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M Cesari

Publications and source records attributed to M Cesari.

At least 19 recordsLinked to original sources

Anticholinergic drugs and physical function among frail elderly population.

Increasing evidence from experimental studies and human observations suggests that drugs with anticholinergic properties can cause physical and mental impairment. The aim of this study was to evaluate the relationship between the use of drugs with anticholinergic activity and measures of physical performance, muscle strength, and functional status in persons aged 80 years or older. Data are from baseline evaluation of 364 subjects enrolled in the ilSIRENTE study. The ilSIRENTE study is a prospective cohort study performed in the mountain community living in the Sirente geographic area (L'Aquila, Abruzzo) in Central Italy. Physical performance was assessed using the physical performance battery score (Short Physical Performance Battery), which is based on three timed tests: 4-meter walking speed, balance, and chair stand tests. Muscle strength was measured by hand grip strength. We defined as anticholinergic drugs all medications for which serum anticholinergic activity was previously demonstrated. Analyses of covariance were performed to evaluate the relationship of anticholinergic drugs with physical function. In the unadjusted model, all the physical performance, muscle strength, and functional measures showed significant associations with the anticholinergic drug use. After adjustment for potential confounders (age, gender, smoking, physical activity level, cognitive performance score, living alone, body mass index, congestive heart failure, lung diseases, diabetes), these associations were weaker but still statistically significant (physical performance battery score: non-users anticholinergic drugs 6.9, SE 0.1, users anticholinergic drugs 6.1, SE 0.2, P=0.05; hand grip strength: non-users anticholinergic drugs 31.3 kg, SE 0.8, users anticholinergic drugs 28.8 kg, SE 1.0, P=0.05; Activities of Daily Living scale score: non-users anticholinergic drugs 1.2, SE 0.1, users anticholinergic drugs 1.6, SE 0.1, P=0.03; Instrumental Activities of Daily Living scale score: non-users anticholinergic drugs 2.7, SE 0.1, users anticholinergic drugs 3.4, SE 0.1, P<0.001). The use of medication with anticholinergic properties is common among community older subjects in Italy. Our results suggest that among old-old subjects the use of anticholinergic drugs is associated with impaired physical performance and functional status.

Activities of Daily Living↗

Low plasma adiponectin is associated with coronary artery disease but not with hypertension in high-risk nondiabetic patients.

OBJECTIVE: To investigate the association of plasma adiponectin levels with coronary artery disease (CAD), arterial hypertension (HT), and insulin resistance (IR) in nondiabetic Caucasian patients. DESIGN: We measured plasma adiponectin levels, IR (HOMA index), and the CAD atherosclerotic burden (angiography-based modified Duke Index score) in 400 nondiabetic patients undergoing coronary angiography. HT was diagnosed by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines or if patients were on antihypertensive treatment. RESULTS: Coronary artery disease was found in 62% of the patients and ruled out in the rest (non-CAD group). Plasma adiponectin levels were inversely related to the CAD score (beta = -0.12, P = 0.029) and predicted the coronary atherosclerotic burden independent of other cardiovascular risk factors. However, they were similar in NT and HT and showed no correlation with blood pressure values. In non-CAD, but not in CAD patients, they were lower in patients with than without IR (8.3 +/- 1.2 vs. 11.3 +/- 1.3, respectively; P = 0.007). CONCLUSIONS: In nondiabetic high-risk Caucasian patients plasma adiponectin levels are inversely related to CAD severity and IR; however, they are not strongly related to blood pressure values.

Adiponectin↗

Functional decline in frail community-dwelling stroke patients.

Patients who suffer a stroke event are at high risk of functional decline after the post-acute rehabilitation period. The aim of the present study was the evaluation of factors associated with functional decline in a large sample of older patients with stroke living in the community. The study population consisted of all patients admitted to home care programs after a post-acute rehabilitation program--with at least 1 year of follow-up--in twenty-two Italian Home Health Agencies from 2000 to 2002 (n=1338). For the present study we selected 355 (26%) patients with diagnosis of stroke. After 1 year of in-home care program, 149 out of 355 stroke survivors (42%) had presented a worsening in the activities of daily living (ADL) scale score. In the final adjusted model, patients with cognitive impairment (OR 2.59, 95% CI, 1.45-4.64), pressure ulcer (OR 2.74, 95% CI, 1.45-5.18), urinary incontinence (OR 1.64, 95% CI, 1.01-3.29), or hearing impairment (OR 1.83, 95% CI, 1.02-3.29) were more likely to significantly decline in physical functioning after a period of 1 year in-home care program. Our study documents that functional decline of stroke patients was largely dependent on specific subjects' clinical characteristics. Three of four concomitant disabling conditions associated in our sample with functional decline--pressure ulcer, urinary incontinence, hearing--can be prevented and eventually treated or modified. Appropriate post-acute rehabilitation programs and adequate home care interventions focused on the prevention and treatment of these conditions might be correlated to better outcomes in older post-stroke patients.

Activities of Daily Living↗

Lifetime occupation and physical function: a prospective cohort study on persons aged 80 years and older living in a community.

BACKGROUND: Several studies have reported predictors for loss of mobility and impairments of physical performance among frail elderly people. AIM: To evaluate the relationship between lifetime occupation and physical function in persons aged 80 years or older. METHODS: Data are from baseline evaluation of 364 subjects enrolled in the ilSIRENTE study (a prospective cohort study performed in a mountain community in Central Italy). Physical performance was assessed using the physical performance battery score, which is based on three timed tests: 4-metre walking speed, balance, and chair stand tests. Muscle strength was measured by hand grip strength. Lifetime occupation was categorised as manual or non-manual work. RESULTS: Mean age of participants was 85.9 (SD 4.9) years. Of the total sample, 273 subjects (75%) had a history of manual work and 91 subjects (25%) a history of non-manual work. Manual workers had significant lower grip strength and physical performance battery score (indicating worse performance) than non-manual workers. After adjustment for potential confounders (including age, gender, education, depression, cognitive performance scale score, physical activity, number of diseases, hearing impairment, history of alcohol abuse, smoking habit, and haemoglobin level), manual workers had significantly worse physical function (hand grip strength: non-manual workers 32.5 kg, SE 1.4, manual workers 28.2 kg, SE 0.8; physical performance battery score: non-manual workers 7.1, SE 0.4, manual workers 6.1, SE 0.2). CONCLUSIONS: A history of manual work, especially when associated with high physical stress, is independently associated with low physical function and muscle strength in older persons.

Aged, 80 and over↗

A new splicing acceptor site and poly(A)+ sequence signal within DQA1*0401 and DQA1*0501 mRNA 3'UTR contribute to increase the extraordinary diversity of mRNA isoforms.

In this paper, we have analysed the diversity of mRNA species generated by DQA1*0501 and DQA1*0401 alleles in homozygous B-lymphoblastoid cell lines. As we previously reported, six mRNA isoforms that differ in the 3'UTR have been identified in these cells. This diversity of mRNA species results both from the alternative use of two acceptor spliced sites and the differential selection of two poly(A)+ sequence signals by the processing machinery. In this report we describe a new acceptor sequence signal that allows generation of a new alternative spliced mRNA species. This acceptor sequence signal was also present in all of the seven DQA1 homozygous cell lines analysed. In addition, we have identified a previously undetected, non-conventional but functional, poly(A)+ sequence signal that lacks an identifiable AATAAA hexamer, one of the most important element of the core. This sequence signal allows the generation of two additional mRNA isoforms both in DQA1*0501 and DQA1*0401 homozygous cell lines but not in the others. We show that DQA1*0501 and DQA1*0401 primary transcripts can be processed into nine mRNA isoforms that differ in the 3'UTR. Finally, we summarized all the DQA1 mRNA species deriving from DQA1*0101, DQA1*0102, DQA1*0103, DQA1*0201, DQA1*0301, DQA1*0401 and DQA1*0501 alleles and shown in B-lymphoblastoid cell lines.

3' Untranslated Regions↗

Homocysteine-lowering treatment in coronary heart disease.

Homocysteine (Hcy) is a sulphur-containing amino acid product of methionine's metabolism. Hyperhomocysteinemia (HHcy) is considered an independent risk factor for cardiovascular (CV) disease, at least in high-risk patients. In fact, evidence indicates that although mild HHcy may be regarded as a minor risk factor for CHD in low-risk patients, it can play a role in triggering new events in patients with known CHD, also by interacting with the "classical" CV risk factors. This is of much interest because HHcy represents a correctable risk factor, inasmuch vitamin supplementation as has been shown to effectively lower total homocysteine plasma levels (tHcy). While case-control and cross-sectional studies have consistently demonstrated an association of HHcy with CV disease, prospective studies have given conflicting results. Moreover, the effect of the homocysteine-lowering treatment in preventing CV events is still under debate. Thus, it remains unclear which patients should be screened for HHcy and which ones should be treated to lower tHcy. In this paper we shall report and discuss knowledge on the potential role of HHcy in the development of CHD and on the benefits due to tHcy-lowering treatment with vitamins.

Adult↗

HLA DQA1 genes generate multiple transcripts by alternative splicing and polyadenylation of the 3' untranslated region.

Regulation of the human leucocyte antigen (HLA) class II genes expression is an important field in immunology, because these molecules play a crucial role in the function of the immune system. HLA DQ genes expression is a complex phenomenon regulated at both transcriptional and post-transcriptional levels. In this study, we have investigated the post-transcriptional mechanisms accounting for alleles-dependent length polymorphism of DQA1 mRNA. We have first sequenced the genomic DNA encoding the 3' untranslated region (UTR) of DQA1 *0101, *0102, *0103, *0201, *0301, *0401, and *0501 alleles. We have identified two competing splicing sites: a unique splicing donor site AG/GTA located 20 nucleotides downstream from the stop codon associated to two spliced acceptor sequences, approximately 165 and approximately 370 nucleotides downstream. In addition, three polyadenylation signals have been identified, respectively, at approximately 475, approximately 795, and approximately 855 nucleotides downstream from the stop codon. Subsequently, we have analyzed mRNAs derived from DQA1 alleles in homozygous B lymphoblastoid cell lines by reverse transcriptase-polymerase chain reaction. We show that allele-dependent length polymorphism of DQA1 mRNA-3' UTR results from a combination of differential splicing and alternative polyadenylations. Four mRNA isoforms (two spliced variant cleaved at two distinct polyadenylation sites) were detected in DQA1 *0101, *0102, and *0103 homozygous cell lines, and six mRNA species (three spliced variant cleaved at two polyadenylation-sequence signal) were generated by the other four alleles. Possible advantages for cells to generate multiple transcripts previously undetected are discussed.

Alleles↗

Comparison of TAP2 frequencies in type 1 diabetes patients and healthy controls from three ethnic groups indicates an African origin for the TAP2 G allele.

In order to determine the ethnic origin of the transporter associated with antigen processing 2 (TAP2) G allele, initially discovered by us in a group of type 1 diabetes (insulin-dependent diabetes mellitus) patients living on Reunion Island, HLA TAP2 typing was performed using the polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) method in type 1 diabetes patients and unrelated healthy controls of three different ethnic groups (Caucasians, Indians and black Africans from Senegal and Mauritius). The comparison of TAP2 allele frequencies in controls showed significant racial (ethnic) differences. The TAP2*0101 and TAP2 C alleles were increased, respectively, in the Caucasian (50% in Caucasians vs. 40% in other groups) and Senegalese (27% in Senegalese vs. 10% in other groups) populations. In comparison with Caucasians, the TAP2*0201 variant was significantly increased in the Indian population and decreased in the Senegalese black population. In addition, the TAP2 G allele was observed in the two African populations studied but not in the Caucasian or Indian population. This observation is consistent with the view that this allele is restricted to populations of African origin. In addition, we have determined the large extended haplotype DQA1-DQB1-DRB1 associated with TAP2 G. We found that this allele is preferentially associated with the large conserved haplotype HLA DQA1*0501-DQB1*0201-DRB1*0301.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Antithrombotic drugs in secondary stroke prevention among a community dwelling older population.

BACKGROUND: Patients who suffer a cerebrovascular event are at high risk of a recurrence. Secondary prevention is crucial in reducing the burden of cerebrovascular disease. OBJECTIVE: To estimate the percentage of stroke survivors receiving antiplatelet or anticoagulant drugs and to identify factors associated with such treatment. DESIGN: Cross sectional retrospective cohort study. METHODS: Data were analysed from a large collaborative observational study, the Italian "silver network" home care project, which collected data (from 1997 to 2001) on patients admitted to home care programmes (n = 5372). Twenty two home health agencies participated in evaluating the implementation of the minimum dataset for home care (MDS-HC) instrument. For the present study, 648 individuals with a diagnosis of stroke were selected and the initial MDS-HC assessment reported. RESULTS: 70% of stroke survivors did not receive any antiplatelet or anticoagulant drugs (95% confidence interval (CI), 66.5 to 73.5). Among all age categories, aspirin and ticlopidine were the two most commonly prescribed drugs. Living alone (odds ratio (OR), 0.49 (95% CI, 0.24 to 0.89)), dependency in activities of daily living (0.66 (0.40 to 0.99)), cognitive impairment (0.58 (0.38 to 0.86)), and low educational level (0.58 (0.34 to 0.98)) were associated with a reduced likelihood of receiving secondary stroke prevention treatment. Cardiac arrhythmias, coronary artery disease, heart failure, and peripheral vascular disease were associated with the use of antiplatelet or anticoagulant treatment. CONCLUSIONS: Negative attitudes among physicians with respect to secondary stroke prevention are prevalent and reinforce the need for increased awareness of existing data on the risks and benefits for elderly individuals. Social problems and functional impairment may be issues concerning physicians when deciding whether or not the risks of treatment exceed the benefit.

Activities of Daily Living↗

Construct validity of the abbreviated mental test in older medical inpatients.

OBJECTIVES: To evaluate validity and internal structure of the Abbreviated Mental Test (AMT), and to assess the dependence of the internal structure upon the characteristics of the patients examined. DESIGN: Cross-sectional examination using data from the Italian Group of Pharmacoepidemiology in the Elderly (GIFA) database. SETTING: Twenty-four acute care wards of Geriatrics or General Medicine. PARTICIPANTS: Two thousand eight hundred and eight patients consecutively admitted over a 4-month period. MEASUREMENTS: Demographic characteristics, functional status, medical conditions and performance on AMT were collected at discharge. Sensitivity, specificity and predictive values of the AMT <7 versus a diagnosis of dementia made according to DSM-III-R criteria were computed. The internal structure of AMT was assessed by principal component analysis. The analysis was performed on the whole population and stratified for age (<65, 65-80 and >80 years), gender, education (<6 or >5 years) and presence of congestive heart failure (CHF). RESULTS: AMT achieved high sensitivity (81%), specificity (84%) and negative predictive value (99%), but a low positive predictive value of 25%. The principal component analysis isolated two components: the former component represents the orientation to time and space and explains 45% of AMT variance; the latter is linked to memory and attention and explains 13% of variance. Comparable results were obtained after stratification by age, gender or education. In patients with CHF, only 48.3% of the cumulative variance was explained; the factor accounting for most (34.6%) of the variance explained was mainly related to the three items assessing memory. CONCLUSION: AMT >6 rules out dementia very reliably, whereas AMT <7 requires a second level cognitive assessment to confirm dementia. AMT is bidimensional and maintains the same internal structure across classes defined by selected social and demographic characteristics, but not in CHF patients. It is likely that its internal structure depends on the type of patients. The use of a sum-score could conceal some part of the information provided by the AMT.

Aged↗

Construct validity of the 15-item geriatric depression scale in older medical inpatients.

The construct validity of the 15-item Geriatric Depression Scale (sfGDS) has been assessed in selected populations. The aim of this study was to assess the appropriateness of applying the sfGDS to unselected older inpatients. The main component analysis of sfGDS was performed in 2032 medical inpatients (mean age = 76.3 +/- 8.4). sfGDS did not qualify as a unidimensional test. Three factors explained 47.7% of variance and explored the following dimensions: positive attitude toward life, distressing thoughts/negative judgment about the own condition, and inactivity/reduced self-esteem. The internal homogeneity was poor (Cronbach's alpha = .46). A higher fraction of variance was explained in patients independent in all or dependent in > or = 1 activity of daily living (ADL). In older medical inpatients, sfGDS is not a single construct, which prevents the univocal interpretation of the final score. The higher fraction of explained variance in patients with comparable ADL performance probably reflects the dependency of affective from physical status.

Activities of Daily Living↗

Treatment of osteoporosis among older adults discharged from hospital in Italy.

OBJECTIVE: Osteoporosis and its complications represent one of the most important causes of morbidity and mortality among the elderly. Despite the availability of several drugs deemed effective at reducing the incidence of fractures, only a minority of patients receive pharmacological treatment. We studied patients with a diagnosis of osteoporosis at discharge from hospital in Italy to identify predictors of receiving specific pharmacological treatment and to analyse how the pattern of drug prescription has changed in the last decade. METHODS: We analysed data from a multicentre pharmacoepidemiology study that collected data on hospitalised patients throughout Italy. Patients with a diagnosis of osteoporosis admitted during five different surveys in 1988, 1991, 1993, 1995 and 1997 were considered for the present study. RESULTS: Of 863 patients with a diagnosis of osteoporosis, 461 (53.4%) received treatment. Age [odds ratio (OR) 0.86 for each decade of increment, 95% confidence interval (CI) 0.73, 0.99], male gender (OR 0.67, 95% CI 0.44, 0.99), number of comorbid conditions (4-5 vs. 0-3 conditions: OR 0.66, 95% CI 0.47, 0.91; 6 or more vs. 0-3 conditions: OR 0.47, 95% CI 0.31, 0.72) and number of medications (OR 0.92 for each drug increase, 95% CI 0.85, 0.99) were all associated with a reduced likelihood of receiving pharmacological treatment for osteoporosis. In contrast, concomitant corticosteroid use (OR 2.00, 95% CI 1.05, 3.80), admission for hip or vertebral fracture (OR 2.10, 95% Cl 1.12, 3.93) and year of survey (OR 1.11, 95% CI 1.01, 1.24) were independent predictors of a higher treatment rate. Among individual drugs, calcitonin use remarkably declined from 42.1% in 1988 to 0.8% in 1997 (P for trend <0.001), while bisphosphonate prescriptions increased from 1.3% in 1988 to 34.9% in 1997 (P for trend <0.001). Prescription of calcium did not change significantly throughout the decade examined, while vitamin D had a twofold increase (14.2% in 1988 to 26.2% in 1997, P for trend <0.001). CONCLUSIONS: Among patients discharged from hospital in Italy, osteoporosis is an uncommon diagnosis. Even when the diagnosis is made, osteoporosis is often undertreated, and treatment is reserved for younger and less medically complex patients.

Aftercare↗

A new model of integrated home care for the elderly: impact on hospital use.

The objective of the present study was to examine the effect of a home care program based on comprehensive geriatric assessment-Minimum Data Set for Home Care-and case management on hospital use/cost of frail elderly individuals. We determined all hospital admissions and days spent in hospital during the first year since the implementation of the home care program, and compared them to the rate of hospitalization that the same patients had experienced in the year preceding the implementation of such program. Following the implementation of this program, there was a significant reduction of the number of hospitalizations (pre 44% vs. post 26%, P < 0.001), associated with a reduction of hospital days, both at the individual patient level and for each admission. In conclusion, an integrated home care program based on the implementation of a comprehensive geriatric assessment instrument guided by a case manager has a significant impact on hospitalization and is cost-effective.

Aged↗

Trends in antihypertensive drugs in the elderly: the decline of thiazides.

The last decade has seen the publication of different editions of guidelines for the pharmacological treatment of hypertension that were based on the results of large, randomised trials. Since these guidelines were meant to inform practitioners, we analysed the pattern of prescription of antihypertensive agents between 1988 and 1997 among older hospitalised adults. Because of the wealth of data supporting the use of thiazides diuretics, we focused on diuretic prescription, to identify independent predictors of their utilisation. To this end, we used the GIFA database that includes patients admitted to academic medical centres throughout Italy between 1988 and 1997. We studied 5061 patients over 65 years of age selected among a population of 28 411, based on the diagnosis of arterial hypertension at discharge. The use of ACE-inhibitors has been raising steadily through the years, and they are the agents most commonly used since 1996. Calcium channel blockers showed a similar trend and were the top prescribing drug until 1995; afterwards, the documentation of potentially severe side effects has resulted in a nearly 20% reduction of their use. Beta-blockers have remained unpopular throughout the decade. Instead, the prescription of diuretics as a class showed a biphasic trend; an initial decrease with a prolonged steady state and a more recent raise. However, at a separate analysis, it was a evident that a progressive increase of the use of loop diuretics since 1988 has been paralleled by a nearly 50% reduction of thiazides prescriptions. Loop diuretics were more likely to be prescribed to older individuals, those with cardiac heart failure, coronary heart disease and high creatinine level. In contrast, independent predictors of thiazides use were female gender, good functional status, preserved renal function, and absence of cardiovascular comorbidity. In conclusion, despite continued recommendations to use thiazides diuretics for the treatment of hypertension among older individuals, their use has been declining steadily between 1988 and 1997. A possible explanation is that the choice to prescribe a thiazides diuretic is influenced by age, functional status and comorbidity.

Age Factors↗

Functional status and clinical correlates in cognitively impaired community-living older people.

We describe the prevalence of cognitive impairment in a population of community-living older people, its association with functional decline, and degree of comorbidity. In addition, we examined the relationship between different levels of cognitive impairment and mortality. We conducted an observational study of 1787 patients aged 65 years and above with any degree of cognitive impairment. Patient data were collected with the Minimum Data Set for Home Care. More than 50% of patients had some level of cognitive impairment, which correlates with the degree of physical frailty. On the contrary, patients with cognitive impairment appear to have fewer comorbid conditions and are less likely to receive medications than patients with normal cognitive status. In particular, hypertension, congestive heart failure, chronic obstructive pulmonary disease, cancer, diabetes mellitus, and osteoporosis are found more frequently among patients with normal mental status compared with those showing some level of cognitive defects. Yet, more severe cognitive impairment is associated with a higher mortality rate. Demented patients are characterized by a high prevalence of functional disability and by increased mortality. This increased morbidity and mortality rate is associated with a lower prevalence of comorbid clinical conditions and drug use, relative to patients with normal cognitive performance. The present findings support the possibility that severe cognitive impairment has an independent effect on survival.

Activities of Daily Living↗

Dose-related impact of alcohol consumption on cognitive function in advanced age: results of a multicenter survey.

BACKGROUND: Moderate alcohol consumption has been associated in several studies with decreased risk of cardiovascular and cerebrovascular events; however, available data on the effects of alcohol intake on cognitive functioning are conflicting. We assessed the association between alcohol consumption and cognitive impairment in a series of older subjects enrolled in a multicenter pharmacoepidemiology survey. METHODS: The association between average alcoholic intake and cognitive performance was assessed in 15,807 patients admitted to participating centers during the survey periods. Demographic variables, comorbid conditions, medications, and objective tests that were associated with cognitive impairment (as indicated by a Hodkinson Abbreviated Mental Test score <7) in separate logistical regression models were examined as potential confounders in a summary model. RESULTS: Cognitive impairment was detected in 1693 (19%) of 8755 drinkers and 2008 (29%) of 7052 nondrinkers (Fisher's exact test, p < 0.0001). After adjusting for potential confounders, alcohol consumption was associated with decreased probability of cognitive impairment (odds ratio, 0.75; 95% confidence interval, 0.66-0.85). The relationship between drinking level and cognitive dysfunction was nonlinear, because the probability of cognitive impairment was decreased for moderate alcohol use as compared with abstinence, but it was increased for daily consumption exceeding one wine-equivalent liter among men and 0.5 liter among women. This nonlinear association persisted when cerebrovascular and Alzheimer's disease were considered separately. CONCLUSIONS: Alcohol abuse is associated with increased prevalence of cognitive dysfunction among older subjects; however, a daily alcohol consumption of less than 40 g for women and 80 g or less for men might be associated with a decreased probability of cognitive impairment. This possible protective effect of alcohol consumption should be further assessed by prospective studies.

Aged↗