Claudio Pedone

Adverse drug reactions (ADRs) are common causes of in-hospital complications for elderly people. The purpose of the present study is to verify whether concealed renal insufficiency, that is, reduction of the estimated glomerular filtration rate (GFR) in people with normal serum creatinine levels, is a risk factor for ADRs in elderly hospitalized patients. We used data on 11,687 hospitalized patients enrolled in the Gruppo Italiano di Farmacovigilanza nell'Anziano study. The outcomes of the study were any ADR, ADR to hydrosoluble drugs, and ADR to any other drug during the hospital stay. We compared 3 groups: normal renal function (normal serum creatinine levels and normal estimated GFRs), concealed (normal serum creatinine levels and reduced estimated GFRs), or overt (increased creatinine levels and reduced estimated GFRs) renal insufficiency. The relationship between renal function and ADR was evaluated using contingency tables and multiple regression analysis including potential confounders. Concealed renal insufficiency was detected in 1631 (13.9%) patients and was frequently associated with male sex and poor nutritional status. Hydrosoluble drugs were responsible for 301 of the 941 recorded ADRs. After adjusting for potential confounders, both concealed (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.15-1.25) and overt (OR, 2.02; 95% CI, 1.54-2.65) renal failure were associated with ADR to hydrosoluble drugs, but not with ADR to other drugs (OR, 0.83 [95% CI, 0.65-1.08], and OR, 1.01 [95%CI, 0.83-1.23], respectively). Older hospitalized patients frequently have impaired renal function despite normal serum creatinine levels and are exposed to an increased risk of ADRs to hydrosoluble drugs.

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.

Body mass index (weight in kilograms divided by the square of the height in meters [BMI]) is known to be associated with overall mortality. However, the effect of age on excess mortality from all causes associated with obesity is controversial. The aim of the present study is to determine the effect of age on the relationship between BMI and mortality. We analyzed data from a large collaborative observational study group, the Italian Group of Pharmacoepidemiology in the Elderly (GIFA), that collected data on hospitalized patients. A total of 18,316 patients consecutively admitted to 79 clinical centers during 5 different surveys in 1998, 1991, 1993, 1995, and 1997 were enrolled in the present study. The main outcome measure was the relative hazard ratio of death for different levels of BMI. Mortality rate was lowest among men and women with BMIs from 25.0 through 27.4 kg/m(2) (relative risk, 0.24; 95% confidence interval, 0.15-0.38). The graphed relationship between BMI and mortality in younger patients was hyperbolic, with increased death rates at the lowest and highest BMI rankings. On the contrary, the older patients showed an increased death rate at the lowest BMIs with only a slight elevation at the highest BMIs (>35 kg/m(2)). Our results suggest that BMI, a simple anthropometric measure of nutritional status, is an important predictor of mortality among young and old hospitalized patients. Even when controlling for clinical and functional variables, a low BMI remained a significant and independent predictor of shortened survival. Furthermore, the finding of the high BMI associated with minimum hazard in elderly subjects supports some past findings and opposes others and, if confirmed, has important implications for geriatric clinical guidelines.

Use of atypical antipsychotics for "off-label" indications, such as behavioral and psychological symptoms of dementia, depression, and bipolar disorder, have been frequently reported, although not systematically studied. We describe the pattern of atypical antipsychotic use among nursing home residents and identify demographic and clinical correlates. We conducted a cross-sectional study on 139,714 nursing home residents living in 1732 nursing homes in 5 U.S. states from Jan. 1, 1999, to Jan. 31, 2000. Data were obtained from the computerized Minimum Data Set (MDS) assessment records. Behavior problems associated with cognitive impairment were manifest in 86,514 residents, and, of these, 18.2% received an antipsychotic. Approximately 11% received an atypical antipsychotic, while 6.8% received a conventional agent. Clinical correlates of atypical antipsychotic use were Parkinson's disease (adjusted odds ratio [OR] = 1.57, 95% confidence interval [CI] = 1.34 to 1.84), depression (OR = 1.35, 95% CI = 1.24 to 1.46), antidepressant use (OR = 1.38, 95% CI = 1.27 to 1.49), Alzheimer's disease (OR = 1.21, 95% CI = 1.12 to 1.32), non-Alzheimer dementia (OR = 1.15, 95% CI = 1.07 to 1.24), and cholinesterase inhibitor use (OR = 1.74, 95% CI = 1.52 to 1.98). Severe functional impairment was inversely related to atypical antipsychotic use (OR = 0.76, 95% CI = 0.65 to 0.89). Atypical antipsychotics are now used more than conventional antipsychotic agents in U.S. nursing homes. Indications and dosages seem appropriate relative to labeling. Clinical and demographic differences between atypical and conventional antipsychotic users tend to be relatively small, suggesting that other factors may explain the choice of prescribing physicians. The impact of facility factors, economic forces, and physician characteristics needs to be investigated.

PurposeTo assess the effect of moderate alcohol consumption on Adverse Drug Reactions (ADRs) among older adults admitted to acute care hospitals and to examine the consistency of this effect across gender and age groups.To assess the effect of moderate alcohol consumption on Adverse Drug Reactions (ADRs) among older adults admitted to acute care hospitals and to examine the consistency of this effect across gender and age groups.MethodsWe used the GIFA (Italian Group of Pharmacoepidemiology in the Elderly) database, which includes information on patients admitted to 81 medical centers in Italy. For this study we examined exclusively the ADRs detected at hospital admission that were classified as definite or probable based on the Naranjo algorithm.We used the GIFA (Italian Group of Pharmacoepidemiology in the Elderly) database, which includes information on patients admitted to 81 medical centers in Italy. For this study we examined exclusively the ADRs detected at hospital admission that were classified as definite or probable based on the Naranjo algorithm.ResultsAmong 22 778 participants, 894 were found to have one or more ADRs (3.9%). Gastrointestinal complications (n = 210; 0.9% of the population) were the most frequent ADRs, followed by metabolic/endocrine (n = 156; 0.7%), dermatological/allergic (n = 102; 0.4%) and arrhythmic (n = 78; 0.3%) complications. Diuretics were the most frequent culprit drugs, followed by NSAIDs and digoxin. An ADR was recorded in 383/10 427 (3.7%) non-drinkers and in 511/12 351 (4.1%) moderate drinkers. After adjusting for potential confounders, moderate alcohol consumption was associated with a 24% increased risk of ADRs (OR 1.24; 95%CI: 1.08–1.43). This effect seemed more evident among women (OR 1.30; 95%CI: 1.09–1.55), than men (OR 1.14; 95%CI: 0.90–1.43), while it was similar across different age groups (< 65 years OR 1.28; 95%CI: 0.99–1.66; 65–79 years OR 1.22; 95%CI: 0.98–1.52; ≥80 years OR 1.20; 95%CI: 0.93–1.56). Considering the most common ADRs, moderate alcohol users presented a significantly higher risk of drug-related headache (OR 3.89; 95%CI: 1.43–10.61) and metabolic/endocrine complications (OR 1.67; 95%CI: 1.19–2.33).Among 22 778 participants, 894 were found to have one or more ADRs (3.9%). Gastrointestinal complications (n = 210; 0.9% of the population) were the most frequent ADRs, followed by metabolic/endocrine (n = 156; 0.7%), dermatological/allergic (n = 102; 0.4%) and arrhythmic (n = 78; 0.3%) complications. Diuretics were the most frequent culprit drugs, followed by NSAIDs and digoxin. An ADR was recorded in 383/10 427 (3.7%) non-drinkers and in 511/12 351 (4.1%) moderate drinkers. After adjusting for potential confounders, moderate alcohol consumption was associated with a 24% increased risk of ADRs (OR 1.24; 95%CI: 1.08–1.43). This effect seemed more evident among women (OR 1.30; 95%CI: 1.09–1.55), than men (OR 1.14; 95%CI: 0.90–1.43), while it was similar across different age groups (< 65 years OR 1.28; 95%CI: 0.99–1.66; 65–79 years OR 1.22; 95%CI: 0.98–1.52; ≥80 years OR 1.20; 95%CI: 0.93–1.56). Considering the most common ADRs, moderate alcohol users presented a significantly higher risk of drug-related headache (OR 3.89; 95%CI: 1.43–10.61) and metabolic/endocrine complications (OR 1.67; 95%CI: 1.19–2.33).ConclusionsModerate alcohol intake is associated with an increased risk of ADRs; this effect seems more evident among women than men, and it does not differ across age groups. Copyright © 2002 John Wiley & Sons, Ltd.Moderate alcohol intake is associated with an increased risk of ADRs; this effect seems more evident among women than men, and it does not differ across age groups. Copyright © 2002 John Wiley & Sons, Ltd.

To assess whether serum creatinine and age are associated with headache induced by nitrates, 2742 hospitalized patients taking nitrates were studied during their hospital stay. Those patients with admission serum creatinine levels from 97 to 133 mumol/L and &amp;amp;amp;gt; 133 mumol/L were compared with patients with creatinine levels &amp;amp;amp;lt; 97 mumol/L. Gender, body mass index, comorbidity, cognitive status, new intake of nitrates, number of daily administrations, and daily dosage, as well as intake of angiotensin converting enzyme inhibitors, calcium antagonists, diuretics and nonsteroidal anti-inflammatory drugs were examined as possible confounders. Fifty-six patients had headaches that had a causal link with intake of nitrates. Compared with the lowest creatinine group, after adjustment for potential confounding variables, the odds ratios and 95% confidence interval (95% CI) for headache caused by nitrates associated with increasing serum creatinine levels were 0.6 (95% CI, 0.3 to 1.1) and 0.2 (95% CI, 0.0 to 1.2), respectively (p for trend = 0.013). Increasing age was inversely associated with headache (odds ratio for 10-year increase, 0.6 [95% CI, 0.5 to 0.7]). Serum creatinine and age were independently and inversely associated with headache caused by nitrates.

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. 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7. 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). Out-of-hospital mortality was 27% (51/191) among patients with cognitive impairment and 15% (115/777) among other participants (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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. 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.

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% CI 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 under-treated, and treatment is reserved for younger and less medically complex patients.

To assess the association between in-hospital use of calcium antagonists and incident reduction in hemoglobin levels, as well as the impact of individual baseline risk for gastrointestinal bleeding on such an association. The association between calcium antagonists and hemoglobin decrease &amp;amp;amp;gt; 1.2 g/dL was examined in 6,721 patients enrolled in a collaborative pharmacoepidemiology study who did not take calcium antagonists before admission and with baseline hemoglobin &amp;amp;amp;gt; or =12 g/dL. Among these participants, 1,076 patients started taking calcium antagonists during their hospital stays. Demographic variables, comorbid conditions, medications, and objective tests that were associated with incident hemoglobin loss in separate age- and sex-adjusted logistic regression models were examined as potential confounders in a summary model. Higher risk for gastrointestinal bleeding was defined by diagnosis, treatment for peptic disease, or both. Hemoglobin decrease was detected in 24% of participants who started treatment with calcium antagonists and in 19% of other patients (P &amp;amp;amp;lt; .0001). In addition, use of calcium antagonists was independently associated with increased probability of hemoglobin loss (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.03 to 1.45; P = .018) after adjusting for potential confounders. Treatment with calcium antagonists was associated with hemoglobin loss in patients with higher baseline risk for gastrointestinal bleeding (OR, 1.67; 95% CI, 1.26 to 2.22; P &amp;amp;amp;lt; .0001) but not among other participants (OR, 1.02; 95% CI, 0.82 to 1.25). Starting treatment with calcium antagonists is associated with a reduction in hemoglobin levels during a hospital stay. However, the increased risk of hemoglobin loss seems to be limited to patients with diagnosis or symptoms of peptic disease.

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.