Rate, type, and cost of adverse drug reactions in emergency department admissions.

Background: Adverse drug reactions (ADRs) are a threat to patients' health and quality of life, and can generate significant expenses. They are generally underreported, with different rates in different health care systems. Methods: We conducted a 6-month survey of all primary admissions to the medical emergency department of a university hospital and assessed the rate, characteristics, avoidability, and marginal costs of ADRs. Results: A total of 7% of all admissions were mainly caused by ADRs. The most frequent were gastrointestinal bleeding (22.3%) and febrile neutropenia (14.4%). Anticancer drugs were involved in 22.7% of the cases, and anticoagulants, analgesics, and non-steroidal anti-inflammatory drugs in 8% each. Physicians had prescribed 70% of these drugs. Patients were predominantly treated in intermediate care units and ordinary wards. The mean cost per case amounted to CHF 3586+/-342, or a total of CHF 821204 over the 6-month-period (1 CHF=0.56 US$=0.87 Euro). A total of 67% were considered definitely imputable to drug effects and 32% were retrospectively regarded as avoidable. Conclusions: Interventions aimed at reducing the incidence of ADRs should be directed towards both patient education and physician training. This could save hospitals admissions and money, and could be used as an indicator of prescription quality.

Influence of the timing of low-dose aspirin on tolerability of prolonged-release nicotinic acid in patients at elevated cardiovascular risk

OBJECTIVES: To investigate the effect of low-dose aspirin administered in the morning or evening on the rate of discontinuation of prolonged-release nicotinic acid (Niaspan) due to flushing in patients at elevated cardiovascular risk. RESEARCH DESIGN AND METHODS: This was an observational, non-interventional study in patients at elevated cardiovascular risk due to cardiovascular disease or type 2 diabetes. Patients received prolonged-release nicotinic acid and aspirin under the usual care of their physician for 15 weeks. MAIN OUTCOME MEASURES: The main outcome measure was the rate of treatment discontinuation for flushing. Other adverse drug reactions (ADRs) were also recorded. Lipid parameters were also measured. RESULTS: The patient population included 539 subjects (70% male); 36% had type 2 diabetes, 80% had prior cardiovascular disease, and 37% had a family history of cardiovascular disease. The rate of treatment discontinuation due to flushing did not differ (p = 0.3375) between the morning aspirin group (10.6%) and the evening aspirin group (13.8%). The overall incidence of flushing was 57%. Most flushes were of mild or moderate severity and decreases occurred over time in both frequency and intensity. ADRs unrelated to flushing occurred in 6.6% of the morning aspirin group and 7.4% of the evening aspirin group. HDL-cholesterol increased by +21.3% in the overall population, together with moderate improvements in other lipid parameters. CONCLUSIONS: Flushing was the most common ADR with prolonged-release nicotinic acid treatment, as expected. The timing of aspirin administration did not influence the rate of treatment discontinuations for flushing. Marked increases in HDL-cholesterol were observed.

Stimulated-echo acquisition mode (STEAM) MRI for black-blood delayed hyperenhanced myocardial imaging.

PURPOSE: To develop a breathhold method for black-blood viability imaging of the heart that may facilitate identifying the endocardial border. MATERIALS AND METHODS: Three stimulated-echo acquisition mode (STEAM) images were obtained almost simultaneously during the same acquisition using three different demodulation values. Two of the three images were used to construct a black-blood image of the heart. The third image was a T(1)-weighted viability image that enabled detection of hyperintense infarcted myocardium after contrast agent administration. The three STEAM images were combined into one composite black-blood viability image of the heart. The composite STEAM images were compared to conventional inversion-recovery (IR) delayed hyperenhanced (DHE) images in nine human subjects studied on a 3T MRI scanner. RESULTS: STEAM images showed black-blood characteristics and a significant improvement in the blood-infarct signal-difference to noise ratio (SDNR) when compared to the IR-DHE images (34 +/- 4.1 vs. 10 +/- 2.9, mean +/- standard deviation (SD), P < 0.002). There was sufficient myocardium-infarct SDNR in the STEAM images to accurately delineate infarcted regions. The extracted infarcts demonstrated good agreement with the IR-DHE images. CONCLUSION: The STEAM black-blood property allows for better delineation of the blood-infarct border, which would enhance the fast and accurate measurement of infarct size.

Successful embolization of a delayed splenic rupture following trauma in a child.

Delayed rupture of the spleen following trauma is an exceedingly rare phenomenon in children. In the case we have experienced, arterial embolization was successfully performed, surgery was avoided, and functional splenic tissue was preserved. Embolization is of value in the management of blunt splenic injuries in hemodynamically stable children, even after delayed rupture. The exact criteria for its use remain to be established.

Characterization of surface functional groups present on laboratory-generated and ambient aerosol particles by means of heterogeneous titration reactions

A Knudsen flow reactor has been used to quantify surface functional groups on aerosols collected in the field. This technique is based on a heterogeneous titration reaction between a probe gas and a specific functional group on the particle surface. In the first part of this work, the reactivity of different probe gases on laboratory-generated aerosols (limonene SOA, Pb(NO3)2, Cd(NO3)2) and diesel reference soot (SRM 2975) has been studied. Five probe gases have been selected for the quantitative determination of important functional groups: N(CH3)3 (for the titration of acidic sites), NH2OH (for carbonyl functions), CF3COOH and HCl (for basic sites of different strength), and O3 (for oxidizable groups). The second part describes a field campaign that has been undertaken in several bus depots in Switzerland, where ambient fine and ultrafine particles were collected on suitable filters and quantitatively investigated using the Knudsen flow reactor. Results point to important differences in the surface reactivity of ambient particles, depending on the sampling site and season. The particle surface appears to be multi-functional, with the simultaneous presence of antagonistic functional groups which do not undergo internal chemical reactions, such as acid-base neutralization. Results also indicate that the surface of ambient particles was characterized by a high density of carbonyl functions (reactivity towards NH2OH probe in the range 0.26-6 formal molecular monolayers) and a low density of acidic sites (reactivity towards N(CH3)3 probe in the range 0.01-0.20 formal molecular monolayer). Kinetic parameters point to fast redox reactions (uptake coefficient ?0>10-3 for O3 probe) and slow acid-base reactions (?0<10-4 for N(CH3)3 probe) on the particle surface. [Authors]

Immediate and delayed effects of subchronic Paraquat exposure during an early differentiation stage in 3D-rat brain cell cultures.

Xenobiotic exposure is a risk factor in the etiology of neurodegenerative disease. It was recently hypothesized that restricted exposure during brain development could predispose for a neurodegenerative disease later in life. As neuroinflammation contributes to progressive neurodegeneration, it is suspected that neurodevelopmental xenobiotic exposure could elicit a neuroinflammatory process, which over time may assume a detrimental character. We investigated the neurotoxic effects of paraquat (PQ) in three-dimensional whole rat brain cell cultures, exposed during an early differentiation stage, comparing immediate effects-directly post exposure-with long-term effects, 20 days after interrupted PQ-administration. Adverse effects and neuroinflammatory responses were assessed by measuring changes in gene- and protein-expression as well as by determining cell morphology changes. Differentiating neural cultures were highly susceptible to PQ and showed neuronal damage and strong astrogliosis. After the 20-day washout period, neurons partially recovered, whereas astrogliosis persisted, and was accompanied by microglial activation of a neurodegenerative phenotype. Our data shows that immediate and long-term effects of subchronic PQ-exposure differ. Also, PQ-exposure during this window of extensive neuronal differentiation led to a delayed microglial activation, of a character that could promote further pro-inflammatory signals that enable prolonged inflammation, thereby fueling further neurodegeneration.

Delayed priming promotes CNS regeneration post-rhizotomy in Neurocan and Brevican-deficient mice.

A wealth of literature has provided evidence that reactive tissue at the site of CNS injury is rich in chondroitin sulfate proteoglycans which may contribute to the non-permissive nature of the CNS. We have recently demonstrated using a murine model of human brachial plexus injury that the chondroitin sulfate proteoglycans Neurocan and Brevican are differentially expressed by two subsets of astrocytes in the spinal cord dorsal root entry zone (DREZ) following dorsal root lesion (Beggah et al., Neuroscience 133: 749-762, 2005). However, direct evidence for a growth-inhibitory role of these proteoglycans in vivo is still lacking. We therefore performed dorsal root lesion (rhizotomy) in mice deficient in both Neurocan and Brevican. Rhizotomy in these animals resulted in no significant increase in the number of sensory fibres regenerating through the DREZ compared to genetically matched controls. Likewise, a conditioning peripheral nerve lesion prior to rhizotomy, which increases the intrinsic growth capacity of sensory neurons, enhanced growth to the same extent in transgenic and control mice, indicating that absence of these proteoglycans alone is not sufficient to further promote entry into the spinal cord. In contrast, when priming of the median nerve was performed at a clinically relevant time, i.e. 7 weeks post-rhizotomy, the growth of a subpopulation of sensory axons across the DREZ was facilitated in Neurocan/Brevican-deficient, but not in control animals. This demonstrates for the first time that (i) Neurocan and/or Brevican contribute to the non-permissive environment of the DREZ several weeks after lesion and that (ii) delayed stimulation of the growth program of sensory neurons can facilitate regeneration across the DREZ provided its growth-inhibitory properties are attenuated. Post-injury enhancement of the intrinsic growth capacity of sensory neurons combined with removal of inhibitory chondroitin sulfate proteoglycans may therefore help to restore sensory function and thus attenuate the chronic pain resulting from human brachial plexus injury.

Allergic reactions following contrast material administration: nomenclature, classification, and mechanisms

In forensic pathology routine, fatal cases of contrast agent exposure can be occasionally encountered. In such situations, beyond the difficulties inherent in establishing the cause of death due to nonspecific or absent autopsy and histology findings as well as limited laboratory investigations, pathologists may face other problems in formulating exhaustive, complete reports, and conclusions that are scientifically accurate. Indeed, terminology concerning adverse drug reactions and allergy nomenclature is confusing. Some terms, still utilized in forensic and radiological reports, are outdated and should be avoided. Additionally, not all forensic pathologists master contrast material classification and pathogenesis of contrast agent reactions. We present a review of the literature covering allergic reactions to contrast material exposure in order to update used terminology, explain the pathophysiology, and list currently available laboratory investigations for diagnosis in the forensic setting.

Systematic review of delayed postoperative hemorrhage after pancreatic resection.

This review assesses the presentation, management, and outcome of delayed postpancreatectomy hemorrhage (PPH) and suggests a novel algorithm as possible standard of care.An electronic search of Medline and Embase databases from January 1990 to February 2010 was undertaken. A random-effect meta-analysis for success rate and mortality of laparotomy vs. interventional radiology after delayed PPH was performed.Fifteen studies comprising of 248 patients with delayed PPH were included. Its incidence was of 3.3%. A sentinel bleed heralding a delayed PPH was observed in 45% of cases. Pancreatic leaks or intraabdominal abscesses were found in 62%. Interventional radiology was attempted in 41%, and laparotomy was undertaken in 49%. On meta-analysis comparing laparotomy vs. interventional radiology, no significant difference could be found in terms of complete hemostasis (76% vs. 80%; P = 0.35). A statistically significant difference favored interventional radiology vs. laparotomy in term of mortality (22% vs. 47%; P = 0.02).Proper management of postoperative complications, such as pancreatic leak and intraabdominal abscess, minimizes the risk of delayed PPH. Sentinel bleeding needs to be thoroughly investigated. If a pseudoaneurysm is detected, it has to be treated by interventional angiography, in order to prevent a further delayed PPH. Early angiography and embolization or stenting is safe and should be the procedure of choice. Surgery remains a therapeutic option if no interventional radiology is available, or patients cannot be resuscitated for an interventional treatment.