Intravenous immunoglobulin treatment in a type 3 von Willebrand disease patient with alloantibodies and a life-threatening gastrointestinal bleed

Non peer reviewe

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Prevalence and appropriateness of drug prescriptions for peptic ulcer and gastro-esophageal reflux disease in a cohort of hospitalized elderly.

BACKGROUND: Proton pump inhibitors (PPI) are among the most commonly prescribed medicines and their overuse is widespread in both primary and secondary care. Inappropriate prescription is of particular concern among elderly patients, who have often multiple comorbidities and need many drugs. METHODS: We evaluate the appropriateness of drugs for peptic ulcer or gastro-esophageal reflux disease (GERD) in a sample of elderly patients (65 years old or older) at admission and discharge in 38 internal medicine wards between January 2008 and December 2008, according to the presence of specific conditions or gastro-toxic drug combinations. RESULTS: Among 1155 patients eligible for the analysis, 466 (40.3%) were treated with drugs for GERD or peptic ulcer were at hospital admission and 647 (56.0%) at discharge; 62.4% of patients receiving a drug for peptic ulcer or GERD at admission and 63.2% at discharge were inappropriately treated. Among these, the number of other drugs prescribed was associated with greater use of drugs for peptic ulcer or GERD, even after adjustment for age, sex and number of diagnoses at admission (OR 95% CI=1.26 (1.18-1.34), p=.0001) or discharge (OR 95% CI=1.11 (1.05-1.18), p=0.0003). CONCLUSIONS: Prevalence of inappropriate prescription of drugs for peptic ulcer or GERD remained almost the same at admission and discharge. Inappropriate use of these drugs is related to the concomitant use of other drugs. Careful assessment of clinical conditions and stricter adherence to evidence-based guidelines are essential for a rational and cost-effective use of drugs for peptic ulcer or GERD

Association between clusters of diseases and polypharmacy in hospitalized elderly patients: results from the REPOSI study.

BACKGROUND: Although the association between multimorbidity and polypharmacy has been clearly documented, no study has analyzed whether or not specific combinations of diseases influence the prescription of polypharmacy in older persons. We assessed which clusters of diseases are associated with polypharmacy in acute-care elderly in-patients. METHODS: This cross-sectional study was held in 38 Italian internal medicine and geriatric wards participating in the Registro Politerapie SIMI (REPOSI) study during 2008. The study sample included 1155 in-patients aged 65 years or older. Clusters of diseases, defined as two or more co-occurring specific chronic diseases, were identified using the odds ratio (OR) for the associations between pairs of diseases followed by cluster analysis. Polypharmacy was defined as the prescription of five or more different medications at hospital discharge. Logistic regression models were run to analyze the association between clusters of diseases and polypharmacy. RESULTS: Among clusters of diseases, the highest mean number of drugs (>8) was found in patients affected by heart failure (HF) plus chronic obstructive pulmonary disease (COPD), HF plus chronic renal failure (CRF), COPD plus coronary heart disease (CHD), diabetes mellitus plus CRF, and diabetes mellitus plus CHD plus cerebrovascular disease (CVD). The strongest association between clusters of diseases and polypharmacy was found for diabetes mellitus plus CHD plus CVD, diabetes plus CHD, and HF plus atrial fibrillation (AF). CONCLUSIONS: The observed knowledge of the relationship among co-occurring diseases and polypharmacy should help to identify and monitor older in-patients at risk of polypharmacy. Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved

The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease"

Storage of Factor VIII Variants with Impaired von Willebrand Factor Binding in Weibel-Palade Bodies in Endothelial Cells

BACKGROUND: Point mutations resulting in reduced factor VIII (FVIII) binding to von Willebrand factor (VWF) are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule biogenesis are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We studied intracellular trafficking of FVIII variants implicated in mild/moderate hemophilia A together with VWF in HEK293 cells and primary endothelial cells. The role of VWF binding was addressed using FVIII variants displaying reduced VWF interaction. Binding studies using purified FVIII proteins revealed moderate (Arg2150His, Del2201, Pro2300Ser) to severe (Tyr1680Phe, Ser2119Tyr) VWF binding defects. Expression studies in HEK293 cells and primary endothelial cells revealed that all FVIII variants were present within VWF-containing organelles. Quantitative studies showed that the relative amount of FVIII storage was independent of various mutations. Substantial amounts of FVIII variants are co-stored in VWF-containing storage organelles, presumably by virtue of their ability to interact with VWF at low pH. CONCLUSIONS: Our data suggest that the potential of FVIII co-storage with VWF is not affected in mild/moderate hemophilia A caused by reduced FVIII/VWF interaction in the circulation. These data support the hypothesis that Weibel-Palade bodies comprise the desmopressin-releasable FVIII storage pool in vivo

Phenotype commitment in vascular smooth muscle cells derived from coronary atherosclerotic plaques: differential gene expression of endothelial Nitric Oxide Synthase

Unstable angina and myocardial infarction are the clinical manifestations of the abrupt thrombotic occlusion of an epicardial coronary artery as a result of spontaneous atherosclerotic plaque rupture or fissuring, and the exposure of highly thrombogenic material to blood. It has been demonstrated that the proliferation of vascular smooth muscle cells (VSMCs) and impaired bioavailabilty of nitric oxide (NO) are among the most important mechanisms involved in the progression of atherosclerosis. It has also been suggested that a NO imbalance in coronary arteries may be involved in myocardial ischemia as a result of vasomotor dysfunction triggering plaque rupture and the thrombotic response. We used 5' nuclease assays (TaqMan™ PCRs) to study gene expression in coronary plaques collected by means of therapeutic directional coronary atherectomy from 15 patients with stable angina (SA) and 15 with acute coronary syndromes (ACS) without ST elevation. Total RNA was extracted from the 30 plaques and the cDNA was amplified in order to determine endothelial nitric oxide synthase (eNOS) gene expression. Analysis of the results showed that the expression of eNOS was significantly higher (p<0.001) in the plaques from the ACS patients. Furthermore, isolated VSMCs from ACS and SA plaques confirmed the above pattern even after 25 plating passages. In situ RT-PCR was also carried out to co-localize the eNOS messengers and the VSMC phenotype