Barbiturate Intoxication: Morbidity and Mortality

The complications encountered in caring for 185 patients intoxicated with barbiturates were reviewed. The population consisted of 142 patients with long-acting barbiturate concentrations of 8 mg per 100 ml or greater, 20 patients with short-acting barbiturate concentrations of 3 mg per 100 ml or greater and 23 consecutive patients with short-acting barbiturate intoxication referred for monitoring. Pneumonia was the major cause of morbidity and mortality and correlated best with the initial depth of coma and the use of an endotracheal tube in treatment. Cardiovascular instability manifested by pulmonary edema was the next leading cause of morbidity and mortality and correlated best with the initial depth of coma and the quantity of intravenous fluid administered. In retrospect, use of eliminative measures such as dialysis would probably not have altered the outcome in most of the patients who died and attempts at forced diuresis may have contributed to several deaths. Particular emphasis should be placed on the problems of sepsis and fluid therapy in the management of these patients.     

The natural variability of vital rates and associated statistics

The first concern of this work is the development of approximations to the distributions of crude mortality rates, age-specific mortality rates, age-standardized rates, standardized mortality ratios, and the like for the case of a closed population or period study. It is found that assuming Poisson birthtimes and independent lifetimes implies that the number of deaths and the corresponding midyear population have a bivariate Poisson distribution. The Lexis diagram is seen to make direct use of the result. It is suggested that in a variety of cases, it will be satisfactory to approximate the distribution of the number of deaths given the population size, by a Poisson with mean proportional to the population size. It is further suggested that situations in which explanatory variables are present may be modelled via a doubly stochastic Poisson distribution for the number of deaths, with mean proportional to the population size and an exponential function of a linear combination of the explanatories. Such a model is fit to mortality data for Canadian females classified by age and year. A dynamic variant of the model is further fit to the time series of total female deaths alone by year. The models with extra-Poisson variation are found to lead to substantially improved fits.     

Cancer incidence and mortality in populations living near uranium milling and mining operations in grants, New Mexico, 1950-2004

In a previous cohort study of workers engaged in uranium milling and mining activities near Grants, Cibola County, New Mexico, we found lung cancer mortality to be significantly increased among underground miners. Uranium mining took place from early in the 1950s to 1990, and the Grants Uranium Mill operated from 1958-1990. The present study evaluates cancer mortality during 1950-2004 and cancer incidence during 1982-2004 among county residents. Standardized mortality (SMR) and incidence (SIR) ratios and 95% confidence intervals (CI) were computed, with observed numbers of cancer deaths and cases compared to expected values based on New Mexico cancer rates. The total numbers of cancer deaths and incident cancers were close to that expected (SMR 1.04, 95% CI 1.01-1.07; SIR 0.97, 95% CI 0.92-1.02). Lung cancer mortality and incidence were significantly increased among men (SMR 1.11, 95% CI 1.02-1.21; SIR 1.40, 95% CI 1.18-1.64) but not women (SMR 0.97, 95% CI 0.85-1.10; SIR 1.01, 95% CI 0.78-1.29). Similarly, among the population of the three census tracts near the Grants Uranium Mill, lung cancer mortality was significantly elevated among men (SMR 1.57; 95% CI 1.21-1.99) but not women (SMR 1.12; 95% CI 0.75-1.61). Except for an elevation in mortality for stomach cancer among women (SMR 1.30; 95% CI 1.03-1.63), which declined over the 55-year observation period, no significant increases in SMRs or SIRs for 22 other cancers were found. Although etiological inferences cannot be drawn from these ecological data, the excesses of lung cancer among men seem likely to be due to previously reported risks among underground miners from exposure to radon gas and its decay products. Smoking, socioeconomic factors or ethnicity may also have contributed to the lung cancer excesses observed in our study. The stomach cancer increase was highest before the uranium mill began operation and then decreased to normal levels. With the exception of male lung cancer, this study provides no clear or consistent evidence that the operation of uranium mills and mines adversely affected cancer incidence or mortality of county residents.     

Time trends in twin perinatal mortality in northern England, 1982-94. Northern Region Perinatal Mortality Survey Steering Group.

The dynamics of perinatal mortality rates (PNMR) and causes of death in twin pregnancies over 13 years in the Northern Region of the National Health Service in England is described. All twin perinatal deaths occurring between 1982-1994 were identified from the Northern Region Perinatal Mortality Survey. The twinning rate increased from 9.9 per 1000 maternities in 1982 to 12.0 in 1994. There was a total of 10,734 twin pregnancies and of these 421 resulted in 530 perinatal deaths. The perinatal mortality rate in twins significantly decreased over time (1982-87, 55.4 per 1000; 1988-94, 44.4 per 1000; P = 0.01). The PNMR was significantly higher for twins from like-sexed than from unlike-sexed pairs (53.5 and 34.4 per 1000 respectively, P < 0.001). Despite no improvement in birthweight distribution in the twin population, birthweight-specific perinatal mortality rates for both like and unlike-sexed twins decreased for each birthweight category in 1988-94 compared with 1982-87. Twins with very low birthweight (< 1500 g) comprised 69%, and preterm twins (< 37 completed weeks of gestation) 74.9% of all twin perinatal deaths. The major immediate cause of early neonatal death was pulmonary immaturity (63%); antepartum anoxia caused 76.9% of antenatal deaths. Unexplained preterm labour and intrauterine death were the leading obstetric factors underlying death in twins. Despite a decrease over the 13 years, the perinatal mortality rate in twins in the Northern Region remains high. Continued monitoring of trends in twinning and mortality rates is needed to inform health care planning.     

Mortality of cerebrovascular diseases in Croatia--1958-1997

The aim of this investigation was to analyze secular trend of mortality from cerebrovascular diseases in Croatia and its regional characteristics. The research comprised all deaths from cerebrovascular diseases in Croatia in persons aged between 35 and 74 years over the period 1958-1997. The investigated period is divided in eight 5-year periods, and for that 5-year periods proportional mortality rates, standardized mortality rates and specific mortality rates, according to the age and gender were calculated. Number of all deaths in the population aged 35-74 in Croatia, by 5-year periods rose from 18,913 to 26,788 (increase of 42%), deaths from cerebrovascular diseases from 2831 to 3959 (increase of 40%). Proportional mortality rate for this disease increased from 9.0% in the first 5-year period to 14.8% in the last 5-year period (increase of 64%). Standardized mortality rates for cerebrovascular diseases increased from 118 to 206 per 100,000 inhabitants (increase of 75%). The specific mortality rates over a 5-year period have shown a trend of increase in all men age groups and stagnation or decrease in women age groups. At the same time the rates standardized by age and sex increased by 62%. Standardized mortality rates for cerebrovascular diseases in continental communities (Osijek, Varazdin) are much higher (twice or even threefold) than those in coastal communities (Split, Rijeka). A data analysis showed that, although mortality trends of cerebrovascular diseases stagnated or even declined in some communities during the recent years, the secular trend for the entire country had a tendency of constant rise over the whole period of research. Therefore, the short-term prognosis predicts further increase of both the number and rates of deaths from cerebrovascular diseases in our country.     

Projected estimates of cancer in Canada in 2022

Background:Regular cancer surveillance is crucial for understanding where progress is being made and where more must be done. We sought to provide an overview of the expected burden of cancer in Canada in 2022.Methods:We obtained data on new cancer incidence from the National Cancer Incidence Reporting System (1984–1991) and Canadian Cancer Registry (1992–2018). Mortality data (1984–2019) were obtained from the Canadian Vital Statistics — Death Database. We projected cancer incidence and mortality counts and rates to 2022 for 22 cancer types by sex and province or territory. Rates were age standardized to the 2011 Canadian standard population.Results:An estimated 233 900 new cancer cases and 85 100 cancer deaths are expected in Canada in 2022. We expect the most commonly diagnosed cancers to be lung overall (30 000), breast in females (28 600) and prostate in males (24 600). We also expect lung cancer to be the leading cause of cancer death, accounting for 24.3% of all cancer deaths, followed by colorectal (11.0%), pancreatic (6.7%) and breast cancers (6.5%). Incidence and mortality rates are generally expected to be higher in the eastern provinces of Canada than the western provinces.Interpretation:Although overall cancer rates are declining, the number of cases and deaths continues to climb, owing to population growth and the aging population. The projected high burden of lung cancer indicates a need for increased tobacco control and improvements in early detection and treatment. Success in breast and colorectal cancer screening and treatment likely account for the continued decline in their burden. The limited progress in early detection and new treatments for pancreatic cancer explains why it is expected to be the third leading cause of cancer death in Canada.

The impact of cancer on the Canadian population and health care systems is substantial. Cancer is the leading cause of death in Canada^1,2 and previous estimates have shown that 43% of all people in Canada are expected to receive a cancer diagnosis in their lifetime.³ With an aging and growing population, the number of new cancer cases and deaths in Canada is also increasing.⁴ In addition to its impact on health, cancer is costly. The economic burden of cancer care in Canada rose from $2.9 billion in 2005 to $7.5 billion in 2012, annually.⁵Given the considerable health and economic impact of cancer in Canada, comprehensive and reliable surveillance information is necessary for identifying where progress has been made and where more attention and resources are needed. To meet these needs, the Canadian Cancer Statistics Advisory Committee, in collaboration with the Canadian Cancer Society, Statistics Canada and the Public Health Agency of Canada, produces the latest surveillance statistics on cancer in Canada.Cancer data often lag the current date by several years, owing to the time associated with collecting, verifying and analyzing the data. Short-term cancer incidence and mortality rates can be projected by extrapolating past trends to estimate future trends, using statistical models. These short-term projections provide a more up-to-date estimate of the cancer landscape in Canada. Incidence and mortality counts, along with age-standardized rates, provide a picture of the impact of cancer in Canada, which is essential for resource planning, research and informing cancer-control programs.Canadian Cancer Statistics 2021³ provided detailed estimates of cancer incidence, mortality and survival in Canada by age, sex, geographic region and over time for 22 cancer types.³ Here, we provide updated estimates of the counts and age-standardized rates of new cancer cases (incidence) and cancer deaths (mortality) expected in 2022 by sex and province and territory, for all ages combined.     

Elective total hip replacement: incidence,emergency readmission rate,and postoperative mortality.

OBJECTIVES--To report the incidence of elective total hip replacement and postoperative mortality, emergency readmission rates, and the demographic factors associated with these rates in a large defined population. DESIGN--Analysis of linked, routine abstracts of hospital inpatient records and death certificates. SETTING--10 hospitals in six districts in Oxford Regional Health Authority covered by the Oxford record linkage study. SUBJECTS--Records for 11,607 total hip replacements performed electively in 1976-85. MAIN OUTCOME MEASURES--Incidence of operation, postoperative mortality, relative mortality ratios, and incidence of emergency readmission. RESULTS--NHS operation rates increased over time from 43 to 58 operations/100,000 population. Variation in operation rates between districts reduced over time. Operation rates were on average 25% higher in women than men. There were 93 deaths (11/1000 operations) within 90 days of the operation and 208 emergency readmissions (28/1000 operations) within 28 days of discharge. Postoperative mortality and emergency readmission rates increased with age. No significant trend with time was found. Mortality in the 90 days after the operation was 2.5-fold higher (1.9 to 3.0) than in the rest of the first postoperative year. This represented an estimated excess of 6.5 (4.2 to 8.8) early postoperative deaths/1000 operations. Most deaths were ascribed to cardiovascular events. Thromboembolic disease was the commonest reason for emergency readmission. CONCLUSIONS--The pronounced increase in operations in districts with initially low rates suggests a trend towards greater equity in the local provision of NHS hip arthroplasty. The early postoperative clusters of deaths attributed to cardiovascular disease and of readmissions for thromboembolic disease suggest that there is scope for investigating ways of reducing the incidence of major adverse postoperative events.     

Lung Cancer Mortality Trends in Canada, 1931-1960

Trends in mortality due to lung cancer in Canada since 1931 were reviewed and data for 1960 presented. In 1960, 2223 male deaths were due to lung cancer. In each five-year age group over 45, there has been a distinct increase in male lung cancer death rates since 1931. The greatest increase occurred between the ages of 65 and 79. The age group 70-74, where the lung cancer mortality rates increased from 10.7 in the period 1931-33 to 173.5 in 1958-60, indicates the trend. Between 1931 and 1960, the proportion of male lung cancer deaths to all male cancer deaths increased from 3% to 18.8%. Female deaths due to lung cancer numbered 321 in 1960. Between 1931 and 1960 the proportion of female lung cancer deaths to all female cancer deaths increased only from 1.4% to 3.2%.     

Reproductive mortality.

The transfer from traditional to modern methods of contraception in recent decades has been accompanied by a transfer of deaths from complications of pregnancy to deaths from complications of the modern contraceptive methods. In 1975, for example, it is estimated that there were more deaths at ages 25-44 years in England and Wales from adverse effects of oral contraceptive use than from all complications of pregnancy, delivery, and the puerperium combined. Thus maternal mortality is no longer an adequate indicator of the deaths associated with reproduction in the community. An alternative measure, the reproductive mortality rate should be used, which includes deaths from complications of contraceptive use as well as those from complications of pregnancy or abortion. The reproductive mortality rate in England and Wales seems to have declined continuously since 1950 for women aged 25-34. But after 1960 it increased for women aged 35-44, because of the higher mortality associated with oral contraceptive use in this age group.     

Excess mortality associated with alcohol consumption.

To estimate the excess mortality due to alcohol in England and Wales death rates specific to alcohol consumption that had been derived from five longitudinal studies were applied to the current population divided into categories of alcohol consumption. Because of the J shaped relation between alcohol consumption and death the excess mortality used as a baseline was an alcohol consumption of 1-10 units/week and an adjustment was made for the slight excess mortality of abstainers. The number of excess deaths was obtained by subtracting the number of deaths expected if all the population had the consumption of the lowest risk group; correction for the total observed mortality in the population was made. This resulted in an estimate of 28,000 deaths each year in England and Wales as the excess mortality among people aged 15-74 associated with alcohol consumption.     

A BARBITURATE ANTIDOTE—Use of Methylethylglutarimide in Barbiturate Intoxication and in Terminating Barbiturate Anesthesia

Methylethylglutarimide was administered to 488 patients ranging in age from 7 to 89 years, in a study on sleep-reversal after harbiturate anesthesia. Sodium surital or sodium pentothal were the barbiturates used. The drug was administered intravenously in doses varying from 25 to 200 mg. Dosage below 25 mg. was found to be ineffective. Almost all patients showed signs of awakening as evidenced by the return of corneal and conjunctival reflexes, the opening of the eyes, and stirring or moving about. Many responded to questioning. Almost all showed evidence of greater responsiveness within five minutes. No untoward reactions were noted. No convulsions were produced.Five patients ranging in age from 24 to 70 years were treated for barbiturate poisoning with Mikedimide® given intravenously in doses varying from 550 mg. to 1950 mg. All recovered consciousness within 30 minutes to an hour. No convulsions were produced.While it is not known whether Mikedimide is a direct barbiturate antagonist, or whether it is an analeptic, it appears to be a useful drug in reversing the respiratory depression and the cerebral depression produced by harbiturate intoxication and barbiturate anesthesia.     

Changing sex ratio of mortality in the Semai Senoi, 1969-1987

An excess of male over female deaths is characteristic of modern national populations, whereas in some high-mortality societies female mortality exceeds that of males. Among the Semai Senoi, a Malaysian Orang Asli ("aboriginal") population, women experienced higher mortality than males in the decades before 1969. This differential occurred in all age classes older than 15 years so that the sex ratio progressively increased with age. A recent (1987) restudy of the Semai population found that sex-specific differential mortality is much reduced. A comparison of the 1969 and 1987 life tables shows a sharp shift in the sex ratios of mortality for the post-15-year-old age classes (the geometric means of age classes 15-44 were 0.768 in 1969 and 0.997 in 1987) so that male and female expectations of further life at age 15 are now nearly identical. In contrast to the best-known cases of high female mortality (mostly in South Asia), Semai sex differential mortality does not include the childhood ages. The Semai have traditionally been relatively sexually egalitarian, and sex bias in care has not occurred. Analysis of sex-specific causes of death for the pre-1969 population suggests that maternal mortality is the major cause of the excess female deaths. The reduced number of maternal deaths seems largely due to better health care, particularly the availability of hospital services. Interestingly, the reduction in female mortality has occurred simultaneously with increased fertility, and overall mortality has continued at relatively high levels (eO less than 36). Thus, rather than forming a component of a unitary demographic transition, declining sex differences in mortality can be accounted for by a specific factor, better maternal care.     

Mortality of employees of the United Kingdom Atomic Energy Authority, 1946-1979.

An analysis was conducted of 3373 deaths among 39 546 people employed by the United Kingdom Atomic Energy Authority between 1946 and 1979, the population having been followed up for an average of 16 years. Overall the death rates were below those prevailing in England and Wales but consistent with those expected in a normal workforce. At ages 15-74 years the standardised mortality ratios (SMRs) were 74 for deaths from all causes and 79 for deaths from all cancers. Mortality from only four causes was above the national average--namely, testicular cancer (SMR 153; 10 deaths), leukaemia (SMR 123; 35 deaths), thyroid cancer (SMR 122; three deaths), non-Hodgkin''s lymphoma (SMR 107; 20 deaths)--but in none was the increase significant at the 5% level. Half of the authority''s employees were recorded as having been monitored for exposure to radiation, their collective recorded exposure being 660 Sv (65 954 rem). Among these prostatic cancer was the only condition with a clearly increased mortality in relation to exposure. Of the 19 men who had a radiation record and died from prostatic cancer at ages 15-74 years, nine had been monitored for several different sources of exposure to radiation. The standardised mortality ratios were 889 (six deaths) in employees monitored for contamination by tritium, 254 (nine deaths) in those monitored for contamination by other radionuclides, and 385 (nine deaths) in those with dosimeter readings totalling more than 50 mSv (5 rem); but the same nine subjects tended to account for each of these significantly raised ratios. Because multiple exposures were common and other relevant information was not available the reason for the increased mortality from prostatic cancer in this population could not be determined and requires further investigation. Excess mortality rates of 2.2 and 12.5 deaths per million person years per 10 mSv (1 rem) were estimated for leukaemia and all cancers, respectively. The confidence limits around these estimates were wide, included zero, and made it unlikely that the International Commission on Radiological Protection''s cancer risk coefficients were underestimated by more than 15-fold. Thus despite this being the largest British workforce whose mortality has been reported in relation to low level ionising radiation exposure, even larger populations will need to be followed up over longer periods before narrower ranges of risk estimates can be derived.     

The increasing incidence of melanoma.

A study of our hospital records has confirmed a striking increase in the number of melanoma cases. An examination of the New York State statistics demonstrates a 202 percent increase in the case rate from 1950 to 1971. The Connecticut statistics extending from 1935 to 1972 show an age-adjusted incidence rate increase of more than 300 percent for men, and more than 600 percent for women. An increased frequency of melanoma has been reported also for Texas, Canada, Australia, England and Wales. The available information on melanoma deaths and mortality rates fails to suggest that these lesions are biologically less significant than those so designated in the past. There has been no change in preferential sites of melanoma location in either sex, despite the increased incidence of the disease reported from these many geographic areas. The cause of the increased incidence remains obscure.     

Opportunities with W.H.O

Available statistics were studied to define the extent of the lung cancer problem in Canada. Because of the low overall survival in treated and untreated cases at one year, mortality figures provide a rough index of morbidity from this disease.Male lung cancer death rates rose steadily from 3.0 to 24.6, and female rates from 1.6 to 4.0 per 100,000 population between 1931 and 1961. In males, the greatest increase occurred in the 70-74 year age group (eighteen-fold) and in females in the 80-84 year age group (seven-fold).Lung cancer caused 2774 deaths in Canada in 1961, and was the leading cause of cancer deaths for males in all age groups from 40 to 79 years. It accounted for approximately 1 in 5 of all cancer deaths in males and 1 in 26 in females.Lung cancer mortality in Canada has not increased to the same extent as in certain other countries, but to counter the rising trend, changes in the smoking habits of the population are required as well as community and industrial control of atmospheric carcinogens.     

SMR analysis of historical follow-up studies with missing death certificates

The evaluation of epidemiological follow-up studies is frequently based on a comparison of the number O of deaths observed in the cohort from a specified cause with the expected number E calculated from person years in the cohort and mortality rates from a reference population. The ratio SMR = 100 x O/E is called the standardized mortality ratio (SMR). While person years can easily be calculated from the cohort and reference rates are generally available from the national statistical offices or the World Health Organization (WHO), problems can arise with the accessibility of the causes of death of the deceased study participants. However, the information that a person has died may be available, e.g., from population registers. In this paper, a statistical model for this situation is developed to derive a maximum likelihood (ML) estimator for the true (but unknown) number O* of deaths from a specified cause, which uses the known number O of deaths from this cause and the proportion p of all known causes of death among all decreased participants. It is shown that the standardized mortality ratio SMR* based on this estimated number is just SMR* = SMR/p. Easily computable confidence limits can be obtained by dividing the usual confidence limits of the SMR by the opposite limit of the proportion p. However, the confidence level alpha has to be adjusted appropriately.     

Aging, cancer, and cancer vaccines

ABSTRACT: World population has experienced continuous growth since 1400 A.D. Current projections show a continued increase - but a steady decline in the population growth rate - with the number expected to reach between 8 and 10.5 billion people within 40 years. The elderly population is rapidly rising: in 1950 there were 205 million people aged 60 or older, while in 2000 there were 606 million. By 2050, the global population aged 60 or over is projected to expand by more than three times, reaching nearly 2 billion people 1. Most cancers are age-related diseases: in the US, 50% of all malignancies occur in people aged 65-95. 60% of all cancers are expected to be diagnosed in elderly patients by 2020 2. Further, cancer-related mortality increases with age: 70% of all malignancy-related deaths are registered in people aged 65 years or older 3. Here we introduce the microscopic aspects of aging, the pro-inflammatory phenotype of the elderly, and the changes related to immunosenescence. Then we deal with cancer disease and its development, the difficulty of treatment administration in the geriatric population, and the importance of a comprehensive geriatric assessment. Finally, we aim to analyze the complex interactions of aging with cancer and cancer vaccinology, and the importance of this last approach as a complementary therapy to different levels of prevention and treatment. Cancer vaccines, in fact, should at present be recommended in association to a stronger cancer prevention and conventional therapies (surgery, chemotherapy, radiation therapy), both for curative and palliative intent, in order to reduce morbidity and mortality associated to cancer progression.