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PubMed2002

Benefit of population-based screening for phenotypic hemochromatosis in young men.

BACKGROUND: Hereditary hemochromatosis (HH) is a common genetic disease leading to accumulation of iron in the body, most notably in the liver. More men than women become clinically ill. The prognosis is excellent if phlebotomy treatment is started before liver cirrhosis develops. Screening has been recommended, but the benefit of population-based screening has never been shown in a randomized clinical trial. In this article, we estimate the benefit of screening young men, using a theoretical model. METHODS: A phenotypic screening scenario was modelled using a decision tree. Gain of quality-adjusted life-years was used as a measure of benefit, and estimated using Markov processes. Data on the accuracy of the screening tests, the prevalence of HH and the risk of liver cirrhosis were mainly derived from a cross-sectional study on the prevalence and morbidity of HH in 30509 men. Data on the excess mortality of cirrhosis were taken from relevant literature. Sensitivity analysis was done for important variables. RESULTS: Assuming basal case values for variables, screening a cohort of 1000 men aged 30 years for phenotypic HH would gain about 8 quality-adjusted life-years, compared to awaiting symptomatic disease. Based on actual costs of our cross-sectional study, the screening cost was US$250 per quality-adjusted life-year gained. The prevalence of phenotypic HH, the excess mortality of liver cirrhosis, the quality of life in non-cirrhotic HH patients, and the fractions of patients compliant with treatment were the most important variables in the sensitivity analysis. CONCLUSION: Incorporating screening for phenotypic HH in health survey programmes for young men may be worthwhile.

Adult↗
PubMed1993

Preventable mortality in Missouri: excess deaths from nine chronic diseases, 1979-1991.

For the period 1979-1991, 54% of the 644,045 deaths in Missouri were attributed to nine chronic diseases--cancers of the breast, uterine cervix, lung, colon/rectum; coronary heart disease; stroke; diabetes; chronic obstructive pulmonary disease; hepatic diseases/cirrhosis. Elimination of risk factors and screening have been shown to reduce the mortality caused by these diseases. To evaluate the range in excess mortality in the state, we calculated excess mortality by county and correlated these rates with three sociodemographic variables. Based on these analyses, an estimated 100,000 deaths may have been prevented through prevention and early detection activities.

Adult↗
PubMed2005

Excess deaths associated with underweight, overweight, and obesity.

CONTEXT: As the prevalence of obesity increases in the United States, concern over the association of body weight with excess mortality has also increased. OBJECTIVE: To estimate deaths associated with underweight (body mass index [BMI] <18.5), overweight (BMI 25 to <30), and obesity (BMI > or =30) in the United States in 2000. DESIGN, SETTING, AND PARTICIPANTS: We estimated relative risks of mortality associated with different levels of BMI (calculated as weight in kilograms divided by the square of height in meters) from the nationally representative National Health and Nutrition Examination Survey (NHANES) I (1971-1975) and NHANES II (1976-1980), with follow-up through 1992, and from NHANES III (1988-1994), with follow-up through 2000. These relative risks were applied to the distribution of BMI and other covariates from NHANES 1999-2002 to estimate attributable fractions and number of excess deaths, adjusted for confounding factors and for effect modification by age. MAIN OUTCOME MEASURES: Number of excess deaths in 2000 associated with given BMI levels. RESULTS: Relative to the normal weight category (BMI 18.5 to <25), obesity (BMI > or =30) was associated with 111,909 excess deaths (95% confidence interval [CI], 53,754-170,064) and underweight with 33,746 excess deaths (95% CI, 15,726-51,766). Overweight was not associated with excess mortality (-86,094 deaths; 95% CI, -161,223 to -10,966). The relative risks of mortality associated with obesity were lower in NHANES II and NHANES III than in NHANES I. CONCLUSIONS: Underweight and obesity, particularly higher levels of obesity, were associated with increased mortality relative to the normal weight category. The impact of obesity on mortality may have decreased over time, perhaps because of improvements in public health and medical care. These findings are consistent with the increases in life expectancy in the United States and the declining mortality rates from ischemic heart disease.

Adult↗
PubMed1996

Influence of occupational accidents and deaths related to lifestyle on mortality among merchant seafarers.

OBJECTIVES: The aim of the present historical cohort study was to enhance the understanding of the unusual mortality pattern seen among seafarers. The main object was to describe the mortality pattern of Danish seafarers in recent years with special reference to the influence of accidents in the maritime workplace and ashore and the influence of diseases related to lifestyle. SUBJECTS: A cohort of 24,132 male seafarers of all job categories employed on a Danish merchant ship between 1986 and 1993, was followed up. Mortality among those who left the occupation before the end of the follow-up period was analysed separately. RESULTS: The standardized mortality ratio was 1.43 (95% CI: 1.33-1.54) from all causes and 3.05 (95% CI: 2.62-3.52) from accidents. An excess mortality from natural causes was attributable mostly to an excess among deck and engine room crew and was mainly caused by diseases related to lifestyle. While active as seafarers, the SMR for accidents was 2.62 (95% CI: 2.12-3.20), accidents at the workplace explaining almost half the deaths. Among those who left shipping, the risk of fatal accidents increased. All categories of seafarers continued to have a high risk of fatal accidents into older age. CONCLUSION: Merchant seafarers were shown to have a higher mortality than the general population. Despite a very high risk of fatal accidents in the workplace, these accidents could only explain a proportion of the observed excess mortality. Accidents ashore and diseases related to lifestyle factors such as drinking and smoking made a major contribution to the observed excess mortality. The results indicate that people in occupations with a high risk of fatal accidents at the workplace also seem to have a high risk of accidents away from the workplace after leaving the occupation. The high risk lifestyle seems to be linked to lifestyle in general and hence the related diseases and high risk of death.

Accidents, Occupational↗
PubMed1994

Impact of HIV infection on non-AIDS mortality among Italian injecting drug users.

OBJECTIVES: To estimate the excess mortality of injecting drug users (IDU) stratified by HIV serostatus compared with the general population in Italy. To compare total and cause-specific mortality in HIV-positive versus HIV-negative IDU, in order to identify possible HIV-related non-AIDS causes of death in this population. METHODS: All IDU attending two drug-treatment centres in Rome who underwent HIV testing between 1985 and 1991 were enrolled into a prospective study. The end-point of the study was death from any cause by 31 December 1991. Mortality rates were compared using age-adjusted standardized mortality ratios and person-time techniques. RESULTS: Of the 2431 IDU, 1661 (68.3%) were HIV-seronegative and 82 seroconverted. Of 181 deaths, comprising 89 from AIDS and 92 from other causes, the mortality rate was 4.5 and 0.8 per 100 person-years in HIV-seropositives and HIV-seronegatives, respectively. For non-AIDS mortality in HIV-seropositives, the overall rate was 1.7 per 100 person-years. Deaths from overdose and endocarditis/embolus tended to be higher in HIV-seropositive than HIV-seronegative IDU, although there was no difference in the rate of deaths due to pneumonia by HIV serostatus. CONCLUSIONS: These data are consistent with other studies demonstrating a higher frequency of mortality among HIV-seropositive IDU. The excess in overdose mortality among HIV-seropositives is disturbing and merits further investigation.

Adult↗
PubMed2001

Service screening with mammography of women aged 50-69 years in Sweden: effects on mortality from breast cancer.

OBJECTIVES: To estimate the effect of the population based service screening programme in Sweden on mortality from breast cancer among women aged 50-69. SETTING; In 1986, population based service screening with mammography started in Sweden, and by 1997 screening had been introduced in all counties. Half of the counties invite women from 40 years of age whereas women 50 and older are invited in the other counties. The upper age limit was either 69 or 74. Women in the age group 50-69 years are thus invited to screening in all counties. METHODS: The counties which started with mammographic screening in 1986-87 constituted the study group and were compared with the counties which started in 1993 or later. In 1987 the mean number of women aged 50-69 was 161,986 and 98,608 in the study and control groups, respectively. Refined excess mortality (smoothed with the Lowess method) from breast cancer and refined cause specific mortality from breast cancer were used as effect measures. To adjust for geographical differences in mortality from breast cancer a reference period was used. Allowance was made for two potential biases: (a) inclusion bias implying the inclusion of cases diagnosed before invitation to screening in the first screening round, and (b) lead time bias. RESULTS: After a mean follow up time of 10.6 years since the start of screening and a mean individual follow up time of 8.4 years, a non-significant reduction in refined excess mortality for breast cancer was estimated as relative risk (RR) 0.84 (95% confidence interval (95% CI) 0.67 to 1.05). After adjustment for inclusion and lead time biases the RR was 0.80 (20% reduction). Only 27% of the deaths from breast cancer in the total mortality for women aged 50-79 at death consisted of women aged 50-69 at diagnosis who were diagnosed after the start of screening. This figure has important implications for judgement of the impact of screening on age specific national breast cancer mortalities. CONCLUSIONS: A non-significant reduction in mortality from breast cancer was found in counties performing service screening with mammography in Sweden. Adjustment for possible biases changed the result towards a larger effect of screening. The results do not contradict the effects found in the Swedish randomised mammography trials.

Aged↗
PubMed1999

Incremental cost of medical care after hip fracture and first vertebral fracture: the Rotterdam study.

The aim of this study was to estimate the additional cost of medical care (the incremental cost) caused by incident hip and vertebral fractures, using a matched case cohort design within a longitudinal follow-up study. Incident hip fractures were recorded using the regular follow-up system of the Rotterdam Study. Incident vertebral fractures were recorded by morphometric comparison of spinal radiographs taken at intervals of 2.2 years on average. The matched control group was randomly selected from other participants of the Rotterdam Study in whom no fracture occurred during follow-up, but who were otherwise comparable at baseline. Cases were matched for age, gender, self-perceived health, ability to perform activities of daily life, living situation and general practitioner. Medical expenditure was assessed by retrieval of the general practice medical records and by recording all hospital and nursing home admissions, and all general practice and outpatient visits. Pharmaceutical consumption was recorded through the computerized records of the central pharmacy. Valid results were obtained for 44 pairs (91%) in the hip fracture and for 42 pairs (93%) in the vertebral fracture group. Cost of medical consumption in the year before the hip fracture was similar in patients and control subjects, but the incremental cost in the first year after the hip fracture was almost US$10 000. In the second year after hip fracture the incremental cost was still about $1000. Accounting for the excess mortality in hip fracture patients had little effect on cost in the first year, but cost in the second year was doubled to almost $2000. For vertebral fractures, we did not detect important acute care costs, but these fractures were associated with a yearly recurrent incremental cost of over $1000. However, almost half this difference was already present before the occurrence of the fracture, and was attributable to hospital admissions. The remainder of the incremental cost was mainly due to pharmaceutical consumption and to a lesser extent to admissions to orthopedic surgery wards. We conclude that hip fractures cause excess mortality and an important incremental cost especially during the first year, and that these could probably be avoided by prevention of hip fractures. For vertebral fractures we found no evidence of important acute care costs but we observed a yearly returning incremental cost. Part of this incremental cost, however, was pre-existing and might therefore by caused by co-morbidity.

Aged↗
PubMed2005

Urban-rural differences in prostate cancer mortality, radical prostatectomy and prostate-specific antigen testing in Australia.

OBJECTIVE: To assess differences in trends for prostate cancer mortality, radical prostatectomy and prostate-specific antigen (PSA) testing for Australian men aged 50-79 years living in capital cities compared with regional and rural areas. DESIGN: Descriptive, population-based study based on data from official sources from 1985 to the 2002/03 financial year (depending on data availability). MAIN OUTCOME MEASURES: Age-standardised rates per 100,000 men aged 50-79 years of mortality from prostate cancer, incidence of prostate cancer, PSA tests and radical prostatectomy. RESULTS: We found a statistically significant and increasing (age-standardised) mortality excess for prostate cancer in regional and rural areas. In 2000-2002 the excess (compared with capital cities) was 21% (95% CI, 14%-29%). Rates of radical prostatectomy in rural and regional Australia were 29% lower (95% CI, 23% lower to 35% lower) than in capital cities. Although PSA testing is common across the whole of Australia, age-standardised rates in 2002/03 were 16% lower (95% CI, 15% lower to 17% lower) in regional and rural areas than in capital cities. CONCLUSIONS: Our results show that the probability of a man having a PSA test and the management of his prostate cancer depend on where he lives. The cause or causes of the prostate cancer mortality excess in regional/rural areas cannot be established in a descriptive study, but fewer radical prostatectomies in regional and rural areas, perhaps associated with less PSA screening, remain among the several competing hypotheses. Other possibilities are related to other differences in management, perhaps associated with access to urologists. Governments and other budget holders need good evidence about the effectiveness of prostate cancer screening and early treatment, but also about the best strategies for providing equitable access to cancer services in both urban and rural areas.

Aged↗
PubMed2002

Avoidance of premature death: a new definition for the proportion cured.

For many cancers, five-year survival is used as a synonym for cure. For some sites, such as breast, this is inappropriate since there is still considerable excess mortality 5-15 years following diagnosis. We propose using the probability of not dying prematurely as a surrogate for the probability of being cured. This is estimated without the need for information on the cause of death by comparing all-cause-mortality rates in patients with cancer to those in the general population. We also consider the probability of 'cure' in those who have survived a certain number of years since diagnosis. These quantities are estimated for various cancer sites using SEER data. The proportion not dying prematurely varies considerably for common cancers from 12% for lung cancer to 84% for prostate cancer. In women, the percentage 'cured' for colon and breast cancer are very similar at 56% and 58% respectively, but in those who survive 5 years, they are quite different--91% and 78% respectively. The proposed statistic is useful. For diseases in which excess mortality is primarily within five years of diagnosis, it agrees well with 5-year relative survival. Interpretation of differences between countries or over time is complicated and requires consideration of incidence and mortality data.

Adult↗
PubMed1997

Breast cancer five-year survival in New South Wales women, 1972 to 1991.

This study of breast cancer survival is based on analysis of five-year relative survival of 38,362 cases of invasive breast cancer in New South Wales (NSW) women, incident between 1972 and 1991, with follow-up to 1992, using data from the population-based NSW Central Cancer Registry. Survival was ascertained by matching the registry file of breast cancers against NSW death certificates from 1972 to 1992, mainly by automated probabilistic linkage. Absolute survival of cases was compared with expected survival of age- and period-matched NSW women. Proportional hazard regression analysis was used for examination of the effects on excess mortality of age, period of diagnosis and degree of spread at diagnosis. Relative survival at five years increased from 70 per cent in 1972-1976 to 77 per cent in 1987-1991. Survival improved during the 1970s and in the late 1980s. Regression analysis suggested that part of the improved survival in the late 1980s was due to lesser degree of spread at diagnosis, whereas the improved survival during the 1970s may have been due to treatment. Survival was better for those aged 40-49 years (RR = 0.86) and worse for those aged > or = 70 years (RR = 1.22) compared with the referent group (60-69 years). Excess mortality was much less for those with invasive localised disease than those with regional spread (RR = 3.1) or metastatic cancer (RR = 15.5) at diagnosis. For the most recent period (1987-1991), relative five-year survival was 90, 70 and 18 per cent, respectively, for the three degree-of-spread categories.

Adult↗
PubMed1988

Respiratory cancer among orchardists in Washington State, 1968 to 1980.

A case-control investigation was conducted to evaluate the hypothesis that past exposure to the pesticide lead arsenate led to an excess mortality from respiratory cancer. Cases included all white male orchardists who died in Washington State between 1968 and 1980 from respiratory cancer. Orchardists who died of other causes during this period served as controls. Occupational and smoking data for 155 case subjects and 155 control subjects were obtained via telephone interview with next-of-kin/informants. Neither presence, intensity, nor duration of lead arsenate exposure differed between case and control subjects. Although cigarette smoking was unusually common among cases of respiratory cancer, smoking habits of the orchardists and a sample of non-orchardists who had died of other causes were quite similar. The cause of the excess mortality from respiratory cancer among Washington State orchardists remains unknown.

Aged↗
PubMed2000

Adult mortality in slums of Karachi, Pakistan.

OBJECTIVE: Cause-specific death rates are rarely available to guide health interventions for adults in South Asia. We report mortality patterns among Karachi's urban poor. METHODS: We conducted verbal autopsies for adult deaths under active surveillance during 1990-1993 in five urban slums of Karachi. Two physicians assigned underlying cause of death by consensus. Analysis included cause- and category-specific rates, 45Q15s and comparison with 1991 Japanese national statistics. RESULTS: All 345 adult deaths (15-59 years) in the 5 slums (total population 45,389) were included. Male mortality exceeded female (4.4 vs 3.3/1000, p = .02). Noncommunicable diseases claimed 59% of deaths, communicable and reproductive 27% and injuries, 15%. The leading identified death rates (/100,000) among women were: circulatory disorders (66), maternal causes (33), tuberculosis (30), and burns (23); and among men they were: circulatory disorders (124) tuberculosis (30) and road traffic accidents (30). Overall Karachi adult mortality was 3.7 times Japanese rate. Compared to Japan, adults in Karachi had one to two orders of magnitude excess mortality due to maternal causes, tuberculosis and burns. Circulatory disorders and tuberculosis accounted for 47% of excess male mortality; these plus maternal causes and burns accounted for 55% of excess female mortality. CONCLUSION: These mortality levels and patterns compel interventions and research for poor urban adults beyond maternal health. Women's health would equally benefit from tuberculosis control or burn prevention. Men need safer travel. Both need improved cardiovascular health.

Adolescent↗
PubMed1996

A study of long-term survival, functional outcome and quality of life in patients with polymyositis or dermatomyositis.

UNLABELLED: There have been few studies of long-term functional outcomes and quality of life in patients with polymyositis or dermatomyositis. PATIENTS: 28 patients, 16 female and 12 male, meeting Bohan's and Peter's criteria and admitted between 1970 and 1993, were studied retrospectively; nine had polymyositis and 19 dermatomyositis (with onset during childhood in five cases); mean age was 43.5 years. METHODS: we reevaluated 18 of the 28 patients, after a mean interval of eight years; among the ten remaining patients, eight had died, one could not be traced and one declined reevaluation. Survival, muscle function, joint function, respiratory function and quality of life (AIMS 1) were determined. Factors predicting the value of these parameters were looked for. RESULTS: significant excess mortality was observed as compared with the general population in the Seine Maritime region of France. Easy fatigability and decreased exercise tolerance were found in 50% of evaluated patients; Ritchie's index was 0 in 67% of patients and between 1 and 7 in 33%; 55% of patients had dyspnea and 50% had abnormal respiratory function parameters; quality of life items were usually rated "fairly good" or "very good", except for "physical activities", which were given "poor" or "very poor" ratings by one third of patients. We found no factors associated with survival or any of the above-mentioned functional parameters, except for male gender, which predicted better muscle function. DISCUSSION: polydermatomyositis is associated with excess mortality; alterations in muscle function persist in half the cases and the ability to carry out physical activities is often reduced. The retrospective design of our study, small sample size and heterogeneity of our population precluded identification of factors predictive of survival, loss of function, or poor quality of life.

Adult↗
PubMed2005

Influenza virus neuraminidase contributes to secondary bacterial pneumonia.

Secondary bacterial pneumonia is a common cause of death during influenza epidemics. We hypothesized that virus-specific factors could contribute to differences in annual excess mortality. Recombinant influenza viruses with neuraminidases from representative strains from the past 50 years were created and characterized. The specific level of their neuraminidase activity correlated with their ability to support secondary bacterial pneumonia. Recombinant viruses with neuraminidases from 1957 and 1997 influenza strains had the highest level of activity, whereas a virus with the neuraminidase from a 1968 strain had the lowest level of activity. The high level of activity of the neuraminidase from the 1957 strain, compared with that of other neuraminidases, more strongly supported the adherence of Streptococcus pneumoniae and the development of secondary bacterial pneumonia in a mouse model. These data lend support to our hypothesis that the influenza virus neuraminidase contributes to secondary bacterial pneumonia and subsequent excess mortality.

Allantois↗
PubMed2006

Use of echocardiography in patients with hypertrophic cardiomyopathy: clinical implications of massive hypertrophy.

We examined the 10-year outcome of 107 patients with hypertrophic cardiomyopathy and massive myocardial hypertrophy as assessed by echocardiography. These patients demonstrated excess mortality in comparison with their expected survival with respect to a general population of individuals (10-year survival 77% vs 95%, P < .001). Adverse events occurred primarily in the youngest and oldest patients. Sudden cardiac death was the most frequent cause of death among the young (overall survival 80%), whereas other causes predominated in older patients (overall survival 31%). For patients aged 30 to 59 years, survival was 97%, no different from their expected survival. Patients with hypertrophic cardiomyopathy and massive hypertrophy identified by echocardiography are at increased risk of death, but this risk is related to age at presentation. Sudden cardiac death is the primary cause in those who are young, whereas other causes predominate in older patients. Middle-aged patients with massive hypertrophy do not experience an excess mortality.

Adult↗
PubMed2003

Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae.

A lethal synergism exists between influenza virus and Streptococcus pneumoniae, accounting for excess mortality during influenza epidemics. Using a model of viral-bacterial synergism, we assessed the role that the influenza virus neuraminidase (NA) has in priming mice for pneumococcal infection. Administration of the selective NA inhibitor oseltamivir improved survival, independent of viral replication and morbidity from influenza. Both pathologic examination of the lungs and live imaging of pneumonic lesions, using a bioluminescent pneumococcus, suggested that the effect of NA inhibition was to limit the extent of pneumococcal pneumonia during early infection. Adherence assays and immunohistochemical staining for sialic acids in lungs from infected mice demonstrated that the influenza virus NA potentiates development of pneumonia by stripping sialic acid from the lung, thus exposing receptors for pneumococcal adherence. Selective NA inhibitors may be useful clinically to interrupt this novel mechanism of synergism and to prevent excess mortality from secondary bacterial pneumonia.

Acetamides↗
PubMed1993

Immunologic parameters 2 years after high-titer measles immunization in Peruvian children.

Immunization with high-titer measles vaccines has been associated with excess mortality in children 2-4 years after vaccination. In this study, immunologic parameters in 64 Peruvian children who had been immunized an average of 27 months earlier with high-titer vaccines were compared with parameters in 76 recipients of low-titer vaccines. Delayed-type hypersensitivity, lymphocyte phenotype distributions by flow cytometry, and lymphoproliferation after phytohemagglutinin (PHA) stimulation were assessed. High-titer recipients had smaller indurations to tetanus, diphtheria, and Proteus (P < .05) antigens, decreased PHA stimulation (P = .04), and a lower percentage of CD4+ lymphocytes (P = .04) than low-titer recipients. After adjustment for sex, concurrent illnesses, and other variables in regression analyses, high-titer recipients had a lower percentage of CD4+ lymphocytes (P = .025) and decreased lymphocyte proliferation to PHA (P = .058). These results may provide a clue to the pathogenesis of delayed excess mortality after high-titer measles vaccination in some developing countries.

Cell Division↗
PubMed1992

Cancer mortality of Swiss men by occupation, 1979-1982.

Results of a study of male cancer mortality are presented by occupation. The data base consisted of the 1979-1982 mortality register and 1980 census data from Switzerland. In a novel approach, a linked subset of death certificates and census records was used to correct the numerator-denominator bias of standardized mortality ratios and their confidence intervals. Agricultural occupations exhibited low cancer mortality (exception: stomach cancer). Electricians suffered excess mortality from cancer of several sites. Foundry and chemical workers had elevated mortality risks for digestive tract cancers. Other metal workers suffered from high mortality from cancers of the respiratory organs. Construction workers were subject to high mortality from cancers of the upper digestive tract and lungs. Innkeepers, cooks, and owners or managers of guest houses had high rates of cancers of the digestive system. Occupations using combustion-powered equipment suffered from excess lung cancer mortality. In general the results of the study agree with those of several other studies.

Abstracting and Indexing↗