Internet paradox. A social technology that reduces social involvement and psychological well-being?

We present a method for estimating age- and time-specific HIV incidence using back-calculations of AIDS incidence data. Two-dimensional penalized likelihood is employed, using a flexible bivariate step function model of HIV incidence, together with a quadratic roughness penalty which leads to thin-plate spline smoothing. This allows incidence estimates to vary flexibly and smoothly in both age and time. We propose generalized cross-validation as a guide for choice of an appropriate level of smoothing and describe an EM algorithm for computing the estimates. We propose the method primarily for qualitative assessment of trends in age-specific incidence over time and apply it to a small Italian data set on men who have sex with men. The analysis suggests a trend over time of increasing relative incidence among younger individuals, consistent with incidence patterns observed in other countries.     

Lifetime risk of dementia and Alzheimer's disease. The impact of mortality on risk estimates in the Framingham Study

We estimated the remaining lifetime risks of developing Alzheimer's disease (AD) and dementia from all causes, based on data from longitudinal population studies. The risk of developing AD during one's lifetime depends on both disease incidence and life expectancy. Conventional estimates of cumulative incidence overestimate the risk when there is a substantial probability of mortality due to competing causes. A total of 2,611 cognitively intact subjects (1,061 men, 1,550 women; mean age, 66 +/- 7 years) were prospectively evaluated for the development of AD or other dementia. A modified survival analysis was used to estimate both cumulative incidence and the sex-specific remaining lifetime risk estimates for quinquennial age groups above age 65 years. Over a 20-year follow-up period, 198 subjects developed dementia (120 with AD). The remaining lifetime risk of AD or other dementia depended on sex, being higher in women, but varied little with age between 65 and 80 years. In a 65-year-old man, the remaining lifetime risk of AD was 6.3% (95% CI, 3.9 to 8.7) and the remaining lifetime risk of developing any dementing illness was 10.9% (95% CI, 8.0 to 13.8); corresponding risks for a 65-year-old woman were 12% (95% CI, 9.2 to 14.8) and 19% (95% CI, 17.2 to 22.5). The cumulative incidence between age 65 and 100 years was much higher: for AD, 25.5% in men and 28.1% in women; for dementia, 32.8% in men and 45% in women. The actual remaining lifetime risk of AD or dementia varies with age, sex, and life expectancy and is lower than the hypothetical risk estimated by a cumulative incidence in the same population.     

The incidence of dementia: a meta-analysis

OBJECTIVE: To carry out a meta-analysis of the age-specific incidence of all dementias, including AD and vascular dementia. BACKGROUND: Several meta-analyses have been carried out on dementia prevalence, but none on its incidence. METHODS: We used loess-curve fitting to analyze data from 23 published studies reporting age-specific incidence data. RESULTS: The incidence of both dementia and AD rose exponentially up to the age of 90 years, with no sign of leveling off. The incidence rates for vascular dementia varied greatly from study to study, but the trend was also for an exponential rise with age. There was no sex difference in dementia incidence (p = 0.21), but women tended to have a higher incidence of AD in very old age, and men tended to have a higher incidence of vascular dementia at younger ages. East Asian countries had a lower incidence of dementia than Europe (p = 0.0004), and also tended to have a lower incidence of AD. CONCLUSIONS: The incidence of dementia rises exponentially to the age of 90 years. Any sex differences are small, and incidence is lower in East Asia than in Europe.     

Epidemiology of renal cell carcinoma in Connecticut, 1935-1973

Data on over 3,700 patients with renal cell carcinoma, reported to the Connecticut Tumor Registry from 1935 through 1973, were used to assess incidence, survival, and associations of risk with demographic characteristics. Incidence increased over time among men, but not among women; a birth cohort effect suggesting increasing incidence rate over time was demonstrated for men. A comparison of male and female age-specific incidence rates indicated that, in the 15- to 39-year-old age group, men were three times more likely than women to develop the disease; after age 40, renal cell carcinoma was diagnosed in men twice as often as in women. Survival probability has increased from 1940 to the present time. A high density of persons per square mile was associated with a higher-than-expected incidence. No trends in incidence according to socioeconomic status were observed.     

Hodgkin's disease: the protective effect of childbearing

Register and census data for complete cohorts of Norwegian men and women born between 1935 and 1974 were used to examine the relationship between reproductive factors and the incidence of Hodgkin's disease (HD). Among 1.3 million men and 1.3 million women under observation, 695 male and 441 female cases of HD were diagnosed during the period of follow-up. Our hazard model estimates showed that women, at a given age and in a given birth cohort, have an HD incidence inversely related to current parity. A clear relationship was found only for the nodular sclerosis subtype. In men, the risk of HD development was higher than that in childless women, and there was no parity effect. The lower HD incidence among high-parity women could not be ascribed to their lower social status. Presumably, there is a still unidentified protective factor associated with the biology of childbearing, the effect of which possibly wears off with increasing length of time since childbirth. In addition, there are indications of a net effect of age at entry into motherhood, which may explain part of the estimated parity effect.     

Multivariate risk estimation for coronary heart disease: the Busselton Health Study

Coronary heart disease (CHD) is a multifactorial disease and CHD risk should be estimated by assessing all cardiovascular risk factors simultaneously. Simply adding up the number of factors with 'at risk' values fails to identify high-risk subjects with multiple risk factors at moderately elevated values. A more efficient approach is to use a quantitative multivariate risk score. A number of overseas studies have produced CHD risk scoring systems for men. There are few risk scores developed for women and no CHD risk scores have been developed from Australian data. This study used data on CHD risk factors and morbidity/mortality follow-up for the 1978 Busselton Health Survey participants to provide age-specific estimates of absolute risk of CHD hospitalisation or death, and to develop multivariate CHD risk scoring systems for men and women. The scores are based on age, blood pressure, anti-hypertensive medication, total and HDL cholesterol, smoking, diabetes, left ventricular hypertrophy and previous history of CHD. The generalisability and applicability of these risk estimation systems to Australian populations in the late 1990s is discussed.     

Asymptomatic incidence and duration of prostate cancer

Prostate cancer is known as a disease with an extremely high prevalence relative to its clinical incidence in the population. The combination of preclinical incidence and duration that could yield this phenomenon is of tremendous interest to researchers trying to understand the natural history of the disease and to develop efficient screening strategies. In this article, the authors present estimates of the age-specific asymptomatic incidence and average preclinical duration of prostate cancer. The methodological approach is to first estimate the age-specific incidence of new (stage AI) prostate cancers using preclinical prevalence data from autopsy studies performed between 1941 and 1964 and clinical incidence data for the years 1960-1986 from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. Then, the preclinical prevalence estimates are divided by the derived preclinical incidence estimates to yield estimates of the average duration of asymptomatic disease. The estimated mean duration among white men is between 11 and 12 years and appears to be approximately 1 year shorter for blacks than for whites. Comparison of the lifetime risks of preclinical and clinical disease suggests that approximately 75% of prostate cancers will never become diagnosed if clinical incidence remains at levels observed in 1984-1986, prior to the introduction of prostate-specific antigen (PSA) screening in the population.     

Declining HIV-2 prevalence and incidence among men in a community study from Guinea-Bissau

OBJECTIVE: To assess the present level of HIV-2 infection in an adult population in Bissau and to evaluate sex and age-specific changes in HIV-2 prevalence and incidence between 1987 and 1996. DESIGN AND METHODS: Sex and age-specific changes in HIV-2 prevalence were evaluated comparing a survey from 1987 in a sample of 100 houses with a survey performed in 1996 in an independent sample of 212 houses from the same study area. HIV-2 incidence rates were examined in an adult population (age > or = 15 years) from 100 randomly selected houses followed with four consecutive HIV serosurveys from 1987 to 1996. RESULTS: The HIV-2 prevalence in 1996 was 6.8% (men, 4.7%; women, 8.4%). Compared with the 1987 survey there was a significant decrease in prevalence among men [age-adjusted relative risk (RR), 0.50; 95% confidence interval (CI), 0.31-0.83], whereas it remained unchanged in women (RR, 1.00; 95% CI, 0.67-1.48). The male-to-female RR decreased from 0.99 (95% CI, 0.61-1.61) in 1987 to 0.51 (95% CI, 0.34-0.76) in 1996. The overall annual incidence rate was 0.54 per 100 person-years of observation (PYO), being higher in women (0.72 per 100 PYO) than in men (0.31 per 100 PYO). With the observation time divided into an early and a late period, there was a decrease in incidence with time among men (0.66 to 0.00 per 100 PYO), but no major change among women (0.59 to 0.85 per 100 PYO). The two trends differed significantly (P = 0.03). We observed a higher annual incidence rate amongst older women aged > 44 years (1.77 per 100 PYO) than among younger women (0.55 per 100 PYO; P = 0.05). CONCLUSION: There are no signs of an epidemic spread of HIV-2 in Bissau even though the HIV-1 prevalence is increasing rapidly. A significant reduction in the male HIV-2 prevalence and incidence rates has resulted in a major shift in the pattern of spread of HIV-2, from being equally distributed to being predominantly a female infection. Currently, older women in particular seem to have a high risk of getting infected.     

Value of exercise treadmill testing in women

OBJECTIVES: We sought to determine the ability of a treadmill score to provide accurate diagnostic and prognostic risk estimates in women. BACKGROUND: Treadmill testing has been reported to have a lower accuracy for diagnosis of chest pain in women. The diagnostic and prognostic value of the Duke Treadmill Score (DTS) in women is unknown. METHODS: We determined the diagnostic and prognostic value of the DTS in 976 women and 2,249 men who underwent both treadmill testing and cardiac catheterization in a single institution from 1984 to 1994. RESULTS: Women and men differed significantly in DTS (1.6 vs. -0.3, p < 0.0001), disease prevalence (32% vs. 72% significant coronary artery disease [CAD], p < 0.001), and 2-year mortality (1.9% vs. 4.9%, p < 0.0001). The DTS provided information beyond clinical predictors of both coronary disease and survival in women and men. Although overall women had better survival, the DTS performed equally well in stratifying both genders into prognostic categories. The DTS actually performed better in women than in men for excluding disease, with fewer low risk women having any significant coronary disease (> or = 1 vessel with > or =75% stenosis) (20% vs. 47%, p < 0.001), or severe disease (3-vessel disease or > or =75% left main stenosis) (3.5% vs. 11.4%, p < 0.001). CONCLUSIONS: By combining several aspects of treadmill testing, the DTS effectively stratifies women into diagnostic and prognostic risk categories.     

Inhibition of intimal hyperplasia after vein grafting by in vivo transfer of human senescent cell-derived inhibitor-1 gene

OBJECTIVE: To define the distribution and determinants of cardiovascular disease events among participants undergoing long-term antihypertensive therapy, and to stratify them into risk groups on the basis of pretreatment clinical profiles. DESIGN: A prospective cohort study of participants in a worksite-based antihypertensive treatment program in New York city (1973-1994). PATIENTS: We studied 8690 systematically treated patients who had at least 6 months of follow-up (average of 5.7 years) and, at entry, had had a systolic blood pressure of > or = 160 mmHg or a diastolic blood pressure of > or = 95 mmHg (after 1992 > or = 140/90 mmHg), or had been being administered antihypertensive medication. MAIN OUTCOME MEASURES: Blood pressure and incidence of morbid and mortal cardiovascular events. RESULTS: Blood pressure control (to 140 +/- 3/87 +/- 7 mmHg) was achieved by the first year and maintained through 18 years of therapy. In nearly 50,000 person-years of follow-up, there were 468 cardiovascular disease events [myocardial infarction including revascularization (282), strokes (93), congestive heart failure (30) and other cardiovascular deaths (63)]. Deaths from cardiovascular disease events accounted for 68% of all deaths. Myocardial infarction was most common throughout, but congestive heart failure incidence surpassed stroke incidence after 10 years. A scheme for risk stratification was constructed after analysis of the independent association of baseline factors and incident cardiovascular events. Upon the basis of ease of ascertainment and their demonstrated associations with occurrence of cardiovascular disease during treatment, we selected five pretreatment factors (history of heart attack, stroke, diabetes, age > or = 55 years and pulse pressure > or = 60 mmHg) to stratify patients into four groups. Those with no risk factor had a low risk (n=2999), those with one had a moderate risk (3042), those with two had a high risk (2237), and those with three or more had a very high risk (412). Overall, the unadjusted rates of incidence of cardiovascular disease events per 1000 person-years for patients in very high and low risk groups differed by factors of six and 14 for men and women, respectively. CONCLUSION: These results demonstrate that long-term control of blood pressure can be achieved in a general population. Nevertheless, cardiovascular disease events still accounted for most morbidity and mortality among these 'recovered' hypertensive patients. At entry, on the basis of readily identifiable characteristics, it was possible to stratify patients according to likelihood of subsequent events occurring despite control of blood pressure. This scheme could provide the basis for targeting more aggressive therapy where the potential for further cardioprotection is greatest.     

Clinical correlation of neuropsychological tests with 1H magnetic resonance spectroscopy in hepatic encephalopathy

The mortality from coronary and cerebrovascular diseases is higher in Finnmark County than in other Norwegian counties. In a population-based cohort study, we compared the incidence of myocardial infarction, stroke, and diabetes mellitus in different ethnic groups in Finnmark. A total of 10,622 subjects of Norse, Sami, and Finnish origin were followed for 14 years. During approximately 150,000 person-years, we identified 509 and 84 cases of myocardial infarction, 107 and 75 cases of stroke, and 96 and 73 cases of clinical diabetes mellitus among men and women, respectively. A total of 533 men and 199 women died. Norse subjects born outside of Finnmark had the most favorable risk factor levels and, in general, the lowest incidence of disease. Men of Finnish origin had a higher incidence rate of all endpoints than other men, and Finnish women had a higher incidence rate of myocardial infarction than other women. Sami women were more obese but did not have a higher diabetes mellitus incidence than other women. After adjustment for major cardiovascular risk factors and height, most ethnic differences were attenuated.     

The effect of age on risk factors for ischemic heart disease: the Manitoba Follow-Up Study, 1948-1993

PURPOSE: The purpose of this paper is to determine the age-specific relationships between risk factors at age 40 through 75 years and ischemic heart disease (IHD), and to determine the effects of aging on these relationships in a cohort of 3983 Canadian males. METHODS: The Manitoba Follow-Up Study is the prospective investigation of cardiovascular disease as it develops in a cohort of 3983 young men. Over a period of 45 years, from 1948 to 1993, 1094 study members (27%) developed clinical evidence of IHD. Blood pressure, body weight, smoking, and presence of diabetes mellitus have been recorded at regular intervals throughout the follow-up period. Using measurements from examinations every 5 years between ages 40 and 75 years, age-specific Cox proportional hazard models were fit to relate these risk factors to IHD. RESULTS: The adjusted relative risk of IHD for systolic blood pressure, diastolic blood pressure and smoking were found to significantly (p < 0.001) decline with advancing age. The adjusted relative risk for body mass index and presence of diabetes mellitus for ischemic heart disease did not vary with age (p > 0.05). After age 65 years, these risk factors were of little value for the prediction of IHD. CONCLUSIONS: The relative risk and statistical significance of blood pressure and smoking, as risk factors for IHD, decline with age.     

Hemodynamic assessment in managing the critically ill: is physician confidence warranted?

Our current knowledge of risk factors for Alzheimer's disease is limited and primarily addresses early-onset disease. This study aimed to determine the risk factors for late-onset Alzheimer's disease using a case-control approach. Ninety-eight cases and 216 controls were gathered from an ongoing population survey on aging and dementia in Stockholm (the Kungsholmen Project). We found a high relative risk (3.2; 95% confidence interval, 1.8-5.7) with the presence of at least one first-degree relative affected by dementia. Among all the other risk factors, alcohol abuse (relative risk, 4.4; 95% confidence interval, 1.4-13.8) and manual work (relative risk for men of 5.3; 95% confidence interval, 1.1-25.5) emerged as positively associated. No clear association was found with a family history of Parkinson disease, advanced parental age at index delivery, season of birth, or previous head trauma. In conclusion, our data suggest that the main risk factor for late-onset Alzheimer's disease is a family history of dementia, as has been previously reported for early-onset disease. Moreover, alcohol abuse and occupational exposure might play a specific role for this form of the disease.     

Estimation of excess risk from case-control data using Aalen's linear regression model

We introduce methods for statistical inference in Aalen's non-parametric linear regression model of disease incidence (Aalen, 1989, Statistics in Medicine 8, 907-925) from nested case-control data. These methods provide the basis for estimation of excess risk as a linear function of dose and absolute risk for a given exposure history. The methods are illustrated by estimating excess and absolute risks associated with radon exposure and smoking from nested case-control samples from the Colorado Plateau uranium miners cohort.     

Orbital development after enucleation in early childhood

We studied the prevalence of dementing disorders in a rural municipality of Japan (Hanazono-mura), using a door-to-door two-phase design. In phase 1, the Hasegawa's Dementia Scale-Revised was applied as a screening test to all subjects aged 65 years and older (n = 201). Among subjects screened positive, 17 were diagnosed with dementia in phase 2. The prevalence (cases/100 aged 65 years and older) was 8.5 for all types of dementia, 3.5 for Alzheimer's disease, 3.0 for vascular dementia, and 2.0 for other dementia (including mixed dementia). The prevalence of dementia was slightly but consistently higher in men than women at all ages. The overall prevalence was higher in women for Alzheimer's disease and in men for vascular dementia.     

Logistic regression models with missing covariate values for complex survey data

Maximum likelihood methods are used to incorporate partially observed covariate values in fitting logistic regression models. We extend these methods to data collected through complex surveys using the pseudo-likelihood approach. One can obtain parameter estimates of the logistic regression model using standard statistical software and their standard errors by Taylor series expansion or the jackknife method. We apply the approach to data from a two-phase survey screening for dementia in a community sample of African Americans age 65 and older living in Indianapolis. The binary response variable is dementia and the covariate with missing values is a daily functioning score collected from interviews with a relative of the study subject.     

Inference for odds ratio regression models with sparse dependent data

Suppose the number of 2 x 2 tables is large relative to the average table size, and the observations within a given table are dependent, as occurs in longitudinal or family-based case-control studies. We consider fitting regression models to the odds ratios using table-level covariates. The focus is on methods to obtain valid inferences for the regression parameters beta when the dependence structure is unknown. In this setting, Liang (1985, Biometrika 72, 678-682) has shown that inference based on the noncentral hypergeometric likelihood is sensitive to misspecification of the dependence structure. In contrast, estimating functions based on the Mantel-Haenszel method yield consistent estimators of beta. We show here that, under the estimating function approach, Wald's confidence interval for beta performs well in multiplicative regression models but unfortunately has poor coverage probabilities when an additive regression model is adopted. As an alternative to Wald inference, we present a Mantel-Haenszel quasi-likelihood function based on integrating the Mantel-Haenszel estimating function. A simulation study demonstrates that, in medium-sized samples, the Mantel-Haenszel quasi-likelihood approach yields better inferences than other methods under an additive regression model and inferences comparable to Wald's method under a multiplicative model. We illustrate the use of this quasi-likelihood method in a study of the familial risk of schizophrenia.     

Kaposi's sarcoma in women with AIDS

OBJECTIVE: To describe the presentation and incidence of Kaposi's sarcoma (KS) in a cohort of women infected with HIV and to compare their clinical characteristics with men at the same institution. DESIGN: Retrospective chart and database review. SETTING: Adult clinical AIDS program outpatient clinics at a municipal teaching hospital. RESULTS: One hundred and seven people with KS were found of whom twelve (11.2%) were women. The prevalence of KS in women was 3.6% compared with 9.9% among men (P < 0.001). Women born outside the United States were at increased risk of developing KS (P < 0.05). At initial KS presentation, no difference in HIV stage or CD4 count was found between men and women. Women presented with more advanced KS than men, with increased incidence of non-cutaneous disease (P < 0.001), lymphedema (P < 0.0001), lymph-node disease (P < 0.0001) and visceral disease (P = 0.03). Women had decreased survival after KS diagnosis compared to men, although the difference was not significant (P = 0.41). CONCLUSIONS: KS is not a rare diagnosis in HIV-infected women followed at our institution. Although the increased risk of KS in men is most likely to be related to differences in exposure, the sex-related differences in presentation and course may be due in part to delay in diagnosis. KS should be considered in the spectrum of HIV-related complications in women as well as in men.     

Treatment of aggression and irritability after head injury

Epidemiological characteristics of colorectal cancer may differ by particular anatomical subsite, suggesting that the subsite-specific colorectal cancers may represent different disease entities. This study explored the time trends over a 23-year period in colorectal cancer incidence at various subsites by sex and age group. Data on the incidence of colorectal cancer were obtained from a population-based cancer registry in Shanghai, People's Republic of China. Between 1972 and 1994, 30,693 patients with colorectal cancer were registered at the Shanghai Cancer Registry. The overall age-adjusted colorectal cancer incidence rates increased > 50%, or 2% per year from 1972-1977 to 1990-1994, from 14 to 22 per 100,000 among men and from 12 to 19 per 100,000 among women. The increases in rates were considerably more rapid for colon cancer, with rates approximately doubling, than they were for rectal cancer. Proximal colon cancer was more common than distal colon cancer over the whole study period, whereas rates for both cancers rose with similar annual percentage changes (> 5% per year) and across virtually all age groups. The estimated annual increases rose from 2% at ages 35-44 years to 7% at ages 75-84 years for proximal colon cancer, but they were more uniform for distal colon cancer (5-6% per year). Age-adjusted and age-specific rectal cancer rates changed little. The male:female age-adjusted rate ratio for colorectal cancer was 1.19 in 1990-1994. The ratios increased over time and varied by subsites, with ratios increasing from the proximal colon to the distal colon and to the rectum. Furthermore, men had higher rates than women for distal colon and rectal cancers at ages 55 and older, whereas women had higher rates than men at younger ages for these two cancers. Male:female rate ratios for proximal colon cancer did not vary substantially with age. The findings from this study indicate that subsite-specific incidence rates of colorectal cancer differ by sex and age and in their time trends. Cancers arising in the proximal colon, distal colon, and rectum may have somewhat different disease etiologies.     

Epidemiological evaluation of incidence of lung cancer in inhabitants of Warsaw in the period 1966--1975

Lung cancer is most frequent in men and occupies the first place among the causes of cancer deaths. In the period 1956--1975 in Poland the incidence rate of lung cancer increased about ten times in men and seven times in women. Analysis of age-specific incidence shows a significant increase in the group age of 35--39 years in men and in 45--49 in women. The absolute increase of incidence of lung cancer, the poor prognosis and the high mortality should call the attention of the whole population to canecerogenic factors, especially the noxious influence of smoking.