survival in esophageal cancer.

PubMed

He, Liru; Chapple, Andrew; Liao, Zhongxing; Komaki, Ritsuko; Thall, Peter F; Lin, Steven H

2016-10-01

To evaluate radiation modality effects on pericardial effusion (PCE), pleural effusion (PE) and survival in esophageal cancer (EC) patients. We analyzed data from 470 EC patients treated with definitive concurrent chemoradiotherapy (CRT). Bayesian semi-competing risks (SCR) regression models were fit to assess effects of radiation modality and prognostic covariates on the risks of PCE and PE, and death either with or without these preceding events. Bayesian piecewise exponential regression models were fit for overall survival, the time to PCE or death, and the time to PE or death. All models included propensity score as a covariate to correct for potential selection bias. Median times to onset of PCE and PE after RT were 7.1 and 6.1months for IMRT, and 6.5 and 5.4months for 3DCRT, respectively. Compared to 3DCRT, the IMRT group had significantly lower risks of PE, PCE, and death. The respective probabilities of a patient being alive without either PCE or PE at 3-years and 5-years were 0.29 and 0.21 for IMRT compared to 0.13 and 0.08 for 3DCRT. In the SCR regression analyses, IMRT was associated with significantly lower risks of PCE (HR=0.26) and PE (HR=0.49), and greater overall survival (probability of beneficial effect (pbe)>0.99), after controlling for known clinical prognostic factors. IMRT reduces the incidence and postpones the onset of PCE and PE, and increases survival probability, compared to 3DCRT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Stathmin Mediates Hepatocyte Resistance to Death from Oxidative Stress by down Regulating JNK

PubMed Central

Zhao, Enpeng; Amir, Muhammad; Lin, Yu; Czaja, Mark J.

2014-01-01

Stathmin 1 performs a critical function in cell proliferation by regulating microtubule polymerization. This proliferative function is thought to explain the frequent overexpression of stathmin in human cancer and its correlation with a bad prognosis. Whether stathmin also functions in cell death pathways is unclear. Stathmin regulates microtubules in part by binding free tubulin, a process inhibited by stathmin phosphorylation from kinases including c-Jun N-terminal kinase (JNK). The involvement of JNK activation both in stathmin phosphorylation, and in hepatocellular resistance to oxidative stress, led to an examination of the role of stathmin/JNK crosstalk in oxidant-induced hepatocyte death. Oxidative stress from menadione-generated superoxide induced JNK-dependent stathmin phosphorylation at Ser-16, Ser-25 and Ser-38 in hepatocytes. A stathmin knockdown sensitized hepatocytes to both apoptotic and necrotic cell death from menadione without altering levels of oxidant generation. The absence of stathmin during oxidative stress led to JNK overactivation that was the mechanism of cell death as a concomitant knockdown of JNK1 or JNK2 blocked death. Hepatocyte death from JNK overactivation was mediated by the effects of JNK on mitochondria. Mitochondrial outer membrane permeabilization occurred in stathmin knockdown cells at low concentrations of menadione that triggered apoptosis, whereas mitochondrial β-oxidation and ATP homeostasis were compromised at higher, necrotic menadione concentrations. Stathmin therefore mediates hepatocyte resistance to death from oxidative stress by down regulating JNK and maintaining mitochondrial integrity. These findings demonstrate a new mechanism by which stathmin promotes cell survival and potentially tumor growth. PMID:25285524

A Retrospective Medical Records Review of Risk Factors for the Development of Respiratory Tract Secretions (Death Rattle) in the Dying Patient.

PubMed

Kolb, Hildegard; Snowden, Austyn; Stevens, Elaine; Atherton, Iain

2018-05-09

Identification of risk factors predicting the development of death rattle. Respiratory tract secretions, often called death rattle, are among the most common symptoms in dying patients around the world. It is unknown whether death rattle causes distress in patients, but it has been globally reported that distress levels can be high in family members. Although there is a poor evidence base, treatment with antimuscarinic medication is standard practice worldwide and prompt intervention is recognised as crucial for effectiveness. The identification of risk factors for the development of death rattle would allow for targeted interventions. A case ̶ control study was designed to retrospectively review two hundred consecutive medical records of mainly cancer patients who died in a hospice inpatient setting between 2009 - 2011. Fifteen potential risk factors including the original factors weight, smoking, final opioid dose and final Midazolam dose were investigated. Binary logistic regression to identify risk factors for death rattle development. Univariate analysis showed death rattle was significantly associated with final Midazolam doses and final opioid doses, length of dying phase and anticholinergic drug load in the pre-terminal phase. In the final logistic regression model only Midazolam was statistically significant and only at final doses of 20 mg/24hrs or over (OR 3.81 CI 1.41-10.34). Dying patients with a requirement for a high dose of Midazolam have an increased likelihood of developing death rattle. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Threats to security and ischaemic heart disease deaths: the case of homicides in Mexico.

PubMed

Lee, Eileen H; Bruckner, Tim A

2017-02-01

Ischaemic heart disease (IHD) ranks as the leading cause of death worldwide. Whereas much attention focuses on behavioural and lifestyle factors, less research examines the role of acute, ambient stressors. An unprecedented rise in homicides in Mexico over the past decade and the attendant media coverage and publicity have raised international concern regarding its potential health sequelae. We hypothesize that the rise in homicides in Mexico acts as an ecological threat to security and elevates the risk of both transient ischaemic events and myocardial infarctions, thereby increasing IHD deaths. We applied time-series methods to monthly counts of IHD deaths and homicides in Mexico for 156 months spanning January 2000 to December 2012. Methods controlled for strong temporal patterns in IHD deaths, the unemployment rate and changes in the population size at risk. After controlling for trend and seasonality in IHD deaths, a 1-unit increase in the logged count of homicides coincides with a 7% increase in the odds of IHD death in that same month (95% confidence interval: 0.04 - 0.10). Inference remains robust to additional sensitivity checks, including a state-level fixed effects analysis. Our findings indicate that the elevated level of homicides in Mexico serves as a population-level stressor that acutely increases the risk of IHD death. This research adds to the growing literature documenting the role of ambient threats, or perceived threats, to security on cardiovascular health. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Correlates of death anxiety in Pakistan.

PubMed

Suhail, Kausar; Akram, Saima

2002-01-01

To ascertain the effect of gender, age, and religiosity on death anxiety, 132 participants were interviewed using Templer Death Anxiety Scale and Collett-Lester Fear of Death Scale (CLS). Women, older participants, and less religious participants were found to be more scared of their impending death. Gender effect was more pronounced, however, on the CLS. Women and less religious people reported to experience greater anxiety than their respective counterparts about different dimensions of death, for example, the shortness of life, total isolation of death, fear of not being, and disintegration of body after dying. The findings of the current work indicate that the general predictors of death anxiety, gender, age, and religiosity reported in Western, predominantly Christian samples also hold in an Eastern, Muslim sample.

Traumatic Brain Injury–Related Emergency Department Visits, Hospitalizations, and Deaths — United States, 2007 and 2013

PubMed Central

Taylor, Christopher A.; Bell, Jeneita M.; Xu, Likang

2017-01-01

Problem/Condition Traumatic brain injury (TBI) has short- and long-term adverse clinical outcomes, including death and disability. TBI can be caused by a number of principal mechanisms, including motor-vehicle crashes, falls, and assaults. This report describes the estimated incidence of TBI-related emergency department (ED) visits, hospitalizations, and deaths during 2013 and makes comparisons to similar estimates from 2007. Reporting Period 2007 and 2013. Description of System State-based administrative health care data were used to calculate estimates of TBI-related ED visits and hospitalizations by principal mechanism of injury, age group, sex, and injury intent. Categories of injury intent included unintentional (motor-vehicle crashes, falls, being struck by or against an object, mechanism unspecified), intentional (self-harm and assault/homicide), and undetermined intent. These health records come from the Healthcare Cost and Utilization Project’s National Emergency Department Sample and National Inpatient Sample. TBI-related death analyses used CDC multiple-cause-of-death public-use data files, which contain death certificate data from all 50 states and the District of Columbia. Results In 2013, a total of approximately 2.8 million TBI-related ED visits, hospitalizations, and deaths (TBI-EDHDs) occurred in the United States. This consisted of approximately 2.5 million TBI-related ED visits, approximately 282,000 TBI-related hospitalizations, and approximately 56,000 TBI-related deaths. TBIs were diagnosed in nearly 2.8 million (1.9%) of the approximately 149 million total injury- and noninjury-related EDHDs that occurred in the United States during 2013. Rates of TBI-EDHDs varied by age, with the highest rates observed among persons aged ≥75 years (2,232.2 per 100,000 population), 0–4 years (1,591.5), and 15–24 years (1,080.7). Overall, males had higher age-adjusted rates of TBI-EDHDs (959.0) compared with females (810.8) and the most common principal mechanisms of injury for all age groups included falls (413.2, age-adjusted), being struck by or against an object (142.1, age-adjusted), and motor-vehicle crashes (121.7, age-adjusted). The age-adjusted rate of ED visits was higher in 2013 (787.1) versus 2007 (534.4), with fall-related TBIs among persons aged ≥75 years accounting for 17.9% of the increase in the number of TBI-related ED visits. The number and rate of TBI-related hospitalizations also increased among persons aged ≥75 years (from 356.9 in 2007 to 454.4 in 2013), primarily because of falls. Whereas motor-vehicle crashes were the leading cause of TBI-related deaths in 2007 in both number and rate, in 2013, intentional self-harm was the leading cause in number and rate. The overall age-adjusted rate of TBI-related deaths for all ages decreased from 17.9 in 2007 to 17.0 in 2013; however, age-adjusted TBI-related death rates attributable to falls increased from 3.8 in 2007 to 4.5 in 2013, primarily among older adults. Although the age-adjusted rate of TBI-related deaths attributable to motor-vehicle crashes decreased from 5.0 in 2007 to 3.4 in 2013, the age-adjusted rate of TBI-related ED visits attributable to motor-vehicle crashes increased from 83.8 in 2007 to 99.5 in 2013. The age-adjusted rate of TBI-related hospitalizations attributable to motor-vehicle crashes decreased from 23.5 in 2007 to 18.8 in 2013. Interpretation Progress has been made to prevent motor-vehicle crashes, resulting in a decrease in the number of TBI-related hospitalizations and deaths from 2007 to 2013. However, during the same time, the number and rate of older adult fall-related TBIs have increased substantially. Although considerable public interest has focused on sports-related concussion in youth, the findings in this report suggest that TBIs attributable to older adult falls, many of which result in hospitalization and death, should receive public health attention. Public Health Actions The increase in the number of fall-related TBIs in older adults suggests an urgent need to enhance fall-prevention efforts in that population. Multiple effective interventions have been identified, and CDC has developed the STEADI initiative (Stopping Elderly Accidents Deaths and Injuries) as a comprehensive strategy that incorporates empirically supported clinical guidelines and scientifically tested interventions to help primary care providers address their patients’ fall risk through the identification of modifiable risk factors and implementation of effective interventions (e.g., exercise, medication management, and Vitamin D supplementation). PMID:28301451

Oncologists' strategies and barriers to effective communication about the end of life.

PubMed

Granek, Leeat; Krzyzanowska, Monika K; Tozer, Richard; Mazzotta, Paolo

2013-07-01

Communicating about the end of life with patients has been reported as one of the most difficult and stressful part of the work of oncologists. Despite this fact, oncologists receive little training in this area, and many do not communicate effectively with patients. The purpose of this analysis, part of a larger study examining oncologists' experiences of patient loss, was to explore oncologists' communication strategies and communication barriers when discussing end-of-life issues with patients. Twenty oncologists were interviewed at three hospitals about their communication strategies on end-of-life issues with patients. The data were analyzed using the grounded theory method. The findings revealed the strategies to effective communication about the end of life included: being open and honest; having ongoing, early conversations; communicating about modifying treatment goals; and balancing hope and reality. Barriers to implementing these strategies fell broadly into three domains, including physician factors, patient factors, and institutional factors. Physician factors included difficulty with treatment and palliation, personal discomfort with death and dying, diffusion of responsibility among colleagues, using the "death-defying mode," lack of experience, and lack of mentorship. Patient factors included, patients and/or families being reluctant to talk about the end of life, language barriers, and younger age. Institutional factors included stigma around palliative care, lack of protocol about end-of-life issues; and lack of training for oncologists on how to talk with patients about end-of-life issues. We conclude by drawing implications from our study and suggest that further research and intervention are necessary to aid oncologists in achieving effective communication about end-of-life issues.

Improving emergency response to motor vehicle crashes : the role of multi-media information.

DOT National Transportation Integrated Search

2013-10-01

The motivation for this study is to reduce the adverse impacts of trauma caused by motor vehicle crash (MVC), including rural regions, where crashes account for a high percentage of trauma injury and death. One key aspect of reducing adverse effects ...

ENVIRONMENTAL RESPONSE TO INTENTIONAL DISSEMINATION OF BACILLUS ANTHRACIS SPORES IN THE UNITED STATES--2001

EPA Science Inventory

The intentional dissemination of Bacillus anthracis (anthrax) spores at multiple locations in the United States in the Fall of 2001 resulted not only in several deaths and illnesses (including psychological effects), but likely changed lifestyles and attitudes, and increased the ...

The Changing Face of Immigration Law.

ERIC Educational Resources Information Center

Nugent, Christopher

2001-01-01

Focuses on laws that influence U.S. immigration, such as the Illegal Immigration Reform and Immigrant Responsibility Act (1996), the Personal Responsibility and Work Opportunity Reconciliation Act (1996), the Anti-Terrorism and Effective Death Penalty Act (1996), and the Legal Immigration and Family Equity Act (2000). Includes discussion…

The time that comes toward us: The Alba Iulia death conferences.

PubMed

Rotar, Marius

2017-01-01

This article illuminates the history of the annual death conference in Alba Iulia, Romania (2007-2015), the only conference on death and dying organized in Eastern Europe. Written by the conference founder, the article tries to set out the main lines of its development over that period. Emphasis is laid on the difficulties of expanding death studies in Romania, the reaction of the wider public to the death conference, and the collaboration beyond borders between death scholars. The articles included in this issue of Death Studies are briefly presented.

77 FR 66554 - Federal Travel Regulation (FTR); Payment of Expenses Connected With the Death of Certain Employees

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-06

... Connected With the Death of Certain Employees AGENCY: Office of Government-wide Policy, General Services... goods, personal effects, and one privately owned vehicle of a covered employee whose death occurred as a... effects of a ``covered employee'' whose death occurred as a result of personal injury sustained while in...

Effect of a very low-protein diet on outcomes: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study.

PubMed

Menon, Vandana; Kopple, Joel D; Wang, Xuelei; Beck, Gerald J; Collins, Allan J; Kusek, John W; Greene, Tom; Levey, Andrew S; Sarnak, Mark J

2009-02-01

The long-term effect of a very low-protein diet on the progression of kidney disease is unknown. We examined the effect of a very low-protein diet on the development of kidney failure and death during long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Long-term follow-up of study B of the MDRD Study (1989-1993). The MDRD Study examined the effects of dietary protein restriction and blood pressure control on progression of kidney disease. This analysis includes 255 trial participants with predominantly stage 4 nondiabetic chronic kidney disease. A low-protein diet (0.58 g/kg/d) versus a very low-protein diet (0.28 g/kg/d) supplemented with a mixture of essential keto acids and amino acids (0.28 g/kg/d). Kidney failure (initiation of dialysis therapy or transplantation) and all-cause mortality until December 31, 2000. Kidney failure developed in 227 (89%) participants, 79 (30.9%) died, and 244 (95.7%) reached the composite outcome of either kidney failure or death. Median duration of follow-up until kidney failure, death, or administrative censoring was 3.2 years, and median time to death was 10.6 years. In the low-protein group, 117 (90.7%) participants developed kidney failure, 30 (23.3%) died, and 124 (96.1%) reached the composite outcome. In the very low-protein group, 110 (87.3%) participants developed kidney failure, 49 (38.9%) died, and 120 (95.2%) reached the composite outcome. After adjustment for a priori-specified covariates, hazard ratios were 0.83 (95% confidence interval, 0.62 to 1.12) for kidney failure, 1.92 (95% confidence interval, 1.15 to 3.20) for death, and 0.89 (95% confidence interval, 0.67 to 1.18) for the composite outcome in the very low-protein diet group compared with the low-protein diet group. Lack of dietary protein measurements during follow-up. In long-term follow-up of the MDRD Study, assignment to a very low-protein diet did not delay progression to kidney failure, but appeared to increase the risk of death.

Long-term Effects of Child Death on Parents' Health Related Quality of Life: A Dyadic Analysis

PubMed Central

Song, Jieun; Floyd, Frank J.; Seltzer, Marsha Mailick; Greenberg, Jan S.; Hong, Jinkuk

2010-01-01

This study examines the long-term effects of child death on bereaved parents' health-related quality of life (HRQoL). Using data from the Wisconsin Longitudinal Study, we compared 233 bereaved couples and 229 comparison couples (mean age = 65.11 years) and examined the life course effects of child death on parents' HRQoL. Variations in bereavement effects were examined by gender and for different causes of death. Bereaved parents had significantly worse HRQoL than comparison group parents, and there was no evidence of gender differences for this effect. With respect to the cause of a child's death, bereaved parents whose child died in violent circumstances had particularly low levels of HRQoL. Multilevel models indicated that marital closeness mitigated the negative effects of bereavement. PMID:20676393

Connecting mitochondrial dynamics and life-or-death events via Bcl-2 family proteins.

PubMed

Aouacheria, Abdel; Baghdiguian, Stephen; Lamb, Heather M; Huska, Jason D; Pineda, Fernando J; Hardwick, J Marie

2017-10-01

The morphology of a population of mitochondria is the result of several interacting dynamical phenomena, including fission, fusion, movement, elimination and biogenesis. Each of these phenomena is controlled by underlying molecular machinery, and when defective can cause disease. New understanding of the relationships between form and function of mitochondria in health and disease is beginning to be unraveled on several fronts. Studies in mammals and model organisms have revealed that mitochondrial morphology, dynamics and function appear to be subject to regulation by the same proteins that regulate apoptotic cell death. One protein family that influences mitochondrial dynamics in both healthy and dying cells is the Bcl-2 protein family. Connecting mitochondrial dynamics with life-death pathway forks may arise from the intersection of Bcl-2 family proteins with the proteins and lipids that determine mitochondrial shape and function. Bcl-2 family proteins also have multifaceted influences on cells and mitochondria, including calcium handling, autophagy and energetics, as well as the subcellular localization of mitochondrial organelles to neuronal synapses. The remarkable range of physical or functional interactions by Bcl-2 family proteins is challenging to assimilate into a cohesive understanding. Most of their effects may be distinct from their direct roles in apoptotic cell death and are particularly apparent in the nervous system. Dual roles in mitochondrial dynamics and cell death extend beyond BCL-2 family proteins. In this review, we discuss many processes that govern mitochondrial structure and function in health and disease, and how Bcl-2 family proteins integrate into some of these processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Who is more vulnerable to death from extremely cold temperatures? A case-only approach in Hong Kong with a temperate climate

NASA Astrophysics Data System (ADS)

Qiu, Hong; Tian, Linwei; Ho, Kin-fai; Yu, Ignatius T. S.; Thach, Thuan-Quoc; Wong, Chit-Ming

2016-05-01

The short-term effects of ambient cold temperature on mortality have been well documented in the literature worldwide. However, less is known about which subpopulations are more vulnerable to death related to extreme cold. We aimed to examine the personal characteristics and underlying causes of death that modified the association between extreme cold and mortality in a case-only approach. Individual information of 197,680 deaths of natural causes, daily temperature, and air pollution concentrations in cool season (November-April) during 2002-2011 in Hong Kong were collected. Extreme cold was defined as those days with preceding week with a daily maximum temperature at or less than the 1st percentile of its distribution. Logistic regression models were used to estimate the effects of modification, further controlling for age, seasonal pattern, and air pollution. Sensitivity analyses were conducted by using the 5th percentile as cutoff point to define the extreme cold. Subjects with age of 85 and older were more vulnerable to extreme cold, with an odds ratio (OR) of 1.33 (95 % confidence interval (CI), 1.22-1.45). The greater risk of extreme cold-related mortality was observed for total cardiorespiratory diseases and several specific causes including hypertensive diseases, stroke, congestive heart failure, chronic obstructive pulmonary disease (COPD), and pneumonia. Hypertensive diseases exhibited the greatest vulnerability to extreme cold exposure, with an OR of 1.37 (95 % CI, 1.13-1.65). Sensitivity analyses showed the robustness of these effect modifications. This evidence on which subpopulations are vulnerable to the adverse effects of extreme cold is important to inform public health measures to minimize those effects.

Hazard Regression Models of Early Mortality in Trauma Centers

PubMed Central

Clark, David E; Qian, Jing; Winchell, Robert J; Betensky, Rebecca A

2013-01-01

Background Factors affecting early hospital deaths after trauma may be different from factors affecting later hospital deaths, and the distribution of short and long prehospital times may vary among hospitals. Hazard regression (HR) models may therefore be more useful than logistic regression (LR) models for analysis of trauma mortality, especially when treatment effects at different time points are of interest. Study Design We obtained data for trauma center patients from the 2008–9 National Trauma Data Bank (NTDB). Cases were included if they had complete data for prehospital times, hospital times, survival outcome, age, vital signs, and severity scores. Cases were excluded if pulseless on admission, transferred in or out, or ISS<9. Using covariates proposed for the Trauma Quality Improvement Program and an indicator for each hospital, we compared LR models predicting survival at 8 hours after injury to HR models with survival censored at 8 hours. HR models were then modified to allow time-varying hospital effects. Results 85,327 patients in 161 hospitals met inclusion criteria. Crude hazards peaked initially, then steadily declined. When hazard ratios were assumed constant in HR models, they were similar to odds ratios in LR models associating increased mortality with increased age, firearm mechanism, increased severity, more deranged physiology, and estimated hospital-specific effects. However, when hospital effects were allowed to vary by time, HR models demonstrated that hospital outliers were not the same at different times after injury. Conclusions HR models with time-varying hazard ratios reveal inconsistencies in treatment effects, data quality, and/or timing of early death among trauma centers. HR models are generally more flexible than LR models, can be adapted for censored data, and potentially offer a better tool for analysis of factors affecting early death after injury. PMID:23036828

SIDS and Other Sleep-Related Infant Deaths: Updated 2016 Recommendations for a Safe Infant Sleeping Environment.

PubMed

2016-11-01

Approximately 3500 infants die annually in the United States from sleep-related infant deaths, including sudden infant death syndrome (SIDS; International Classification of Diseases, 10th Revision [ICD-10], R95), ill-defined deaths (ICD-10 R99), and accidental suffocation and strangulation in bed (ICD-10 W75). After an initial decrease in the 1990s, the overall death rate attributable to sleep-related infant deaths has not declined in more recent years. Many of the modifiable and nonmodifiable risk factors for SIDS and other sleep-related infant deaths are strikingly similar. The American Academy of Pediatrics recommends a safe sleep environment that can reduce the risk of all sleep-related infant deaths. Recommendations for a safe sleep environment include supine positioning, the use of a firm sleep surface, room-sharing without bed-sharing, and the avoidance of soft bedding and overheating. Additional recommendations for SIDS reduction include the avoidance of exposure to smoke, alcohol, and illicit drugs; breastfeeding; routine immunization; and use of a pacifier. New evidence is presented for skin-to-skin care for newborn infants, use of bedside and in-bed sleepers, sleeping on couches/armchairs and in sitting devices, and use of soft bedding after 4 months of age. The recommendations and strength of evidence for each recommendation are included in this policy statement. The rationale for these recommendations is discussed in detail in the accompanying technical report (www.pediatrics.org/cgi/doi/10.1542/peds.2016-2940). Copyright © 2016 by the American Academy of Pediatrics.

The prognostic role of body mass index on mortality amongst the middle-aged and elderly: a competing risk analysis.

PubMed

Ghaem Maralani, Haleh; Tai, Bee Choo; Wong, Tien Y; Tai, E Shyong; Li, Jialiang; Wang, Jie Jin; Mitchell, Paul

2014-01-01

To determine the relationship between body mass index (BMI) including its 5-year changes and mortality, and compare the results obtained using Cox and competing risks models. Our study subjects included 2216 persons aged ≥49 years who participated in the Blue Mountains Eye Study, Australia between 1992 and 1994, and returned for further follow-up examinations between 1997 and 1999. We examined the relationship between BMI and mortality using cubic spline. The Cox and competing risks models were used to assess the associations between baseline BMI and its 5-year changes with all-cause and cause-specific mortality. Amongst subjects aged ≤70 years, the relationship between BMI and all-cause mortality was U-shaped. For those aged >70 years, an L-shaped relationship was seen with no elevation in risk amongst the overweight/obese. Based on the competing risks model, obesity at baseline was associated with increased risk of cardiovascular death and reduction in BMI at 5-year was linked to an increase risk of cancer death amongst those aged ≤70 years. The cause-specific Cox model showed that reduction in BMI at 5-year was associated with cancer-death regardless of age, and with cardiovascular deaths among subjects aged ≤70 years. Cox regression model showed larger magnitude of effect with wider confidence interval as compared with competing risks model. Conditions associated with obesity are more likely to affect mortality among subjects aged ≤70 years, but not among those aged over 70 years. Cox model shows larger magnitude of effect in comparison with competing risks model. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Stressful life events in childhood and risk of infectious disease hospitalization.

PubMed

Nielsen, Nete Munk; Hansen, Anne Vinkel; Simonsen, Jacob; Hviid, Anders

2012-01-01

Individuals exposed to high levels of stress might have an increased risk of infectious diseases. However, most of the previous studies have been conducted among adults. To examine the effect of childhood stress, we conducted a nationwide cohort study including all Danish children born from 1977 to 2004. Stressful life events (SFLE) included parental death, death of sibling or parental divorce. Outcome was defined as hospitalizations due to less severe (LSID) or severe infectious diseases (SID). Children were followed until the age of 15 years. The association between SFLE and risk of infections was evaluated through rate ratios (RR) comparing infectious disease incidence ratios in children with and without a history of SFLE. Overall, children exposed to SFLE were at 13% increased risk of LSID (RR = 1.13 (1.10-1.15)), but at no increased risk of SID hospitalization (RR = 1.05 (0.97-1.14)). Looking at the specific type of SFLE, parental divorce increased the risk of LSID (RR = 1.11 (1.09-1.14)) and SID hospitalization (1.11 (1.02-1.21)) by 11%, whereas no increased risk of LSID and SID hospitalization was observed following parental death. Finally, a 34% increased risk of LSID hospitalization (RR = 1.34 (1.23-1.45)) was observed following death of sibling, in contrast to no increased risk of SID hospitalization. Childhood exposure to SFLE, especially parental divorce seems to increase the risk of infectious disease hospitalization. Although we cannot determine whether our observations are the result of a biological effect of stress, adoption of unhealthy behaviours or increased likelihood of hospitalization, our findings do have public health relevance as a considerable proportion of the children today will be exposed to SFLE, the majority to parental divorce.

Levothyroxine Substitution in Patients with Subclinical Hypothyroidism and the Risk of Myocardial Infarction and Mortality

PubMed Central

Andersen, Mette Nygaard; Olsen, Anne-Marie Schjerning; Madsen, Jesper Clausager; Faber, Jens; Torp-Pedersen, Christian; Gislason, Gunnar Hilmar; Selmer, Christian

2015-01-01

Background Subclinical hypothyroidism is associated with a number of cardiovascular risk factors, yet only limited data exist on long-term outcome of levothyroxine treatment of this condition with respect to hard end-points. The aim of this retrospective cohort study was to determine effects of levothyroxine treatment on myocardial infarction (MI), cardiovascular death and all-cause mortality, in patients with subclinical hypothyroidism. Methods and Results Primary care patients aged 18 years and older that underwent thyroid function tests between 2000 and 2009 were enrolled. Participants were identified by individual-level linkage of nationwide registers. Patients with subclinical hypothyroidism at baseline were included in the study. Exclusion criteria included a history of thyroid disease, related medication or medication affecting thyroid function. The total cohort comprised 628,953 patients of which 12,212 (1.9%) had subclinical hypothyroidism (mean age 55.2 [SD ± 18.8] years; 79.8% female). Within the first six months 2,483 (20.3%) patients claimed a prescription for levothyroxine. During a median follow-up of 5.0 (IQR: 5.2) years, 358 MI’s and 1,566 (12.8%) deaths were observed. Out of these, 766 of the deaths were cardiovascular related. No beneficial effects were found in levothyroxine treated patients on MI (IRR 1.08 [95% CI: 0.81 to 1.44]), cardiovascular death (IRR 1.02 [95% CI: 0.83 to 1.25]) or all-cause mortality (IRR 1.03 [95% CI: 0.90 to 1.19]), except in patients under the age of 65 years (IRR 0.63 [95% CI: 0.40 to 0.99]). Conclusion Levothyroxine substitution in subclinical hypothyroid patients does not indicate an association with lower mortality or decreased risk of MI. PMID:26069971

Levothyroxine Substitution in Patients with Subclinical Hypothyroidism and the Risk of Myocardial Infarction and Mortality.

PubMed

Andersen, Mette Nygaard; Olsen, Anne-Marie Schjerning; Madsen, Jesper Clausager; Faber, Jens; Torp-Pedersen, Christian; Gislason, Gunnar Hilmar; Selmer, Christian

2015-01-01

Subclinical hypothyroidism is associated with a number of cardiovascular risk factors, yet only limited data exist on long-term outcome of levothyroxine treatment of this condition with respect to hard end-points. The aim of this retrospective cohort study was to determine effects of levothyroxine treatment on myocardial infarction (MI), cardiovascular death and all-cause mortality, in patients with subclinical hypothyroidism. Primary care patients aged 18 years and older that underwent thyroid function tests between 2000 and 2009 were enrolled. Participants were identified by individual-level linkage of nationwide registers. Patients with subclinical hypothyroidism at baseline were included in the study. Exclusion criteria included a history of thyroid disease, related medication or medication affecting thyroid function. The total cohort comprised 628,953 patients of which 12,212 (1.9%) had subclinical hypothyroidism (mean age 55.2 [SD ± 18.8] years; 79.8% female). Within the first six months 2,483 (20.3%) patients claimed a prescription for levothyroxine. During a median follow-up of 5.0 (IQR: 5.2) years, 358 MI's and 1,566 (12.8%) deaths were observed. Out of these, 766 of the deaths were cardiovascular related. No beneficial effects were found in levothyroxine treated patients on MI (IRR 1.08 [95% CI: 0.81 to 1.44]), cardiovascular death (IRR 1.02 [95% CI: 0.83 to 1.25]) or all-cause mortality (IRR 1.03 [95% CI: 0.90 to 1.19]), except in patients under the age of 65 years (IRR 0.63 [95% CI: 0.40 to 0.99]). Levothyroxine substitution in subclinical hypothyroid patients does not indicate an association with lower mortality or decreased risk of MI.

A method for deriving leading causes of death.

PubMed Central

Becker, Roberto; Silvi, John; Ma Fat, Doris; L'Hours, André; Laurenti, Ruy

2006-01-01

OBJECTIVE: A standard list for ranking leading causes of death worldwide does not exist. WHO headquarters, regional offices and Member States all use different lists that have varying levels of detail. We sought to derive a standard list to enable countries to identify their leading causes of death and to permit comparison between countries. Our aim is to share the criteria and methodology we used to bring some order to the construction of such a list, to provide a consistent procedure that can be used by others, and to give researchers and data owners an opportunity to utilize the list at national and subnational levels. METHODS: Results were primarily data-driven. Data from individual countries representing different regions of the world were extracted from the WHO Mortality Database. Supplementary information from WHO estimates on mortality was used for regions where data were scarce. In addition, a set of criteria was used to group the candidate causes and to determine other causes that should be included on the list. FINDINGS: A ranking list of the leading causes of death that contains broad cause groupings (such as "all cancers", "all heart diseases" or "all accidents") is not effective and does not identify the leading individual causes within these broad groupings; thus it does not allow policy-makers to generate appropriate health advocacy and cost-effective interventions. Similarly, defining candidate causal groups too narrowly or including diseases that have a low frequency does not meet these objectives. CONCLUSION: For international comparisons, we recommend that countries use this list; it is based on extensive evidence and the application of public health disease-prevention criteria. It is not driven by political or financial motives. This list may be adapted for national statistical purposes. PMID:16628303

Social Security and divorce or death benefits storyboard (S(2)D(2)BS): an interactive participant learning exercise.

PubMed

Brown, Pamela Pitman

2014-01-01

Using the concept of an interactive or living storyboard, the author discusses the use of seven case narratives constructed for the sole purpose of teaching introductory gerontology or geriatric students about the distribution of Social Security benefits after spousal death. Additional information is included pertaining to Social Security benefits payable to divorced persons after the death of the former spouse, including the status of married same-sex couples. Narratives include representations of a male breadwinner model couple, a two-earner couple who have similar/dissimilar earnings prior to retirement, a divorced couple with a remarriage after a death, a gay couple with and without children, and a female primary breadwinner couple. Updated information from the Social Security Administration, as well as information on game preparation, scripts, and debriefing questions are included.

Evaluation of the Effects of Airborne Particulate Matter on Bone Marrow-Mesenchymal Stem Cells (BM-MSCs): Cellular, Molecular and Systems Biological Approaches

PubMed Central

Abu-Elmagd, Muhammad; Alghamdi, Mansour A.; Shamy, Magdy; Khoder, Mamdouh I.; Costa, Max; Assidi, Mourad; Kadam, Roaa; Alsehli, Haneen; Gari, Mamdooh; Pushparaj, Peter Natesan; Kalamegam, Gauthaman; Al-Qahtani, Mohammed H.

2017-01-01

Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with a range of acute and chronic diseases in humans. However, the specific effects they exert on the stem cells remain unclear. Here, we report the effects of PM collected from the city of Jeddah on proliferation, cell death, related gene expression and systems of biological analysis in bone marrow mesenchymal stem cells (BM-MSCs), with the aim of understanding the underlying mechanisms. PM2.5 and PM10 were tested in vitro at various concentrations (15 to 300 µg/mL) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM2.5 increased proliferation of BM-MSCs, while higher concentrations served to decrease it. PM10 decreased BM-MSCs proliferation in a concentration-dependent manner. The X-ray fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses demonstrated that heavy metals were associated with signaling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential expression of the apoptosis genes (BCL2, BAX); inflammation associated genes (TNF-α and IL-6) and the cell cycle regulation gene (p53). We conclude that PM causes inflammation and cell death, and thereby predisposes to chronic debilitating diseases. PMID:28425934

Incidence of the Bertillon and Gompertz effects on the outcome of clinical trials

NASA Astrophysics Data System (ADS)

Roehner, Bertrand M.

2014-11-01

The accounts of medical trials provide very detailed information about the patients’ health conditions. On the contrary, almost no vital data such as marital status or age distribution are usually given. Yet, some of these factors can have a notable impact on the overall death rate, thereby changing the outcome and conclusions of the trial. This paper focuses on two of these variables. The first is marital status; its effect on life expectancy (which will be referred to as the Bertillon effect) may double death rates in all age intervals. The second variable is the age distribution of the oldest patients. Because of the exponential nature of Gompertz’s law changes in the distribution of ages in the oldest age group can have dramatic consequences on the overall number of deaths. One should recall that the death rate at the age of 82 is 40 times higher than at the age of 37. It will be seen that randomization alone can hardly take care of these problems. Appropriate remedies are easy to formulate however. First, the marital status of patients as well as the age distribution of those over 65 should be documented for both study groups. Then, thanks to these data and based on the Bertillon and Gompertz laws, it will become possible to perform appropriate corrections. Such corrections will notably improve the reliability and accuracy of the conclusions, especially in trials which include a large proportion of elderly subjects.

Randomised trial of low-dose amiodarone in severe congestive heart failure. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA)

PubMed

Doval, H C; Nul, D R; Grancelli, H O; Perrone, S V; Bortman, G R; Curiel, R

1994-08-20

In severe heart failure many deaths are sudden and are presumed to be due to ventricular arrhythmias. The GESICA trial evaluated the effect of low-dose amiodarone on two-year mortality in patients with severe heart failure. Our prospective multicentre trial included 516 patients on optimal standard treatment for heart failure. Patients were randomised to 300 mg/day amiodarone (260) or to standard treatment (256). Intention-to-treat analysis showed 87 deaths in the amiodarone group (33.5%) compared with 106 in the control group (41.4%) (risk reduction 28%; 95% CI 4%-45%; log rank test p = 0.024). There were reductions in both sudden death (risk reduction 27%; p = 0.16) and death due to progressive heart failure (risk reduction 23%; p = 0.16). Fewer patients in the amiodarone group died or were admitted to hospital due to worsening heart failure (119 versus 149 in the control group; risk reduction 31%; 95% CI 13-46%; p = 0.0024). The decrease in mortality and hospital admission was present in all subgroups examined and independent of the presence of non-sustained ventricular tachycardia. Side-effects were reported in 17 patients (6.1%); amiodarone was withdrawn in 12. Low-dose amiodarone proved to be an effective and reliable treatment, reducing mortality and hospital admission in patients with severe heart failure independently of the presence of complex ventricular arrhythmias.

Korean red ginseng extract exhibits neuroprotective effects through inhibition of apoptotic cell death.

PubMed

Kim, Sunyoung; Lee, Youngmoon; Cho, Jungsook

2014-01-01

Red ginseng has long been used as a traditional medicine in many East Asian countries including Korea. It is known to exhibit various pharmacological effects, including anti-oxidant, anti-cancer, anti-stress and anti-diabetes activities. To further explore its actions, the present study evaluated effects of Korean red ginseng (KRG) extract on neuronal injury induced by various types of insults using primary cultured rat cortical cells. KRG extract inhibited neuronal damage and generation of intracellular reactive oxygen species (ROS) induced by excitatory amino acids, such as glutamate and N-methyl-D-aspartate (NMDA), or by Aβ(25-35). To elucidate possible mechanism(s) by which KRG extract exerts neuroprotective action, its effects on apoptosis and apoptosis-related signaling molecules in neurons were assessed. KRG extract markedly increased phosphorylation of Bad at Ser 112 and inhibited Bax expression and caspase 3 activity. It also inhibited DNA fragmentation induced by NMDA or Aβ(25-35). These results indicate that KRG extract protects cultured neurons from excitotoxicity and Aβ(25-35)-induced toxicity through inhibition of ROS generation and apoptotic cell death. In addition, KRG extract inhibited β-secretase activity, implying that it may reduce Aβ peptide formation. Taken together, these findings suggest that KRG extract may be beneficial for the prevention and/or treatment of neurodegenerative disorders including Alzheimer's disease.

Sex ratio in multiple sclerosis mortality over 65 years; an age-period-cohort analysis in Norway.

PubMed

Nakken, Ola; Lindstrøm, Jonas Christoffer; Holmøy, Trygve

2018-06-01

Increasing female: male ratio in multiple sclerosis (MS) has been assigned to cohort effects, with females in more recent birth cohorts possibly being more exposed or vulnerable to environmental risk factors than males. We collected MS mortality data in Norway from 1951 to 2015 from The Norwegian Cause of Death registry. Age-Period-Cohort analysis was conducted using log-linear Poisson models, including sex interaction terms. MS was registered as the underlying, contributing or direct cause in 6060 deaths. MS associated mortality remained stable with a slight preponderance among males until after 1980, and have since increased preferentially among females. Throughout the study period the mean annual increase was 1.25% for females and 0.3% for males (p < 0.0001). Age-period-cohort analysis revealed limited evidence of cohort effects for the gender differences; the best fitting model only included gender-age and gender-period interaction terms. The period effect evened out for males in the last three decades but increased for females, especially among the oldest age-groups. In conclusion, the increased female: male mortality ratio in MS associated mortality is driven mainly by increased mortality among females in the three last decades, particularly in the older age groups. It is best explained by disproportional period effects, providing evidence of time-varying external factors including improved access to diagnosis among females.

Manatee mortality in Puerto Rico

USGS Publications Warehouse

Mignucci-Giannoni, A. A.; Montoya-Ospina, R. A.; Jimenez-Marrero, N. M.; Rodriguez-Lopez, M.; Williams, E.H.; Bonde, R.K.

2000-01-01

The most pressing problem in the effective management of the West Indian manatee (Trichechus manatus) in Puerto Rico is mortality due to human activities. We assessed 90 cases of manatee strandings in Puerto Rico based on historical data and a coordinated carcass salvage effort from 1990 through 1995. We determined patterns of mortality, including type of event, condition of carcasses, spatial and temporal distribution, gender, size/age class, and the cause of death. The spatial distribution of stranding events was not uniform, with the north, northeast, and south coasts having the highest numbers. Six clusters representing the highest incidence included the areas of Fajardo and Ceiba, Bahia de Jobos, Toa Baja, Guayanilla, Cabo Rojo, and Rio Grande to Luquillo. The number of reported cases has increased at an average rate of 9.6%/yr since 1990. The seasonality of stranding events showed a bimodal pattern, from February through April and in August and September. Most identified causes of death were due to human interaction, especially captures and watercraft collisions. Natural causes usually involved dependent calves. From 1990 through 1995, most deaths were attributed to watercraft collisions. A reduction in anthropogenic mortality of this endangered species can be accomplished only through education and a proactive management and conservation plan that includes law enforcement, mortality assessment, scientific research, rescue and rehabilitation, and inter- and intraagency cooperation.

Population density and suicide in Scotland.

PubMed

Stark, Cameron; Hopkins, Paddy; Gibbs, Diane; Belbin, Alan; Hay, Alistair

2007-01-01

Suicide rates among men have increased in Scotland while falling in neighbouring countries. A national suicide prevention strategy has been produced. Previous work found that some rural areas of Scotland had higher than average rates of male suicide and undetermined deaths. This article describes the association between population density and suicide and undetermined death rates in Scotland. Anonymised information on deaths from suicide and undetermined cause in Scotland were obtained from the General Registrar Office for 1981-1999, including information on postcode sector. Each postcode sector was assigned a deprivation and population density score. Loglinear models were used to examine the effects of time period (grouped into four periods), deprivation quintiles, population density (grouped into four categories) and their interactions in each sex in three age groups. A significance level of 5% was used throughout. Adjusted rate ratios and 95% confidence intervals were based on models that included only significant factors and interactions. In men, there were higher rate ratios in the most densely populated and least densely populated quartiles, with intermediate rate ratios in other areas. There was no association with population density in women aged less than 25 years, a similar pattern to men in 25-44 year old women, and lower rates in rural areas in older women. Higher levels of deprivation were associated with higher rate ratios of suicide in both sexes and all age groups. Rate ratios over time increased in younger men and women, remained stable in older men, and declined in older women. Deprivation is associated with higher rates of suicide and undetermined deaths at all levels of population density and in all age groups. The highest rates of suicide among men are in the most and least densely populated areas, after adjusting for deprivation. The effect is different among women, with no effect among younger women, and lower rates among older women in areas with lower population density.

Exploring links between greenspace and sudden unexpected death: A spatial analysis.

PubMed

Wu, Jianyong; Rappazzo, Kristen M; Simpson, Ross J; Joodi, Golsa; Pursell, Irion W; Mounsey, J Paul; Cascio, Wayne E; Jackson, Laura E

2018-04-01

Greenspace has been increasingly recognized as having numerous health benefits. However, its effects are unknown concerning sudden unexpected death (SUD), commonly referred to as sudden cardiac death, which constitutes a large proportion of mortality in the United States. Because greenspace can promote physical activity, reduce stress and buffer air pollutants, it may have beneficial effects for people at risk of SUD, such as those with heart disease, hypertension, and diabetes mellitus. Using several spatial techniques, this study explored the relationship between SUD and greenspace. We adjudicated 396 SUD cases that occurred from March 2013 to February 2015 among reports from emergency medical services (EMS) that attended out-of-hospital deaths in Wake County (central North Carolina, USA). We measured multiple greenspace metrics in each census tract, including the percentages of forest, grassland, average tree canopy, tree canopy diversity, near-road tree canopy and greenway density. The associations between SUD incidence and these greenspace metrics were examined using Poisson regression (non-spatial) and Bayesian spatial models. The results from both models indicated that SUD incidence was inversely associated with both greenway density (adjusted risk ratio [RR] = 0.82, 95% credible/ confidence interval [CI]: 0.69-0.97) and the percentage of forest (adjusted RR = 0.90, 95% CI: 0.81-0.99). These results suggest that increases in greenway density by 1 km/km 2 and in forest by 10% were associated with a decrease in SUD risk of 18% and 10%, respectively. The inverse relationship was not observed between SUD incidence and other metrics, including grassland, average tree canopy, near-road tree canopy and tree canopy diversity. This study implies that greenspace, specifically greenways and forest, may have beneficial effects for people at risk of SUD. Further studies are needed to investigate potential causal relationships between greenspace and SUD, and potential mechanisms such as promoting physical activity and reducing stress. Copyright © 2018 Elsevier Ltd. All rights reserved.

Heart Disease Death Rates in Low Versus High Land Elevation Counties in the U.S.

PubMed

Hart, John

2015-01-01

Previous research on land elevation and cancer death rates in the U.S. revealed lower cancer death rates in higher elevations. The present study further tests the possible effect of land elevation on a diffident health outcome, namely, heart disease death rates. U.S. counties not overlapping in their land elevations according to their lowest and highest elevation points were identified. Using an ecological design, heart disease death rates for two races (black and white) corresponding to lower elevation counties were compared to heart disease death rates in higher land elevation counties using the two-sample t-test and effect size statistics. Death rates in higher land elevation counties for both races were lower compared to the death rates in lower land elevation counties (p < 0.001) with large effect sizes (of > 0.70). Since this is an observational study, no causal inference is claimed, and further research is indicated to verify these findings.

Heart Disease Death Rates in Low Versus High Land Elevation Counties in the U.S

PubMed Central

2015-01-01

Previous research on land elevation and cancer death rates in the U.S. revealed lower cancer death rates in higher elevations. The present study further tests the possible effect of land elevation on a diffident health outcome, namely, heart disease death rates. U.S. counties not overlapping in their land elevations according to their lowest and highest elevation points were identified. Using an ecological design, heart disease death rates for two races (black and white) corresponding to lower elevation counties were compared to heart disease death rates in higher land elevation counties using the two-sample t-test and effect size statistics. Death rates in higher land elevation counties for both races were lower compared to the death rates in lower land elevation counties (p < 0.001) with large effect sizes (of > 0.70). Since this is an observational study, no causal inference is claimed, and further research is indicated to verify these findings. PMID:26674102

The effects of drinking and driving laws on car crashes, injuries, and deaths: Evidence from Chile.

PubMed

Otero, Sebastián; Rau, Tomás

2017-09-01

This paper analyzes the effects of lowering the legal blood alcohol content limit for drivers from 0.05 to 0.03 grams of alcohol per deciliter of blood (g/dL) and increasing license suspension periods for offenders. We take advantage of a rich data set of administrative records that allow us to identify direct measures of accidents involving alcohol including fatalities and injuries. Results show a significant decrease of 32% in alcohol-related car accidents right after the law was approved but the effects moderate over time (15% after three years). There is also a significant reduction in injuries (31% right after the approval and 11% after three years) but no statistically significant effects on deaths. Complementary analysis of blood samples shows that the law had an effect on blood alcohol content (BAC) of male drivers up to the 90th percentile of the BAC distribution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Isoniazid for preventing tuberculosis in HIV-infected children

PubMed Central

Zunza, Moleen; Gray, Diane M; Young, Taryn; Cotton, Mark; Zar, Heather J

2017-01-01

Background Tuberculosis (TB) is an important cause of illness and death in HIV-positive children living in areas of high TB prevalence. We know that isoniazid prophylaxis prevents TB in HIV-negative children following TB exposure, but there is uncertainty related to its role in TB preventive treatment in HIV-positive children. Objectives To summarise the effects of TB preventive treatment versus placebo in HIV-positive children with no known TB contact on active TB, death, and reported adverse events. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, Embase and two trial registers up to February 2017. Selection criteria We included trials of HIV-positive children with and without known TB exposure, randomized to receive TB preventive treatment or placebo. Data collection and analysis Two review authors independently used the study selection criteria, assessed risk of bias, and extracted data. We assessed effects using risk, incidence rate and hazard ratios and assessed the certainty of evidence using GRADE. Main results We included three trials, involving 991 participants, below the age of 13 years, from South Africa and Botswana. Children were randomized to isoniazid prophylaxis or placebo, given daily or three times weekly. The median length of follow-up ranged from 5.7 to 34 months; some were on antiretroviral therapy (ART). In HIV-positive children not on ART, isoniazid prophylaxis may reduce the risk of active TB (hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.11 to 0.87; 1 trial, 240 participants, low certainty evidence), and death (HR 0.46, 95% CI 0.22 to 0.95; 1 trial, 240 participants, low certainty evidence). One trial (182 participants) reported number of children with laboratory adverse events, which was similar between the isoniazid prophylaxis and placebo groups. No clinical adverse events were reported. In HIV-positive children on ART, we do not know if isoniazid prophylaxis reduces the risk of active TB (risk ratio (RR) 0.76, 95% CI 0.50 to 1.14; 3 trials, 737 participants, very low certainty evidence) or death (RR 1.45, 95% CI 0.78 to 2.72; 3 trials, 737 participants, very low certainty evidence). Two trials (714 participants) reported number of clinical adverse events and three trials (795 participants) reported number of laboratory adverse events; for both categories, the number of adverse events were similar between the isoniazid prophylaxis and placebo groups. Authors' conclusions Isoniazid prophylaxis given to all children diagnosed with HIV may reduce the risk of active TB and death in HIV-positive children not on ART in studies from Africa. For children on ART, no clear benefit was detected. . Isoniazid prophylaxis for preventing active tuberculosis and death in HIV-positive children What was the aim of this review? To summarise the effects of isoniazid prophylaxis on TB, death, and adverse effects in HIV-positive children. Key messages In areas of high tuberculosis endemicity, isoniazid prophylaxis prevents active TB and death in HIV-positive children who are not on ART. We conducted a review to assess the effect of TB medication on active TB or death and its safety in HIV-positive children. What was studied in the review? TB is a common cause of severe lung disease and death in HIV-positive children. Childhood TB is common in poor countries, especially those with a coexisting burden of HIV/AIDS disease. HIV-positive children have a higher risk of developing TB than HIV-negative children. Isoniazid prevents TB in HIV-positive adults and is currently used in children who are at high risk of developing TB disease after exposure to someone with TB. However, there is limited information on the effect of isoniazid medication in reducing active TB or death if given to HIV-positive children without known TB contact. We searched for studies up to 17 February 2017, and found three studies published between 2007 and 2014 that addressed the effect of isoniazid medication compared to no medication on active TB and death in 991 HIV-positive children, below the age of 13 years. Most of the children were on antiretroviral therapy (ART) and the studies were conducted in South Africa and Botswana. The median length of follow-up ranged from 5.7 to 34 months. What are the main results of the review? In HIV-positive children not taking ART, isoniazid medication reduced the number of children developing active TB by 69% (low certainty evidence), and death by 54% (low certainty evidence). One trial was conducted in HIV-positive children taking ART, and this did not detect any benefit or harm of isoniazid (very low certainty evidence). The number of children with adverse effects were similar in children receiving isoniazid medication as the control group in both children on ART and not on ART. How up to date is the review? The review authors searched for studies published up to February 2017. PMID:28850172

Screening for Ovarian Cancer: US Preventive Services Task Force Recommendation Statement.

PubMed

Grossman, David C; Curry, Susan J; Owens, Douglas K; Barry, Michael J; Davidson, Karina W; Doubeni, Chyke A; Epling, John W; Kemper, Alex R; Krist, Alex H; Kurth, Ann E; Landefeld, C Seth; Mangione, Carol M; Phipps, Maureen G; Silverstein, Michael; Simon, Melissa A; Tseng, Chien-Wen

2018-02-13

With approximately 14 000 deaths per year, ovarian cancer is the fifth most common cause of cancer death among US women and the leading cause of death from gynecologic cancer. More than 95% of ovarian cancer deaths occur among women 45 years and older. To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on screening for ovarian cancer. The USPSTF reviewed the evidence on the benefits and harms of screening for ovarian cancer in asymptomatic women not known to be at high risk for ovarian cancer (ie, high risk includes women with certain hereditary cancer syndromes that increase their risk for ovarian cancer). Outcomes of interest included ovarian cancer mortality, quality of life, false-positive rate, surgery and surgical complication rates, and psychological effects of screening. The USPSTF found adequate evidence that screening for ovarian cancer does not reduce ovarian cancer mortality. The USPSTF found adequate evidence that the harms from screening for ovarian cancer are at least moderate and may be substantial in some cases, and include unnecessary surgery for women who do not have cancer. Given the lack of mortality benefit of screening, and the moderate to substantial harms that could result from false-positive screening test results and subsequent surgery, the USPSTF concludes with moderate certainty that the harms of screening for ovarian cancer outweigh the benefit, and the net balance of the benefit and harms of screening is negative. The USPSTF recommends against screening for ovarian cancer in asymptomatic women. (D recommendation) This recommendation applies to asymptomatic women who are not known to have a high-risk hereditary cancer syndrome.

Innate immune response during Yersinia infection: critical modulation of cell death mechanisms through phagocyte activation.

PubMed

Bergsbaken, Tessa; Cookson, Brad T

2009-11-01

Yersinia pestis, the etiological agent of plague, is one of the most deadly pathogens on our planet. This organism shares important attributes with its ancestral progenitor, Yersinia pseudotuberculosis, including a 70-kb virulence plasmid, lymphotropism during growth in the mammalian host, and killing of host macrophages. Infections with both organisms are biphasic, where bacterial replication occurs initially with little inflammation, followed by phagocyte influx, inflammatory cytokine production, and tissue necrosis. During infection, plasmid-encoded attributes facilitate bacterial-induced macrophage death, which results from two distinct processes and corresponds to the inflammatory crescendo observed in vivo: Naïve cells die by apoptosis (noninflammatory), and later in infection, activated macrophages die by pyroptosis (inflammatory). The significance of this redirected cell death for the host is underscored by the importance of phagocyte activation for immunity to Yersinia and the protective role of pyroptosis during host responses to anthrax lethal toxin and infections with Francisella, Legionella, Pseudomonas, and Salmonella. The similarities of Y. pestis and Y. pseudotuberculosis, including conserved, plasmid-encoded functions inducing at least two distinct mechanisms of cell death, indicate that comparative studies are revealing about their critical pathogenic mechanism(s) and host innate immune responses during infection. Validation of this idea and evidence of similar interactions with the host immune system are provided by Y. pseudotuberculosis-priming, cross-protective immunity against Y. pestis. Despite these insights, additional studies indicate much remains to be understood concerning effective host responses against Yersinia, including chromosomally encoded attributes that also contribute to bacterial evasion and modulation of innate and adaptive immune responses.

ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective.

PubMed

Chang, Jeffrey S; Hsiao, Jenn-Ren; Chen, Che-Hong

2017-03-03

The occurrence of more than 200 diseases, including cancer, can be attributed to alcohol drinking. The global cancer deaths attributed to alcohol-consumption rose from 243,000 in 1990 to 337,400 in 2010. In 2010, cancer deaths due to alcohol consumption accounted for 4.2% of all cancer deaths. Strong epidemiological evidence has established the causal role of alcohol in the development of various cancers, including esophageal cancer, head and neck cancer, liver cancer, breast cancer, and colorectal cancer. The evidence for the association between alcohol and other cancers is inconclusive. Because of the high prevalence of ALDH2*2 allele among East Asian populations, East Asians may be more susceptible to the carcinogenic effect of alcohol, with most evidence coming from studies of esophageal cancer and head and neck cancer, while data for other cancers are more limited. The high prevalence of ALDH2*2 allele in East Asian populations may have important public health implications and may be utilized to reduce the occurrence of alcohol-related cancers among East Asians, including: 1) Identification of individuals at high risk of developing alcohol-related cancers by screening for ALDH2 polymorphism; 2) Incorporation of ALDH2 polymorphism screening into behavioral intervention program for promoting alcohol abstinence or reducing alcohol consumption; 3) Using ALDH2 polymorphism as a prognostic indicator for alcohol-related cancers; 4) Targeting ALDH2 for chemoprevention; and 5) Setting guidelines for alcohol consumption among ALDH2 deficient individuals. Future studies should evaluate whether these strategies are effective for preventing the occurrence of alcohol-related cancers.

Garcinia xanthochymus Benzophenones Promote Hyphal Apoptosis and Potentiate Activity of Fluconazole against Candida albicans Biofilms

PubMed Central

Jackson, Desmond N.; Yang, Lin; Wu, ShiBiao; Kennelly, Edward J.

2015-01-01

Xanthochymol and garcinol, isoprenylated benzophenones purified from Garcinia xanthochymus fruits, showed multiple activities against Candida albicans biofilms. Both compounds effectively prevented emergence of fungal germ tubes and were also cytostatic, with MICs of 1 to 3 μM. The compounds therefore inhibited development of hyphae and subsequent biofilm maturation. Xanthochymol treatment of developing and mature biofilms induced cell death. In early biofilm development, killing had the characteristics of apoptosis, including externalization of phosphatidyl serine and DNA fragmentation, as evidenced by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) fluorescence. These activities resulted in failure of biofilm maturation and hyphal death in mature biofilms. In mature biofilms, xanthochymol and garcinol caused the death of biofilm hyphae, with 50% effective concentrations (EC50s) of 30 to 50 μM. Additionally, xanthochymol-mediated killing was complementary with fluconazole against mature biofilms, reducing the fluconazole EC50 from >1,024 μg/ml to 13 μg/ml. Therefore, xanthochymol has potential as an adjuvant for antifungal treatments as well as in studies of fungal apoptosis. PMID:26195512

In vitro cytotoxic effects of benzalkonium chloride in corticosteroid injection suspension.

PubMed

Davis, Daniel; Cyriac, Mathew; Ge, Dongxia; You, Zongbing; Savoie, Felix H

2010-01-01

Some deleterious effects on cartilage and even severe arthropathy have been reported after intra-articular corticosteroid injections. The objective of the present in vitro study was to determine if an injectable corticosteroid suspension is toxic to articular chondrocytes and synovial cells. Human and bovine articular chondrocytes, bovine synovial cells, mouse C3H10T1/2 cells, and human osteosarcoma MG-63 cells were treated for thirty minutes in monolayer or suspension culture with an injectable corticosteroid suspension or its chemical components, including betamethasone sodium phosphate, betamethasone acetate, and benzalkonium chloride (as preservative). Cell viability was determined by means of microscopy or flow cytometry analysis. In monolayer culture, the betamethasone corticosteroids per se did not cause cell death, whereas benzalkonium chloride caused death of articular chondrocytes. In suspension culture, betamethasone sodium phosphate at dosages of as high as 6 mg/mL did not cause significant death of human or bovine articular chondrocytes (p > 0.05). In contrast, benzalkonium chloride caused a death rate of 10.6% in human articular chondrocytes at a dosage of 10 microg/mL (p < 0.01), 21.0% at a dosage of 13.3 microg/mL (p < 0.01), and 99.3% and 99.4% at dosages of 20 and 200 microg/mL, respectively (p < 0.001 for both). Similarly, benzalkonium chloride caused death of bovine articular chondrocytes, bovine synovial cells, C3H10T1/2 cells, and MG-63 cells in a dose-dependent manner. When treated with a combination of betamethasone sodium phosphate and 200 microg/mL benzalkonium chloride, >99% of human or bovine articular chondrocytes were dead (p < 0.001). The injectable corticosteroid suspension caused death in in vitro culture of human and bovine articular chondrocytes as well as bovine synovial cells because of its preservative benzalkonium chloride. The betamethasone corticosteroids per se did not cause significant chondrocyte death under the conditions tested.

Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial.

PubMed

McMurray, John J V; Ezekowitz, Justin A; Lewis, Basil S; Gersh, Bernard J; van Diepen, Sean; Amerena, John; Bartunek, Jozef; Commerford, Patrick; Oh, Byung-Hee; Harjola, Veli-Pekka; Al-Khatib, Sana M; Hanna, Michael; Alexander, John H; Lopes, Renato D; Wojdyla, Daniel M; Wallentin, Lars; Granger, Christopher B

2013-05-01

We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin. The risk of a number of outcomes, including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding, or death (net clinical benefit) were calculated in 3 patient groups: (1) no HF/no LVSD (n=8728), (2) HF/no LVSD (n=3207), and (3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding, or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24), and lowest in patients without HF or LVSD (1.54; 5.27); each comparison P<0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death was 0.89 (95% confidence interval, 0.81-0.98; P=0.02); for SSE, major bleed, or death it was 0.85 (0.78-0.92; P<0.001). There was no heterogeneity of treatment effect across the 3 groups. Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Cellular Stress and p53-Associated Apoptosis by Juniperus communis L. Berry Extract Treatment in the Human SH-SY5Y Neuroblastoma Cells.

PubMed

Lantto, Tiina A; Laakso, Into; Dorman, H J Damien; Mauriala, Timo; Hiltunen, Raimo; Kõks, Sulev; Raasmaja, Atso

2016-07-13

Plant phenolics have shown to activate apoptotic cell death in different tumourigenic cell lines. In this study, we evaluated the effects of juniper berry extract (Juniperus communis L.) on p53 protein, gene expression and DNA fragmentation in human neuroblastoma SH-SY5Y cells. In addition, we analyzed the phenolic composition of the extract. We found that juniper berry extract activated cellular relocalization of p53 and DNA fragmentation-dependent cell death. Differentially expressed genes between treated and non-treated cells were evaluated with the cDNA-RDA (representational difference analysis) method at the early time point of apoptotic process when p53 started to be activated and no caspase activity was detected. Twenty one overexpressed genes related to cellular stress, protein synthesis, cell survival and death were detected. Interestingly, they included endoplasmic reticulum (ER) stress inducer and sensor HSPA5 and other ER stress-related genes CALM2 and YKT6 indicating that ER stress response was involved in juniper berry extract mediated cell death. In composition analysis, we identified and quantified low concentrations of fifteen phenolic compounds. The main groups of them were flavones, flavonols, phenolic acids, flavanol and biflavonoid including glycosides of quercetin, apigenin, isoscutellarein and hypolaetin. It is suggested that juniper berry extract induced the p53-associated apoptosis through the potentiation and synergism by several phenolic compounds.

A randomized trial of one versus three doses of Augmentin as wound prophylaxis in at-risk abdominal surgery.

PubMed Central

Bates, T.; Roberts, J. V.; Smith, K.; German, K. A.

1992-01-01

In a randomized prospective trial of prophylactic antibiotics in at-risk abdominal surgery, one dose of intravenous Augmentin (amoxycillin 250 mg and clavulanic acid 125 mg) on induction has been compared with three 8 hourly doses in 900 patients. Wound infection rates which included minor and delayed infections were very similar in those given one dose: 48/449 (10.7%) compared with those given three doses: 49/451 (10.9%) 95% confidence limits - 4.25% + 3.9%. There were more septic and sepsis-related deaths in those patients given one dose (14 deaths) than in those given three doses (7 deaths) P > 0.1 95% CL - 0.4% + 3.0%. However, there were more very elderly patients in the one dose group: 64% of the deaths were aged over 80 and all but one had an emergency operation. There was no difference in the other outcome measures studied which included non-fatal deep sepsis, length of postoperative hospital stay, duration of postoperative fever or the use of antibiotics for postoperative infection. One dose of a suitable intravenous antibiotic gives prophylaxis against wound infection in at-risk abdominal surgery which is at least as effective as multiple doses. However, there may be a risk of overwhelming systemic sepsis in very elderly patients having emergency surgery. PMID:1461853

Illnesses and deaths among persons attending an electronic dance-music festival - New York City, 2013.

PubMed

Ridpath, Alison; Driver, Cynthia R; Nolan, Michelle L; Karpati, Adam; Kass, Daniel; Paone, Denise; Jakubowski, Andrea; Hoffman, Robert S; Nelson, Lewis S; Kunins, Hillary V

2014-12-19

Outdoor electronic dance-music festivals (EDMFs) are typically summer events where attendees can dance for hours in hot temperatures. EDMFs have received increased media attention because of their growing popularity and reports of illness among attendees associated with recreational drug use. MDMA (3,4-methylenedioxymethamphetamine) is one of the drugs often used at EDMFs. MDMA causes euphoria and mental stimulation but also can cause serious adverse effects, including hyperthermia, seizures, hyponatremia, rhabdomyolysis, and multiorgan failure. In this report, MDMA and other synthetic drugs commonly used at dance festivals are referred to as "synthetic club drugs." On September 1, 2013, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) received reports of two deaths of attendees at an EDMF (festival A) held August 31-September 1 in NYC. DOHMH conducted an investigation to identify and characterize adverse events resulting in emergency department (ED) visits among festival A attendees and to determine what drugs were associated with these adverse events. The investigation identified 22 cases of adverse events; nine cases were severe, including two deaths. Twenty-one (95%) of the 22 patients had used drugs or alcohol. Of 17 patients with toxicology testing, MDMA and other compounds were identified, most frequently methylone, in 11 patients. Public health messages and strategies regarding adverse health events might reduce illnesses and deaths at EDMFs.

The near death experience: observations and reflections from a retired chaplain.

PubMed

Nelson, H R

2000-01-01

In this article I have attempted to draw connections between the near-death experience, biblical spirituality, and the ministry of the spiritual caregiver. Also, I have described the near-death phenomena and given particular emphasis to the dying and death processes, including the offering of guidelines for approaching death. In my ministry and studies, I have come to believe that the near-death experience prepares us not only to die but to live life to the fullest until we say good-bye.

Transfemoral, transapical and transcatheter aortic valve implantation and surgical aortic valve replacement: a meta-analysis of direct and adjusted indirect comparisons of early and mid-term deaths.

PubMed

Ando, Tomo; Takagi, Hisato; Grines, Cindy L

2017-09-01

Clinical outcomes of transfemoral-transcatheter aortic valve implantation (TF-TAVI) versus surgical aortic valve replacement (SAVR) or transapical (TA)-TAVI are limited to a few randomized clinical trials (RCTs). Because previous meta-analyses only included a limited number of adjusted studies or several non-adjusted studies, our goal was to compare and summarize the outcomes of TF-TAVI vs SAVR and TF-TAVI vs TA-TAVI exclusively with the RCT and propensity-matched cohort studies with direct and adjusted indirect comparisons to reach more precise conclusions. We hypothesized that TF-TAVI would offer surgical candidates a better outcome compared with SAVR and TA-TAVI because of its potential for fewer myocardial injuries. A literature search was conducted through PUBMED and EMBASE through June 2016. Only RCTs and propensity-matched cohort studies were included. A direct meta-analysis of TF-TAVI vs SAVR, TA-TAVI vs SAVR and TF-TAVI vs TA-TAVI was conducted. Then, the effect size of an indirect meta-analysis was calculated from the direct meta-analysis. The effect sizes of direct and indirect meta-analyses were then combined. A random-effects model was used to calculate the hazards ratio and the odds ratio with 95% confidence intervals. Early (in-hospital or 30 days) and mid-term (≥1 year) all-cause mortality rates were assessed. Our search resulted in 4 RCTs (n = 2319) and 14 propensity-matched cohort (n = 7217) studies with 9536 patients of whom 3471, 1769 and 4296 received TF, TA and SAVR, respectively. Direct meta-analyses and combined direct and indirect meta-analyses of early and mid-term deaths with TF-TAVI and SAVR were similar. Early deaths with TF-TAVI vs TA-TAVI were comparable in direct meta-analyses (odds ratio 0.64, P = 0.35) and direct and indirect meta-analyses combined (odds ratio 0.73, P = 0.24). Mid-term deaths with TF-TAVI vs TA-TAVI were increased (hazard ratio 0.83, P = 0.07) in a direct meta-analysis and became significant after addition of the indirect meta-analysis (hazard ratio 0.78, 95% confidence interval 0.67-0.92, P = 0.003). In conclusion, TF-TAVI was associated with similar early and mid-term deaths compared with SAVR. The number of early deaths was not significantly different between TF-TAVI and TA-TAVI, whereas there were fewer mid-term deaths with TF-TAVI than with TA-TAVI. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Proceedings of the sudden oak death second science symposium: the state of our knowledge

Treesearch

Susan J. Frankel; Patrick J. Shea; Michael I. Haverty

2006-01-01

The Sudden Oak Death Second Science Symposium provided a forum for current research on sudden oak death, caused by the exotic, quarantine pathogen, Phytophthora ramorum. Ninety papers and forty-six posters on the following sudden oak death/P. ramorum topics are included: biology, genetics, nursery and wildland management,...

26 CFR 1.652(c)-2 - Death of individual beneficiaries.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Death of individual beneficiaries. 1.652(c)-2... Death of individual beneficiaries. If income is required to be distributed currently to a beneficiary... beneficiary (because of the beneficiary's death), the extent to which the income is included in the gross...

26 CFR 1.652(c)-2 - Death of individual beneficiaries.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Death of individual beneficiaries. 1.652(c)-2... Death of individual beneficiaries. If income is required to be distributed currently to a beneficiary... beneficiary (because of the beneficiary's death), the extent to which the income is included in the gross...

26 CFR 1.652(c)-2 - Death of individual beneficiaries.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Death of individual beneficiaries. 1.652(c)-2... Death of individual beneficiaries. If income is required to be distributed currently to a beneficiary... beneficiary (because of the beneficiary's death), the extent to which the income is included in the gross...

26 CFR 1.652(c)-2 - Death of individual beneficiaries.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Death of individual beneficiaries. 1.652(c)-2... Death of individual beneficiaries. If income is required to be distributed currently to a beneficiary... beneficiary (because of the beneficiary's death), the extent to which the income is included in the gross...

Two decades of terror management theory: a meta-analysis of mortality salience research.

PubMed

Burke, Brian L; Martens, Andy; Faucher, Erik H

2010-05-01

A meta-analysis was conducted on empirical trials investigating the mortality salience (MS) hypothesis of terror management theory (TMT). TMT postulates that investment in cultural worldviews and self-esteem serves to buffer the potential for death anxiety; the MS hypothesis states that, as a consequence, accessibility of death-related thought (MS) should instigate increased worldview and self-esteem defense and striving. Overall, 164 articles with 277 experiments were included. MS yielded moderate effects (r = .35) on a range of worldview- and self-esteem-related dependent variables (DVs), with effects increased for experiments using (a) American participants, (b) college students, (c) a longer delay between MS and the DV, and (d) people-related attitudes as the DV. Gender and self-esteem may moderate MS effects differently than previously thought. Results are compared to other reviews and examined with regard to alternative explanations of TMT. Finally, suggestions for future research are offered.

Late Maternal Deaths and Deaths from Sequelae of Obstetric Causes in the Americas from 1999 to 2013: A Trend Analysis.

PubMed

de Cosio, Federico G; Jiwani, Safia S; Sanhueza, Antonio; Soliz, Patricia N; Becerra-Posada, Francisco; Espinal, Marcos A

2016-01-01

Data on maternal deaths occurring after the 42 days postpartum reference time is scarce; the objective of this analysis is to explore the trend and magnitude of late maternal deaths and deaths from sequelae of obstetric causes in the Americas between 1999 and 2013, and to recommend including these deaths in the monitoring of the Sustainable Development Goals (SDGs). Exploratory data analysis enabled analyzing the magnitude and trend of late maternal deaths and deaths from sequelae of obstetric causes for seven countries of the Americas: Argentina, Brazil, Canada, Colombia, Cuba, Mexico and the United States. A Poisson regression model was developed to compare trends of late maternal deaths and deaths from sequelae of obstetric causes between two periods of time: 1999 to 2005 and 2006 to 2013; and to estimate the relative increase of these deaths in the two periods of time. The proportion of late maternal deaths and deaths from sequelae of obstetric causes ranged between 2.40% (CI 0.85% - 5.48%) and 18.68% (CI 17.06% - 20.47%) in the seven countries. The ratio of late maternal deaths and deaths from sequelae of obstetric causes per 100,000 live births has increased by two times in the region of the Americas in the period 2006-2013 compared to the period 1999-2005. The regional relative increase of late maternal death was 2.46 (p<0.0001) times higher in the second period compared to the first. Ascertainment of late maternal deaths and deaths from sequelae of obstetric causes has improved in the Americas since the early 2000's due to improvements in the quality of information and the obstetric transition. Late and obstetric sequelae maternal deaths should be included in the monitoring of the SDGs as well as in the revision of the International Classification of Diseases' 11th version (ICD-11).

Late Maternal Deaths and Deaths from Sequelae of Obstetric Causes in the Americas from 1999 to 2013: A Trend Analysis

PubMed Central

de Cosio, Federico G.; Sanhueza, Antonio; Soliz, Patricia N.; Becerra-Posada, Francisco; Espinal, Marcos A.

2016-01-01

Background Data on maternal deaths occurring after the 42 days postpartum reference time is scarce; the objective of this analysis is to explore the trend and magnitude of late maternal deaths and deaths from sequelae of obstetric causes in the Americas between 1999 and 2013, and to recommend including these deaths in the monitoring of the Sustainable Development Goals (SDGs). Methods Exploratory data analysis enabled analyzing the magnitude and trend of late maternal deaths and deaths from sequelae of obstetric causes for seven countries of the Americas: Argentina, Brazil, Canada, Colombia, Cuba, Mexico and the United States. A Poisson regression model was developed to compare trends of late maternal deaths and deaths from sequelae of obstetric causes between two periods of time: 1999 to 2005 and 2006 to 2013; and to estimate the relative increase of these deaths in the two periods of time. Findings The proportion of late maternal deaths and deaths from sequelae of obstetric causes ranged between 2.40% (CI 0.85% – 5.48%) and 18.68% (CI 17.06% – 20.47%) in the seven countries. The ratio of late maternal deaths and deaths from sequelae of obstetric causes per 100,000 live births has increased by two times in the region of the Americas in the period 2006-2013 compared to the period 1999-2005. The regional relative increase of late maternal death was 2.46 (p<0.0001) times higher in the second period compared to the first. Interpretation Ascertainment of late maternal deaths and deaths from sequelae of obstetric causes has improved in the Americas since the early 2000’s due to improvements in the quality of information and the obstetric transition. Late and obstetric sequelae maternal deaths should be included in the monitoring of the SDGs as well as in the revision of the International Classification of Diseases’ 11th version (ICD-11). PMID:27626277

Neurotox-98 Neuroprotection by Progesterones Through Stimulation of Mitochondrial Gene Expression

DTIC Science & Technology

2006-06-01

excitotoxicity that leads to neuronal cell loss. However, surprisingly little is known of the mechanism for this effect . The working hypothesis for the...regulation that is independent of energy status of the cell . Although not included in the publication, we tested for effects of progesterone on... effects (Goodman et al., 1996); however, high levels of progesterone did nothing to protect the animals from seizures or neuronal cell death. In summary

The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials

PubMed Central

Preiss, David; Campbell, Ross T.; Murray, Heather M.; Ford, Ian; Packard, Chris J.; Sattar, Naveed; Rahimi, Kazem; Colhoun, Helen M.; Waters, David D.; LaRosa, John C.; Amarenco, Pierre; Pedersen, Terje R.; Tikkanen, Matti J.; Koren, Michael J.; Poulter, Neil R.; Sever, Peter S.; Ridker, Paul M.; MacFadyen, Jean G.; Solomon, Scott D.; Davis, Barry R.; Simpson, Lara M.; Nakamura, Haruo; Mizuno, Kyoichi; Marfisi, Rosa M.; Marchioli, Roberto; Tognoni, Gianni; Athyros, Vasilios G.; Ray, Kausik K.; Gotto, Antonio M.; Clearfield, Michael B.; Downs, John R.; McMurray, John J.

2015-01-01

Aims The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events. Methods and results We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring <30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects meta-analyses. In up to 17 trials with 132 538 participants conducted over 4.3 [weighted standard deviation (SD) 1.4] years, statin therapy reduced LDL-cholesterol by 0.97 mmol/L (weighted SD 0.38 mmol/L). Statins reduced the numbers of patients experiencing non-fatal HF hospitalization (1344/66 238 vs. 1498/66 330; RR 0.90, 95% confidence interval, CI 0.84–0.97) and the composite HF outcome (1234/57 734 vs. 1344/57 836; RR 0.92, 95% CI 0.85–0.99) but not HF death (213/57 734 vs. 220/57 836; RR 0.97, 95% CI 0.80–1.17). The effect of statins on first non-fatal HF hospitalization was similar whether this was preceded by MI (RR 0.87, 95% CI 0.68–1.11) or not (RR 0.91, 95% CI 0.84–0.98). Conclusion In primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not. PMID:25802390

Pifithrin-α provides neuroprotective effects at the level of mitochondria independently of p53 inhibition.

PubMed

Neitemeier, Sandra; Ganjam, Goutham K; Diemert, Sebastian; Culmsee, Carsten

2014-12-01

Impaired mitochondrial integrity and function are key features of intrinsic death pathways in neuronal cells. Therefore, key regulators of intrinsic death pathways acting upstream of mitochondria are potential targets for therapeutic approaches of neuroprotection. The tumor suppressor p53 is a well-established regulator of cellular responses towards different kinds of lethal stress, including oxidative stress. Recent reports suggested that p53 may affect mitochondrial integrity and function through both, transcriptional activation of mitochondria-targeted pro-death proteins and direct effects at the mitochondrial membrane. In the present study, we compared the effects of pharmacological inhibition of p53 by pifithrin-α with those of selective p53 gene silencing by RNA interference. Using MTT assay and real-time cell impedance measurements we confirmed the protective effect of both strategies against glutamate-induced oxidative stress in immortalized mouse hippocampal HT-22 neurons. Further, we observed full restoration of mitochondrial membrane potential and inhibition of glutamate-induced mitochondrial fragmentation by pifithrin-α which was, in contrast, not achieved by p53 gene silencing. Downregulation of p53 by siRNA decreased p53 transcriptional activity and reduced expression levels of p21 mRNA, while pifithrin-α did not affect these endpoints. These results suggest a neuroprotective effect of pifithrin-α which occurred at the level of mitochondria and independently of p53 inhibition.

Global and regional health effects of future food production under climate change: a modelling study.

PubMed

Springmann, Marco; Mason-D'Croz, Daniel; Robinson, Sherman; Garnett, Tara; Godfray, H Charles J; Gollin, Douglas; Rayner, Mike; Ballon, Paola; Scarborough, Peter

2016-05-07

One of the most important consequences of climate change could be its effects on agriculture. Although much research has focused on questions of food security, less has been devoted to assessing the wider health impacts of future changes in agricultural production. In this modelling study, we estimate excess mortality attributable to agriculturally mediated changes in dietary and weight-related risk factors by cause of death for 155 world regions in the year 2050. For this modelling study, we linked a detailed agricultural modelling framework, the International Model for Policy Analysis of Agricultural Commodities and Trade (IMPACT), to a comparative risk assessment of changes in fruit and vegetable consumption, red meat consumption, and bodyweight for deaths from coronary heart disease, stroke, cancer, and an aggregate of other causes. We calculated the change in the number of deaths attributable to climate-related changes in weight and diets for the combination of four emissions pathways (a high emissions pathway, two medium emissions pathways, and a low emissions pathway) and three socioeconomic pathways (sustainable development, middle of the road, and more fragmented development), which each included six scenarios with variable climatic inputs. The model projects that by 2050, climate change will lead to per-person reductions of 3·2% (SD 0·4%) in global food availability, 4·0% (0·7%) in fruit and vegetable consumption, and 0·7% (0·1%) in red meat consumption. These changes will be associated with 529,000 climate-related deaths worldwide (95% CI 314,000-736,000), representing a 28% (95% CI 26-33) reduction in the number of deaths that would be avoided because of changes in dietary and weight-related risk factors between 2010 and 2050. Twice as many climate-related deaths were associated with reductions in fruit and vegetable consumption than with climate-related increases in the prevalence of underweight, and most climate-related deaths were projected to occur in south and east Asia. Adoption of climate-stabilisation pathways would reduce the number of climate-related deaths by 29-71%, depending on their stringency. The health effects of climate change from changes in dietary and weight-related risk factors could be substantial, and exceed other climate-related health impacts that have been estimated. Climate change mitigation could prevent many climate-related deaths. Strengthening of public health programmes aimed at preventing and treating diet and weight-related risk factors could be a suitable climate change adaptation strategy. Oxford Martin Programme on the Future of Food. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prediction of mode of death in heart failure: the Seattle Heart Failure Model.

PubMed

Mozaffarian, Dariush; Anker, Stefan D; Anand, Inder; Linker, David T; Sullivan, Mark D; Cleland, John G F; Carson, Peter E; Maggioni, Aldo P; Mann, Douglas L; Pitt, Bertram; Poole-Wilson, Philip A; Levy, Wayne C

2007-07-24

Prognosis and mode of death in heart failure patients are highly variable in that some patients die suddenly (often from ventricular arrhythmia) and others die of progressive failure of cardiac function (pump failure). Prediction of mode of death may facilitate decisions about specific medications or devices. We used the Seattle Heart Failure Model (SHFM), a validated prediction model for total mortality in heart failure, to assess the mode of death in 10,538 ambulatory patients with New York Heart Association class II to IV heart failure and predominantly systolic dysfunction enrolled in 6 randomized trials or registries. During 16,735 person-years of follow-up, 2014 deaths occurred, which included 1014 sudden deaths and 684 pump-failure deaths. Compared with a SHFM score of 0, patients with a score of 1 had a 50% higher risk of sudden death, patients with a score of 2 had a nearly 3-fold higher risk, and patients with a score of 3 or 4 had a nearly 7-fold higher risk (P<0.001 for all comparisons; 1-year area under the receiver operating curve, 0.68). Stratification of risk of pump-failure death was even more pronounced, with a 4-fold higher risk with a score of 1, a 15-fold higher risk with a score of 2, a 38-fold higher risk with a score of 3, and an 88-fold higher risk with a score of 4 (P<0.001 for all comparisons; 1-year area under the receiver operating curve, 0.85). The proportion of deaths caused by sudden death versus pump-failure death decreased from a ratio of 7:1 with a SHFM score of 0 to a ratio of 1:2 with a SHFM score of 4 (P trend <0.001). The SHFM score provides information about the likely mode of death among ambulatory heart failure patients. Investigation is warranted to determine whether such information might predict responses to or cost-effectiveness of specific medications or devices in heart failure patients.

Bassinet Use and Sudden Unexpected Death in Infancy

PubMed Central

Pike, Jodi; Moon, Rachel Y.

2008-01-01

Objective To analyze risk factors of infants who die suddenly and unexpectedly in bassinets. Study design Retrospective review of all deaths of infants involving bassinets reported to the Consumer Product Safety Commission (CPSC) in 1990–2004. Results Of 53 deaths, the mean age at death was 84 days. The cause of death in 85% was anoxia, asphyxiation, or suffocation; SIDS was the cause of death in 9.4%. 37% were placed prone for sleep, and half were found prone. Additional items, including soft bedding, were noted in 74%. In 17%, specific mechanical problems with the bassinets were noted. Conclusions The risk of sudden unexpected death in infancy in bassinets can be reduced by following American Academy of Pediatrics (AAP) guidelines, including use of supine positioning and avoidance of soft bedding within the bassinet. Additionally, parents must assure that the bassinet is mechanically sound, and that objects that can lead to suffocation are not in or near the bassinet. PMID:18582899

Photodynamic Cancer Therapy—Recent Advances

NASA Astrophysics Data System (ADS)

Abrahamse, Heidi

2011-09-01

The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when "photoradiation therapy" was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular localization of PS is of vital importance when cell death mechanism is identified. Programmed cell death (PCD) viz. apoptosis, necrosis and autophagy have all been identified as inducible cell death mechanisms during PDT. While apoptosis is probably the preferred cell death mechanism, understanding the molecular differences and identifying the cross-talk between these mechanisms are crucial to the development of new PSs aimed at improving the killing efficiency and overall effectiveness of PDT as a cancer treatment modality. This paper reviews the process of PDT cancer therapy, the available PSs, their effectiveness for different cancers as well as the cell death mechanisms identified during PDT of different cancers associated with specific PSs.

Photodynamic Cancer Therapy - Recent Advances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abrahamse, Heidi

The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when 'photoradiation therapy' was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first ormore » second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular localization of PS is of vital importance when cell death mechanism is identified. Programmed cell death (PCD) viz. apoptosis, necrosis and autophagy have all been identified as inducible cell death mechanisms during PDT. While apoptosis is probably the preferred cell death mechanism, understanding the molecular differences and identifying the cross-talk between these mechanisms are crucial to the development of new PSs aimed at improving the killing efficiency and overall effectiveness of PDT as a cancer treatment modality. This paper reviews the process of PDT cancer therapy, the available PSs, their effectiveness for different cancers as well as the cell death mechanisms identified during PDT of different cancers associated with specific PSs.« less