Marilisa Franceschi

Development and Validation of a Multidimensional Prognostic Index for One-Year Mortality from Comprehensive Geriatric Assessment in Hospitalized Older Patients

Our objective was to construct and validate a Multidimensional Prognostic Index (MPI) for 1-year mortality from a Comprehensive Geriatric Assessment (CGA) routinely carried out in elderly patients in a geriatric acute ward. The CGA included clinical, cognitive, functional, nutritional, and social parameters and was carried out using six standardized scales and information on medications and social support network, for a total of 63 items in eight domains. A MPI was developed from CGA data by aggregating the total scores of the eight domains and expressing it as a score from 0 to 1. Three grades of MPI were identified: low risk, 0.0-0.33; moderate risk, 0.34-0.66; and severe risk, 0.67-1.0. Using the proportional hazard models, we studied the predictive value of the MPI for all causes of mortality over a 12-month follow-up period. MPI was then validated in a different cohort of consecutively hospitalized patients. The development cohort included 838 and the validation cohort 857 elderly hospitalized patients. Of the patients in the two cohorts, 53.3 and 54.9% were classified in the low-risk group, respectively (MPI mean value, 0.18 +/- 0.09 and 0.18 +/- 0.09); 31.2 and 30.6% in the moderate-risk group (0.48 +/- 0.09 and 0.49 +/- 0.09); 15.4 and 14.2% in the severe-risk group (0.77 +/- 0.08 and 0.75 +/- 0.07). In both cohorts, higher MPI scores were significantly associated with older age (p = 0.0001), female sex (p = 0.0001), lower educational level (p = 0.0001), and higher mortality (p = 0.0001). In both cohorts, a close agreement was found between the estimated mortality and the observed mortality after both 6 months and 1 year of follow-up. The discrimination of the MPI was also good, with a ROC area of 0.751 (95%CI, 0.70-0.80) at 6 months and 0.751 (95%CI, 0.71-0.80) at 1 year of follow-up. We conclude that this MPI, calculated from information collected in a standardized CGA, accurately stratifies hospitalized elderly patients into groups at varying risk of mortality.

Multidimensional Prognostic Index Based on a Comprehensive Geriatric Assessment Predicts Short-Term Mortality in Older Patients With Heart Failure

Background—Multidimensional impairment of older patients may influence the clinical outcome of diseases. The aim of this study was to evaluate whether a Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment predicts short-term mortality in older patients with heart failure. Methods and Results—In this prospective study with a 1-month follow-up, 376 patients aged 65 and older with a diagnosis of heart failure were enrolled. A standardized comprehensive geriatric assessment that included information on functional (activities of daily living and instrumental activities of daily living), cognitive (Short Portable Mental Status Questionnaire), and nutritional status (Mini Nutritional Assessment), as well as on risk of pressure sore (Exton-Smith Scale), comorbidities (Cumulative Illness Rating Scale Index), medications, and social support network, was used to calculate the MPI for mortality using a previously validated algorithm. The New York Heart Association, the Enhanced Feedback for Effective Cardiac Treatment, and the Acute Decompensated Heart Failure National Registry regression model scores were also calculated. Higher MPI values were significantly associated with higher 30-day mortality, both in men (MPI-1, 2.8%; MPI-2, 15.3%; MPI-3, 47.4%; P=0.000) and women (MPI-1, 0%; MPI-2, 6.5%; MPI-3, 14.6%; P=0.011). The discrimination of the MPI was also good, with areas under the receiver operating characteristic curves (men: 0.83; 95% CI, 0.75 to 0.90; women: 0.80; 95% CI, 0.71 to 0.89) greater than receiver operating characteristic areas of New York Heart Association (men: 0.63; 95% CI, 0.57 to 0.69; P=0.015; women: 0.65; 95% CI, 0.55 to 0.75; P=0.064), Enhanced Feedback for Effective Cardiac Treatment (men: 0.69; 95% CI, 0.58 to 0.79; P=0.045; women: 0.71; 95% CI, 0.55 to 0.87; P=0.443), and Acute Decompensated Heart Failure National Registry scores (men: 0.65; 95% CI, 0.52 to 0.78; P=0.023; women: 0.67; 95% CI, 0.49 to 0.83, P=0.171). Conclusions—The MPI, calculated from information collected in a standardized comprehensive geriatric assessment, is useful to estimate the risk of 1-month mortality in older patients with heart failure.

Role of Helicobacter pylori Infection on Upper Gastrointestinal Bleeding in the Elderly (A Case-Control Study)

Nonsteroidal antiinflammatory drug (NSAID) useis known to be associated with a high incidence of uppergastrointestinal tract bleeding in the elderly. Theincreased prevalence of Helicobacter pylori (HP) infection, which also occurs with age, suggeststhat an interaction between NSAID use and HP infectionmay explain the higher incidence of ulcer complicationsin the elderly. The aim of the present study was to determine if a relationship existsbetween HP infection and NSAID use in elderly patientswith upper gastrointestinal bleeding. This was a case-control study on 146 elderly patients (73/group). The bleeding group consisted of 37 males and 36females (mean age 80.4 years, range 70-96) with symptoms(hematemesis, melena, anemia with loss of more than 3 ghemoglobin), and endoscopic stigmata of bleeding. The control group consisted of 73 age- andsex-matched patients with the same endoscopic diagnosisbut with no endoscopic stigmata of bleeding. NSAID usewas evaluated by interview at the time of endoscopy, and HP infection was confirmed in all cases byhistology and the rapid urease test. Statisticalanalyses were performed using the chisquare test andlogistic regression. In both groups, 46.57% of patients were affected with gastric ulcer, 36.98% withduodenal ulcer, and 16.43% with erosive gastritis. Thebleeding group had a significantly higher percentage ofNSAID users (53.42% vs 19.17%, P < 0.0001) and a lower percentage of HP-positive patients(47.94% vs 72.60%, P = 0.004). The NSAID use pattern wasas follows: occasional users (sporadic, as needed duringthe previous week): 53.8% of bleeding cases and 50% of controls; acute users (continuoustherapy for less than one month): 17.9% of bleedingcases and 28.5% of controls; and chronic users(continuous therapy for more than one month): 28.2% ofbleeding cases and 21.4% of controls. The logisticregression demonstrated that NSAID use was significantlyrelated to an increase risk of bleeding both in gastric(odds ratio: 4.98, 95% CI: 1.83-13.6) and duodenal ulcer patients (odds ratio: 10.2, 95% CI: 2.25-46.7) while HP-positivity presented a significantinverse relationship with bleeding only in subjects withgastric lesions (odds ratio: 0.20, 95% CI: 0.07- 0.55). NSAID use and HP infection were alsoshown to be independent, unrelated factors, with theoverall risk of bleeding in HP-positive NSAID usersidentified to be significantly less than in HP-negative NSAID users. In conclusion, in elderlypatients: (1) NSAID use increases the risk of uppergastrointestinal bleeding while HP infection wasassociated with a low risk for gastric bleeding; and (2)the two factors are independent variables, thereforethe HP-positive NSAID user has a lower risk than theHP-negative NSAID user.

Clinical features of reflux esophagitis in older people : A study of 840 consecutive patients

OBJECTIVES: To compare symptoms and other clinical characteristics of reflux esophagitis in patients of different ages.

Effect of a CYP2D6 polymorphism on the efficacy of donepezil in patients with Alzheimer disease.

Objective: To evaluate the influence of the single nucleotide polymorphism rs1080985 in the cytochrome P450 2D6 (CYP2D6) gene on the efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD). Methods: This was a multicenter, prospective cohort study of 127 white patients with AD according to the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association Work Group criteria. Patients were treated with donepezil 5–10 mg/daily for 6 months. Cognitive and functional statuses were evaluated at baseline and at 6-month follow-up. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Compliance and drug-related adverse events were also evaluated. The analyses identifying the CYP2D6 and APOE polymorphisms were performed in blinded fashion. Results: At 6-month follow-up, 69 of 115 patients (60%) were responders and 46 patients (40%) were nonresponders to donepezil treatment. A significantly higher frequency of patients with the G allele of rs1080985 was found in nonresponders than in responders (58.7% vs 34.8%, p = 0.013). Logistic regression analysis adjusted for age, sex, Mini-Mental State Examination score at baseline, and APOE demonstrated that patients with the G allele had a significantly higher risk of poor response to donepezil treatment (odds ratio 3.431, 95% confidence interval 1.490–7.901). Conclusions: The single nucleotide polymorphism rs1080985 in the CYP2D6 gene may influence the clinical efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD). The analysis of CYP2D6 genotypes may be useful in identifying subgroups of patients with AD who have different clinical responses to donepezil.

The effect of Helicobacter pylori infection on NSAID-related gastroduodenal damage in the elderly

Objective: To evaluate the effect of Helicobacter pylori infection on the prevalence and severity of non‐steroidal anti‐inflammatory drug (NSAID)‐related upper gastrointestinal lesions in the elderly. Patients and methods: One hundred and twenty‐eight symptomatic NSAID users (47 males, 81 females; mean age 79.5 years, range 67‐95 years) were evaluated by endoscopy. NSAID use was evaluated at the time of endoscopy by interview and general practitioners’ clinical records. Patients were separated by the following use patterns: (1) Occasional Users: patients who had taken NSAIDs sporadically, on an as‐needed basis in the 7‐day period before endoscopy; (2) Acute Users: patients who had taken NSAIDs regularly during the last month; and (3) Chronic Users: patients who had taken NSAIDs regularly for more than 1 month. H. pylori infection was diagnosed by gastric histology (modified Giemsa stain) and the rapid urease test. Statistical analysis was performed by means of the x2 test with standardized deviates. Results: Of the 128 subjects, 107 (83.6%) presented with gastroduodenal damage: 3 patients (2.3%) had erosive oesophagitis; 38 patients (29.7%) had gastric ulcer (GU); 43 patients (33.6%) had duodenal ulcer (DU); 3 patients (2.3%) had both GU and DU and 20 patients (15.6%) had erosive gastritis. Seventy‐four of the 128 patients (57.8%) were found to be H. pylori positive. In comparison to H. pylori‐negative subjects, those who were H. pylori‐positive had a significantly higher percentage of GU and DU (74.3% vs. 53.7%, P=0.02) and a lower percentage of non‐gastroduodenal lesions (10.8% vs. 24.0%, P=0.05). No significant trend in H. pylori positivity was found in the 50/128 (39.06%) patients who presented with bleeding lesions (H. pylori positive 36.5%, H. pylori negative 42.6%, not significant). At endoscopy 78% of occasional NSAID users, 93.8% of acute users and 88.7% of chronic users presented with upper gastrointestinal lesions (not significant). No significant differences in NSAID use patterns were observed between H. pylori‐positive and H. pylori‐negative subjects. Conclusion: H. pylori infection in the elderly is associated with an increase in the NSAID‐related GU and DU, but not with a higher prevalence of upper gastrointestinal bleeding.

The risk of upper gastrointestinal bleeding in elderly users of aspirin and other non-steroidal antiinflammatory drugs: The role of gastroprotective drugs

Background and aims: Although the administration of gastroprotective drugs may reduce the risk of gastrointestinal (GI) bleeding due to intake of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin during chronic treatment, no consensus exists as to whether such co-therapy is effective in short-term prevention, particularly in old age. The aim of our study was to evaluate the risk of bleeding associated with acute and chronic NSAID or aspirin therapy in elderly subjects, and the influence of gastroprotective treatment on such a risk. Methods: The study included 467 elderly NSAID or aspirin users and 1784 non-users, who consecutively underwent upper GI endoscopy. The use of NSAIDs and/or aspirin as well as gastroprotective drugs (misoprostol, H2-blockers, proton pump inhibitors) was evaluated during a structured interview. Upper GI tract bleeding was diagnosed on the basis of symptoms and endoscopic signs of recent hemorrhage. Results: 54.2% of patients were acute and 45.8% chronic users of NSAIDs or aspirin. The risk of bleeding was higher in acute [odds ratio (OR) 4.14, 95% CI 2.97-5.78] than chronic users (OR 1.71, 95% CI 1.1-2.67). The risk of bleeding, adjusted for age, gender, Helicobacter (H) pylori infection, and gastroprotective drug use were 7.87 (CI 4.90-12.60) in acute users and 3.97 (95% CI 2.27-6.96) in chronic users of NSAIDs and/or aspirin. The risk of bleeding was significantly associated with acute but not chronic use of regular-dose aspirin (OR 5.53, 95% CI 2.29-13.3), diclofenac (OR 4.44, 95% CI 2.21-8.93), ketorolac (OR 4.81, 95% CI 2.13-10.9), naproxen (OR 14.9, 95% CI 4.23-52.4) or nimesulide (OR 4.06, 95% CI 1.2-13.8). Piroxicam increased the risk of bleeding in both acute (OR 5.36, 95% CI 1.94-14.8) and chronic therapy (OR 5.53, 95% CI 1.23-24.9). In acute users, concomitant therapy with proton pump inhibitors reduced the risk of bleeding compared with non-users (OR 1.05, 95% CI 0.19-5.65), whereas co-treatment with H2-blockers was associated with a significantly higher risk of bleeding than in non-users (OR 3.40, 95% CI 1.28-9.02). Chronic users of NSAIDs or aspirin co-treated with proton pump inhibitors had a lower risk of bleeding (OR 1.12, 95% CI 0.21-6.07) than those treated with misoprostol (OR 1.91, 95% CI 0.33-10.9) or H2 blockers (OR 2.26, 95% CI 0.81-6.36). Conclusions: The risk of upper GI bleeding is significantly higher in elderly acute vs chronic users of NSAIDs or regular-dose aspirin. In acute NSAID or aspirin users, co-treatment with proton pump inhibitors, but not with H2-blockers, may reduce the risk of bleeding compared with non-users.

NSAID and Aspirin Use by the Elderly in General Practice Effect on Gastrointestinal Symptoms and Therapies

BackgroundThe relationship between NSAID use and gastrointestinal (GI) symptoms and their treatment in elderly patients is not well defined.ObjectivesTo identify the prevalence of specific drug use in elderly outpatients and to identify the relationship between NSAID use and GI disturbances and treatments in elderly subjects treated by their general practitioner (GP).Settingand participantsThe study was carried out by 63 GPs in north-eastern Italy; 3154 elderly subjects were included in the study over a 2-week period.DesignBy using a structured interview, subjects’ medical histories and current medication were identified. In particular, the presence and use pattern (i.e. occasional, ‘acute’ or ‘chronic’) of NSAIDs and/or aspirin (acetylsalicylic acid) were recorded. In all subjects, the presence of upper GI symptoms, i.e. abdominal pain, reflux symptoms and indigestion syndrome, were noted.ResultsThe prevalence of drug use was 96.4% (males 96%, females 96.7%). The most prescribed drugs were ACE inhibitors (38%), diuretics (26.7%), NSAIDs and regular-dose aspirin (24.7%), GI drugs (20.6%), and anxiolytics/hypnotics (20.3%). Of 779 subjects who had taken NSAIDs or regular-dose aspirin, 32.9% were ‘chronic’ users, 24.9% were ‘acute’ users and 42.1% occasional users. A significantly higher prevalence of upper GI symptoms was observed in elderly NSAID and low-dose aspirin users compared with non-users (24.9% vs 28% vs 16.6% respectively, p < 0.0001). GI symptoms were reported by 27.6% of ‘chronic’ NSAID users, 22.9% of ‘acute’ users and 24.7% of occasional users. A significantly higher prescription rate for any GI drug was found in NSAID users than in low-dose aspirin users and non-users (24.0% vs 19.6% vs 19.4% respectively, p = 0.007). This difference was mainly because of a higher number of upper GI drugs taken by NSAID users than by low-dose aspirin users and non-users (18.1% vs 16% vs 13.7% respectively, p = 0.004). Multivariate analysis demonstrated that female gender (odds ratio [OR] = 1.32, 95% CI = 1.16–1.44), low-dose aspirin (OR = 1.88, 95% CI = 1.33–2.65), NSAIDs and/or regular-dose aspirin (OR = 1.48, 95% CI = 1.19–1.83) and multiple therapies, i.e. taking more than four drugs per day (OR = 1.42, 95% CI = 1.14–1.77) were risk factors for GI symptoms in elderly outpatients.ConclusionNSAIDs and/or aspirin use was very high in this elderly outpatient population. The use of these drugs was significantly associated with a greater number of upper GI symptoms and prescriptions for GI drugs. Educational and clinical strategies need to be implemented in order to reduce the GI impact of NSAID and aspirin use in elderly people.

The Multidimensional Prognostic Index (MPI), Based on a Comprehensive Geriatric Assessment Predicts Short- and Long-Term Mortality in Hospitalized Older Patients with Dementia

Aim of this study was to evaluate the usefulness of a Multidimensional Prognostic Index (MPI) based on a Comprehensive Geriatric Assessment (CGA) for predicting mortality risk in older patients with dementia. The present was a retrospective study with a year of follow-up that included 262 patients aged 65 years and older with a diagnosis of dementia. A standardized CGA that included information on clinical, cognitive, functional, and nutritional aspects, as well as comorbidity, medications, and social support network, was used to calculate MPI. The predictive value of the MPI for all-cause mortality over 1 month, 6 months, and 12 months of follow-up was evaluated. Higher MPI values were significantly associated with higher mortality at 1 month (MPI-1, low risk = 0%, MPI-2, moderate risk = 5.2%, MPI-3, severe risk = 13.7%; p < 0.002), 6-months (MPI-1 = 2.7%, MPI-2 = 11.2%, MPI-3 = 28.8%; p < 0.001), and 12-months (MPI-1 = 2.7%, MPI-2 = 18.2%, MPI-3 = 35.6%; p < 0.001) of follow-up. The discrimination of the MPI was also good, with areas under the ROC curves of 0.77 (sensitivity = 82.9%, specificity = 66.0%, with a cut off value > 0.16) at 12-months of follow up. In conclusion, the MPI, calculated from information collected in a standardized CGA, accurately stratified hospitalized elderly patients with dementia into groups at varying risk of short- and long-term mortality.

Prevention of acute NSAID-related gastroduodenal damage: a meta-analysis of controlled clinical trials.

No consensus exists as to whether cotherapy is effective in the short-term prevention of severe NSAID-related gastroduodenal damage. The aim of this study was to provide a quantitative systematic review of the efficacy of gastroprotective drugs, such as misoprostol, H2-blockers, and proton pump inhibitors (PPI) in preventing the severe acute NSAID-related gastroduodenal damage. Placebo-controlled randomized clinical trials on the use of misoprostol, H2-blockers, and PPIs as preventative agents published between January 1986 and May 1999 were identified through Medline and reference lists from clinical reviews. Studies on patients or healthy subjects were considered to be eligible for data pooling if they were performed in acute NSAID users (not longer than 30 days) and with at least one endoscopic evaluation during therapy that reported results specifically for gastric and duodenal damage. Risk difference (RD), heterogeneity χ2 test, publication bias assessment and number needed to treat (NnT) were calculated for each meta-analysis by a customized program. Twenty-one trials met the inclusion criteria evaluating a total of 636 healthy subjects and 1904 patients with arthritis randomized to active drug or placebo. The baseline risk of NSAID-related gastric (68% vs 16.6%, P < 0.001) and duodenal (22% vs 8.5%, P < 0.001) damage was higher in healthy subjects compared to patients with arthritis. Meta-analysis demonstrated a significant heterogeneity between trials performed in the two populations (P < 0.0001). In healthy subjects the active drug treatment induced a significant prevention of severe gastric (misoprostol RD = 69%, 95% CI = 60.3–77.7, H2-blocker RD = 38.3%, 95% CI = 17.8–58.9 and PPI RD = 43%, 95% CI = 28.2–57.7) and duodenal damage (misoprostol RD = 22.3%, 95% CI = 13.6–31, H2-blocker RD = 13.2%, 95% CI = 5.2–21.3 and PPI RD = 17.7%, 95% CI = 3.5–31.8). NnT values were, respectively, 1, 3, and 2 for gastric and 4, 8, and 6 for duodenal damage. In patients with arthritis lower RD and higher NnT values were found compared to healthy subjects. In conclusions, cotreatment with gastroprotective drugs for short-term prevention of severe gastroduodenal NSAID-related damage was more effective in healthy subjects than in patients with arthritis; misoprostol and PPIs were more effective than H2-blockers in the prevention of both gastric and duodenal severe damage; more studies need to evaluate the role of short-term prevention in patients with arthritis who require acute NSAID treatment.