Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures

Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma, few have shown the same benefit using sublingual immunotherapy (SLIT) in asthmatic patients. This study was conducted to assess the efficacy of house dust mite (HDM) SLIT in addition to allergen avoidance and standard pharmacologic treatment. A double-blind, placebo-controlled trial was performed in 111 children (aged 5-15 yr) with HDM-induced mild-to-moderate asthma. After a 4-week baseline phase, patients were randomly assigned to receive SLIT with tablets of HDM extract (n = 55) or placebo (n = 56) for 18 months. Pharmacologic treatment was adjusted every 3 months following a step-down approach. Asthma symptom scores, reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists, rhinitis symptoms, lung function tests, skin sensitivity to HDM, dust mite-specific immunoglobulin (Ig) E and IgG(4), and quality of life (QoL) were assessed during the study. After 18 months of treatment, diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups. Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups. There were no significant differences in lung function (forced expiratory volume in 1 s and peak flow rate variations) between groups. Rhinitis symptom score decreased in both groups, with no difference between the two groups. The severity dimension of QoL was significantly improved in the SLIT group (age 6-12 yr). SLIT induced a significant reduction of skin sensitivity to HDM (p < 0.01) and a significant increase in HDM-specific IgE and IgG(4) antibodies (p < 0.001) in the SLIT group compared with the placebo group. SLIT was well tolerated with mild/moderate local adverse events. No severe systemic reactions were reported. This study indicates that, when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance, SLIT does not provide additional benefit, despite a significant reduction in allergic response to HDM. Under such conditions, only a complete, but ethically unfeasible, discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT.     

Unrealistic Weight-Loss Goals among Obese Patients Are Associated with Age and Causal Attributions

Unrealistic weight-loss goals may impede the success of weight-loss attempts. The aim of this study was to examine the frequency of unrealistic goals and their association with other patient characteristics at the start of a weight-loss program. For patients with a body mass index (calculated as kg/m²) of 30 to 35, 35 to 40, or 40 to 50, medically advised weight-loss goals were set at 10%, 15%, and 20% of current weight, respectively. Personal weight-loss goals exceeding the medically advised goal by >50% were considered unrealistic. Obesity-related beliefs were measured by the “Obesity Cognition Questionnaire” and the eating-behavior self-efficacy scale of the “Obesity Psychosocial State Questionnaire.” From September 2003 until March 2006, 90 patients were enrolled in the study, 26 men and 64 women, with a mean age of 43 years (range=18 to 68 years) and body mass indexes ranging from 30 to 50. Unrealistic goals were observed in 49% of the patients and were more frequent in younger patients (P=0.03), in patients attributing their obesity to physical causes (r=0.35, P=0.001), and in patients not attributing their obesity to behavioral causes (r=−0.28, P=0.008). This study confirms that discrepancies in weight-loss goals between obese patients and professionals occur frequently. Because unrealistic goals can hamper long-term outcomes of weight-loss programs, better outcomes could possibly be achieved by addressing unrealistic weight-loss goals before treatment.     

Tacrolimus Pharmacokinetics and Dose Monitoring After Lung Transplantation for Cystic Fibrosis and Other Conditions

In cystic fibrosis (CF), absorption of tacrolimus through the gastrointestinal tract may be impaired due to fat malabsorption. The aim of this pilot study was to compare tacrolimus pharmacokinetics and inter- and intrasubject variability of exposure in stable lung transplant recipients with and without CF, and to determine the best single-time predictors of exposure. The study included 11 lung transplant recipients with CF and 11 without CF who received tacrolimus twice daily. Blood samples were obtained predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 h postdose on 3 separate days within 1 week. Tacrolimus pharmacokinetics and inter- and intrasubject variability of exposure were similar in the two groups, though exposure-per-milligram-dose was approximately 50% lower in CF patients. Tacrolimus trough concentration did not accurately predict the area under the concentration curve (AUC(0-12)), but the concentration measured 3 h postdose (C(3)) was tightly correlated with the AUC(0-12) in both CF (r(2)= 0.86) and non-CF (r(2)= 0.92) patients. In summary, patients with CF have a higher tacrolimus oral clearance, but nonsignificant differences in short-term inter- and intrasubject variability of exposure compared to patients without CF. C(3) is tightly correlated with AUC(0-12) in lung transplant recipients with and without CF.     

Complications associated with the Esophageal-Tracheal Combitube® in the pre-hospital setting

PURPOSE: The Esophageal-Tracheal Combitube (Combitube) is widely used for the management of the airway during cardiopulmonary resuscitation in the pre-hospital setting. Although serious complications have been reported with the Combitube, there is a paucity of data relative to the frequency and nature of such complications. The objective of this retrospective study was to determine the incidence and the nature of complications associated to the Combitube in the pre-hospital setting. METHODS: Since 1993, in the Quebec City Health Region, the basic life support treatment algorithm for emergency medical technicians has included the use of a Combitube as the primary airway device for management of all patients presenting with cardiac or respiratory arrest. The database of the emergency coordination services was searched for the period between 1993 and 2003 (2,981 patients). Only those patients who survived at least 12 hr were included. Medical records of these patients were reviewed to identify complications related to the use of the Combitube. RESULTS: Two-hundred-eighty (280) patients were identified. Fifty-eight (58) patients (20.7%, confidence interval (CI)95%=16.0%-25.4%) presented 69 complications: aspiration pneumonitis (n=31), pulmonary aspiration (n=16), pneumothorax (n=6), upper airway bleeding (n=4), esophageal laceration (n=3), sc emphysema (n=2), esophageal perforation and mediastinitis (n=2), tongue edema (n=2), vocal cord injury (n=1), tracheal injury (n=1), and pneumomediastinum (n=1). Thirteen of these complications (12 patients, 4.3%, CI95%=2.0%-6.3%) were judged as most likely resulting from trauma associated with insertion of the Combitube. CONCLUSION: The use of the Combitube in the pre-hospital setting is associated with a notable incidence of serious complications.     

Microcrack frequency and bone remodeling in postmenopausal osteoporotic women on long-term bisphosphonates: a bone biopsy study.

We sought whether microdamage could rise in postmenopausal osteoporotic women on long-term bisphosphonates, as suggested by recent animal studies. We found few microcracks in iliac bone biopsies, despite a marked reduction in bone turnover. INTRODUCTION: Animal studies suggest that bisphosphonates (BPs) could increase microdamage frequency in a dose-dependent manner, caused by excessively suppressed bone turnover. However, there is limited data in humans receiving BP therapeutic doses for >3 yr. MATERIALS AND METHODS: We measured microcrack frequency and histomorphometry parameters on transiliac bone biopsies in 50 postmenopausal osteoporotic women (mean age = 68 yr) who had received BP therapy (3 on intravenous pamidronate, 37 on oral alendronate, and 10 on oral risedronate) for at least 3 yr (mean treatment duration = 6.5 yr). We compared these results with transiliac bone biopsies obtained from 12 cadavers. We used bulk staining with green calcein as a fluorochrome. The microcracks were quantified in three 100-microm-thick sections using optic microscopy and were confirmed by laser confocal microscopy. Microcrack frequency (number of microcracks/mm2 of bone tissue) was compared between treated women and controls using nonparametric tests. We also explored predictors of microcrack frequency, including age, duration of BP therapy, and activation frequency. RESULTS: Among treated women, cancellous bone microcrack frequency was low (mean, 0.13 microcracks/mm2) and did not differ significantly from that observed in controls (0.05 microcracks/mm2; p = 0.59). Of note, 54% of the treated women and 58% of the controls had no observable microcracks. There was no association between microcrack frequency and the duration of BP therapy (for microcracks/mm2 and duration, Spearman r = 0.04, p = 0.80) and between patients' ages and the number of microcracks (Spearman r = -0.09, p = 0.61). Although bone remodeling parameters were suppressed in treated women, we found no relationship between microcrack density and activation frequency (Spearman r = -0.003, p = 0.99). Also, microcrack frequency was not increased in women with prevalent vertebral fracture compared with those without fractures. CONCLUSIONS: Among postmenopausal osteoporotic women on long-term BPs, microcrack frequency in the iliac bone is low, despite a marked reduction of bone turnover.     

Defective implant osseointegration under protein undernutrition: prevention by PTH or pamidronate.

Protein deficiency is associated with impaired titanium osseointegration. We studied whether systemic treatment with PTH or pamidronate could influence the resistance to pull-out of titanium rods implanted into rats proximal tibia under normal and isocaloric low protein intake. PTH or pamidronate prevented the deleterious effects of protein undernutrition on bone microarchitecture close to the implant and on mechanical fixation. PTH even significantly improved implant osseointegration. INTRODUCTION: Protein deficiency is highly prevalent among elderly patients hospitalized in orthopedic wards. Reduced protein intake impairs titanium osseointegration in rats. Whether stimulator of bone formation or inhibitor of bone resorption could improve implant osseointegration under protein deprivation is not known. We studied the effects of systemic treatment with PTH or pamidronate on the resistance to pull-out of titanium rods implanted into rats proximal tibia under normal and isocaloric low protein intake. MATERIALS AND METHODS: We measured the resistance to pull-out 1-mm-diameter titanium rods implanted into the proximal tibias of 49 adult female rats receiving a normal or an isocaloric low protein diet. After 2 wk on either diet, the implants were inserted, and the rats received PTH(1-34), pamidronate or saline vehicle for 8 wk. The tibias were removed for microCT morphometry, followed by the evaluation of pull-out strength. RESULTS: Pull-out strength was lower in rats fed an isocaloric low protein diet compared with rats fed a normal protein intake (-29%). PTH and pamidronate significantly increased pull-out strength in animals fed a normal or a low protein diet, the effect of PTH being of higher magnitude. The PTH- or pamidronate-mediated increase in pull-out strength was associated with significant increases of relative bone volume, bone-to-implant contact, and trabecular thickness, whereas trabecular spacing was reduced, in the vicinity of the implants. CONCLUSIONS: We confirmed that isocaloric low protein intake impairs titanium implant osseointegration. PTH or pamidronate prevented the deleterious effects of protein undernutrition and even significantly improved the implant osseointegration. These results indicate that systemic administration of PTH or pamidronate could be considered for preventing uncemented arthroplasty loosening in protein undernourished patients.     

Does the extent of lymph node dissection influence outcome in patients with stage I non-small-cell lung cancer?

OBJECTIVE: To assess the therapeutic effect of the extent of lymph node dissection performed in patients with a stage pI non-small-cell lung cancer (NSCLC). METHODS: We analysed data on 465 patients with stage I NSCLC who were treated with surgical resection and some form of lymph node sampling. The median number of lymph node sampled was 10 and the median number of ipsilateral mediastinal lymph node stations sampled was two. We chose to define a procedure that harvested 10 or more lymph nodes and sampled two or more ipsilateral mediastinal stations as a lymphadenectomy, by contrast with sampling when one or both criteria were not satisfied. The effect of the surgical techniques: lymph node sampling (LS; n=207) vs. lymphadenectomy (LA; n=258) on 30-day mortality and overall survival were investigated. RESULTS: A total of 6244 lymph nodes was examined, including 4306 mediastinal lymph nodes. The mean (+/-SD) numbers of removed lymph nodes were 7+/-6.1 per patient following LS vs.18.6+/-9.3 following LA (P=0.001). An average mean of 1+/-0.90 mediastinal lymph node station per patient was sampled following LS vs. 2.7+/-0.8 following LA (P<10(-6)). Overall 30-day mortality rates were 2.4 and 3.1%, respectively. LA was disclosed as a favourable prognosticator at multivariate analysis (Hazard Risk: 1.43; 95% Confidence Interval: 1.00-2.04; P=0.048), together with younger patient age, absence of blood vessels invasion, and smaller tumour size. CONCLUSIONS: Importance of lymph node dissection affects patients outcome, while it does not enhance the operative mortality. A minimum of 10 lymph nodes assessed, and two mediastinal stations sampled are suggested as possible pragmatic markers of the quality of lymphadenectomy.     

Influence of time elapsed between myocardial infarction and coronary artery bypass grafting surgery on operative mortality.

OBJECTIVE: Optimal timing for CABG surgery after myocardial infarction (MI) remains controversial. We examined the influence of patient age and time elapsed between MI and isolated CABG surgery on operative mortality. METHODS: Perioperative data of 13,545 patients who underwent isolated CABG surgery from 1991 to 2005 were reviewed. A previous MI was found in 7219 patients, classified among groups A-E whether they underwent surgery less than 6h (A, n=26), between 6 and 24h (B, n=51), between 1 and 7 days (C, n=313), between 8 and 30 days (D, n=917), or more than 30 days (E, n=5912) after the event. Crude percentages and odds ratio estimates of operative mortality were calculated. RESULTS: In patients who had no history of MI, the mortality rate was 1.7%, while it was, respectively, 19.2, 9.8, 8.6, 3.2, and 2.4% in patients from groups A to E. Among 6589 patients over 65 years of age, 3027 had no history of MI. Their mortality was 2.4%, compared to, respectively, 35.7, 13.8, 11.3, 5.1, and 3.9% for those belonging to groups A-E. Overall odds ratio estimates of operative mortality were 3.92 (p=0.19), 5.08 (p=0.002), 4.33 (p=0.0001), 1.50 (p=0.08), and 1.18 (p=0.24) for groups A-E, respectively. CONCLUSIONS: Operative mortality is not influenced by a history of MI sustained more than 30 days prior to isolated CABG surgery, but is highly and most significantly increased between 6h and 1 week after MI, especially in older patients. That critical period should be avoided whenever possible.     

“Inorganic and Organometallic Clusters and Polymers: Syntheses and Applications” Symposium

Conference Reports: This section contains reports on topical conferences. Reports are usually written at the request of the editorial office, but unsolicited contributions are also welcome. Suggestions should be sent to the editorial office of the Macromolecular journals, preferably by E‐mail to macromol@wiley‐vch.de.