Claudio Pedone

Adverse Drug Reactions as Cause of Hospital Admissions: Results from the Italian Group of Pharmacoepidemiology in the Elderly (GIFA)

OBJECTIVES: To determine the prevalence of adverse drug reaction (ADR)‐related hospital admissions in an older population, to describe the most common clinical manifestations and drugs most frequently responsible for ADR‐related hospital admissions, and to identify independent factors predictive of these ADRs.

The effects of cognitive impairment on mortality among hospitalized patients with heart failure

PURPOSE Cognitive impairment is a common, potentially reversible condition among older patients with heart failure. Because cerebral metabolic abnormalities have been associated with reduced survival in younger patients with advanced heart failure, we assessed the effect of cognitive impairment on the survival of older patients with heart failure. METHODS The association between cognitive dysfunction and in-hospital mortality was assessed in 1113 patients (mean [+/- SD] age, 78 +/- 9 years) who had been admitted for heart failure to 81 hospitals throughout Italy. One-year mortality was assessed in 968 patients with heart failure (age, 76 +/- 10 years) participating in the same study. Cognitive impairment was defined as a Hodkinson Abbreviated Mental Test score <7. RESULTS In-hospital death occurred in 65 (18%) of the 357 participants with cognitive impairment and in 26 (3%) of the 756 patients with normal cognition (P <0.0001). Out-of-hospital mortality was 27% (51/191) among patients with cognitive impairment and 15% (115/777) among other participants (P <0.0001). In multivariate Cox regression models, decreasing levels of cognitive functioning were associated with increasing in-hospital mortality; cognitive impairment was associated with an almost fivefold increase in mortality (relative risk = 4.9; 95% confidence interval: 2.9 to 8.3) after adjusting for several potential confounders. CONCLUSION Cognitive impairment is an independent prognostic marker in older patients with heart failure. Assessment of cognitive functioning, even by simple screening tests, should be part of the routine assessment of elderly patients with heart failure.

Hypotension and cognitive impairment Selective association in patients with heart failure

Background: Arterial hypotension has been associated with increased risk of dementia in some large prospective studies; and cognitive impairment is common among elderly with left ventricular function. The authors assessed whether arterial hypotension might be associated with cognitive impairment among older subjects with heart failure. Methods: This study involved all 13,635 patients (of whom 1,583 had heart failure) without cerebrovascular disease or AD, admitted to 81 Italian academic hospitals in 1995 and 1997. The association between blood pressure and cognitive impairment (as indicated by a Hodkinson Mental Test score < 7) according to the presence of heart failure was assessed by univariate analyses, including linear discriminant analysis. This association was also verified by multivariate analyses after stratifying for diagnosis of heart failure. Results: Cognitive impairment was found in 26% of patients with heart failure and in 19% of remaining subjects (Fisher exact p < 0.0001). Blood pressure levels did not differ according to diagnosis of heart failure, but discriminant analysis indicated that systolic blood pressure levels below 130 mm Hg predicted cognitive impairment only among participants with heart failure. Among such participants, systolic blood pressure was associated with cognitive impairment in multiple logistic regression modeling (for 10 mm Hg intervals, OR = 0.78; 95% CI = 0.71 to 0.86). Again, this association was not found among participants without heart failure. Conclusions: Systolic hypotension is selectively associated with cognitive impairment in older patients with heart failure. As early treatment of cardiac low-output states can reverse cognitive dysfunction, the routine management of heart failure should include systematic assessment of cognitive performance.

Age-Related Pharmacokinetic and Pharmacodynamic Changes and Related Risk of Adverse Drug Reactions

Aging is known to be associated with an increased prevalence of multiple chronic diseases, which frequently causes the use of complex therapeutic regimens. The aging process is characterized by relevant changes in drug handling, physiological reserve, and pharmacodynamic response. Hepatic drug clearance of several drugs decreases with aging, mainly due to reduced blood flow, and hepatocyte mass. Renal function also declines with aging, mainly due to sclerotic changes in the glomeruli. Furthermore, due to reduced muscle mass, older subjects frequently have depressed glomerular filtration rate despite normal serum creatinine, and such a concealed renal insufficiency may impact significantly the clearance of hydrosoluble drugs. Changes in pharmacodynamics are also well documented in the cardiovascular and nervous system. Age-related changes in pharmacokinetics and pharmacodynamics, together with comorbidity and polypharmacy, make elderly patients at special risk for adverse drug reactions, which in turn are cause of relevant health burden and costs. Selected measures can assist in preventing or detecting timely such adverse events.

Oral Specific Desensitization in Food-Allergic Children

The possibility of obtaining oral desensitization in patients with food allergy is still a matter of debate. We decided to evaluate the safety and efficacy of standardized protocols for oral desensitization with the most common food allergens. Forty-two children (ages up to 16 years) diagnosed as affected by food allergy (on the basis of clinical history, skin prick tests, measurement of specific IgE, and double-blind, placebo-controlled food challenge) underwent a sublingual-oral desensitizing treatment according to new standardized protocols. The control group consisted of 10 patients who followed an elimination diet. The treatment was successfully completed by 85.7% of the patients. Specific IgE showed a significant decrease, while specific IgG4 showed a significant increase, in all treated patients. The immunological modifications observed in our patients lead us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory and insect sting allergy.

Chronic Renal Failure: A Neglected Comorbidity of COPD

BACKGROUND To the best of our knowledge, the association between COPD and chronic renal failure (CRF) has never been assessed. Lean mass is frequently reduced in COPD, and the glomerular filtration rate (GFR) might be depressed in spite of normal serum creatinine (concealed CRF). We investigated the prevalence and correlates of both concealed and overt CRF in elderly patients with COPD. METHODS We evaluated 356 consecutive elderly outpatients with COPD enrolled in the Extrapulmonary Consequences of COPD in the Elderly Study and 290 age-matched outpatients free from COPD. The GFR was estimated using the Modification of Diet in Renal Disease Study Group equation. Patients were categorized as having normal renal function (GFR > or = 60 mL/min/1.73 m(2)), concealed CRF (normal serum creatinine and reduced GFR), or overt CRF (increased serum creatinine and reduced GFR). Independent correlates of CRF were investigated by logistic regression analysis. RESULTS The prevalence of concealed and overt CRF in patients with COPD was 20.8% and 22.2%, respectively. Corresponding figures in controls were 10.0% and 13.4%, respectively. COPD and age were significantly associated with both concealed CRF (COPD: odds ratio [OR] = 2.19, 95% CI = 1.17-4.12; age: OR = 1.06, 95% CI = 1.04-1.09) and overt CRF (COPD: OR = 1.94, 95% CI = 1.01-4.66; age: OR = 1.06, 95% CI = 1.04-1.10). Diabetes (OR = 1.96, 95% CI = 1.02-3.76), hypoalbuminemia (OR = 2.83, 95% CI = 1.70-4.73), and muscle-skeletal diseases (OR = 1.78, 95% CI = 1.01-3.16) were significant correlates of concealed CRF. BMI (OR = 1.05, 95% CI = 1.01-1.10) and diabetes (OR = 2.25, 95% CI = 1.26-4.03) were significantly associated with overt CRF. CONCLUSIONS CRF is highly prevalent in patients with COPD, even with normal serum creatinine, and might contribute to explaining selected conditions such as anemia that are frequent complications of COPD.

Community care in Europe. The Aged in HOme Care project (AdHOC)

Background and aims: Community care for older people is increasing dramatically in most European countries as the preferred option to hospital andlong-term care. While there has been a rapid expansion in Evidence-Based Medicine, apart from studies of specific interventions such as home visiting and hospital at home (specialist visits or hospital services provided to people in their own homes in the community), there is little evidence of characteristics of the recipients of community care services or the organisation of services that produce the best outcomes for them and their informal carers. The AdHOC Study was designed to compare outcomes of different models of community care using a structured comparison of services and a comprehensive standardised assessment instrument across 11 European countries. This paper describes the study and baseline data. Methods: 4,500 people 65 years and older already receiving home care services within the urban areas selected in each country were randomly sampled. They were assessed with the MDS-HC (Minimum Data Set-Home Care) instrument, containing over 300 items, including socio-demographic, physical and cognitive characteristics of patients as well as medical diagnoses and medications received. These data were linked to information on the setting, services structures and services utilization, including use of hospital and long-term care. After baseline assessment, patients were re-evaluated at 6 months with an abbreviated version of the instrument, and then at the end of one year. Data collection was performed by specially-trained personnel. In this paper, socio-demographics, physical and cognitive function and provision of hours of formal care are compared between countries at baseline. Results: The final study sample comprised 3,785 patients; mean age was 82±7.2 years, 74.2% were females. Marital and living status reflected close family relationships in southern Europe relative to Nordic countries, where 5 times as many patients live alone. Recipients of community care in France and Italy are characterised by very high physical and cognitive impairment compared with those in northern Europe, who have comparatively little impairment in Activities of Daily Living and cognitive function. The provision of formal care to people with similar dependency varies extremely widely with very little formal care in Italy and more than double the average across all levels of dependency in the UK. Conclusions: The AdHOC study, by virtue of the use of a common comprehensive standardised assessment instrument, is a unique tool in examining older recipients of community care services in European countries and their widely varied organisation. The extreme differences seen in dependency and hours of care illustrate the probable contribution the study will make to developing an evidence based on the structure, quantity and targeting of community care, which will have major policy implications.

Original ResearchCOPDChronic Renal Failure: A Neglected Comorbidity of COPD

BACKGROUND To the best of our knowledge, the association between COPD and chronic renal failure (CRF) has never been assessed. Lean mass is frequently reduced in COPD, and the glomerular filtration rate (GFR) might be depressed in spite of normal serum creatinine (concealed CRF). We investigated the prevalence and correlates of both concealed and overt CRF in elderly patients with COPD. METHODS We evaluated 356 consecutive elderly outpatients with COPD enrolled in the Extrapulmonary Consequences of COPD in the Elderly Study and 290 age-matched outpatients free from COPD. The GFR was estimated using the Modification of Diet in Renal Disease Study Group equation. Patients were categorized as having normal renal function (GFR > or = 60 mL/min/1.73 m(2)), concealed CRF (normal serum creatinine and reduced GFR), or overt CRF (increased serum creatinine and reduced GFR). Independent correlates of CRF were investigated by logistic regression analysis. RESULTS The prevalence of concealed and overt CRF in patients with COPD was 20.8% and 22.2%, respectively. Corresponding figures in controls were 10.0% and 13.4%, respectively. COPD and age were significantly associated with both concealed CRF (COPD: odds ratio [OR] = 2.19, 95% CI = 1.17-4.12; age: OR = 1.06, 95% CI = 1.04-1.09) and overt CRF (COPD: OR = 1.94, 95% CI = 1.01-4.66; age: OR = 1.06, 95% CI = 1.04-1.10). Diabetes (OR = 1.96, 95% CI = 1.02-3.76), hypoalbuminemia (OR = 2.83, 95% CI = 1.70-4.73), and muscle-skeletal diseases (OR = 1.78, 95% CI = 1.01-3.16) were significant correlates of concealed CRF. BMI (OR = 1.05, 95% CI = 1.01-1.10) and diabetes (OR = 2.25, 95% CI = 1.26-4.03) were significantly associated with overt CRF. CONCLUSIONS CRF is highly prevalent in patients with COPD, even with normal serum creatinine, and might contribute to explaining selected conditions such as anemia that are frequent complications of COPD.

Regimen complexity and medication nonadherence in elderly patients

Objective: To assess whether the number of daily administrations of individual drugs, as a measure of regimen complexity, contributes to the profile of an elderly patient who adheres poorly to the prescribed therapy. Population: Six hundred ninety patients over 64 years who were consecutively admitted to 11 acute medical care and three long term/rehabilitation wards in Italy. Main outcome measure: Self-reported adherence to drugs taken at home before admission was measured by a single question assessment for each listed drug supplemented with a latter question about the circumstances of the missed administration. For cognitively impaired patients the question was put to patients’ relatives or caregivers. Methods: A structured multidimensional assessment was performed to identify nonadherence and its potential correlates. Correlates of nonadherence were identified by multivariable logistic regression. Results: We recorded 44 cases (6.4%) of nonadherence to at least one drug. Being assisted by foreign caregivers (OR 2.17; 95% CI 1.02–4.63) and the use of at least one multiple daily dosing drug (OR 2.99; 95% CI 1.24–7.17) were significant independent correlates of medication nonadherence, while age, selected indexes of frailty and the cumulative number of prescribed drugs were not. Conclusion: Regimen complexity and type of assistance are independent correlates of medication nonadherence.

Cerebral hemodynamics and cognitive performance in patients with asymptomatic carotid stenosis

Objective: The aim of this study was to investigate whether the presence of severe internal carotid artery stenosis may be associated with different cognitive performance in relation to the side of the stenosis and its hemodynamic consequences. Methods: Eighty-three patients with asymptomatic severe unilateral internal carotid stenosis were included. A neuropsychological investigation including Verbal Fluency using phonemic and category access, Coloured Progressive Matrices, and Complex Figure Test Copy was performed. Each patient underwent an assessment of cerebrovascular reactivity (CVR) to hypercapnia with transcranial Doppler ultrasonography using the breath-holding index (BHI). Thirty healthy subjects comparable for demographic characteristics and vascular risk profile served as controls. Subjects with carotid stenosis were classified into two groups: preserved CVR (BHI ≥0.69), 48 patients (25 with left and 23 with right stenosis); and impaired CVR (BHI <0.69), 35 patients (19 with left and 16 with right stenosis). Results: Subjects with left stenosis and reduced CVR had significantly lower performances at phonemic verbal fluency with respect to controls and the other groups of stenosis. In subjects with right stenosis and reduced CVR, scores obtained in Coloured Progressive Matrices and in Complex Figure Test Copy were significantly lower with respect to the other groups. Conclusions: These results suggest that an alteration of cerebrovascular reactivity may be responsible for reduction in some cognitive abilities involving the function of the hemisphere ipsilateral to carotid stenosis. Such findings may be of interest for providing a more comprehensive indication to surgical treatment in subgroups of subjects with asymptomatic carotid stenosis.