Transfusion-associated graft-versus-host disease in immunocompetent patients: report of a fatal case associated with transfusion of blood from a second-degree relative, and a survey of predisposing factors

A patient without evident immune deficiency who received a transfusion of blood from a second-degree family member developed fatal transfusion- associated graft-versus-host disease (TA-GVHD). The donor was homozygous for an HLA haplotype for which the recipient was heterozygous (one-way HLA match). All 39 reported cases of TA-GVHD in immunocompetent patients were reviewed to ascertain the predisposing factors and to define the indications for irradiating blood for this population. HLA typing was described in 15 cases; in 13, including seven related and six unrelated donors, a one-way HLA match was present. Thirty-one (79%) of the 39 cases were reported from Japan (and 196 other cases are cited in the Japanese literature), but a one-way HLA match among unrelated donors at HLA-A, -B, -DR loci is only approximately two to four times more likely in Japanese persons than in whites. Fresh blood (< 96 hours old) was used in 29 (94%) of the 31 cases reported from Japan and in 33 (87%) of 38 cases overall (in one case, the age of the blood used was not reported). Thus, factors that appear to predispose to TA-GVHD in immunocompetent patients are a one- way HLA match, fresh blood, and, possibly, Japanese ancestry. Irradiating cellular blood components from all blood relatives of transfusion recipients will not completely eliminate the risk of TA- GVHD.     

Coronary calcification and its association with mortality in haemodialysis patients

Aim:   Coronary artery calcification (CAC) has been associated with higher mortality in chronic renal disease. The purpose of this study was to assess coronary artery calcium score (CaCs) in haemodialysis patients and to correlate calcium scores with clinical parameters and mortality.
Methods:   A cross-sectional study was conducted in 59 haemodialysis patients. CaCs was assessed by multidetector-row computed tomography and stratified as: CaCs of less than 10 Agatston units (U), no calcification; CaCs of 10–400 U, mild-to-moderate; and CaCs of more than 400 U, severe calcification. The effects of age, haemodialysis duration and biochemical and inflammatory markers on CaCs logarithm were evaluated by multiple linear regression analysis. Cox regression analysis was used to measure the impact of CaCs of more than 400 on 2-year mortality.
Results:   Coronary calcifications were detected in 64.5% of patients, and the median of CaCs was 31.7 U (0–589.7) with a range of 0–5790.0 U. Twenty-one (35.5%) patients had mild-to-moderate and 17 (29%) severe CaCs. Patients with severe CaCs were older and showed a higher prevalence of ischaemic heart disease and a higher body mass index ( P  = 0.04). A trend towards higher C-reactive protein levels was found in patients with severe CaCs. Advanced age was the only variable that influenced CaCs logarithm independently. The effect of severe CaCs on 2-year mortality did not persist after adjustment for other covariates.
Conclusion:   Coronary calcification was highly prevalent in these uraemic patients on chronic haemodialysis. A correlation was evidenced between CaCs and advanced age, but severity of the CAC score did not have an impact on 2-year mortality of this cohort.     

Pharmacoeconomic evaluation of a combination of ipratropium plus albuterol compared with ipratropium alone and albuterol alone in COPD

STUDY OBJECTIVE: To conduct a post hoc pharmacoeconomic evaluation of two double-blind, randomized, prospective, parallel group studies comparing the long-term efficacy and safety of ipratropium combined with albuterol in a single inhalational canister against either bronchodilator agent alone in patients with COPD. Patients: One thousand sixty-seven patients with COPD. METHODS: The dose of each bronchodilator was two puffs four times a day (42 microg of ipratropium bromide, 240 microg of albuterol sulfate). Pulmonary function testing was performed on days 1, 29, 57, and 85 of treatment. Outcomes, health-care resource consumption, and costs were compared for the three treatment groups over the 85-day study period. A total of 1,067 patients were randomized in the two studies (albuterol alone, n = 347; ipratropium alone, n = 362; albuterol plus ipratropium, n = 358). RESULTS: Improvement in FEV1 and area under the FEV1 response-time curve from time 0 to 4 h (FEV1AUC0-4) was significantly greater for the combination of albuterol plus ipratropium than either agent alone on all test days. Compared with albuterol, patients receiving ipratropium and ipratropium plus albuterol experienced significantly fewer COPD exacerbations and patient-days of exacerbation. In addition, the increased frequency of exacerbations observed in the albuterol group was associated with a significant increase in the number of patient hospital days and antibiotic and corticosteroid use. As a result, the total cost of treatment over the study period was significantly less for ipratropium ($156 per patient) and ipratropium plus albuterol ($197 per patient) than for albuterol ($269 per patient). Increased cost-effectiveness, defined as total estimated treatment cost per mean change in FEV1AUC0-4, was observed in both treatment arms containing ipratropium. CONCLUSIONS: The inclusion of ipratropium in a pharmacologic treatment regimen is associated with a lower rate of exacerbations in COPD. The result is lower total treatment costs and improved cost-effectiveness.     

Analysis of inhaled corticosteroid and oral theophylline use among patients with stable COPD from 1987 to 1995

STUDY OBJECTIVE: To document temporal usage trends for commonly used respiratory medications in patients with COPD. DESIGN: We retrospectively evaluated baseline concomitant medications of 3,720 patients with COPD enrolled in 10 bronchodilator clinical trials from 1987 to 1995. The proportion of patients in each trial using inhaled corticosteroids, inhaled beta-adrenergics, inhaled anticholinergics, oral theophylline, and oral corticosteroids was analyzed using the Cochran-Armitage trend test. PATIENTS: All patients had stable, moderate-to-severe COPD without evidence of asthma or atopy. Reversibility to beta3-agonists was not a requirement. RESULTS: The percentage of patients using inhaled corticosteroids increased significantly over time (p < 0.001) from 13.2% in 1987 to 41.4% in 1995. The percentage of patients receiving oral theophylline decreased significantly (p < 0.001) over this same time interval (63.4 to 29.0%). In addition, the percentage of patients using oral corticosteroids and the percentage using oral beta-adrenergics decreased moderately (p < 0.05) (30.1 to 16.4% and 11.7 to 4.5%, respectively); the percentage of patients using inhaled anticholinergics increased slowly (p < 0.05) (48.2 to 53.8%). The percentage of patients receiving inhaled beta-adrenergics did not significantly (p > 0.05) change. CONCLUSIONS: The observed changes in use of inhaled corticosteroids and theophylline were not likely related to differences in disease severity or other patient characteristics in the evaluated trials, but related to changing prescribing and COPD management practices.     

The combination of ipratropium and albuterol optimizes pulmonary function reversibility testing in patients with COPD

STUDY OBJECTIVES: To determine whether the combination of ipratropium bromide and albuterol results in greater and more consistent pulmonary function test (PFT) response rates than ipratropium bromide or albuterol alone in patients with COPD. DESIGN: Retrospective review of two recently completed 3-month, randomized, double-blind, parallel, multicenter, phase III trials. SETTING: Outpatient. PATIENTS: A total of 1,067 stable patients with COPD. INTERVENTIONS: Ipratropium bromide (36 microg qid), albuterol base (180 microg qid), or an equivalent combination of ipratropium bromide and albuterol sulfate (42 microg and 240 microg qid, respectively). MEASUREMENTS AND RESULTS: PFT response rates were analyzed using 12% and 15% increases in FEV1 compared with baseline values and were measured in the various treatment groups on days 1, 29, 57, and 85 in these trials. Regardless of whether a 12% or a 15% increase in FEV1 was used to define a positive response, an equivalent combination of ipratropium bromide and albuterol sulfate was superior to the individual agents (p < 0.05; all comparisons within 30 min). In addition, a 15% or more increase in FEV1 was seen in > 80% of patients who received the combination of ipratropium and albuterol sulfate during the initial PFT and continued to be observed 3 months after initial testing. CONCLUSIONS: Use of a combination of ipratropium bromide and albuterol sulfate is superior to the individual agents in identifying PFT reversibility in patients with COPD.     

Cytopathological and chemico‐physical analyses of smears of mucosa surrounding oral piercing

Oral Diseases (2010) 16 , 160–166 Objective: The aim of this comparative study was to analyze cytopathologically and chemico‐physically the mucosa surrounding oral piercing to correlate results with adverse tissue signs. Materials and methods: The tongue superficial mucosa of 15 young subjects (control group) and the superficial mucosa surrounding oral piercing of 15 young subjects (test group, TG) were smeared on slides, Papanicolaou stained and analyzed under the optical microscope. Some smears were prepared for (back‐scattered) scanning electron microscope (SEM) and X‐ray microanalysis to study piercing fragments. Results: Smears of TG displayed a variable extent of bacterial cytolysis of epithelial cells, fungi, hyperkeratosis, parakeratosis, granulocyte infiltration, calcium formations and bacterial flora; the four last statistically significant (P < 0.05). Foreign bodies surrounded by keratinocytes were detected under both light and SEM. X‐ray microanalyses highlighted piercing alloy aggression, ion release and an inverse gradient of ion concentration inside keratinocytes. Conclusions: The pathological findings in smears correlated with adverse effects of oral piercing. Ion release may be related to direct toxic effects and belated reactions because of metal sensitization. A strict regulation of piercing is warranted.     

Complementary medicine: use and attitudes among GPs

BACKGROUND: Information about use and attitudes of GPs towards complementary medicine is required in order to inform the debate about its place within mainstream medicine. There is evidence that public use of complementary medicine is particularly high in the South-West of England. OBJECTIVE: This study aimed to determine the use of, and attitudes towards, complementary medicine among GPs. METHODS: A questionnaire survey was performed of all primary care physicians working in the health service in Devon and Cornwall. RESULTS: Replies were received from 461 GPs, a response rate of 47%. A total of 314 GPs (68%, range 32-85%) had been involved in complementary medicine in some way during the previous week. One or other form of complementary medicine was practised by 74 of the respondents (16%), the two most common being homoeopathy (5.9%) and acupuncture (4.3%). In addition, 115 of the respondents (25%) had referred at least one patient to a complementary therapist in the previous week, and 253 (55%) had endorsed or recommended treatment with complementary medicine. Chiropractic, acupuncture and osteopathy were rated as the three most effective therapies, and the majority of respondents believed that these three therapies should be funded by the health service. A total of 176 (38%) of respondents reported adverse effects, most commonly after manipulation. CONCLUSION: Over two-thirds of the GPs in Devon and Cornwall who responded to the survey had been involved with complementary medicine in some way during the previous week. This figure is higher than the national average. The majority of respondents believed that acupuncture, chiropractic and osteopathy were effective and should be funded by the NHS.