California's male suicide rate at record high.

Breast cancer is the most commonly occurring cancer in women and, until recently surpassed by lung cancer, was the leading cause of cancer-related death in women. It is the leading cause of death in women aged 39 to 44 years. The American Cancer Society has estimated that there will be 135,000 new cases of breast cancer and 42,300 breast cancer-related deaths in 1988. It is now predicted that breast cancer will develop in one out of every ten women in the United States. Given the clinical and public health significance of breast cancer, annual screening with mammography and clinical breast examination is recommended for women aged 50 and older to reduce breast cancer mortality.     

Death certification and epidemiological research. Medical Services Study Group of the Royal College of Physicians of London.

The cause of death shown on 191 death certificates was compared with the cause indicated by the hospital case notes, the consultants'' opinions, and the necropsy findings. All 191 deaths occurred among medical hospital patients aged under 50. In 39 cases there was a major discrepancy between the two sources over the cause of death and in another 54 ther was a minor but epidemiologically important difference. Death certificates are not primarily intended for epidemiological research, but researchers often rely on them. This and other studies have shown, however, that death certificates are often inaccurate records of the cause of death--even coroner''s certificates issued after a coroner''s necropsy. The accuracy of death certificates might be improved if coroners consulted clinicians more closely and if senior hospital staff completed hospital death certificates.     

Community study of the causes of "natural" sudden death.

Three hundred and fifty cases of "natural" sudden death within six hours of onset of symptoms in people ranging in age from 18 to 69 years in Wandsworth were studied using a detailed necropsy protocol to determine the cause of death. Sudden death occurred in 28 (8%) Asians and blacks, but because of the small number they were excluded from the study, leaving 322 cases. Ischaemic heart disease accounted for 189 (59%) of the 322 sudden deaths (155 (65%) men; 34 (41%) women) and no proportional increase in instantaneous compared with non-instantaneous sudden death was found. Non-ischaemic cardiac disease was the cause of sudden death in 24 cases (7.5%). Non-cardiac disease included pulmonary emboli, aortic aneurysms, and intracerebral haemorrhage and caused 89 (27.6%) deaths. Alcohol was the cause of nine deaths (2.8%) and in 11 (3.4%) cases (six men and five women) no cause of death was found. This study shows that although ischaemic heart disease is the single largest cause of sudden natural death there are other major causes.     

University acknowledges special risks,introduces drug program for anesthetists.

Anesthetists are at special risk for becoming addicted to some of the drugs they work with. The problem was highlighted by the recent death of a physician in Comox, BC, and a doctor''s brush with death at a hospital near Ottawa. The University of Ottawa has responded with a program, the professional Assistance Program for the Impaired or Disabled Physician, that is in the final stages of approval. Although it will be aimed initially at anesthetists and anesthesia residents in the university''s teaching hospitals, there are hopes the program will spread eventually to other medical departments.     

Death from asthma.

The factors associated with the deaths of 31 asthma patients were examined. The subjects, whose deaths occurred in the period 1967 through 1979, had all received some care at the Hospital for Sick Children in Toronto, but only nine died there. The greatest single cause of death was the inappropriate use of beta-agonists, with or without the concurrent use of epinephrine. In seven patients an asthma attack that occurred outside hospital progressed so rapidly that there was insufficient time for them to obtain adequate therapy. In five cases the assessment of the patient''s condition or the therapy recommended by the attending physician appeared to have been inadequate. Two patients suffered an acute attack in hopital and did not respond to treatment that appeared to have been adequate. In six cases the available information was insufficient to indicate the cause of death. Over half (18) of the deaths occurred in teenagers. Various ways of preventing death from asthma are discussed, including better education of physicians and patients, adequate management of factors that provoke bronchospasm, sufficient follow-up -- especially in teenagers -- and the use of approaches with teenagers that encourage better compliance.     

Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study.

OBJECTIVE--To estimate the prevalence of dementia and its subtypes in the general population and examine the relation of the disease to education. DESIGN--Population based cross sectional study. SETTING--Ommoord, a suburb of Rotterdam. SUBJECTS--7528 participants of the Rotterdam study aged 55-106 years. RESULTS--474 cases of dementia were detected, giving an overall prevalence of 6.3%. Prevalence ranged from 0.4% (5/1181 subjects) at age 55-59 years to 43.2% (19/44) at 95 years and over. Alzheimer''s disease was the main subdiagnosis (339 cases; 72%); it was also the main cause of the pronounced increase in dementia with age. The relative proportion of vascular dementia (76 cases; 16%), Parkinson''s disease dementia (30; 6%), and other dementias (24; 5%) decreased with age. A substantially higher prevalence of dementia was found in subjects with a low level of education. The association with education was not due to confounding by cardiovascular disease. CONCLUSIONS--The prevalence of dementia increases exponentially with age. About one third of the population aged 85 and over has dementia. Three quarters of all dementia is due to Alzheimer''s disease. In this study an inverse dose-response relation was found between education and dementia--in particular, Alzheimer''s disease.     

Evaluation of cause of deaths' validity using outcome measures from a prospective, population based cohort study in Tehran, Iran

Objective

The aim of this study was to evaluate the validity of cause of death stated in death certificates in Tehran using outcome measures of the Tehran Lipid and Glucose Study (TLGS), an ongoing prospective cohort study.

Methods

The cohort was established in 1999 in a population of 15005 people, 3 years old and over, living in Tehran; 3551 individuals were added to this population three years later. As part of cohort''s outcome measures, deaths occurring in the cohort are investigated by a panel of medical specialists (Cohort Outcome Panel-COP) and underlying cause of death is determined for each death. The cause of death assigned in a deceased''s original death certificate was evaluated against the cause of death determined by COP and sensitivity and positive predictive values (PPV) were determined. In addition, determinants of assigning accurate underlying cause of death were determined using logistic regression model.

Result

A total of 231 death certificates were evaluated. The original death certificates over reported deaths due to neoplasms and underreported death due to circulatory system and transport accidents. Neoplasms with sensitivity of 0.91 and PPV of 0.71 were the most valid category. The disease of circulatory system showed moderate degree of validity with sensitivity of 0.67 and PPV of 0.78. The result of logistic regression indicated if the death certificate is issued by a general practitioner, there is 2.3 (95% CI 1.1, 5.1) times chance of being misclassified compared with when it is issued by a specialist. If the deceased is more than 60 years, the chance of misclassification would be 2.5 times (95% CI of 1.1, 5.9) compared with when the deceased is less than 60 years.     

Validation of the symptom pattern method for analyzing verbal autopsy data

Background

Cause of death data are a critical input to formulating good public health policy. In the absence of reliable vital registration data, information collected after death from household members, called verbal autopsy (VA), is commonly used to study causes of death. VA data are usually analyzed by physician-coded verbal autopsy (PCVA). PCVA is expensive and its comparability across regions is questionable. Nearly all validation studies of PCVA have allowed physicians access to information collected from the household members'' recall of medical records or contact with health services, thus exaggerating accuracy of PCVA in communities where few deaths had any interaction with the health system. In this study we develop and validate a statistical strategy for analyzing VA data that overcomes the limitations of PCVA.

Methods and Findings

We propose and validate a method that combines the advantages of methods proposed by King and Lu, and Byass, which we term the symptom pattern (SP) method. The SP method uses two sources of VA data. First, it requires a dataset for which we know the true cause of death, but which need not be representative of the population of interest; this dataset might come from deaths that occur in a hospital. The SP method can then be applied to a second VA sample that is representative of the population of interest. From the hospital data we compute the properties of each symptom; that is, the probability of responding yes to each symptom, given the true cause of death. These symptom properties allow us first to estimate the population-level cause-specific mortality fractions (CSMFs), and to then use the CSMFs as an input in assigning a cause of death to each individual VA response. Finally, we use our individual cause-of-death assignments to refine our population-level CSMF estimates. The results from applying our method to data collected in China are promising. At the population level, SP estimates the CSMFs with 16% average relative error and 0.7% average absolute error, while PCVA results in 27% average relative error and 1.1% average absolute error. At the individual level, SP assigns the correct cause of death in 83% of the cases, while PCVA does so for 69% of the cases. We also compare the results of SP and PCVA when both methods have restricted access to the information from the medical record recall section of the VA instrument. At the population level, without medical record recall, the SP method estimates the CSMFs with 14% average relative error and 0.6% average absolute error, while PCVA results in 70% average relative error and 3.2% average absolute error. For individual estimates without medical record recall, SP assigns the correct cause of death in 78% of cases, while PCVA does so for 38% of cases.

Conclusions

Our results from the data collected in China suggest that the SP method outperforms PCVA, both at the population and especially at the individual level. Further study is needed on additional VA datasets in order to continue validation of the method, and to understand how the symptom properties vary as a function of culture, language, and other factors. Our results also suggest that PCVA relies heavily on household recall of medical records and related information, limiting its applicability in low-resource settings. SP does not require that additional information to adequately estimate causes of death.     

Husbandry,morbidity, and mortality of slender‐tailed cloud rats (Phleomys pallidus)

The Wildlife Conservation Society's Bronx Zoo has been housing and breeding slender‐tailed cloud rats (Phleomys pallidus) since 1985. Records of 82 animals from 1985 to 2013 were reviewed for this study. The animals were kept successfully in small family groups with a single adult male, multiple adult females, and their offspring. Sexual maturity was noted at approximately 2 years of age and gestation length ranged from 52 to 55 days. Animals were fed a diet including a complete commercial pelleted feed, mixed greens, carrot or yam, mixed hard nuts, and locally sourced browse. Medical conditions requiring treatment in neonates were often fatal whereas most medical conditions in adults were survivable. The most common cause of morbidity and mortality in neonates was maternal neglect or trauma (42%, 5/12 antemortem problems; cause of death in 32%, 8/25). The most significant problems in adults were cryptococcal pneumonia and trauma. Cryptococcus sp. was the cause of death in 11 cases (34%, 11/32) and significant comorbidity in an additional three cases. Treatment with antifungal medications was attempted but was unsuccessful in four cases. Many cases of trauma were treated successfully with conservative management or limited intervention. In four cases, treatment was complicated by extensive self‐mutilation after surgical repair of traumatic lesions, which resulted in death or euthanasia. Lymphoplasmacytic thyroiditis was a common postmortem finding in adults (95%, 21/22 for which the thyroid gland was examined histologically). It is unclear if thyroiditis resulted in functional hypothyroidism so the significance of this finding is undetermined.     

Deaths from rhesus haemolytic disease in England and Wales in 1977: accuracy of records and assessment of anti-D prophylaxis.

All the death certificates for deaths in 1977 where haemolytic disease of the newborn (HDN) was the principal, an antecedent, or a contributory cause were obtained from the Office of Population Censuses and Surveys (OPCS). The hospital notes of all 54 of the live-born cases and all of the 101 stillbirths were also obtained. The cause of the death indicated by the notes was compared with the cause and coding on the death certificate. In about a quarter of the cases death was not due to haemolytic disease of any type. The commonest errors arose because the International Classification of Diseases (8th edition) stipulates that hydrops without mention of cause should be coded as HDN and because stillbirths to rhesus-negative mothers tend to be attributed to rhesus HDN automatically. Though deaths from HDN may be overestimated in this way, they are also underestimated because rhesus disease, although mentioned on the certificate, is not selected as the underlying cause, which it may be. These cases were found through multiple coding of all the contributory causes of death, which OPCS performs on a 25% sample of all death certificates for research purposes. These two sources of inaccuracy tend to cancel each other out, but statistics from death certificates give a misleading picture of the efficacy of anti-D prophylaxis because anti-D can never prevent cases which are not in fact due to rhesus HDN. Most of the mothers studied had become immunised before anti-D became available, but in those who could have been treated 75% had not received prophylaxis. As this was a sample of deaths, however, it would not be accurate to extrapolate this high figure to the population at risk. Nevertheless, the organisation of prophylaxis is clearly deficient and should be remedied before providing antenatal anti-D to supplement postnatal treatment.     

The evolution of virus-induced apoptosis.

Viruses from several different families are able to exploit their host''s cell death programmes so as to maximize viral fitness. Consideration of the evolution of such strategies has lead to the suggestion that the virus should inhibit apoptosis, in order to prolong the life of the cell and thereby maximize the number of progeny virions. The host, on the other hand, should stimulate apoptosis thereby inhibiting viral growth and blocking viral spread. For example, the function of the latent membrane protein I (LMPI) of the Epstein-Barr virus and the bcl-2 homologue gene A179L of African swine fever virus is to inhibit apoptosis. However, in other cases it is the virus that stimulates cell death or the host that benefits from inhibiting apoptosis, such as in fatal alphavirus encephalitis. This has been explained by assuming that virus-induced apoptosis in non-regenerating cells would be detrimental to the host. We present a mathematical framework for understanding virus-induced apoptosis which accounts for these two opposite solutions to virus infection with respect to the mode of virus replication and the life cycle of the target cell.     

Accuracy of clinical diagnosis in a Canadian teaching hospital.

Two hundred autopsies were investigated to determine the correlation between the clinical and pathological diagnoses in three categories--major underlying disease, cause of death and significant incidental pulmonary findings. There was concurrence in diagnosis of the major underlying disease in 76% of cases, with 12% of disagreements being considered minor and 12% major. In only three cases might different management have affected the outcome had the correct diagnosis of the major underlying disease been made during life. There was concurrence of the diagnosis of the cause of death (which was often different from the underlying disease) in 64% of cases, and in 10% of cases the outcome might have been different had the clinical diagnosis been accurate. The clinical opinion that lung disease was the cause of death was confirmed at autopsy in 54% of cases, and 45% of the pulmonary causes of death as determined at autopsy had been recognized clinically. Major incidental pulmonary findings diagnosed clinically were confirmed in 76% of cases, and major pulmonary findings diagnosed at autopsy had been recognized clinically in 83%. The major sources of these discrepancies were pulmonary embolism and pneumonia. If autopsies are to play a role in patient management, clinicians will have to be made aware of discrepancies between clinical and autopsy diagnosis. The real test of efficacy would be modification of patient management for the good.     

The role of tau in neurodegeneration

Since the identification of tau as the main component of neurofibrillary tangles in Alzheimer's disease and related tauopathies, and the discovery that mutations in the tau gene cause frontotemporal dementia, much effort has been directed towards determining how the aggregation of tau into fibrillar inclusions causes neuronal death. As evidence emerges that tau-mediated neuronal death can occur even in the absence of tangle formation, a growing number of studies are focusing on understanding how abnormalities in tau (e.g. aberrant phosphorylation, glycosylation or truncation) confer toxicity. Though data obtained from experimental models of tauopathies strongly support the involvement of pathologically modified tau and tau aggregates in neurodegeneration, the exact neurotoxic species remain unclear, as do the mechanism(s) by which they cause neuronal death. Nonetheless, it is believed that tau-mediated neurodegeneration is likely to result from a combination of toxic gains of function as well as from the loss of normal tau function. To truly appreciate the detrimental consequences of aberrant tau function, a better understanding of all functions carried out by tau, including but not limited to the role of tau in microtubule assembly and stabilization, is required. This review will summarize what is currently known regarding the involvement of tau in the initiation and development of neurodegeneration in tauopathies, and will also highlight some of the remaining questions in need of further investigation.     

Where Manitoba children obtain their cigarettes.

People who start to smoke as children put themselves at greater risk of dying prematurely or being disabled by tobacco-induced disease. One solution is to restrict children''s access to cigarettes, thereby reducing consumption of the product and, ultimately, damage to health. This study found that in 1985 the majority of Manitoba public school children 8 to 15 years of age who smoked "regularly" (defined as usually every day) obtained their cigarettes from stores. This source could be reduced, if not eliminated, were a federal regulation passed in 1908 enforced. Under Canada''s Tobacco Restraint Act it is illegal for merchants to sell tobacco to anyone under the age of 16 years. By implementing this existing law, authorities would not only be keeping the profit from almost a million dollars in cigarette sales in Manitoba alone out of tobacco company coffers but also be having an impact on the leading cause of preventable premature death and disability in Canada.     

Oxidative stress–mediated photoactivation of carbazole inhibits human skin cell physiology

Prolonged exposure of the earth's surface to the sun's ultraviolet radiation may result in various skin diseases and cataract. Carbazole (CBZ), as a polycyclic-aromatic hydrocarbon (PAH), is blended with a five-member nitrogen-containing ring. It is found in cigarette smoke, coal, eye kohl, tattoo ink, and wood combustion and affects various types of flora and fauna. Our findings suggest that CBZ generates reactive oxygen species (ROS) like through type-I photodynamic reaction and causes phototoxicity in the human keratinocyte cell line (HaCaT), which has been proved by mitochondrial dehydrogenase and neutral red uptake assays. CBZ induces single strand DNA damage. We have investigated the involvement of the apoptotic pattern of cell death and confirmed it by cytochrome C release from mitochondria and caspase-9 activation. Similarly, photo-micronuclei formation was associated to CBZ-induced phototoxicity. The results of this study strongly support that the upregulation of bax, cyto-C, apaf-1, casp-9 and down regulation of bcl2, keap-1, nrf-2, and hmox-1 genes cause apoptopic cell death. Downregulation of antioxidant genes showed a significant amount of ROS generation by photosensitized CBZ. Therefore, the current study will be a step forward to safeguard human beings from sunlight-induced photosensitive CBZ prolonged exposure.     

Contributions to the mathematical theory of epidemics—III. Further studies of the problem of endemicity

(1) The mathematical investigation of the progress of an infectious disease in a community of susceptible individuals has been extended to include the case where members of the community are removed as the result of some general cause of death acting according to constant non-specific death rates, as well as by death from the disease itself. Under the more general conditions here dealt with the main conclusions arrived at in the previous paper remain qualitatively unaltered. The limitations which remain are that the susceptibility and the infective power of the individual are supposed to be independent of his age, and further that specific individual immunity does not exist in the sense that the part of the population which escapes infection is assumed to be just as susceptible as the whole population would have been if it had not been infected. (2) In the general case a unique steady state is found to exist provided that certain relatively simple conditions are satisfied. In the special cases considered a unique steady state in general exists when these conditions continue to be satisfied; but in particular instances, when these conditions are not satisfied, unique steady states will exist provided that certain other requirements are fulfilled. (3) Increase of birth rates, in general, increases both the absolute and the relative prevalence of the disease in its steady state. The effect of increase in the non-specific death rates is less simple, but has been worked out at some length. Decrease in the infectivity of the disease or in the susceptibility of the uninfected results in an increase in the whole population density as well as in an increase in the number of infected. The effect upon the relative incidence of the disease cannot be simply expressed, but it has been worked out in detail in the text. In the absence of immigration, and with the birth rates and also the non-specific death rates equal for virgins and recovered, variation in infectivity or susceptibility will not alter the relative incidence of the disease. The total population, however, will increase with decrease of either of these two factors, whilst the number of diseased will also increase proportionately. (4) Two types of threshold values have been encountered. In the first type the quantity in question must initially exceed the threshold value if the event or process is to occur in the population. Two examples of this type have been found, namely, in Cases (4) and (2'd).(ABSTRACT TRUNCATED AT 400 WORDS)     

Heart Damage Associated with Intracranial Lesions

Focal myocytolysis, a form of myocardial damage, has been found to occur in about 8% of patients dying of intracranial lesions. Electrocardiographic abnormalities in patients with brain damage may be due to this. The cause of focal myocytolysis remains unknown, but if it could be prevented it might avert the patient''s death from cardiac arrest or arrhythmia. Moreover, more than a minimal degree of this type of damage to the heart might make it unsuitable for transplantation.     

Prediction of resources needed to achieve the national target for treatment of renal failure.

A model of the treatment of end stage renal failure has been primed with observed survival statistics and used to predict the steady state that will be achieved when the present annual target of at least 40 new patients per million population is in equilibrium with the death rate. The number of patients expected to receive each type of dialysis or a transplant is given per million of population. The personnel and facilities required to care for these patients and the costs of each programme were derived using analyses of workloads and costs in the North Western Regional Health Authority. The study has documented the considerable need for "back up" beds for patients on dialysis who require temporary care as inpatients. The cost effectiveness of transplantation has been demonstrated; at steady state it is calculated that each successful graft saves the service pounds 30,000. Implementation of the minister''s minimum target requires a build up to some three times the resources currently allocated, with parallel increases in numbers of medical, nursing, and other essential staff.     

Screening for carriers of cystic fibrosis--a general practitioner's perspective.

The identification of the gene for cystic fibrosis has led to the possibility of population based screening for carriers of cystic fibrosis to identify couples at risk of having an affected child. Pilot studies have shown that screening is feasible and does not cause untoward anxiety, though the uptake of testing varies considerably with the setting and method of invitation. Screening offered at times when individuals (and health professionals) perceive it as directly relevant will probably gradually become established in the United Kingdom. This review examines the role of general practice in genetic carrier screening as exemplified by cystic fibrosis. General practice has a pivotal role from the beginning in providing individuals and couples with information, facilitating testing of patients'' relatives and of carriers identified by screening elsewhere (such as antenatal clinics), and offering testing in the context of reproduction. Screening for the cystic fibrosis gene will probably be followed by other genetic screening programmes.