A conceptual model of adaptation to illness and quality of life for cancer patients treated with bone marrow transplants

OBJECTIVES: Our goal was to determine the risk of cancer after hospitalization for endometriosis. STUDY DESIGN: Records of 20,686 women hospitalized with endometriosis during the period 1969 to 1983, as identified through the nationwide Swedish Inpatient Register, were linked against the National Swedish Cancer Registry through 1989 to identify all subsequent diagnoses of cancer. The study subjects were followed up for a mean of 11.4 years, with the cohort contributing 216,851 woman years of follow-up. Standardized incidence ratios were computed by the use of age- and period-specific incidence rates derived from the Swedish population. Because of the high proportion of subjects with gynecologic operations (55.6%), evaluation of the risk of gynecologic cancers involved truncation of person years at the time of any such operation. RESULTS: The overall cancer risk was 1.2 (95% confidence interval 1.1 to 1.3). Significant excesses were observed for breast cancer (standardized incidence ratio = 1.3, 95% confidence interval 1.1 to 1.4), ovarian cancer (1.9, 1.3 to 2.8), and hematopoietic malignancies (1.4, 1.0 to 1.8); this latter excess was largely driven by an excess risk of non-Hodgkin's lymphoma (1.8, 1.2 to 2.6). The risk of ovarian cancer was particularly elevated among subjects with a long-standing history of ovarian endometriosis (4.2, 2.0 to 7.7). Cervical cancer risk was slightly reduced (0.7, 0.4 to 1.3) whereas no association was observed for cancer of the endometrium (1.1, 0.6 to 1.9). CONCLUSIONS: These findings suggest that further attention be given to the risk of breast, ovarian and hematopoietic cancers among women with endometriosis and to exploring possible hormonal and immunologic reasons for the excess risks.     

Foetal rat pancreatic transplantation: posttransplantation development of foetal pancreatic iso- and allografts and suppression of rejection with mycophenolate mofetil (MMF) and cyclosporine based immunesuppression

CONTEXT: High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic (131)I to the development of cancer, its extensive medical use indicates the need for additional evaluation. OBJECTIVE: To evaluate cancer mortality among hyperthyroid patients, particularly after (131)I treatment. DESIGN: A retrospective cohort study. SETTING: Twenty-five clinics in the United States and 1 clinic in England. PATIENTS: A total of 35 593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91 % had Graves disease, 79% were female, and 65% were treated with (131)I. MAIN OUTCOME MEASURE: Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism. RESULTS: Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86). CONCLUSIONS: Neither hyperthyroidism nor (131)I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following (131)I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, (131)I appears to be a safe therapy for hyperthyroidism.     

Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46 000 women from Royal College of General Practitioners' oral contraception study

OBJECTIVE: To describe the long term effects of the use of oral contraceptives on mortality. DESIGN: Cohort study with 25 year follow up. Details of oral contraceptive use and of morbidity and mortality were reported six monthly by general practitioners. 75% of the original cohort was "flagged" on the NHS central registers. SETTING: 1400 general practices throughout Britain. SUBJECTS: 46 000 women, half of whom were using oral contraceptives at recruitment in 1968-9. Median age at end of follow up was 49 years. MAIN OUTCOME MEASURES: Relative risks of death adjusted for age, parity, social class, and smoking. RESULTS: Over the 25 year follow up 1599 deaths were reported. Over the entire period of follow up the risk of death from all causes was similar in ever users and never users of oral contraceptives (relative risk=1.0, 95% confidence interval 0.9 to 1.1; P=0.7) and the risk of death for most specific causes did not differ significantly in the two groups. However, among current and recent (within 10 years) users the relative risk of death from ovarian cancer was 0.2 (0.1 to 0.8; P=0.01), from cervical cancer 2.5 (1.1 to 6.1; P=0.04), and from cerebrovascular disease 1.9 (1.2 to 3.1, P=0.009). By contrast, for women who had stopped use >/= 10 years previously there were no significant excesses or deficits either overall or for any specific cause of death. CONCLUSION: Oral contraceptives seem to have their main effect on mortality while they are being used and in the 10 years after use ceases. Ten or more years after use ceases mortality in past users is similar to that in never users.     

Mortality in a cohort of men expressing the glucose-6-phosphate dehydrogenase deficiency

The objective of this study was to test the hypothesis of a lower mortality from cancer and cardiovascular diseases among men expressing glucose-6-phosphate dehydrogenase (G6PD) deficiency. We designed a mortality study based on death certificates from January 1, 1982 through December 31, 1992 in a cohort of G6PD-deficient men. Cohort members were 1,756 men, identified as expressing the G6PD-deficient phenotype during a 1981 population screening of the G6PD polymorphism. The setting was the island of Sardinia, Italy. Outcome measures were cause-specific standardized mortality ratios (SMRs), which were computed as 100 times the observed/expected ratio, with the general Sardinian male population as the reference. Deaths from all causes were significantly less than expected due to decreased SMRs for ischemic heart disease (SMR, 28; 95% confidence interval [CI], 10 to 62), cerebrovascular disease (SMR, 22; 95% CI, 6 to 55), and liver cirrhosis (SMR, 12; 95% CI, 0 to 66), which explained 95.6% of the deficit in total mortality. All cancer mortality was close to the expectation, with a significant increase in the SMR for non-Hodgkin's lymphoma (SMR, 545; 95% CI, 147 to 1,395). A decrease in mortality from cardiovascular diseases was one of the study hypotheses, based on an earlier human report and experimental evidence. However, selection bias is also a likely explanation. Further analytic studies are warranted to confirm whether subjects expressing the G6PD-deficient phenotype are protected against ischemic heart disease and cerebrovascular disease. This cohort study is consistent with more recent case-control studies in rejecting the hypothesis of a decreased cancer risk among G6PD-deficient subjects. The observed increase in mortality from non-Hodgkin's lymphoma and decrease in mortality from liver cirrhosis were not previously reported.     

A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group

BACKGROUND: The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate. METHODS: Using a two-by-two factorial design, we randomly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients). The rates of recurrent venous thromboembolism, death, and major bleeding were analyzed at day 12 and at two years. RESULTS: At day 12, two patients assigned to receive filters (1.1 percent), as compared with nine patients assigned to receive no filters (4.8 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). At two years, 37 patients assigned to the filter group (20.8 percent), as compared with 21 patients assigned to the no-filter group (11.6 percent), had had recurrent deep-vein thrombosis (odds ratio, 1.87; 95 percent confidence interval, 1.10 to 3.20). There were no significant differences in mortality or the other outcomes. At day 12, three patients assigned to low-molecular-weight heparin (1.6 percent), as compared with eight patients assigned to unfractionated heparin (4.2 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38). CONCLUSIONS: In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.     

Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994

BACKGROUND AND METHODS: To clarify the determinants of contemporary trends in mortality from coronary heart disease (CHD), we conducted surveillance of hospital admissions for myocardial infarction and of in-hospital and out-of-hospital deaths due to CHD among 35-to-74-year-old residents of four communities of varying size in the United States (a total of 352,481 persons in 1994). Between 1987 and 1994, we estimate that there were 11,869 hospitalizations for myocardial infarction (on the basis of 8572 hospitalizations sampled) and 3407 fatal coronary events (3023 sampled). RESULTS: The largest average annual decrease in mortality due to CHD occurred among white men (change in mortality, -4.7 percent; 95 percent confidence interval, -2.2 to -7.1 percent), followed by white women (-4.5 percent; 95 percent confidence interval, -0.7 to -8.2 percent), black women (-4.1 percent; 95 percent confidence interval, -10.3 to +2.5 percent), and black men (-2.5 percent; 95 percent confidence interval, -6.9 to +2.2 percent). Overall, in-hospital mortality from CHD fell by 5.1 percent per year, whereas out-of-hospital mortality declined by 3.6 percent per year. There was no evidence of a decline in the incidence of hospitalization for a first myocardial infarction among either men or women; in fact, such hospital admissions increased by 7.4 percent per year (95 percent confidence interval for the change, +0.5 to +14.8 percent) among black women and 2.9 percent per year (95 percent confidence interval, -3.6 to +9.9 percent) among black men. Rates of recurrent myocardial infarction decreased, and survival after myocardial infarction improved. CONCLUSIONS: From 1987 to 1994, we observed a stable or slightly increasing incidence of hospitalization for myocardial infarction. Nevertheless, there were significant annual decreases in mortality from CHD. The decline in mortality in the four communities we studied may be due largely to improvements in the treatment and secondary prevention of myocardial infarction.     

First analysis of mortality and occupational radiation exposure based on the National Dose Registry of Canada

A cohort mortality study of occupational radiation exposure was conducted using the records of the National Dose Registry of Canada. The cohort consisted of 206,620 individuals monitored for radiation exposure between 1951 and 1983 with mortality follow-up through December 31, 1987. A total of 5,426 deaths were identified by computerized record linkage with the Canadian Mortality Data Base. The standardized mortality ratio for all causes of death was 0.61 for both sexes combined. However, trends of increasing mortality with cumulative exposure to whole body radiation were noted for all causes of death in both males and females. In males, cancer mortality appeared to increase with cumulative exposure to radiation, without any clear relation to specific cancers. Unexplained trends of increasing mortality due to cardiovascular diseases (males and females) and accidents (males only) were also noted. The excess relative risk for both sexes, estimated to be 3.0% per 10 mSv (90% confidence interval 1.1-4.8) for all cancers combined, is within the range of risk estimates previously reported in the literature.     

Lowered risks of hypertension and cerebrovascular disease after vitamin/mineral supplementation: the Linxian Nutrition Intervention Trial

A total of 3,318 men and women from a region in rural China were randomized to receive daily either a multiple vitamin/mineral supplement or a placebo. Deaths that occurred in the participants were ascertained and classified according to cause over the 6-year period from 1985 to 1991. At the end of supplementation, blood pressure readings were taken, and the prevalence of hypertension was determined. There was a slight reduction in overall mortality in the supplement group (relative risk (RR) = 0.93, 95 percent confidence interval (CI) 0.75-1.16), with the decreased relative risk most pronounced for cerebrovascular disease deaths (RR = 0.63, 95 percent CI 0.37-1.07). This benefit was greater for men (RR = 0.42, 95 percent CI 0.19-0.93) than for women (RR = 0.93, 95 percent CI 0.44-1.98). Among the survivors, the presence of elevations in both systolic and diastolic blood pressures was less common in those who received the supplement (RR for men = 0.43, 95% CI 0.28-0.65; RR for women = 0.92, 95 percent CI 0.68-1.24). This study indicates that supplementation with a multivitamin/mineral combination may have reduced mortality from cerebrovascular disease and the prevalence of hypertension in this rural population with a micronutrient-poor diet.     

Determination of monensin, salinomycin and narasin in muscle, liver and eggs from domestic fowl using liquid chromatography-electrospray mass spectrometry

Historical records were used to reconstruct an outbreak of chlorance and acute liver toxicity due to chlorinated naphthalene exposure at a New York State plant which manufactured "Navy cables" during World War II. A cohort mortality study was conducted of the population (n = 9,028) employed at the plant from 1940 to 1944. Vital status was followed through December 31, 1985. The study found an excess of deaths from cirrhosis of the liver [observed (OBS) = 150; standardized mortality ratio (SMR) = 1.84; 95% confidence interval (CI) = 1.56-2.16]; cirrhosis deaths were elevated to a similar degree in the 460 individuals who had chlorance (OBS = 8; SMR = 1.51; CI = 0.65-2.98). The SMR for "non-alcoholic cirrhosis" (OBS = 83; SMR = 1.67; CI = 1.33-2.07) was similar to the SMR for "alcoholic cirrhosis" (OBS = 59; SMR = 1.96; CI = 1.49-2.53). There was no evidence for increased alcoholism in the overall cohort based on mortality from alcohol-related causes of death other than cirrhosis (SMR for esophageal cancer = 1.01 and for deaths from alcoholism = 0.99). We conclude that the excess mortality from cirrhosis of the liver observed in this cohort is due to the chronic effect of chlorinated naphthalene exposure.     

Mortality among fire fighters in metropolitan Toronto

Fire fighters are exposed to substances which are recognized or suspected causal agents in cancer or heart disease. The purpose of this study was to determine whether or not fire fighters experience increased risk for any specific cause of death. A retrospective cohort study was conducted, with 5,995 subjects recruited from all six fire departments within Metropolitan Toronto. The mortality experience of the cohort was ascertained through computerized record linkage and compared to that of the male Ontario population specific to cause, age, and calendar period from 1950 through 1989. Average duration of follow-up was 21 years, and there were 777 deaths among the 5,414 males included in the analysis, giving an all-cause standardized mortality ratio of 95 (95% confidence interval: 88-102). Three specific causes of death exhibit statistically significant excesses (brain tumors, "other" malignant neoplasms, and aortic aneurysms). There are also slight increases in risk for some other sites of cancer, and for various diseases of the respiratory, circulatory, and digestive systems. This study is consistent with others in demonstrating that fire fighters experience increased risk of death from cancer of the brain, and in suggesting increased risk for various other causes of death.     

Excess mortality in England and Wales, and in Greater London, during the 1995 heatwave

STUDY OBJECTIVE: To assess the impact on mortality of the heatwave in England and Wales during July and August 1995 and to describe any difference in mortality impact between the Greater London urban population and the national population. DESIGN: Analysis of variation in daily mortality in England and Wales and in Greater London during a five day heatwave in July and August 1995, by age, sex, and cause. SETTING: England and Wales, and Greater London. MAIN RESULTS: An estimated 619 extra deaths (8.9% increase, approximate 95% confidence interval 6.4, 11.3%) were observed during this heatwave in England and Wales, relative to the expected number of deaths based on the 31-day moving average for that period. Excess deaths were apparent in all age groups, most noticeably in women and for deaths from respiratory and cerebrovascular disease. Using published daily mortality risk coefficients for air pollutants in London, it was estimated that up to 62% of the excess mortality in England and Wales during the heatwave may be attributable to concurrent increases in air pollution. In Greater London itself, where daytime temperatures were higher (and with lesser falls at night), mortality increased by 16.1% during the heatwave. Using the same risk coefficients to estimate the excess mortality apparently attributable to air pollution, more than 60% of the total excess in London was apparently attributable to the effects of heat. CONCLUSION: Analysis of this episode shows that exceptionally high temperatures in England and Wales, though rare, do cause increases in daily mortality.     

The significance of coronary death for the excess mortality in alcohol-dependent men

General and validated cause-specific mortality, especially regarding coronary disease, was studied in a population-based cohort of 1049 alcohol-dependent (DSM-III-R) men, who were discharged from a detoxification ward. The observed and expected numbers of deaths were 140 and 23.2, respectively (P < 0.001). The estimated risk quotient of death was 6.0 (95% confidence interval 5.1-7.1). The concordance between revised and official causes of death was approximately 50%, but the resulting variation of risk quotients of cause-specific deaths generally remained within the statistical uncertainty. Coronary disease contributed to 19% of the total excess mortality in cases with a validated definite death diagnosis. The risk of coronary death tended to be augmented during the first 2 years of discharge (P = 0.05). Thus, coronary death contributed significantly to the excess mortality in alcohol-dependent men, and an increased vulnerability for sudden coronary death seemed to persist for a considerable time after discharge from detoxification.     

Risk of leukemia after platinum-based chemotherapy for ovarian cancer

BACKGROUND: Platinum-based chemotherapy is the cornerstone of modern treatment for ovarian, testicular, and other cancers, but few investigations have quantified the late sequelae of such treatment. METHODS: We conducted a case-control study of secondary leukemia in a population-based cohort of 28,971 women in North America and Europe who had received a diagnosis of invasive ovarian cancer between 1980 and 1993. Leukemia developed after the administration of platinum-based therapy in 96 women. These women were matched to 272 control patients. The type, cumulative dose, and duration of chemotherapy and the dose of radiation delivered to active bone marrow were compared in the two groups. RESULTS: Among the women who received platinum-based combination chemotherapy for ovarian cancer, the relative risk of leukemia was 4.0 (95 percent confidence interval, 1.4 to 11.4). The relative risks for treatment with carboplatin and for treatment with cisplatin were 6.5 (95 percent confidence interval, 1.2 to 36.6) and 3.3 (95 percent confidence interval, 1.1 to 9.4), respectively. We found evidence of a dose-response relation, with relative risks reaching 7.6 at doses of 1000 mg or more of platinum (P for trend <0.001). Radiotherapy without chemotherapy (median dose, 18.4 Gy) did not increase the risk of leukemia. CONCLUSIONS: Platinum-based treatment of ovarian cancer increases the risk of secondary leukemia. Nevertheless, the substantial benefit that platinum-based treatment offers patients with advanced disease outweighs the relatively small excess risk of leukemia.     

Neuropathology in the neurosciences. A system in transition

BACKGROUND: Despite the use of warfarin, major systemic embolism remains an important complication in patients with heart-valve replacement. Although the addition of antiplatelet agents has the potential to reduce this complication, their efficacy and safety when given in combination with warfarin are uncertain. METHODS: In a randomized, double-blind, placebo-controlled trial, we assessed the efficacy and safety of adding aspirin (100 mg per day) to warfarin treatment (target international normalized ratio, 3.0 to 4.5) in 370 patients with mechanical heart valves or with tissue valves plus atrial fibrillation or a history of thromboembolism. RESULTS: A total of 186 patients were randomly assigned to aspirin and 184 to placebo, and they were followed for up to 4 years (average, 2.5). Major systemic embolism or death from vascular causes occurred in 6 aspirin-treated patients (1.9 percent per year) and 24 placebo-treated patients (8.5 percent per year) (risk reduction with aspirin, 77 percent; 95 percent confidence interval, 44 to 91 percent; P < 0.001). Major systemic embolism, nonfatal intracranial hemorrhage, or death from hemorrhage or vascular causes occurred in 12 patients assigned to aspirin (3.9 percent per year) and 28 patients assigned to placebo (9.9 percent per year) (risk reduction, 61 per cent; 95 percent confidence interval, 24 to 80 percent; P = 0.005); major systemic embolism or death from any cause occurred in 13 patients (4.2 percent) and 33 patients (11.7 percent), respectively (risk reduction, 65 percent; 95 percent confidence interval, 33 to 82 percent; P < 0.001); and death from all causes occurred in 9 patients (2.8 percent) and 22 patients (7.4 percent), respectively (risk reduction, 63 percent; 95 percent confidence interval, 19 to 83 percent; P = 0.01). Bleeding occurred in 71 patients in the aspirin group (35.0 percent), as compared with 49 patients in the placebo group (22.0 percent) (increase in risk, 55 percent; 95 percent confidence interval, 8 to 124 percent; P = 0.02); major bleeding occurred in 24 and 19 patients, respectively (increase in risk, 27 percent; 95 percent confidence interval, -30 to 132 percent; P = 0.43). CONCLUSIONS: In patients with mechanical heart valves and high-risk patients with prosthetic tissue valves, the addition of aspirin to warfarin therapy reduced mortality, particularly mortality from vascular causes, together with major systemic embolism. Although there was some increase in bleeding, the risk of the combined treatment was more than offset by the considerable benefit.     

Postservice mortality of US Air Force veterans occupationally exposed to herbicides in Vietnam: 15-year follow-up

The US Air Force continues to assess the mortality of veterans of Operation Ranch Hand, the unit responsible for aerially spraying herbicides in Vietnam. The authors of this study found that the cumulative all-cause mortality experience of these veterans was not different from that expected (standardized mortality ratio (SMR) = 1.0). Overall, cause-specific mortality did not differ from that expected regarding deaths from accidents, cancer, or circulatory system diseases, but the authors found that there was an increased number of deaths due to digestive diseases (SMR = 1.7, 95% confidence interval (CI) 0.9-3.2). When analyzing by military occupation, they found an increase in the number of deaths caused by circulatory system diseases (SMR = 1.5, 95% CI 1.0-2.2) among enlisted ground personnel, the subgroup with the highest dioxin levels. Most of the increase in the number of deaths from digestive diseases was caused by chronic liver disease and cirrhosis, and more than half of the increase in the number of deaths from circulatory system diseases was a result of atherosclerotic heart disease. In the subgroup of Ranch Hand veterans who had survived more than 20 years since their military service in Southeast Asia, the authors found no significant increase in the risk of death due to cancer at all sites (SMR = 1.1) and a nonsignificant increase in the number of deaths due to cancers of the bronchus and lung (SMR = 1.3).     

Associations between hemorrhoids and other diagnoses

PURPOSE: The risk factors and mechanisms that contribute to the occurrence of hemorrhoids are not well understood. The study of the comorbid occurrences of hemorrhoids with other diagnoses in identical patients may point to a common underlying pathophysiology. The present study was undertaken to determine which diagnoses are associated with the occurrence of hemorrhoids. METHODS: A case-control study compared the occurrence of comorbid diseases in case subjects with hemorrhoids with that of control subjects without hemorrhoids. The case population comprised all patients with hemorrhoids (International Classification of Diseases codes 455.0-455.9), who were discharged from hospitals of the U.S. Department of Veterans Affairs between 1986 and 1996. In a multiple logistic regression analysis, the occurrence of hemorrhoids served as outcome variable, and age, gender, ethnicity, and the comorbid occurrence of other diagnoses served as predictor variables. RESULTS: A total of 96,314 individual patients with hemorrhoids and the same number of control subjects were identified. In a chart review of a random sample of 100 cases, the diagnosis of hemorrhoids could be confirmed in 97 percent of all instances checked. The variety of diagnoses associated with hemorrhoids could be broken down into five large categories: 1) diseases associated with diarrhea (odds ratio, 1.30; 95 percent confidence interval, 1.27-1.33); 2) spinal cord injuries (odds ratio, 1.17; 95 percent confidence interval, 1.09-1.26); 3) constipation and related diseases (odds ratio, 1.48; 95 percent confidence interval, 1.43-1.54); 4) various types of anorectal diseases (odds ratio, 4.71; 95 percent confidence interval, 4.44-5.0); and 5) conditions that could be considered manifestations or sequelae of the hemorrhoidal disease itself (odds ratio, 3.41; 95 percent confidence interval, 3.30-3.51). CONCLUSIONS: The types and spectrum of comorbid diagnoses associated with hemorrhoids suggest that an increased tone of the anal sphincter constitutes a common pathophysiologic mechanism for the development of hemorrhoids.     

Power-law relationship of heart rate variability as a predictor of mortality in the elderly

BACKGROUND: The prognostic role of heart rate (HR) variability analyzed from 24-hour ECG recordings in the general population is not well known. We studied whether analysis of 24-hour HR behavior is able to predict mortality in a random population of elderly subjects. METHODS AND RESULTS: A random sample of 347 subjects of > or =65 years of age (mean, 73+/-6 years) underwent a comprehensive clinical evaluation, laboratory tests, and 24-hour ECG recordings and were subsequently followed up for 10 years. Various spectral and nonspectral measures of HR variability were analyzed from the baseline 24-hour ECG recordings. Risk factors for all-cause, cardiac, cerebrovascular, cancer, and other causes of death were assessed. By the end of 10-year follow-up, 184 subjects (53%) had died and 163 (47%) were still alive. Seventy-four subjects (21%) had died of cardiac disease, 37 of cancer (11%), 25 of cerebrovascular disease (7%), and 48 (14%) of various other causes. Among all analyzed variables, a steep slope of the power-law regression line of HR variability (< -1.50) was the best univariate predictor of all-cause mortality (odds ratio, 7.9; 95% confidence interval [CI], 3.7 to 17.0; P<.0001). After adjusting for age and sex and including all univariate predictors of mortality in the proportional hazards analysis, ie, measures of HR variability, history of heart disease, functional class, smoking, medication, and blood cholesterol and glucose concentrations, all-cause mortality was predicted only by the slope of HR variability (adjusted relative risk, 1.74; 95% CI, 1.42 to 2.13; P<.0001) and a history of congestive heart failure (adjusted relative risk, 1.70; P=.0002). The slope of HR variability predicted both cardiac (adjusted relative risk, 2.05; P=.0002) and cerebrovascular death (adjusted relative risk, 2.84; P=.0001) but not cancer or other causes of death. CONCLUSIONS: Power-law relationship of 24-hour HR variability is a more powerful predictor of death than the traditional risk markers in elderly subjects. Altered long-term behavior of HR implies an increased risk of vascular causes of death rather than being a marker of any disease or frailty leading to death.     

A 15-year follow-up study after deliberate self-poisoning

The 15-year follow-up of mortality and the factors associated with death from various causes were studied in an unselected group of patients surviving deliberate self-poisoning in 1978. The cohort included 152 females and 101 males. By the end of 1993 a total of 37 (24%) of the females and 33 (33%) of the males admitted in 1978 had died. The total follow-up mortality was 4.5 times greater than expected for the female group (95% confidence interval: 3.1-6.1) and 3.6 times greater than expected (2.5-5.1) for the male group. It was highest in the first 5-year period. With regard to specific causes the mortality ratio was highest for deaths from suicide. For females it was 61.1 (30.5-109.4) and for males: 38.8 (20.4-65.4) times the expected ratio. It was also significantly raised for deaths from cardiovascular diseases in females: SMR = 3.7 (2.0-6.4) and from respiratory diseases in males: SMR = 3.3 (1.2-7.1). Significant predictors for death from all causes were age > or = 30 years: RR = 4.4 (2.3-8.5) and male sex: RR = 2.1 (1.2-3.5). Imprisonment was found to be a protective factor: RR = 0.2 (0.1-0.5). Predictors for death from suicide were age > or = 30: RR = 3.1 (1.2-8.1), male sex: RR = 3.3 (1.4-7.9) and a serious suicidal attempt, as evaluated by a psychiatrist: RR = 3.4 (1.4-7.9). It is concluded that patients who survive parasuicide by deliberate self-poisoning are at increased risk of death. The predictors for death are not very specific and are difficult to apply in clinical work with these patients.     

Renal eco Doppler in pediatrics

In this study, the authors investigated mortality and cancer patterns among a group of individuals accidentally exposed to methyl chloride 32 y earlier. This group of 24 persons had survived the immediate intoxication, which had occurred on a trawler during a fishing trip. The authors selected a reference group, which contained five times as many individuals as the study group, from registers of crews, and they controlled for age, occupation, social class, and lifestyle factors. The authors established a record linkage through personal identification numbers with the national death register and cancer register, thus securing 100% follow-up. The Mantel-Haenszel point estimate (M-H) was 2.2, and the 95% confidence interval (CI) was 1.3-3.1 for all causes of death. There was an excess of deaths from cardiovascular diseases (M-H = 2.1, 95% CI = 1.2-3.8). This excess mortality was more prominent among deckhands who had been subject to higher exposure; risk ratios (RRs) were elevated for all causes of death (RR = 2.5, 95% CI = 1.0-5.7), as well as for cardiovascular diseases (RR = 3.9, 95% CI = 1.0-14.4). In addition, the authors noted elevated risks for all cancers (M-H = 1.5, 95% CI = 0.3-5.6) and for lung cancer (M-H = 2.7, 95% CI = 0.1-52.6). The authors concluded that exposure to methyl chloride may have contributed to the risk of cardiovascular disease. Investigators need to conduct further studies on groups exposed to methyl chloride to refute or confirm this result.     

The Estonian study of Chernobyl cleanup workers: II. Incidence of cancer and mortality

A cohort of 4,742 men from Estonia who had participated in the cleanup activities in the Chernobyl area sometime between 1986 and 1991 and were followed through 1993 was analyzed with respect to the incidence of cancer and mortality. Incidence and mortality in the cleanup workers were assessed relative to national rates. No increases were found in all cancers (25 incident cases compared to 26.5 expected) or in leukemia (no cases observed, 1.0 expected). Incidence did not differ statistically significantly from expectation for any individual cancer site or type, though lung cancer and non-Hodgkin's lymphoma both occurred slightly more often than expected. A total of 144 deaths were observed [standardized mortality ratio (SMR) = 0.98; 95% confidence interval (CI) = 0.82-1.14] during an average of 6.5 years of follow-up. Twenty-eight deaths (19.4%) were suicides (SMR = 1.52; 95% CI = 1.01-2.19). Exposure to ionizing radiation while at Chernobyl has not caused a detectable increase in the incidence of cancer among cleanup workers from Estonia. At least for the short follow-up period, diseases directly attributable to radiation appear to be of relatively minor importance when compared with the substantial excess of deaths due to suicide.