Burden of corticosteroid use in patients with systemic lupus erythematosus: results from a Delphi panel.

Corticosteroid-related adverse events (AEs) are commonly reported in systemic lupus erythematosus (SLE), but are often under-represented in claims data. The most common corticosteroid-related AEs are not necessarily the most costly. The present study aimed to examine corticosteroid-related AE rates and identify the associated cost consequences in patients with SLE from the perspective of rheumatologists treating SLE in the United States (US). A modified Delphi process and RAND Appropriateness Method was used to estimate corticosteroid-related AEs and costs based on data from SLE-treating US rheumatologists and estimates from alternative sources. The panel (n=10) participated in two web-based questionnaires, covering disease severity, corticosteroid use, corticosteroid-related AEs, and resource utilization associated with treatment of the AEs. Eight members of the panel then participated in a guided discussion by interactive teleconference, in which the costs associated with specific corticosteroid-related AEs were also discussed. Consensus was achieved in the teleconference when a single response category (consensus values from 1 to 4 [4=strongly agree, 1=strongly disagree]) accounted for ≥80% of responses. Thirteen consensus statements were developed following two Delphi rounds. Costs were estimated for eight corticosteroid-associated AEs from the panel of rheumatologists. In the patients with SLE treated by these physicians, 41.5% were considered to have mild disease, 36.5% moderate disease, and 22.0% severe disease. The number of specialist visits, corticosteroid use, and corticosteroid dose increased with disease severity. The estimated rates of all AEs (except for cataracts) were at least doubled in patients receiving corticosteroid doses>20 mg/day compared with ≤20 mg/day. The highest estimated mean total costs of an event (for the required treatment duration for one patient) were for avascular necrosis ($14,460) and serious infection ($11,660). The costs of more common AEs, such as osteoporosis, obesity, diabetes, and fractures, ranged from $1190 to $8220. Ten rheumatologists concluded that as disease severity increases, corticosteroid doses increased. Greater utilization of resources is needed to manage patients and corticosteroid-related AEs.

[Twenty-five statements on early initiation of fixed combination ICS/LABA treatment for asthma and COPD in primary and secondary care: consensus research by a modified Delphi process].

BACKGROUND: Guidelines recommend the addition of a long-acting ß2-agonist (LABA) for patients whose asthma is uncontrolled on inhaled corticosteroid (ICS) monotherapy. For COPD patients the addition of an ICS to a long-acting bronchodilator is recommended for symptomatic patients at high risk of exacerbations. We examined whether in real-life practice guideline recommendations may delay optimal timing for initiation of combination treatment. METHODS: A modified Delphi process was undertaken with a panel of physicians, including six GPs and four pulmonologists, in practice in Germany. The first round comprised a semi-structured questionnaire, the second stage was an online discussion to reach consensus on 25 statements concerning the use of ICS/LABA in patients with asthma or COPD. RESULTS: Consensus was achieved on 24 of 25 prepared statements for early initiation of fixed ICS/LABA combination treatment. The panel agreed that a meaningful share of their asthma patients on ICS monotherapy experienced symptoms and exacerbations that should lead to addition of LABAs and that timely initiation of ICS/LABA therapy in asthma patients could improve asthma control, and prevent a significant number of emergency room visits, hospitalisations or additional specialist visits. The panel agreed that symptomatic patients with moderate to severe COPD, and frequent exacerbations should receive ICS without any delay in addition to their bronchodilator maintenance therapy. These patients could benefit from fewer exacerbations and a reduction in symptoms. The panel reached a consensus that fixed-dose ICS/LABA could have a positive effect on adherence, compared with separate inhalers for ICS and LABA, which may impact treatment outcomes. CONCLUSION: A panel of ten physicians working in primary and secondary care agreed on 24 out of 25 statements that supported the early initiation of fixed combination treatment, if indicated in a meaningful number of their asthma and COPD patients.

Interaction of cationic amphiphilic drugs with lipid A: implications for development of endotoxin antagonists.

This report presents evidence for the interactions of several classes of cationic amphiphilic drugs including the phenothiazines, aminoquinolines, biguanides, and aromatic diamidines, with lipid A, the endotoxic principle of lipopolysaccharides. The interactions of the drugs were quantitatively assessed by fluorescence methods. The affinities of the drugs for lipid A parallel their endotoxin-antagonistic effects in the Limulus gelation assay. Dicationic compounds bind lipid A with greater affinity; the affinity of such molecules increases exponentially as a function of the distance between the basic moieties. The bis-amidine drug--pentamidine--examined in greater detail, binds lipid A with high affinity (apparent Kd: 0.12 microM), and LPS, probably due to simultaneous interactions of the terminal amidine groups with the anionic phosphates on lipid A. The sequestration of endotoxin by pentamidine reduces its propensity to bind to cells, and the complex exhibits attenuated toxicity in biological assays. These results have implications in the development of therapeutic strategies against endotoxin-related disease states.

Addressing ethical boundaries among nurses.

Sexual intimacy is the primary boundary issue studied and reported in the literature, though it is not addressed directly in the ANA Code of Ethics. However, perhaps equally important are behaviors which may stem from nurses' meeting their own social and emotional needs through their work. Results of "Boundaries" workshops for more than 3000 nurses and other healthcare professionals are summarized. Recommendations are made, relative to both personal and professional behavior, along with a list of suggestions for nurse managers.

Intragastric long-term pH-metry in hemodialysis patients. A study with famotidine.

The onset and duration of famotidine action were studied in 14 hemodialysis (HD) patients and 16 healthy controls (control group: CG) who were examined by ambulatory intragastric 24-hour pH-metry. 20 mg famotidine was administered i.v. 90 min after HD in the afternoon (AN; 2 p.m.; n = 8) or evening (E; 8 p.m.; n = 6), followed by a standard meal. Mean onset of action in the AN and E groups of the HD patients was 90.3 +/- 28.2 min and 98.8 +/- 29.8 min, and in CG patients 36.3 +/- 11.9 min and 53.6 +/- 22.3 min, respectively (p less than 0.05). Duration of action in the AN and E groups of the HD patients was 22.7 +/- 2.1 h and 21.6 +/- 2.6 h, and in CG patients 6.0 +/- 1.1 h and 11.4 +/- 1.6 h, respectively (p less than 0.05). Our study showed a retarded and prolonged action of famotidine in HD patients. The time of administration of famotidine had no effect on its action in HD patients. This is in contrast to normal subjects in whom evening administration delays the onset and prolongs the duration of famotidine action in comparison to afternoon administration.

Conformational analysis of the tumor-associated carbohydrate antigen 19-9 and its Lea blood group antigen component as related to the specificity of monoclonal antibody CO19-9.

A structural comparison between the synthetic, tumor-associated 19-9 tetrasaccharide, NeuAc alpha 2----3Gal beta 1----3GlcNAc(4----1 alpha Fuc)-O(CH2)8CO2CH3 and its Lea blood group antigen component, Gal beta 1----3GlcNAc(4----1 alpha Fuc)-O(CH2)8CO2CH3 was carried out by two-dimensional 1H NMR spectroscopy and hard-sphere energy calculations. Significant chemical shift differences between the two molecules were detected only for protons at or near the linkage site of NeuAc to the Lea trisaccharide core. Coupling constants for the ring protons of both molecules did not suggest major deviation from the 4C1 chair conformation for Gal and GlcNAc, the 1C4 conformation for Fuc, or the 2C5 conformation for NeuAc. Two-dimensional nuclear Overhauser enhancement experiments revealed through-space, inter-proton interactions that corresponded to some extent with those predicted by diffraction data and hard-sphere energy minimization programs for both saccharides. However, a significant number of interactions did not obey the distance dependence predicted from a rigid structure model. These data suggest that, while the average conformation of the 19-9 antigen's Lea core may be invariant to NeuAc alpha 2----3Gal linkage, the dynamics of the Lea trisaccharide are altered upon sialylation. Data also indicate that the terminal NeuAc linkage is more flexible than the inter-residue bonds of the core trisacharide. This analysis, in combination with the fact that the monoclonal anti-19-9 antibody CO 19-9 does not cross-react with the Lea antigen, provides evidence in favor of NeuAc as an epitope-creating unit involved directly at the antibody binding site. However, given the possible role of variable dynamics in epitope formation, these results do not preclude crucial roles in antibody recognition for regions on the 19-9 antigen that are distanced from NeuAc.

Novel isoglobo-neolacto-series hybrid glycolipid detected by a monoclonal antibody is a rat colon tumor-associated antigen.

Isoglobotetraosylceramide (GalNAc(beta 1-3)Gal(alpha 1-3)Gal(beta 1-4)Glc (beta 1-1)Cer), the major glycolipid species in dimethylhydrazine-induced rat tumors of colorectal origin, was not detected in epithelial cells of normal colon but was present in the non-epithelial stroma and could be extracted from each of nine tumors studied. Monoclonal antibodies produced against isoglobotetraosylceramide detected this and another novel rat tumor-associated glycolipid not present in epithelial cells nor in non-epithelial stroma of normal rat colon (Brodin, T., Thurin, J., Strömberg, N., Karlsson, K.-A. and Sjögren, H.O. (1985) Eur. J. Immunol. 16, 951-956). This novel glycolipid was present in 8/9 of the studied tumors and was also present in two in vitro cell clones. These were originally obtained from a W49/T4 colon tumor isograft. The novel glycolipid was characterized by mass spectrometry, 1H-NMR, and methylation analysis as a hybrid between the isoglobo- and neolacto-series, with the structure GalNAc(beta 1-3)Gal(alpha 1-3)Gal(beta 1-4)GlcNA(beta 1-3)Gal (beta 1-4)Glc(beta 1-1)Cer.