Enzyme-potentiated desensitization in children with asthma and mite allergy: a double-blind study. Desmopressin and imipramine in the management of nocturnal enuresis: a multicentre study. A controlled trial of desmopressin and behavioral therapy for nocturnal enuresis. Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study.
The aim of this study was to evaluate the efficacy and safety of enzyme-potentiated desensitization (EPD) in children with asthma. Twenty asthmatic children (14 males and 6 females; median age: 8.5 years) were included in the study. They had positive skin tests to Dermatophagoides pteronyssinus (Dpt), no history of other allergy and had suffered from asthma for at least two years. The children were examined before starting the trial, at the first EPD dose, after 8 weeks, at the second EPD dose and 3 months after the second EPD dose. Blood samples for PRIST and RAST were drawn before the first and at the second EPD dose, and at the last follow-up. Conjunctival provocation tests (CPT) and skin test endpoint determinations were performed with dilutions of a freeze-dried Dpt extract (10-100,000 SQ-U/ml) at the start of the trial and at the last follow-up. Parents kept a diary record of the days with asthma and daily drug usage. The children were randomized to receive either two intradermal placebo injections or the active material with an 8-week interval (November 1991 and January 1992). Ten children received EPD and 10 children placebo. The intradermal injection of EPD (0.05 ml) contained 0.01 ml of beta-glucuronidase (40 Fishman units) and 0.04 ml of a mixture of inhalant allergens (1 Noon unit). The placebo injection consisted of buffer solution only. The EPD-treated children had significantly fewer days with asthma (p = 0.00000). In addition, the EPD-treated children used significantly less medication for the management of asthma attacks (p = 0.00000). At the start of the trial, three out of 10 children in the EPD group and two out of 10 in the placebo group reacted only to the highest dose of allergen used in the CPT (100,000 SQ/ml) (NS). At the last follow-up, the threshold dose in the CPT was 100,000 SQ/ml or more in nine out of 10 children in the EPD group and in four out of 10 children of the placebo group (p = 0.0349). At the last follow-up, one child in the EPD group had a negative CPT with all doses tested. Global clinical evaluation by the investigators showed that eight out of 10 EPD-treated children improved, in comparison with three out of 10 children in the placebo group (p = 0.0349). Assessment by the parents was six out of 10 and four out of 10 improved, respectively (NS). Specific IgE to Dpt, total IgE and skin prick test endpoints before and after EPD showed no significant changes. One child in the placebo group experienced mild urticaria several hours following the second injection. No other local or systemic side effects were reported. The results of the present study provide further data on the effectiveness and safety of EPD in patients with asthma. The efficacy and safety of desmopressin (Minirin/DDAVP) treatment compared with imipramine were investigated in a multicentre, open, cross-over design in 57 patients, aged 6-15 years, affected by nocturnal enuresis to establish the best therapeutic approach to this condition. After a two-weeks observation and control period, patients were randomised to one of two groups: intranasal administration of desmopressin, 30 micrograms/day for three weeks, followed by imipramine, 0.9 mg/kg for a further three weeks, or imipramine 0.9 mg/kg for three weeks, followed by desmopressin, 30 micrograms/day for a further three weeks. Following treatment, all patients were observed for a further two weeks. Administration of either treatment protocol resulted in a statistically significant decline in the number of enuretic episodes per week compared to the control. The greater antidiuretic effect observed in the group receiving imipramine followed by desmopressin suggests the two compounds have different profiles. Also, when the treatment period was compared with the follow-up, the antidiuretic effect had a longer duration in the group initially given imipramine. No further improvement was seen when desmopressin was administered first, with a mild worsening of the effect sometimes occurring, suggesting a different carry-over effect between the two treatments. This suggests that desmopressin offers a better approach to the management of nocturnal enuresis. The combination of desmopressin (DDAVP) and behavioral therapy for treatment of nocturnal enuresis was compared with use of each of these modes alone. We randomly assigned 226 enuretic children being treated in primary care clinics of a major medical center in the largest health maintenance organization in Israel into 3 groups: Group A) DDAVP plus behavioral therapy (double-blind); Group B) behavioral therapy plus placebo (double-blind); and Group C) DDAVP alone (open group). DDAVP (20 micrograms/naris) and placebo were administered by intranasal spray. Both pharmacologic and behavioral therapy were initiated after a 2-week observation period and continued for 8 weeks. All patients were followed for 2 months after completion of treatment. A significant reduction in the number of wet nights/week was registered for all 3 groups: 49% in Group A, 45% in Group B, and 19% in Group C. After controlling for confounding factors, no significant difference in effect was noted among the 3 types of treatment during the trial period. However, on follow-up the results for the DDAVP patients were significantly less stable compared with the other 2 groups (p = 0.015). Minor side effects were registered, but none of the participants withdrew from the trial. To our knowledge, this is the largest randomized trial of nocturnal enuresis conducted to date. Our findings suggest that simply discussing the problem with the patient and family leads to improvement, and that behavioral therapy is also beneficial. DDAVP can help, but the relapse rate on discontinuation is high. Cow's milk allergy (CMA) in children is a important problem in medical practice. Oral desensitization has been proposed as a therapeutic approach, but current protocols are time-consuming and impractical.
                To establish a patient-friendly desensitization regimen with weekly up-dosing and to evaluate it in a randomized controlled trial.
                Thirty children with IgE-mediated CMA confirmed by double-blind placebo-controlled food challenge were equally randomized to desensitization with CM or soy milk as control. The weekly up-dosing lasted 18 weeks. The occurrence and severity of reactions after each dose was evaluated, and the desensitization was stopped if severe reactions occurred. Specific IgE and IgG4 levels to CM were measured at baseline, after 8 weeks, and at the end of the study. The double-blind food challenge was repeated once the desensitization was completed or after premature discontinuation.
                Two active and 1 control patient dropped out. Full tolerance to CM (200 mL) was achieved in 10 active patients and partial tolerance in 1. Two active patients discontinued the desensitization after experiencing severe reactions, whereas no reactions occurred in controls, whose sensitivity to CM remained unchanged. A significant increase in specific IgG4 levels was found only in the active group.
                This weekly up-dosing desensitization protocol for CMA performed under medical supervision was effective and reasonably safe and induced consistent immunologic changes.
                Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Studies to date have involved small numbers of patients and the quality of evidence is generally low. The current evidence shows that MOIT can lead to desensitization in the majority of individuals with IMCMA although the development of long-term tolerance has not been established. A major drawback of MOIT is the frequency of adverse effects, although most are mild and self-limited. The use of parenteral epinephrine is not infrequent. Because there are no standardized protocols, guidelines would be required prior to incorporating desensitization into clinical practice.