Prospective validation of a new priority allocation model for liver transplant candidates: an interim analysis.

BACKGROUND: The system that controls the waiting list (WL) and organ allocation for liver transplantation (OLT) seeks to achieve 3 main goals: objectivity, low dropout risks and good post-OLT results. We sought to prospectively validate a priority allocation model that is believed to achieve objectivity without penalizing dropout risk and post-OLT results. METHODS: We evaluated a study group of 272 patients enrolled in 2006-2007. WL candidates were divided into 2 categories: cirrhotic patients classified according to Model for End-Stage Liver Disease (MELD) score (MELD list and patients with hepatocellular carcinoma (HCC) organized according to a specific score (non-MELD list). The allocation algorithm for donor-recipient match assigned an optimal graft to the first MELD candidate with a MELD score of >or=20; a suboptimal graft, to the first non-MELD patient. A respective control group of 327 patients transplanted from 2003-2006 was characterized by a unique WL with a free allocation policy. We performed an interim analysis of this prospectively controlled study. RESULTS: Although the study group showed a lower percentage of OLT (P < .05) than the control group (37% vs 45%), it selected patients for OLT based on a higher MELD score (P < .05), thus obtaining similar dropout, post-OLT survivals, and intention-to-treat (ITT) survival probabilities as the controls. Among MELD patients, we observed a significantly reduced dropout and better ITT survival profiles than those of the control group (P = .02), whereas the similar results were delivered among non-MELD patients (P > .05). Among patients with a MELD score of >or=20, the prevalences of suboptimal grafts (0% vs 48%) and of early graft losses (0% vs 21%) were lower in the study than in the control group (P < .05). CONCLUSIONS: We prospectively validated a priority allocation model based on objective criteria that achieved high ITT survival rates.

Intention-to-treat analysis of liver transplantation in selected, aggressively treated HCC patients exceeding the Milan criteria.

This prospective study analyzed the dropout probability and intention-to-treat survival rates of patients with hepatocellular carcinoma (HCC) selected and treated according to our policy before liver transplantation (LT), with particular attention to those exceeding the Milan criteria. Exclusion criteria for LT were macroscopic vascular invasion, metastases, and poorly differentiated disease at percutaneous biopsy. A specific multi-modal adjuvant algorithm was used to treat HCC before LT. A total of 100 HCC patients were listed for LT: 40 exceeded the Milan criteria in terms of nodule size and number (MILAN OUT) either at listing or in list, while 60 patients continued to meet the criteria (MILAN IN). The Milan criteria did not prove to be a significant predictor of dropout probability or survival rates using Cox's analysis. Cumulative dropout probability at 6 and 12 months was 0% and 4% for MILAN OUT, and 6% and 11% for MILAN IN. The intention-to-treat survival rates at 1 and 3 years were 95% and 85% in MILAN OUT, and 84% and 69% in MILAN IN. None of the 68 transplanted patients had recurrent HCC after a median 16-month follow-up (0-69 months). In conclusion, LT may be effective for selected, aggressively-treated HCC patients exceeding the Milan criteria.

Pharmacokinetic and demographic markers of 5-fluorouracil toxicity in 181 patients on adjuvant therapy for colorectal cancer.

BACKGROUND: The relationship between 5-fluorouracil (5-FU) pharmacokinetics and toxicity following i.v. bolus administration has not been extensively studied. PATIENTS AND METHODS: One hundred and eighty-one patients on adjuvant therapy with 5-FU plus leucovorin for colorectal cancer were the study population. 5-FU pharmacokinetics was determined on day 2 of the first, third, and fifth cycles; type and the grade of adverse reactions were recorded on the next cycle. RESULTS: The 5-FU area under the curve (AUC) measured at the first cycle ranged between 146 and 1236 mg x min/l and was significantly correlated with drug dose, patients' body weight (BW) and gender, females having higher AUCs. These covariates explained only 23% of AUC variability. AUC and age were the only covariates which discriminated between toxic (grade > or =2) and nontoxic cycles (grade <2), with an optimal AUC cut-off value of 596 mg x min/l. Such a correlation was lost during the next cycles following dose reduction because of toxicity in 80 patients. CONCLUSIONS: A method for calculating the initial 5-FU dose is proposed which takes into account patient BW, gender and a target AUC of 596 mg x min/l. Nevertheless, it appears that a substantial part of 5-FU toxicity is not linked to pharmacokinetic factors and dose adjustments must still be on the basis of careful clinical surveillance.

Atherosclerotic risk factors and renal function in the elderly: the role of hyperfibrinogenaemia and smoking. Results from the Italian Longitudinal Study on Ageing (ILSA).

BACKGROUND: We examined associations between cardiovascular diseases and risk factors with pathological levels of and significant changes in serum creatinine (SCr) in a large prevalence phase and longitudinal phase community-based sample of an elderly Italian population (ILSA Study) showing no clinical evidence of renal impairment. METHODS: The prevalence phase was performed on 2981 subjects, aged 65-84 years, who were negative for renal diseases, had available SCr values and had complete clinical information on their cardiovascular risk factors. Of these, 371 were considered 'healthy' since they were not affected by cardiovascular diseases or diabetes, whereas 2610 tested positive for cardiovascular diseases and were considered 'diseased'. The sex-specific 95th percentiles for SCr (cut-off points) were calculated in the healthy reference sample to define the upper limit for normal SCr values. The distribution and prevalence of diseased subjects having values over the cut-off point values were then estimated. Associations between values over the cut-off point levels and pathological or clinical conditions were analysed from the diseased sample. The longitudinal phase was carried out on 1906 subjects who had SCr values and sufficient clinical information for our investigation. The incidence of an increase of >26.5 micromol/l of SCr was evaluated in the longitudinal cohort. RESULTS: In healthy subjects, the 95th SCr percentiles (cut-off points) were 123.8 micromol/l in men and 97.2 micromol/l in women. In diseased subjects, the prevalence of SCr values over the cut-off point was 4.6% in men and 9.3% in women. In logistic regression analysis, independent variables that correlated with over the cut-off point SCr values were: age >75 years [odds ratio (OR) = 2.2; 95% confidence interval (CI) = 1.5-3.4], atherosclerosis of the lower limbs (OR = 2.0; 95% CI = 1.2-3.3), cerebrovascular disease (OR = 1.9; 95% CI = 1.2-3.3), angiotensin-converting enzyme (ACE) inhibitor medication (OR = 1.8; 95% CI = 1.2-2.8), fibrinogen values >3.5 g/l (OR = 1.2; 95% CI = 1.2-2.7) and diuretic treatment (OR = 1.6; 95% CI = 1.1-2.4). After a mean 3.6 years follow-up, multiple logistic regression analysis showed that risk factors for pathological loss of renal function (rise of SCr >26.5 micromol/l) were: current smokers >20 cigarettes/day (OR = 2.3; 95% CI = 1.0-5.3), fibrinogen values >3.5 g/l (OR = 2.2; 95% CI = 1.6-3.3), diabetes (OR = 1.8; 95% CI = 1.1-2.8), age >75 years (OR = 1.7; 95% CI = 1.2-2.4) and isolated systolic hypertension (OR = 1.6; 95% CI = 1.0-2.6). The loss of renal function examined during the longitudinal phase appeared to be independent of baseline SCr levels. CONCLUSION: The present prevalence and longitudinal studies show that age-associated decline in renal function in elderly subjects is associated with co-existing cardiovascular diseases and risk factors. These observations should be incorporated into clinical practice since some of the factors detrimental to kidney function, such as smoking, altered fibrinogen levels and elevated systolic blood pressure, can be prevented and/or modified when appropriate measures are taken.

Vascular risk factors, incidence of MCI, and rates of progression to dementia.

OBJECTIVE: To estimate prevalence, incidence, and rate of progression of mild cognitive impairment (MCI) to dementia and correlated vascular risk factors with incident MCI and its progression to dementia. METHODS: The authors evaluated 2,963 individuals from the population-based sample of 5,632 subjects 65 to 84 years old, at the first (1992 to 1993) and second survey (1995 to 1996) of the Italian Longitudinal Study on Aging (ILSA), with a 3.5-year follow-up. Dementia, Alzheimer disease (AD), vascular dementia (VaD), other types of dementia, and MCI were classified using current clinical criteria. RESULTS: Among the 2,963 participants, 139 MCI patients were diagnosed at the first ILSA survey. During the 3.5-year follow-up, 113 new events of MCI were diagnosed with an estimated incidence rate of 21.5 per 1,000 person-years. We found a progression rate to dementia (all causes) of 3.8/100 person-years. Specific progression rates for AD, VaD, and other types of dementia were 2.3, 1.3, and 0.3/100 person-years. Furthermore, age was a risk factor for incident MCI (RR: 5.93, 95% CI: 3.17 to 11.10), while education was protective (RR: 0.06, 95% CI: 0.03 to 0.10), and serum total cholesterol evidenced a borderline nonsignificant trend for a protective effect. There was a nonsignificant trend for stroke as a risk factor of progression of MCI to dementia. CONCLUSIONS: In this population, among those who progressed to dementia, 60% progressed to AD and 33% to VaD. Vascular risk factors influence incident mild cognitive impairment and the rate of progression to dementia.

Prognosis of severe attacks in ulcerative colitis: effect of intensive medical treatment.

BACKGROUND: Severe attacks of ulcerative colitis have a high risk of colectomy. AIMS: To evaluate the effects of standard medical management and to identify the clinical and laboratory variables capable of predicting the clinical outcome. MATERIALS AND METHODS: Prospective study monitoring the clinical and laboratory variables in 67 patients with severe colitis. Therapy consisted of prednisone, cyclosporin if no response, and azathioprine for maintenance. End-points were colectomy or remission. Logistic regression analysis was applied for statistical evaluation. RESULTS: Fourteen (20%) patients required colectomy, 34 (50%) patients achieved remission with steroids, 25 (37%) patients received cyclosporin, 19 (76%) with benefit. Increased body temperature, pulse rate, sedimentation rate and C-reactive protein levels on admission were significantly associated with colectomy. Sedimentation rate greater than 75 mm/h and body temperature exceeding 38 degrees C at admission had 4.6- and 8.8-fold increased risk of colectomy. Less than 40% reduction in the bowel movements within 5 days predicted no response to steroids. Azathioprine maintained remission in 70% of the patients. CONCLUSIONS: Elevated sedimentation rate and fever at day 1 best predict colectomy in severe colitis. Less than 40% reduction in the bowel movements at day 5 predicts no response to steroids. Cyclosporin has a high rate of success in acute attacks and azathioprine in maintaining remission.

Door-to-door prevalence survey of epilepsy in three Sicilian municipalities.

A door-to-door prevalence survey of epilepsy was conducted in 3 Sicilian municipalities, as of November 1, 1987. In phase 1, the screening by questionnaire of 24,496 eligible subjects (participation = 92%) identified 544 suspected to have epilepsy. In phase 2, neurological evaluation of the 544 subjects yielded 111 with epilepsy. Of the 111 subjects, 103 (93%) had been previously diagnosed, 68 (61%) were taking antiepileptic medication, and 81 (73%) had active epilepsy. Referring to the 81 subjects with active epilepsy, the seizure type was generalized in 60 (74%), partial in 19 (23%) and undetermined in 2 (3%). The prevalence of active epilepsy (per 1,000 population) was 3.3 overall, 3.5 for men and 3.2 for women. The age-specific patterns for active epilepsy differed by sex, with higher figures for men at younger ages (5-19 years) and older ages (50-99 years). The age-specific prevalence figures for active epilepsy were lower than those from previous Italian surveys.

Parkinson's disease, smoking, and family history. EUROPARKINSON Study Group.

There is growing evidence that both genetic and environmental factors play a role in the etiology of Parkinson's disease (PD). The hypothesis of an interaction between genetic and environmental risk factors has been little explored, and never using a population-based case-control study design. Our objective was to investigate the possible interaction between smoking and family history in the etiology of PD, as part of a collaborative population-based case-control study. We included 149 nondemented PD patients ascertained in three European prevalence surveys using a two-phase design. Each patient was matched by age (+/-2 years), gender, and center to three controls drawn from the same populations (n=375). Presence of PD among first-degree relatives and smoking history were assessed through an interview for 127 cases and 306 controls. In the overall sample we found suggestive evidence that family history and ever-smoking interact in determining the risk of PD (P=0.09), with individuals exposed to both risk factors having the highest risk (OR=10.0; 95% CI=2.0-49.6). Analyses were repeated after stratification into two age-groups (cutoff: 75 years). In older patients, the joint exposure to both risk factors was associated with a significant increase in the risk of PD (OR=17.6; 95% CI=1.9-160.5). Among younger subjects, the OR for joint exposure was not significant. In conclusion, our findings suggest that smoking and family history interact synergistically on a multiplicative scale in determining the risk of PD in individuals older than 75 years.

Parkinson's disease and parkinsonism in a longitudinal study: two-fold higher incidence in men. ILSA Working Group. Italian Longitudinal Study on Aging.

OBJECTIVE: To determine the incidence of parkinsonism and PD in the Italian elderly, and to explore the relation with age and gender. METHODS: In eight Italian municipalities, a population-based, parkinsonism-free cohort was followed for an average of 3 years. At the end of the follow-up, the cohort survivors were directly contacted (screening and clinical examination). Cohort members who had died were studied using death certificates, clinical records, and information gathered from relatives and general practitioners. Parkinsonism diagnosis and subtyping were made according to specified diagnostic criteria. RESULTS: The cohort consisted of 4,341 individuals (65 to 84 years of age): 596 died before the examination, 2,863 (76.4% of the survivors) completed the screening procedure, and 882 refused to participate. The authors found 68 incident cases of parkinsonism: 42 PD (62%), 7 drug-induced parkinsonism (10%), 8 parkinsonism in dementia (12%), 8 vascular parkinsonism (12%), and 3 parkinsonism, unspecified (5.8%). Average annual incidence rate (per 100,000 person-years) in the population aged 65 to 84 years, adjusted to the 1992 Italian population, was 529.7 (95% CI, 400.5 to 658.9) for parkinsonism, and 326.3 (95% CI, 224.1 to 427.5) for PD. Incidence rates for both parkinsonism and PD increased with age in both men and women; men had higher rates in every age group. Age-adjusted relative risk in men compared with women was 1.66 (95% CI, 1.02 to 2.70) for parkinsonism and 2.13 (95% CI, 1.11 to 4.11) for PD. CONCLUSIONS: Incidence of parkinsonism and PD increased with age, PD was the most common type of parkinsonism, and men had a risk of developing PD twice that of women.

Cognitive impairment without dementia in older people: prevalence, vascular risk factors, impact on disability. The Italian Longitudinal Study on Aging.

OBJECTIVES: To investigate prevalence of "cognitive impairment, no dementia" (CIND) in the Italian older population, evaluating the association with cardiovascular disease and the impact on activities of daily living (ADL). CIND may provide pathogenic clues to dementia and independently affect ADL. DESIGN: Cross-sectional examination in the context of the Italian Longitudinal Study on Aging. SETTING: Random population sample from eight Italian municipalities. PARTICIPANTS: A total of 3,425 individuals aged 65-84 years, residing in the community or institutionalized. MEASUREMENTS: Study participants were screened for cognitive impairment by using the Mini-Mental State Examination. Trained neurologists examined those scoring <24. CIND diagnosis relied on clinical and neuropsychological examination, informant interview, and assessment of functional activities. Age-related cognitive decline (ARCD) was diagnosed in CIND cases without neuropsychiatric disorders responsible for the cognitive impairment. RESULTS: Prevalence was 10.7% for CIND and 7.5% for ARCD, increased with age, and was higher in women. Age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.06-1.12), stroke (OR, 2.05; 95% CI, 1.26-3.35) and heart failure (OR, 1.73; 95% CI, 1.11-2.68) were significantly and positively associated with CIND at multivariate analysis. Education (OR, 0.61; 95% CI, 0.56-0.65) and smoking (OR, 0.72; 95% CI, 0.54-0.98) showed a negative correlation. Age and myocardial infarction were positively associated with ARCD, whereas a negative correlation was found for education and smoking. The effect of smoking was no more significant either on CIND or ARCD considering current habits or "pack year" exposure. CIND showed an independent impact on ADL (OR, 1.88; 95% CI, 1.41-2.49). CONCLUSIONS: CIND is very frequent in older people. The effect of demographic variables and vascular conditions offers opportunities for prevention. The association with functional impairment is useful to evaluate the burden of disability and healthcare demands.

Parkinson disease survival: a population-based study.

OBJECTIVE: To evaluate whether the survival of patients with Parkinson disease (PD) is shorter than that of the general population. DESIGN: Survival was investigated in a cohort of patients with PD previously identified during a population-based prevalence study (prevalence day, November 1, 1987, reference follow-up date, October 31, 1995). The survival of patients with PD was compared with that of a control sample randomly selected from the same population (2 controls for each case, matched for age, sex, and study municipality). The causes of death in the 2 groups were also compared. Both univariate and multivariate survival analyses were performed to investigate the association with disease-related variables. SETTING: A door-to-door 2-phase prevalence survey performed in 3 Sicilian municipalities. PATIENTS: Fifty-nine patients with PD and 118 controls. RESULTS: Patients with PD showed a high risk of death (relative risk, 2.3; 95% confidence interval, 1.60-3.39). Greater age at November 1, 1987, high Hoehn-Yahr score, and lack of levodopa therapy were associated with a lower survival on univariate analysis. Multivariate analysis confirmed the association between shorter survival among patients with PD and greater age on November 1, 1987. One-way analysis of variance indicated a different effect of levodopa therapy according to age. Multivariate analysis did not confirm this finding. Pneumonia was the cause of death most frequently associated with PD. CONCLUSION: This study indicates that patients with PD have a shorter survival time than the general population.

Norms for the Mini-Mental State Examination in a healthy population.

BACKGROUND: Although the Mini-Mental State Examination (MMSE) is widely used in clinical practice, few norms exist for healthy populations covering a broad range of ages. OBJECTIVE: To obtain MMSE norms specific for age, gender, and education in healthy adults. METHODS: From the population registers of seven communities across Italy, we selected a proportionate random sample of residents age 20 to 79 years to evaluate their health status with respect to conditions affecting cognitive performance. This sample yielded 908 persons who were deemed to be without cognitive impairment and who were then given the MMSE. We calculated fifth percentile norms and presented them as step functions. We then validated the norms as a screening tool for dementia in persons age 65 to 79 years. The validation was based on unpublished data from a separate study and involved estimates of sensitivity and specificity. RESULTS: The norms declined with advancing age, especially for less educated women. Given any age and sex, the norms were higher for individuals with higher educational levels. In screening for dementia, the norms had a sensitivity of 85% and a specificity of 89%. CONCLUSIONS: When using MMSE scores, it is important to account for age, gender, and education, especially in populations where the educational level is low. Expressing MMSE norms as step functions provides an easy-to-use tool for neurologists and other clinicians.

Influence of different screening procedures on the stroke prevalence estimates: the Italian Longitudinal Study on Aging.

Stroke prevalence surveys are more and more needed for health care and facility planning. Prevalence estimates and costs of the definition procedure may vary depending on different screening strategies. We evaluated the impact of these different strategies on the overall diagnostic procedure and on stroke prevalence estimates in the Italian Longitudinal Study on Aging. A population sample of 5, 632 individuals aged 65-84 years was screened for stroke by a simple question on previous stroke diagnosis, questions on possible stroke symptoms and a simple neurological examination. Those screened positive by any of these procedures were fully examined by a neurologist for conclusive diagnosis. We determined the positive predictive value of each procedure on the final stroke diagnosis and calculated prevalence as if each procedure had been used separately. Using the three procedures combined, the prevalence rate was 6.0% (95% confidence interval, 5.4-6.7%). If each procedure had been used as the unique screening tool, the rates would have been 5.1% (4.5-5. 7%), 4.1% (3.6-4.7%) and 2.3% (1.9-2.7%), and positive predictive values 66.4, 55.2 and 45.1%, respectively. Different screening procedures can affect stroke prevalence estimates. Compared to more complex screening strategies, the use of a simple question about previous diagnosis as the unique screening tool leads to only a slight underestimation of stroke prevalence and avoids a 66% increase in the number of subjects to be examined in a second-level specialist evaluation, potentially reducing the costs of the overall diagnostic procedure.

Familial aggregation of Parkinson's disease: a population-based case-control study in Europe. EUROPARKINSON Study Group.

OBJECTIVE: To investigate the familial aggregation of PD in a large collaborative population-based case-control study. BACKGROUND: Most previous case-control studies of the familial aggregation of PD have been hospital- or clinic-based. METHODS: We included 219 prevalent cases ascertained in three European populations (centers), using a two-phase design consisting of screening and examination by a neurologist. Each case was matched by age, sex, and center to three controls drawn from the same populations (n = 657). Presence of PD among first-degree relatives (parents and siblings) was determined using the family history approach for 175 cases and 481 controls. RESULTS: Overall, a positive family history (at least one parent or sibling affected by PD) was reported in 10.3% of patients and 3.5% of controls (odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.6 to 6.6). A similar association was observed when analyses were restricted to nondemented patients and controls (OR = 3.9; 95% CI = 1.7 to 8.7) or to newly diagnosed patients (OR = 3.3; 95% CI = 0.9 to 11.9). We found a significant trend of increasing risk with increasing number of affected relatives (p = 0.003). Analyses stratified by age showed a stronger association for younger PD patients (OR = 7.6; 95% CI = 1.5 to 38.9) than for older patients (OR = 2.5; 95% CI = 1.1 to 5.7). CONCLUSIONS: In this large sample of prevalent PD patients and population-matched controls, PD significantly aggregates in families, with the strength of the association being age-dependent. Therefore, familial factors, which can be genetic, environmental, or both, play a role in PD.

Dementia is a major predictor of death among the Italian elderly. ILSA Working Group. Italian Longitudinal Study on Aging.

BACKGROUND: Neurologic diseases are rarely listed on death certificates because death is more often attributed to cardiovascular and pneumonic events occurring during terminal stages. OBJECTIVE: To evaluate the effect of major age-associated neurologic and non-neurologic diseases on survival in a cohort of Italian elderly. METHODS: A population-based multicenter survey, carried out in eight Italian municipalities, with a sample of 5,632 individuals aged 65 to 84 years. The entire sample was screened for all the diseases under study, and all individuals were interviewed about risk factors. Those who screened positive underwent clinical assessments by specialists. Two years after the baseline survey, the study population was followed up to determine the vital status either directly from the individuals or from proxy respondents. A copy of the death certificate was obtained for each individual who had died. The risk of dying (mortality risk ratio [MRR]) was calculated using the Cox proportional hazards model in which we included all the diseases under study, age, gender, and years of education. RESULTS: At follow-up (mean duration 26.7 +/- 5.4 months) 444 individuals had died. The Cox proportional hazards model selected the following as significant predictors of death: age (for year of age MRR = 1.12; 95% confidence interval [CI], 1.08 to 1.15), male gender (MRR = 1.72; 95% CI, 1.27 to 2.34), institutionalization (MRR = 4.17; 95% CI, 2.20 to 7.94), dementia (MRR = 3.61; 95% CI, 2.55 to 5.11), neoplasm (MRR = 2.01; 95% CI, 1.20 to 3.38), heart failure (MRR = 1.87; 95% CI, 1.27 to 2.76), and diabetes (MRR = 1.62; 95% CI, 1.12 to 2.34). CONCLUSIONS: These data provide further evidence on the malignancy of dementia, which proved the major predictor of death in the elderly, with an MRR higher than neoplastic diseases and other severe age-associated conditions.

Education and the risk of physical disability and mortality among men and women aged 65 to 84: the Italian Longitudinal Study on Aging.

BACKGROUND: Most studies report that people with higher education enjoy better health and longer life. Although it is well known that most risk factors are more common among individuals with a lower level of education, the underlying mechanism of this association is not fully understood. The objective of this study was to assess the association between education, disability, and mortality. METHODS: We analyzed data on 1,817 men and 1,643 women, aged 65-84 years, to assess the association of educational level with physical disability and mortality adjusting for age, sex, smoking habit, occupation, and major chronic conditions. RESULTS: The association between educational level and disability was characterized by a dose-response effect, with the relative odds significantly decreased by about 30%, 60%, and 79% in those with 4 or 5, 6 to 8, and more than 8 years of education, compared to those with 3 or less years of education. Death rates were lower among persons with 4 or more years of education compared to those with less education. However, after adjusting for disability status, education was no longer associated with mortality (RR=0.97, CI=0.65-1.43). CONCLUSIONS: The strong association of low education with disability found in this study may explain the inverse association with mortality reported in previous studies. Disability, indeed, seems to be the mediator between education and mortality and might be due to the higher severity level of diseases, leading to death, in the lower educated group.

Case ascertainment uncertainties in prevalence surveys of Parkinson's disease.

Using unpublished data from five completed prevalence surveys of Parkinson's disease (PD), we investigated case ascertainment uncertainties that potentially have a direct effect on prevalence. These uncertainties arise from the choice of diagnostic criteria, the choice of screening method, and the amount of information lost because of nonresponse. The surveys were conducted in Argentina, India, China, Italy, and the Netherlands. Our analyses consisted of simple comparisons of prevalence results, positive predictive values (a screening measure), and nonresponse percentages. We found that (a) prevalence comparisons between surveys have diminished value if the surveys used different diagnostic criteria for PD; (b) screening performance may be affected adversely if symptom questions are answered by one family member for the entire family living together rather than by each family member individually; and (c) nonresponse from refusal or unavailability does not necessarily lead to bias, but special caution may be appropriate with prevalence results pertaining to elderly women.

LEIPAD, an internationally applicable instrument to assess quality of life in the elderly.

A questionnaire to assess quality of life in the elderly was developed under the auspices of the European office of the World Health Organization. Stages in construction of the instrument, which was designed for international application, particularly at the primary level, are described. The latest version of the questionnaire is composed of 49 self-assessment item, 31 of which can be grouped into 7 subscales: Physical Function, Self-Care, Depression and Anxiety, Cognitive Functioning, Sexual Functioning, and Life Satisfaction. The remaining 18 items serve as moderators for assessing the influence of social desirability factors and personality characteristics on the individual scores for the 7 core instrument subscales. The questionnaire has been administered to 586 individuals aged 65 years and over recruited in communities in Italy (Padua and Brescia), the Netherlands (Leiden), and Finland (Helsinki). The main psychometric characteristics of the instrument, together with its concurrent validity with the Rotterdam Questionnaire, are illustrated.

Estrogen-replacement therapy and Alzheimer's disease in the Italian Longitudinal Study on Aging.

OBJECTIVE: To study the association of estrogen-replacement therapy and other estrogen-related variables with Alzheimer's disease in postmenopausal women. BACKGROUND: Postmenopausal estrogen use has been reported to lower the risk of Alzheimer's disease. DESIGN: A population-based, multicenter survey was carried out in eight Italian municipalities. The sample of 2,816 women, aged 65 to 84 years, was randomly selected from the population register of each municipality and stratified in 5-year age groups. All women were screened using the Mini-Mental State Examination and interviewed concerning risk factors. Those who screened positive underwent a clinical assessment. Dementia syndrome was diagnosed according to DSM-III-R criteria, and Alzheimer's disease was diagnosed according to NINCDS-ADRDA criteria for possible and probable Alzheimer's disease. RESULTS: The estimated prevalence of postmenopausal estrogen use adjusted to the 1991 Italian female population was 12.3%. The frequency of estrogen use was higher among nonpatients compared with Alzheimer's disease patients (odds ratio, 0.24; 95% confidence interval, 0.07 to 0.77). The inverse association between estrogen therapy and Alzheimer's disease remained significant after adjustment for age, education, age at menarche, age at menopause, smoking and alcohol habits, body weight at the age of 50 years, and number of children (odds ratio, 0.28; 95% confidence interval, 0.08 to 0.98). CONCLUSIONS: Our data from a population-based study support the hypothesis that estrogen-replacement therapy is associated with a reduced prevalence of Alzheimer's disease in postmenopausal women. Prospective clinical trials are required to enable women and their physicians to weigh risks and benefits of estrogen-replacement therapy for the prevention of dementia.

Sleep complaints in community-dwelling older persons: prevalence, associated factors, and reported causes.

OBJECTIVES: To determine the prevalence rates of self-reported sleep complaints and their association with health-related factors. DESIGN: A cross-sectional study. SETTING: People living in the community. PARTICIPANTS: A total of 2398 noninstitutionalized individuals, aged 65 years and older, residing in the Veneto region, northeast Italy. MEASUREMENTS: Odds ratios for the association of sleep complaints with potential risk factors. RESULTS: The prevalence of insomnia was 36% in men and 54% in women, with increased risks for women (odds ratio (OR) = 1.69, 95% CI: 1.3-2.1), depression (OR = 1.93, 95% CI, 1.5-2.5), and regular users of sleep medications (OR = 5.58, 95% CI, 4.3-7.3). About 26% of men and 21% of women reported no sleep complaints. Night awakening, reported by about two-thirds of the participants, was the most common sleep disturbance. Women and regular users of sleep medications had significantly increased odds for insomnia and for not feeling rested upon awakening in the morning. Depressive symptomatology was more strongly associated with insomnia and night awakening than with awakening not rested, whereas physical disability was more strongly associated with awakening not rested than with the other two sleep disturbances. CONCLUSION: Our findings show that sleep complaints, highly common among older Italians, are associated with a wide range of medical conditions and with the use of sleep medications. Further longitudinal studies are needed to investigate the causes and the negative health consequences of sleep disturbances to improve both the diagnosis and treatment.