Are pleiotropic effects of statins real?

The clinical benefits of statins are strongly related to their low density lipoprotein-cholesterol (LDL-C) lowering properties. However, because mevalonic acid (MVA), the product of 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase reaction, is the precursor not only of cholesterol but also of nonsteroidal isoprenoid compounds, the inhibition of HMG-CoA reductase may result in pleiotropic effects, independent of their hypocholesterolemic properties. The discrimination between the pleiotropic from LDL-C lowering effects may potentially be more evident during the early phase of treatment since plasma MVA levels drop up to 70% within 1–2 hours while a reduction of LDL-C, detectable after 24 hours, became significant after 6–7 days. Therefore, the deprivation of circulating MVA-derived isoprenoids in the early phase of treatment could be the main mechanism responsible for the atheroprotective effect of statins. This early window of protection in the absence of LDL-C lowering suggests that the anti-inflammatory and the pleiotropic properties of statins may have clinical importance. Therefore, acute coronary syndromes could represent a clinical condition for addressing the early benefits of statins therapy, ie, within 24 h of the event, independent of LDL-C lowering

Performance of PSI, CURB-65, and SCAP scores in predicting the outcome of patients with community-acquired and healthcare-associated pneumonia

The objective was to compare three score systems, pneumonia severity index (PSI), the Confusion-Urea-Respiratory Rate-Blood pressure-65 (CURB-65), and severe community-acquired pneumonia (SCAP), for prediction of the outcomes in a cohort of patients with community-acquired (CAP) and healthcare-associated pneumonia (HCAP). Large multi-center, prospective, observational study was conducted in 55 hospitals. HCAP patients were included in the high classes of CURB-65, PSI and SCAP scores have a mortality rate higher than that of CAP patients. HCAP patients included in the low class of the three severity rules have a significantly higher incidence of adverse events, including development of septic shock, transfer into an ICU, and death (p < 0.01). At multivariate Cox regression analysis, inclusion in the severe classes of PSI, CURB-65, or SCAP scores and receipt of an empirical therapy not adherent to international guidelines prove to be risk factors independently associated with poor outcome. PSI, CURB-65, and SCAP score have a good performance in patients with CAP but are less useful in patients with HCAP, especially in patients classified in the low-risk classes

Outcomes of patients hospitalized with community-acquired, health care-associated, and hospital-acquired pneumonia

BACKGROUND: Traditionally, pneumonia has been classified as either community- or hospital-acquired. Although only limited data are available, health care-associated pneumonia has been recently proposed as a new category of respiratory infection. "Health care-associated pneumonia" refers to pneumonia in patients who have recently been hospitalized, had hemodialysis, or received intravenous chemotherapy or reside in a nursing home or long-term care facility. OBJECTIVE: To ascertain the epidemiology and outcome of community-acquired, health care-associated, and hospital-acquired pneumonia in adults hospitalized in internal medicine wards. DESIGN: Multicenter, prospective observational study. SETTING: 55 hospitals in Italy comprising 1941 beds. PATIENTS: 362 patients hospitalized with pneumonia during two 1-week surveillance periods. MEASUREMENTS: Cases of radiologically and clinically assessed pneumonia were classified as community-acquired, health care-associated, or hospital-acquired and rates were compared. RESULTS: Of the 362 patients, 61.6% had community-acquired pneumonia, 24.9% had health care-associated pneumonia, and 13.5% had hospital-acquired pneumonia. Patients with health care-associated pneumonia had higher mean Sequential Organ Failure Assessment scores than did those with community-acquired pneumonia (3.0 vs. 2.0), were more frequently malnourished (11.1% vs. 4.5%, and had more frequent bilateral (34.4% vs. 19.7%) and multilobar (27.8% vs. 21.5%) involvement on a chest radiograph. Patients with health care-associated pneumonia also had higher fatality rates (17.8% [CI, 10.6% to 24.9%] vs. 6.7% [CI, 2.9% to 10.5%]) and longer mean hospital stay (18.7 days [CI, 15.9 to 21.5 days] vs. 14.7 days [CI, 13.4 to 15.9 days]). Logistic regression analysis revealed that depression of consciousness (odds ratio [OR], 3.2 [CI, 1.06 to 9.8]), leukopenia (OR, 6.2 [CI, 1.01 to 37.6]), and receipt of empirical antibiotic therapy not recommended by international guidelines (OR, 6.4 [CI, 2.3 to 17.6]) were independently associated with increased intrahospital mortality. LIMITATIONS: The number of patients with health care-associated pneumonia was relatively small. Microbiological investigations were not always homogeneous. The study included only patients with pneumonia that required hospitalization; results may not apply to patients treated as outpatients. CONCLUSION: Health care-associated pneumonia should be considered a distinct subset of pneumonia associated with more severe disease, longer hospital stay, and higher mortality rates. Physicians should differentiate between patients with health care-associated pneumonia and those with community-acquired pneumonia and provide more appropriate initial antibiotic therapy

Adherence to antibiotic treatment guidelines and outcomes in the hospitalized elderly with different types of pneumonia

Background: Few studies evaluated the clinical outcomes of Community Acquired Pneumonia (CAP), Hospital-Acquired Pneumonia (HAP) and Health Care-Associated Pneumonia (HCAP) in relation to the adherence of antibiotic treatment to the guidelines of the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) in hospitalized elderly people (65 years or older). Methods: Data were obtained from REPOSI, a prospective registry held in 87 Italian internal medicine and geriatric wards. Patients with a diagnosis of pneumonia (ICD-9 480-487) or prescribed with an antibiotic for pneumonia as indication were selected. The empirical antibiotic regimen was defined to be adherent to guidelines if concordant with the treatment regimens recommended by IDSA/ATS for CAP, HAP, and HCAP. Outcomes were assessed by logistic regression models. Results: A diagnosis of pneumonia was made in 317 patients. Only 38.8% of them received an empirical antibiotic regimen that was adherent to guidelines. However, no significant association was found between adherence to guidelines and outcomes. Having HAP, older age, and higher CIRS severity index were the main factors associated with in-hospital mortality. Conclusions: The adherence to antibiotic treatment guidelines was poor, particularly for HAP and HCAP, suggesting the need for more adherence to the optimal management of antibiotics in the elderly with pneumonia

Antipsychotic prescription and mortality in hospitalized older persons

Background: Recent scientific reports have shown that older persons treated with antipsychotics for dementia-related behavioural symptoms have increased mortality. However, the impact of these drugs prescribed during hospitalization has rarely been assessed. We aimed to investigate whether antipsychotics are associated with an increased risk of mortality during hospitalization and at 3-month follow-up in elderly inpatients. Methods: We analyzed data gathered during two waves (2010 and 2012) by the REPOSI (Registro Politerapie Società Italiana Medicina Interna). All new prescriptions of antipsychotic drugs during hospitalization, whether maintained or discontinued at discharge, were collected, and logistic regression models were used to analyze their association with in-hospital and 3-month mortality. Covariates were age, sex, the Short Blessed Test (SBT) score, and the Cumulative Illness Rating Scale. Results: Among 2703 patients included in the study, 135 (5%) received new prescriptions for antipsychotic drugs. The most frequently prescribed antipsychotic during hospitalization and eventually maintained at discharge was haloperidol (38% and 36% of cases, respectively). Patients newly prescribed with antipsychotics were older and had a higher Cumulative Illness Rating Scale comorbidity index both at admission and at discharge compared to those who did not receive a prescription. Of those prescribed antipsychotics, 71% had an SBT score ≥10 (indicative of dementia), 12% had an SBT score of 5–9 (indicative of questionable dementia); and 17% had an SBT score <5 (indicative of normal cognition). In-hospital mortality was slightly higher in patients prescribed antipsychotic drugs (14.3% vs 9.4%; P = 0.109), but in multivariate analysis only male sex, older age, and higher SBT scores were significantly related to mortality during hospitalization. At 3-month follow-up, only male sex, older age, and higher SBT scores were associated with mortality. Conclusion: We found that the prescription of antipsychotic drugs during hospitalization was not associated with in-hospital or follow-up mortality. Short-term antipsychotic prescriptions (for acutely ill patients) may have a different effect than long-term, repeated prescriptions

Heart failure and chronic kidney disease in a registry of internal medicine wards

Background: The aim of the present study was to evaluate the association between heart failure (HF) and chronic kidney disease (CKD) in tertiary care centers using the clinical records of patients enrolled in internal medicine departments.Patients and methods: We used the clinical records of 1380 elderly patients to identify patients with a history of HF and CKD using admission ICD codes and glomerular filtration rate (GFR) formulas. Magnitude and strength of such associations were investigated by univariable and multivariable analysis.Results: Of the 1380 patients enrolled, 27.9% had HF (age 80 \ub1 7, BMI 27 \ub1 6 kg/m2) and 17.4% CKD (age 81 \ub1 7, BMI 26.8 \ub1 6 kg/m2). Both groups were significantly older (P <' 0.0001) with BMI higher than the patients without those diagnosis (P < 0.02). Patients with a history of CKD showed higher non-fasting glycaemia (140 \ub1 86 vs. 125 \ub1 63 mg/dL, P < 0.001). CKD was significantly associated with HF (P < 0.0001). Patients with HF had an estimated GFR lower than patients without HF (P < 0.0001). Comorbidity and severity indices were significantly higher in subjects with HF (P < 0.0001) and CKD (P < 0.0001) than in those without. Multivariable analysis showed a significant association between HF and age (for five years increase OR 1.13, P < 0.009), BMI (for each 3 kg/m2 increase OR 1.15, P < 0.001), GFR (for each decrease of 10 mL/min increase OR 0.92, P < 0.002) and severity index (IS) (for each 0.25 units increase OR 1.43, P < 0.001).Conclusion: HF on admission is strongly associated with CKD, older age, BMI, and SI. These data focus the value of epidemiological studies such REPOSI in identifying and monitoring multimorbidity in elderly

Multimorbidity and polypharmacy in the elderly: Lessons from REPOSI

The dramatic demographic changes that are occurring in the third millennium are modifying the mission of generalist professionals such as primary care physicians and internists. Multiple chronic diseases and the related prescription of multiple medications are becoming typical problems and present many challenges. Unfortunately, the available evidence regarding the efficacy of medications has been generated by clinical trials involving patients completely different from those currently admitted to internal medicine: much younger, affected by a single disease and managed in a highly controlled research environment. Because only registries can provide information on drug effectiveness in real-life conditions, REPOSI started in 2008 with the goal of acquiring data on elderly people acutely admitted to medical or geriatric hospital wards in Italy. The main goals of the registry were to evaluate drug prescription appropriateness, the relationship between multimorbidity/polypharmacy and such cogent outcomes as hospital mortality and re-hospitalization, and the identification of disease clusters that most often concomitantly occur in the elderly. The findings of 3-yearly REPOSI runs (2008, 2010, 2012) suggest the following pertinent tasks for the internist in order to optimally handle their elderly patients: the management of multiple medications, the need to become acquainted with geriatric multidimensional tools, the promotion and implementation of a multidisciplinary team approach to patient health and care and the corresponding involvement of patients and their relatives and caregivers. There is also a need for more research, tailored to the peculiar features of the multimorbid elderly patient

Therapeutic Duplicates in a Cohort of Hospitalized Elderly Patients: Results from the REPOSI Study.

BACKGROUND: Explicit criteria for potentially inappropriate prescriptions in the elderly are recommended to avoid prescriptions of duplicate drug classes and to optimize monotherapy within a single drug class before a new agent is considered. Duplicate drug class prescription (or therapeutic duplicates) puts the patient at increased risk of adverse drug reactions with no additional therapeutic benefits. To our knowledge, the prevalence of elderly inpatients receiving therapeutic duplicates has never been studied. OBJECTIVES: Our objective was to assess the prevalence of therapeutic duplicates at admission, discharge, and 3-month follow-up of hospitalized elderly patients. METHODS: This cross-sectional prospective study was conducted in 97 Italian internal medicine and geriatric wards. Therapeutic duplicates were defined as at least two drugs of the same therapeutic class prescribed simultaneously to a patient. A patient's drug therapy at admission relates to prescriptions from general practitioners, whereas prescriptions at discharge are those from hospital internists or geriatricians. RESULTS: The study sample comprised 5821 admitted and 4983 discharged patients. In all, 143 therapeutic duplicates were found at admission and 170 at discharge. The prevalence of patients exposed to at least one therapeutic duplicate rose significantly from hospital admission (2.5 %) to discharge (3.4 %; p = 0.0032). Psychotropic drugs and drugs for peptic ulcer or gastroesophageal reflux disease were the most frequently involved. A total of 86.8 % of patients discharged with at least one therapeutic duplicate were still receiving them at 3-month follow-up. CONCLUSIONS: Hospitalization and drugs prescribed by internists and geriatricians are both factors associated with a small but definite increase in overall therapeutic duplicates in elderly patients admitted to internal medicine and geriatric wards. More attention should be paid to the indications for each drug prescribed, because therapeutic duplicates are not supported by evidence and increase both the risk of adverse drug reactions and costs. Identification of unnecessary therapeutic duplicates is essential for the optimization of polypharmacy

Gender-differences in disease distribution and outcome in hospitalized elderly: Data from the REPOSI study

Background and purpose Women live longer and outnumber men. On the other hand, older women develop more chronic diseases and conditions such as arthritis, osteoporosis and depression, leading to a greater number of years of living with disabilities. The aim of this study was to describe whether or not there are gender differences in the demographic profile, disease distribution and outcome in a population of hospitalized elderly people. Methods Retrospective observational study including all patients recruited for the REPOSI study in the year 2010. Analyses are referred to the whole group and gender categorization was applied. Results A total of 1380 hospitalized elderly subjects, 50.5% women and 49.5% men, were considered. Women were older than men, more often widow and living alone or in nursing homes. Disease distribution showed that malignancy, diabetes, coronary artery disease, chronic kidney disease and chronic obstructive pulmonary disease were more frequent in men, but hypertension, osteoarthritis, anemia and depression were more frequent in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment evaluated by the Short Blessed Test (SBT), mood disorders by the Geriatric Depression Scale (GDS) and disability in daily life measured by Barthel Index (BI) were worse in women. In-hospital and 3-month mortality rates were higher in men. Conclusions Our study showed a gender dimorphism in the demographic and morbidity profiles of hospitalized elderly people, emphasizing once more the need for a personalized process of healthcare