Improved survival of Hodgkin's patients in south-east Netherlands since 1972

In the past 30 years, staging and treatment of Hodgkin's disease have changed dramatically, and prolonged remission can now be induced in the majority of patients. Our purpose was to assess improvement in long-term survival, previously reported for specific patient groups, among unselected patients diagnosed and treated between 1972 and 1993 in general hospitals in South-East Netherlands. Data on all 345 Hodgkin's patients were derived from the population-based Eindhoven Cancer Registry; histopathology and clinical records were reviewed. Follow-up was attained up to 1994. Relative survival rates, i.e. the ratio of observed to expected rates, were 80% after 5, 70% after 10 and 67% after 15 years. Independent prognostic factors for lower overall survival were (in decreasing order of significance): advanced age, histology (lymphocyte depletion), advanced stage and earlier period of diagnosis. Distribution of age and stage did not change over the study period, but there was a modest increase in the incidence of the nodular sclerosis histological subtype. Crude 5-year survival rates improved from 60% in the period 1972-1976 to 81% in the period of 1987-1992 (P < 0.005). The largest improvement occurred in the 1970s and was most prominent among those aged over 50 years. As previously reported, cured Hodgkin's patients exhibit a higher mortality rate, which can be explained by treatment-related long-term complications such as second malignancies and cardiovascular diseases. The relatively high survival rates compared to other population-based studies may be attributable to the existence of a regional network within the framework of a comprehensive cancer centre. Better staging, new combinations of chemotherapy, improved radiation technology, advances in supportive care as well as more frequent intensive treatment of the elderly could explain the improvement in prognosis.     

Hepatic mass in Budd-Chiari syndrome: CT and MRI findings

The North Karelia Project, a community-based demonstration project for prevention of cardiovascular diseases since 1972 in Finland, was successful in reducing the population levels of the major cardiovascular risk factors. A net decline in risk factors and coronary heart disease mortality was observed in North Karelia in the 1970s. Thereafter, the mortality from coronary heart disease has declined markedly in all of Finland. The aim of the study was to find out how the cancer mortality has changed in North Karelia during this longer follow-up period. Age-adjusted mortality trends were calculated for the male population aged between 35 and 64 years in the province of North Karelia, and in all of Finland for the period 1969-91, using the official mortality data. The trends and the changes were calculated using general linear model procedures. During the 20-year period, cancer mortality declined in North Karelia by 45.4% and in all of Finland by 32.7% (P = 0.006 for difference). The greater decline in North Karelia occurred particularly in the second decade of the follow up, and lung cancer. The results support the hypothesis that reduction in the population levels of the cardiovascular risk factors lead to beneficial changes in cancer mortality rates, but such changes take longer time to manifest than for coronary heart disease.     

Cloning and characterization of a novel membrane-associated antigenic protein of Helicobacter pylori

BACKGROUND: The aim of this study was to evaluate the effect of convective [hemodiafiltration (HDF) or hemofiltration (HF)] versus diffusive treatments [hemodialysis (HD)] on end-stage renal disease (ESRD) patient mortality and dialysis-related amyloidosis (DRA) using data from the Lombardy Registry. METHODS: For this purpose, 6, 444 patients (aged 56.4 +/- 15.6 years, females 39.5%, diabetics 10. 6%) who started renal replacement therapy (RRT) on HD, HDF, or HF between 1983 and 1995 were considered. A total of 1,082 patients were treated with HDF or HF (first choice in the case of 188), with a median follow-up of 29.7 months. The median follow-up of the 6,298 patients on HD (first choice in the case of 6256) was 22.4 months. The time of survival on dialysis to carpal tunnel syndrome (CTS) surgery was evaluated as a hard marker of DRA morbidity. Survival was compared by means of the Cox proportional regression hazards model, using CTS surgery and all deaths as events for morbidity and mortality, respectively. Explanatory covariates were age, gender, and comorbidities; dialysis modality was tested as a time-dependent covariate. RESULTS: The relative risk (RR) for CTS surgery was significantly higher in older patients [RR = 1.04 per year of age on admission to RRT, 95% confidence interval (CI) 1.02 to 1.06; P = 0. 0001], in diabetics (RR = 2.63, 95% CI 1.30 to 5.31; P = 0.0007), and in patients with heart disease (RR = 5.36, 95% CI 2.27 to 12.68 P = 0.0001). Adjusting for age and diabetic status, the RR for CTS surgery was 42% lower in the patients treated with HDF or HF (RR = 0. 58, 95% CI 0.35 to 0.95, P = 0.03). The RR for mortality, adjusted for age, gender, and comorbidities, was 10% lower in patients treated with HDF or HF (RR = 0.90, 95% CI 0.76 to 1.06; P = NS). CONCLUSION: These results support the hypothesis that convective treatments are associated with a nonsignificant trend toward better survival and significantly delay the need for CTS surgery. An older age and the presence of diabetes and heart disease are other important risk factors for CTS surgery. These results could have an important clinical impact given the relevance of DRA in dialysis patient morbidity.     

No increased risk of malignancies and mortality in cyclosporin A-treated patients with rheumatoid arthritis

OBJECTIVE: To evaluate the cyclosporin A (CSA)-attributed risk of developing malignancies in general and malignant lymphoproliferative diseases (LPDs) and skin cancers in particular, as well as the CSA-attributed incidence of mortality in patients with rheumatoid arthritis (RA). METHODS: In a retrospective, controlled cohort study, the incidence of malignancies and mortality was evaluated in 208 CSA-treated patients with RA compared with 415 matched control patients with RA between 1984 and 1995. Patients were followed up for a median of 5.0 years (range 1.4-12.0). RESULTS: Forty-eight cases of malignancy (8 in the CSA group and 40 in the control group; relative risk [RR] 0.40, 95% confidence interval [95% CI] 0.19-0.84) were identified, of which 8 were malignant LPDs (2 CSA versus 6 control; RR 0.67, 95% CI 0.14-3.27) and 14 were skin cancers (2 CSA versus 12 control; RR 0.33, 95% CI 0.08-1.47). Seventy-three patients died (16 CSA versus 57 control; RR 0.56, 95% CI 0.33-0.95) due primarily to cardiovascular diseases (4 CSA versus 22 control; RR 0.36, 95% CI 0.13-1.04) or a malignancy (3 CSA versus 8 control; RR 0.67, 95% CI 0.18-2.43). Proportional hazards regression analysis with correction for potential confounding factors did not significantly change the results. CONCLUSION: The study findings suggest that CSA treatment in RA patients does not increase the risk of malignancies in general or the risk of malignant LPDs or skin cancers in particular. Moreover, the incidence of mortality in CSA-treated RA patients was comparable to that in matched control RA patients.     

Trends in mortality of childhood-onset insulin-dependent diabetes mellitus in Leicestershire: 1940-1991

The relative risk of death by calendar date of diagnosis was investigated in a population-based incident cohort of 845 (463 males:382 females) IDDM diagnosed in Leicestershire before the age of 17 years between 1940 and 1989. The mortality status of 844 (99.9%) patients was determined as of the 31 December 1991, representing 14,346 person-years of risk. Trends in relative risk of death were investigated using Cox proportional hazards modelling for within cohort comparisons and age/sex and calendar time adjusted standardized mortality ratios (SMR) using generalized linear modelling for external comparisons. Median age at diagnosis was 10 years (range 3 months to 16 years); median duration of diabetes 15 years (range 1-51 years). Forty-four patients had died (5.2%; median age at death 31 years, range 11-51 years). A further four patients died at presentation (within 24 h) from ketoacidosis and are excluded from all analyses. Calendar date of diagnosis was found to be an important predictor of mortality. Adjusting for attained age there was evidence of a decline in relative risk of death with calendar date of diagnosis of 3.4% (95% CI, 0.005-6.9%) per annum, equivalent to a 32% fall per decade (95% CI, 5-51%), or 84% (95% CI, 21-97) from 1940 to 1989. The data are consistent with a large fall in mortality between the 1940s and 1950s representing over 50% of the total reduction in mortality between 1940 and 1991. Neither sex nor age at diagnosis were significant predictors of mortality. Over the study period 1940-89 the SMR (male and female combined) fell from 981 (541-1556) to 238 (60-953) relative to the general population. This population-based study shows that the prognosis for Type 1 (insulin-dependent) diabetes mellitus has improved markedly over the period 1940-1991.     

Increased mortality after successful treatment for Hodgkin's disease

PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.     

Induction of IgE antibody production in mice with different DPT-vaccine preparations

A historical cohort study was performed to assess cardiovascular morbidity and mortality in Type 2 (non-insulin-dependent) diabetic patients. The data were collected from 1967 to 1989 in four Dutch general practices performing the Continuous Morbidity Registration Nijmegen. Each newly diagnosed Type 2 diabetic patient fulfilling the WHO criteria (n = 265) was matched to a control patient for practice, sex, age, and social class. Inclusion started in 1967, the first year of the still ongoing, Continuous Morbidity Registration Nijmegen. On average, a follow-up of 6.8 years (range 1 month-22 years) was realized. Compared to the non-diabetic control patients, the Type 2 diabetic patients showed higher cardiovascular morbidity (risk ratio 1.76, 95% CI 1.34-2.30) and a higher mortality rate (risk ratio 1.54, 95% CI 1.07-2.23). Mortality after 10 years was 36% vs 20% (p < 0.01), the median survival time 16 years vs 19 years. The cumulative survival rates were significantly different (p < 0.01) between patients and controls in the age group 65-74 years. The higher mortality in Type 2 diabetic patients was completely due to an excess of cardiovascular death (risk ratio 2.05, 95% CI 1.24-3.37).     

Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients

OBJECTIVES: Our aim was to identify prognostic variables for long-term postoperative survival in trimodality management of malignant pleural mesothelioma. METHODS: From 1980 to 1997, 183 patients underwent extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapy. RESULTS: Forty-three women and 140 men (age range 31-76 years) had a median follow-up of 13 months. The perioperative mortality rate was 3.8% (7 deaths) and the morbidity, 50%. Survival in the 176 remaining patients was 38% at 2 years and 15% at 5 years (median 19 months). Univariate analysis identified 3 prognostic variables associated with improved survival: epithelial cell type (52% 2-year survival, 21% 5-year survival, 26-month median survival; P =.0001), negative resection margins (44% at 2 years, 25% at 5 years, median 23 months; P =.02), and extrapleural nodes without metastases (42% at 2 years, 17% at 5 years, median 21 months; P =.004). Using the Cox proportional hazards, the relative risk of death was calculated for nonepithelial cell type (OR 3.0, CI 2.0-4.5; P <.0001), positive resection margins (OR 1.7, CI 1.2-2.6; P =.0082), and metastatic extrapleural nodes (OR 2.0, CI 1.3-3.2; P =.0026). Thirty-one patients with 3 positive variables had the best survival (68% 2-year survival, 46% 5-year survival, median 51 months; P =.013). A previously published staging system using these variables stratified survival (P <.05). CONCLUSIONS: (1) Multimodality therapy including extrapleural pneumonectomy is feasible in selected patients with malignant pleural mesotheliomas, (2) pre-resectional evaluation of extrapleural nodes may select patients for radical therapy, (3) microscopic resection margins affect long-term survival, highlighting the need for further investigation of locoregional control, and (4) patients with epithelial, margin-negative, extrapleural node-negative resection had extended survival.     

Aspirin use in middle-aged men with cardiovascular disease: are opportunities being missed?

BACKGROUND: Since the 1980s, clinical trial evidence has supported aspirin use in the secondary prevention of cardiovascular disease (CVD). AIM: To explore aspirin use among British men with known CVD in a population-based study. METHOD: Longitudinal study (British Regional Heart Study), in which subjects have been followed up for cardiovascular morbidity and mortality since 1978-1980. Aspirin use was assessed by questionnaires to study participants in November 1992 (Q92); cardiovascular diagnoses are based on general practice notifications to October 1992. A total of 5751 men aged 52-73 years (87% of survivors) completed questions on aspirin use. RESULTS: Overall, 547 men (9.5%) were taking aspirin daily, of whom 321 (59%) had documented CVD. Among men with pre-existing disease, 153 out of 345 (44%) men with myocardial infarction, 42 out of 109 (39%) with stroke, and 75 out of 247 (29%) with angina were taking aspirin daily. Among men with angina (54% versus 26%) or myocardial infarction (59% versus 42%), those who had undergone coronary artery bypass surgery (CABG) or angioplasty were more likely to be receiving aspirin. Higher rates of aspirin use were also found in those whose last major event occurred after January 1990 (47% versus 34%). There was no association between aspirin use and social class or region of residence. CONCLUSION: Despite strong evidence of its effectiveness, many patients with established CVD were not receiving aspirin. Daily aspirin treatment was less likely in men with less recent major CVD events and in those who had not received invasive treatment.     

Do cardiovascular risk factors explain the relation between socioeconomic status, risk of all-cause mortality, cardiovascular mortality, and acute myocardial infarction?

Much remains to be understood about how low socioeconomic status (SES) increases cardiovascular disease and mortality risk. Data from the Kuopio Ischemic Heart Disease Risk Factor Study (1984-1993) were used to estimate the associations between acute myocardial infarction and income, all-cause mortality, and cardiovascular mortality in a population-based sample of 2,272 Finnish men, with adjustment for 23 biologic, behavioral, psychologic, and social risk factors. Compared with the highest income quintile, those in the bottom quintile had age-adjusted relative hazards of 3.14 (95% confidence interval (CI) 1.77-5.56), 2.66 (95% CI 1.25-5.66), and 4.34 (95% CI 1.95-9.66) for all-cause mortality, cardiovascular mortality, and AMI, respectively. After adjustment for risk factors, the relative hazards for the same comparisons were 1.32 (95% CI 0.70-2.49), 0.70 (95% CI 0.29-1.69), and 2.83 (95% CI 1.14-7.00). In the lowest income quintile, adjustment for risk factors reduced the excess relative risk of all-cause mortality by 85%, that of cardiovascular mortality by 118%, and that of acute myocardial infarction by 45%. These data show how the association between SES and cardiovascular mortality and all-cause mortality is mediated by known risk factor pathways, but full "explanations" for these associations will need to encompass why these biologic, behavioral, psychologic, and social risk factors are differentially distributed by SES.     

Hyperglycemia and compositional lipoprotein abnormalities as predictors of cardiovascular mortality in type 2 diabetes: a 15-year follow-up from the time of diagnosis

OBJECTIVE: We studied the 15-year cardiovascular mortality and morbidity of newly diagnosed patients with type 2 diabetes and of nondiabetic control subjects and the predictors of cardiovascular mortality in diabetic patients. RESEARCH DESIGN AND METHODS: We performed a 15-year prospective study of 133 middle-aged patients with newly diagnosed type 2 diabetes and 144 control subjects. Cardiovascular risk factors were assessed in both groups at baseline and after 5 and 10 years. RESULTS: Total mortality was markedly higher in patients with type 2 diabetes (total: 44.3 vs. 12.9% for men, age-adjusted odds ratio [OR] 5.0, P < 0.001; 44.4 vs. 11.0% for women, OR 5.2, P < 0.001), which was due to increased cardiovascular mortality (ORs for men and women: 6.2 and 11.2, respectively, P < 0.001 for both). The incidences of fatal and nonfatal myocardial infarction and stroke were likewise higher in diabetic patients. In univariate analyses and various multiple logistic regression analyses, hyperglycemia was a constant predictor of cardiovascular mortality assessed at the time of diagnosis or at 5- or 10-year examinations. Moreover, lipoprotein abnormalities characteristic of type 2 diabetes (low HDL cholesterol, high LDL triglycerides or apolipoprotein B levels, and low LDL cholesterol/apolipoprotein B ratio as a marker for LDL size) were predictive of cardiovascular death in these analyses. CONCLUSIONS: This long-term study of a well-characterized group of newly diagnosed patients strengthens the view that the prognosis in middle-aged subjects is markedly impaired and that both hyperglycemia and compositional lipoprotein abnormalities are predictors of cardiovascular mortality in patients with type 2 diabetes.     

Risk of subsequent malignant neoplasms among 1,641 Hodgkin's disease patients diagnosed in childhood and adolescence: a population-based cohort study in the five Nordic countries. Association of the Nordic Cancer Registries and the Nordic Society of Pediatric Hematology and Oncology

PURPOSE: To assess the risk of subsequent malignant neoplasms among Hodgkin's disease patients diagnosed before 20 years of age in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). PATIENTS AND METHODS: There were 1,641 Hodgkin's disease patients identified through the national cancer registries since the 1940s or 1950s. The patients were monitored for 17,000 person-years until the end of 1991. Expected figures were derived from the age-specific incidence rates in each country and standardized incidence ratios (SIR) were calculated. RESULTS: A total of 62 subsequent neoplasms were diagnosed (SIR, 7.7; 95% confidence interval [CI], 5.9 to 9.9). The overall cumulative risk of subsequent neoplasms was 1.9% at the 10-year follow-up point, 6.9% at 20 years, and 18% at 30 years. There were 26 subsequent neoplasms among males (SIR, 6.5; 95% CI, 4.3 to 9.6) and 36 among females (SIR, 8.9; 95% CI, 6.2 to 12), of which 16 were breast cancers (SIR, 17; 95% CI, 9.9 to 28). High risks were seen for thyroid cancer (SIR, 33; 95% CI, 15 to 62), for secondary leukemia (SIR, 17; 95% CI, 6.9 to 35), and for non-Hodgkin's lymphoma (SIR, 15; 95% CI, 4.9 to 35). The relative risk increased from 3.3 (95% CI, 1.2 to 7.1) for Hodgkin's disease patients diagnosed in the 1940s and 1950s to 15 (95% CI, 7.4 to 27) in the 1980s. The highest risk of secondary leukemia (SIR, 68; 95% CI, 18 to 174) was seen among those diagnosed with Hodgkin's disease in the 1980s. CONCLUSION: Patients who survive Hodgkin's disease at a young age are at very high relative risk of subsequent malignant neoplasms throughout their lives. In particular, the high relative risk of breast cancer following Hodgkin's disease in the teenage years calls for enhanced activity for early diagnosis.     

Comparison of mortality from acute myocardial infarction between 1979 and 1992 in a geographically defined stable population

This study documents mortality from acute myocardial infarction (AMI), in hospital and at 1 year, for each of 3 selected 1-year periods in a stable community over a 13-year period beginning in 1979 and continuing into the thrombolytic era, to detect any changes occurring in conjunction with the introduction of new therapies. Every patient with AMI occurring in a geographically defined stable community (Hamilton, Ontario, Canada) in 3 1-year periods (1979 to 1980 [n = 816], 1986 to 1987 [n = 816], and 1991 to 1992 [n = 831]) was identified and clinically characterized by standardized criteria. Subsequent in-hospital and 1-year survival were ascertained prospectively. The 3 cohorts were similar in prognostic factors. Mean age was progressively greater over the study period from 63 years in 1979 to 1980, to 67 years in 1991 to 1992 (p = 0.02). There was no change in in-hospital mortality rates from 1979 to 1980 (17%) and 1986 to 1987 (16%). However, from 1986 to 1987 and 1991 to 1992, in-hospital mortality decreased from 16% to 9% (p < 0.001) and 1-year mortality decreased from 26% to 19% (p < 0.001). For patients who survived the hospital phase of AMI, 1-year mortality did not change and was between 11% and 12% in each of the 3 study periods. From 1986 to 1987 and 1991 to 1992, there was an increase in the use of thrombolytic therapy from 5% to 44% of patients. The acute use of aspirin increased from 30% to 88% and the acute use of beta blockers increased from 19% to 48% of patients. The observed increase in use of these agents could account for half of the actual mortality reduction observed. This prospective population-based survey demonstrates improved in-hospital survival after AMI associated with increased use of established effective therapies between 1987 and 1992. The 1-year mortality of hospital survivors of AMI was unchanged throughout the period of study, remaining at 11% to 12%.     

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.     

High prevalence of risk factors for cardiovascular disease in parents of IDDM patients with albuminuria

Life expectancy is shorter in the subset of insulin-dependent diabetic (IDDM) patients who are susceptible to kidney disease. Familial factors may be important. In this study the prevalence of cardiovascular disease mortality and morbidity and of risk factors for cardiovascular disease was compared in the parents of 31 IDDM patients with elevated albumin excretion rate (AER > 45 microg/min; group A) with that of parents of 31 insulin-dependent diabetic patients with normoalbuminuria (AER < 20 microg/min; group B). The two diabetic patient groups were matched for age and duration of disease. Information on deceased parents was obtained from death certificates and clinical records and morbidity for cardiovascular disease was ascertained using the World Health Organization questionnaire and Minnesota coded ECG. Hyperlipidaemia was defined as serum cholesterol higher than 6 mmol/l and/or plasma triglycerides higher than 2.3 mmol/l and/or lipid lowering therapy; arterial hypertension as systolic blood pressure higher than 140 mmHg and/or diastolic blood pressure higher than 90 mmHg and/or antihypertensive treatment. The percentage of dead parents was similar in the two groups (26 vs 20% for parents of group A vs group B, respectively), but the parents of the diabetic patients with elevated AER had died at a younger age (58 +/- 10 vs 70 +/- 14 years; p < 0.05). Parents of diabetic patients with nephropathy had a more than three times greater frequency of combined mortality and morbidity for cardiovascular disease than that of the parents of diabetic patients without nephropathy (26 vs 8%; odds ratio 3.96, 95% CI 1.3 to 12.2; p < 0.02). Living parents of group A had a higher prevalence of arterial hypertension (42 vs 14% p < 0.01) and hyperlipidaemia (49 vs 26% p < 0.05) as well as higher levels of lipoprotein (a) [median (range) 27.2 (1-107) vs 15.6 (0.2-98) mg/dl; p < 0.05]. They also had reduced insulin sensitivity [insulin tolerance test: median (range) K(itt) index: 3.7 (0.7-6.2) vs 4.8 (0.7-6.7)% per min; p < 0.05]. In the families of IDDM patients with elevated AER there was a higher frequency of risk factors for cardiovascular disease as well as a predisposition to cardiovascular disease events. This may help explain, in part, the high prevalence of cardiovascular disease mortality and morbidity in those IDDM patients who develop nephropathy.     

Clinicopathologic features of patients with hepatocellular carcinoma surviving >10 years after hepatic resection

BACKGROUND: This study was performed to clarify the clinicopathologic features of hepatocellular carcinoma (HCC) patients surviving >10 years after hepatic resection. METHODS: Between January 1971 and April 1987, 142 patients underwent hepatic resection. Thirty-nine patients who died of surgical morbidity (surgical mortality rate: 27.5%) were excluded from this study. Among the 103 patients who survived and were observed for >10 years after surgery, 12 patients (11.7%) survived >10 years after hepatectomy. The surviving patients were divided into 2 groups: 10-year survivors (n = 12) and nonsurvivors (n = 91). A comparative study between the two groups was made. RESULTS: Preoperative liver function tests such as the indocyanine green retention test at 15 minutes and albumin levels showed that 10-year survivors had better liver function than nonsurvivors. With regard to virus markers, 5 of 12 patients (41.7%) were positive for hepatitis B surface antigen (HBs-Ag) and the incidence of hepatitis B virus-related HCC was significantly higher than in nonsurvivors (P = 0.020). The results also showed that 4 of 12 long term survivors had hepatitis C virus (HCV) antibody and 1 patient did not have any HCV antibody or HBs-Ag. In two other patients, the HCV antibody was not measured and HBs-Ag was negative. Among four patients with the HCV antibody, the serum HCV RNA concentration, measured by branched DNA probe assay, was <0.5 in 3 patients and 1.72 in 1 patient. Therefore, the HCV RNA concentration tended to be lower in 10-year survivors. Tumor recurrence occurred in 8 of the 10-year survivors. Solitary recurrence was observed in five patients whereas multiple recurrence was observed in three patients. All five patients with solitary recurrence underwent a second resection. CONCLUSIONS: Based on the results of the current study, good liver function, HBs-Ag positivity, and a low concentration of serum HCV RNA in HCV-related HCC should be considered potentially good predictors of a long term survival.     

Changes in physical fitness and changes in mortality

BACKGROUND: Point estimates of physical fitness give important information on the risk of death in healthy people, but there is little information available on effects of sequential changes in physical fitness on mortality. We studied this latter aspect in healthy middle-aged men over a total follow-up period of 22 years. METHODS: 2014 healthy men aged 40-60 years had a bicycle exercise test and clinical examination, and completed a questionnaire in 1972-75 (survey 1). This was repeated for 1756 (91%) of 1932 men still alive by Dec 31, 1982 (survey 2). The exercise scores were adjusted for age. The change in exercise scores between surveys was divided into quartiles (Q1=least fit, Q4=fittest). An adjusted Cox's proportional hazards model was used to study the association between changes in physical fitness and mortality, with the Q1 men used as controls. FINDINGS: By Dec 31, 1994, 238 (17%) of the 1428 men had died, 120 from cardiovascular causes. There were 37 deaths in the Q4 group (19 cardiovascular); their relative risks of death were 0.45 (95% CI 0.29-0.69) for any cause and 0.47 (0.26-0.86) for cardiovascular causes. There was a graded, inverse relation between changes in physical fitness and mortality irrespective of physical fitness status at survey 1. INTERPRETATION: Change in physical fitness in healthy middle-aged men is a strong predictor of mortality. Even small improvements in physical fitness are associated with a significantly lowered risk of death. If confirmed, these findings should be used to influence public health policy.     

Mortality after deliberate self-poisoning. A prospective follow-up study of 587 persons observed for 5279 person years: risk factors and causes of death

A follow-up study of mortality and factors associated with death from various causes were done on two unselected groups of patients surviving deliberate self-poisoning in 1978 and 1987. The persons were studied up to the end of 1993. In 1978 the group included 152 female and 101 male subjects and in 1987 the group included 190 female and 144 male subjects. By the end of 1993 a total of 37 (24%) of the female and 33 (33%) of the male patients admitted in 1978 had died (n.s.) and 18 (10%) of the female and 29 (20%) of the male patients admitted in 1987 had died (P < 0.01). The main causes of death were suicide and death from cardiovascular disease. The 5-year follow-up mortality more than doubled in males from 1978 to 1987 but decreased in females. In female subjects, the total follow-up mortality was 3.6 times the expected ratio, with a 95% confidence interval (95% CI of 2.7-4.6); in male subjects it was 5.0 times the expected ratio (95% CI = 3.8-6.4). The cause-specific mortality ratio was highest for deaths from suicide--in the female group it was 65.5 (39.4-102.3) times the expected and in the male group 41.5 (26.0-62.8)--and from accidental poisoning--for females 50.0 (6.1-180.6) times the expected and for males 66.7 (24.5-145.1). In the female group none of the variables examined reached significance as predictors for subsequent suicide or death from unnatural causes. In the male group being aged 30 years or more came out as a predictor for subsequent suicide [relative risk (RR) = 5.66 (1.05-30.37)], while imprisonment came out as a protective factor [RR = 0.08 (0.01-0.64)]. Significant predictors for death from unnatural causes were: having been convicted (but not been in jail) [RR = 34.01 (1.07-1078.15)] and a serious suicidal intent [RR = 138.62 (1.38-13,946.79)]. It is concluded that patients who survive deliberate self-poisoning are at increased risk of death. The predictors for death are not very specific and are considered difficult to apply in the clinical work with these patients.     

The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens

AIMS: To evaluate the prognostic value of the QT interval and QT interval dispersion in total and in cardiovascular mortality, as well as in cardiac morbidity, in a general population. METHODS AND RESULTS: The QT interval was measured in all leads from a standard 12-lead ECG in a random sample of 1658 women and 1797 men aged 30-60 years. QT interval dispersion was calculated from the maximal difference between QT intervals in any two leads. All cause mortality over 13 years, and cardiovascular mortality as well as cardiac morbidity over 11 years, were the main outcome parameters. Subjects with a prolonged QT interval (430 ms or more) or prolonged QT interval dispersion (80 ms or more) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360 ms, or whose QT interval dispersion was less than 30 ms. Cardiovascular death relative risk ratios, adjusted for age, gender, myocardial infarct, angina pectoris, diabetes mellitus, arterial hypertension, smoking habits, serum cholesterol level, and heart rate were 2.9 for the QT interval (95% confidence interval 1.1-7.8) and 4.4 for QT interval dispersion (95% confidence interval 1.0-19-1). Fatal and non-fatal cardiac morbidity relative risk ratios were similar, at 2.7 (95% confidence interval 1.4-5.5) for the QT interval and 2.2 (95% confidence interval 1.1-4.0) for QT interval dispersion. CONCLUSION: Prolongation of the QT interval and QT interval dispersion independently affected the prognosis of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years.     

Long-term effects of therapy on respiratory health

Only scant information is available on the long-term consequences to respiratory health of treatment with bronchodilators and oral corticosteroids. In the present study, we aimed to gain more information about these consequences. We examined 712 men working in the Paris area, by means of a subjective assessment of whether their respiratory health worsened or improved from 1960 to 1972, the decline in forced expiratory volume in one second (FEV1) over this time-period, and mortality from 1972 to 1992, in relation to respiratory therapy dispensed during a 2 year period in 1970-1971, as recorded in social security reimbursement records. As expected, subjects with respiratory symptoms or airflow limitation were more likely to have been prescribed respiratory therapy. After accounting for the effect of lung function level and smoking, subjects dispensed inhaled beta-agonists were likely to feel their condition had worsened and had a greater decline in FEV1 from 1960 to 1972. Among subjects with airflow limitation who reported asthma or persistent wheeze, having been dispensed oral corticosteroids on an intermittent basis was associated with improved survival (relative risk (RR) 0.32; 95% confidence interval (95% CI): 0.10-0.91) after adjusting for FEV1 level and smoking category. Our results add to the evidence that regular use of beta-agonist bronchodilators may be associated with adverse effects on respiratory health, whilst intermittent use of corticosteroids may be of long-term benefit.