Drug-drug interactions in a cohort of hospitalized elderly patients.

PURPOSE: The aim of this study is to assess the prevalence of patients exposed to potentially severe drug-drug interactions (DDIs) at hospital admission and discharge and the related risk of in-hospital mortality and adverse clinical events, readmission, and all-cause mortality at 3 months. METHODS: This cross-sectional, prospective study was held in 70 Italian internal medicine and geriatric wards. Potentially severe DDIs at hospital admission and discharge; risk of in-hospital mortality and of adverse clinical events, readmission, and all-cause mortality at 3-month follow-up. RESULTS: Among 2712 patients aged 65 years or older recruited at hospital admission, 1642 (60.5%) were exposed to at least one potential DDI and 512 (18.9%) to at least one potentially severe DDI. Among 2314 patients discharged, 1598 (69.1%) were exposed to at least one potential DDI and 1561 (24.2%) to at least one potentially severe DDI. Multivariate analysis found a significant association with an increased risk of mortality at 3 months in patients exposed to at least two potentially severe DDIs (Odds ratio 2.62; 95% confidence interval, 1.00-6.68; p = 0.05). Adverse clinical events were potentially related to severe DDIs in two patients who died in the hospital, in five readmitted, and one who died at 3 months after discharge. CONCLUSIONS: Hospitalization was associated with an increase in potentially severe DDIs. A significant association was found for mortality at 3 months after discharge in patients with at least two potentially severe DDIs. Careful monitoring for potentially severe DDIs, especially those created at discharge or recently generated, is important to minimize the risk of harm.

Fibrotic interstitial lung diseases and air pollution: a systematic literature review.

BACKGROUND: Air pollution is hypothesised to be a risk factor for interstitial lung diseases (ILD). This study systematically reviewed the literature regarding the impact of air pollution on idiopathic pulmonary fibrosis (IPF) and fibrotic interstitial lung diseases (ILD). METHODS: A computer-assisted literature search of electronic databases was performed to identify studies focused on the association between ILDs and air pollution. Other inclusion criteria required that the article had to be: 1) original; 2) a prospective or retrospective study; and 3) fully published in English. Both randomised clinical trials and observational studies were considered. RESULTS: Only seven studies met the inclusion criteria. All studies investigated the relationship between pollution and IPF, except one that dealt with the relationship between pollution and hypersensitivity pneumonitis. Outcome measures included exacerbation of IPF, mortality, disease severity, prevalence of hypersensitivity pneumonitis, progression and incidence of IPF. On the whole, air pollution levels were negatively associated with outcomes in patients with IPF and fibrotic ILD outcome. The heterogeneity in the measurement and reporting of the end-points limited the performance of a quantitative synthesis of data. CONCLUSIONS: This systematic review provides supporting evidence linking exposure to air pollution to poor outcomes in patients with IPF and fibrotic ILD.

Time to face the challenge of multimorbidity. A European perspective from the joint action on chronic diseases and promoting healthy ageing across the life cycle (JA-CHRODIS).

Research on multimorbidity has rapidly increased in the last decade, but evidence on the effectiveness of interventions to improve outcomes in patients with multimorbidity is limited. The European Commission is co-funding a large collaborative project named Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) in the context of the 2nd EU Health Programme 2008-2013. The present manuscript summarizes first results of the JA-CHRODIS, focuses on the identification of a population with multimorbidity who has a high or very high care demand. Identification of characteristics of multimorbid patients associated with a high rate of resource consumption and negative health outcomes is necessary to define a target population who can benefit from interventions. Indeed, multimorbidity alone cannot explain the complexity of care needs and further, stratification of the general population based on care needs is necessary for allocating resources and developing personalized, cost-efficient, and patient-centered care plans. Based on analyses of large databases from European countries a profile of the most care-demanding patients with multimorbidity is defined. Several factors associated with adverse health outcomes and resource consumption among patients with multimorbidity were identified in these analyses, including disease patterns, physical function, mental health, and socioeconomic status. These results underline that a global assessment is needed to identify patients with multimorbidity who are at risk of negative health outcomes and that a comprehensive approach, targeting not only diseases, but also social, cognitive, and functional problems should be adopted for these patients.

Efficacy and inhibitor development in previously treated patients with haemophilia A switched to a B domain-deleted recombinant factor VIII.

There have been recent reports of unexpected poor efficacy of a B-domain-deleted recombinant factor VIII (BDD-rFVIII) in haemophiliacs, and inhibitor development in previously treated patients (PTPs) switched to BDD-rFVIII. The results of a 6-month prospective study of 25 PTPs and of a retrospective survey of 94 PTPs, all switched to BDD-rFVIII, were used to evaluate efficacy and inhibitor development. The prospective study showed that 89% of 362 bleeds were controlled by one to two infusions, reproducing the efficacy profiles of other recombinant products (rFVIIIs). One patient, previously treated with plasma-derived FVIII only, developed a high titre inhibitor (30 BU) after 5 days of exposure. The retrospective survey, carried out in the total Italian PTP population switched to BDD-rFVIII, involved 19 PTPs at higher inhibitor risk due to previous exposure of < or = 50 days and 75 PTPs at lower inhibitor risk due to previous exposure of > 50 days. One patient developed an inhibitor: he was a high-risk, severe PTP previously exposed to another rFVIII for 3 days only. Among the entire low-risk population of severe Italian PTPs switched to BDD-rFVIII (25 in the prospective study, 49 in the retrospective cohort) only one developed an inhibitor (1.3%). These data indirectly support the views that BDD-rFVIII is equivalent to other rFVIIIs in term of efficacy and inhibitor development.

A rare inherited coagulation disorder: combined homozygous factor VII and factor X deficiency.

The combined presence in the homozygous state of more than one recessively transmitted coagulation defect may rarely occur in countries with a high rate of consanguinity. In an Iranian family consisting of two parents (second cousins) and two affected siblings, initial phenotypic analysis led to a diagnosis of mild FX deficiency (10-19% FX activity, 42-54% FX:Ag), and genotyping revealed a new homozygous missense mutation in the corresponding gene (Ser3Cys). As both of the sibs had a severe bleeding history that was not compatible with mild deficiency of FX, further phenotypic analysis revealed the additional presence of severe FVII deficiency (<1% FVII activity; 63-111% FVII:Ag) associated with the homozygous missense gene mutation Cys310Phe. In this kindred, lack of identification of the double coagulation defect might have led not only to incomplete understanding of the clinical phenotype but also to an incorrect prenatal diagnosis.