Respiratory Paradoxical Adverse Drug Reactions Associated with Acetylcysteine and Carbocysteine Systemic Use in Paediatric Patients: A National Survey

OBJECTIVE: To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in France and then Italy. DESIGN: The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population. SETTING: Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases. PATIENTS: The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg) and at least until the day before the first signs of the suspected ADR. RESULTS: The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old) were increased bronchorrhea or mucus vomiting (n = 27), worsening of respiratory distress during respiratory tract infection (n = 35), dyspnoea (n = 18), cough aggravation or prolongation (n = 11), and bronchospasm (n = 1). Fifty-one (86%) children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting. CONCLUSION: Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence

Locally continuous-fiber reinforced sheet molding compound

The process of co-molding of locally continuous-fiber reinforced structures with Sheet Molding Compound (SMC) has the potential to realize structures economically combining high stiffness with freedom in design. The objective is to combine the flowability of the SMC, needed to form ribs and to integrate inlays, with accurate position and intact shape of the continuous-fiber reinforcement. State-of-the-art in co-molding is still a near net-shape mold coverage of the SMC to prevent any flow. The introduction of a two-step curing resin results in a stiff reinforcement during co-molding, which endures the forces applied by the flowing SMC and therefore is not deformed. Furthermore, the second reaction step allows for chemical bonding to the SMC. To prevent displacement of the reinforcement, a novel fixation method is introduced by using magnetic. To realize this innovative co-molding concept a multidisciplinary approach is needed, including material characterization and material modelling, process simulation and magnetic field simulation and like-wise experiments. Hereby, the performance as well as the reliability of these hybrid structures are significantly improved

Rheological In-Mold Measurements and Characterizations of Sheet-Molding-Compound (SMC) Formulations with Different Constitution Properties by Using a Compressible Shell Model

The rheological characterization of Sheet Molding Compound (SMC) and its modelling is crucial for reliable process simulations. In the past, characterization and material modelling were mainly focusing on SMC with low glass fiber content and a high filler fraction. Due to new application areas, SMC without fillers and with high glass fiber contents, and SMC with carbon fibers become more important. Therefore, these three types of SMCs are characterized in this work, using an inline rheological tool. Differences regarding their compressibility and their flow dependency are identified and considered in an analytical shell modelling. The comparison of the different materials leads to a better understanding of the phenomenological parameters related to the viscosity and friction in the models. Furthermore, the importance to properly consider all relevant material-specific effects becomes evident

Hydrofilm Polyurethane Films Reduce Radiation Dermatitis Severity in Hypofractionated Whole-Breast Irradiation: An Objective, Intra-Patient Randomized Dual-Center Assessment

Radiation-induced skin injury represents the most frequent side effect in breast cancer patients undergoing whole-breast irradiation (WBI). Numerous clinical studies on systemic and topical treatments for radiation dermatitis have failed to provide sustainable treatment strategies. While protective skin products such as dressings are undoubtedly the standard of care in wound care management, their utilization as preventive treatment in radiotherapy has been somewhat neglected in recent years. In this prospective, intra-patient randomized observational study, Hydrofilm polyurethane films were prophylactically applied to either the medial or lateral breast-half of 74 patients with breast cancer undergoing hypofractionated whole-breast irradiation following breast-preserving surgery. Maximum radiation dermatitis severity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 toxicity scores, photospectrometric erythema and pigmentation measurements and patient-assessed modified Radiation-Induced Skin Reaction Assessment Scale (RISRAS) scale. Phantom studies revealed a clinically negligible dose build-up of less than 0.1% with Hydrofilm. Compared to the control compartments physician-assessed radiation dermatitis severity was reduced in the hydrofilm compartments (mean 0.54 vs. 1.34; p = < 0.001). Objective photospectrometric skin measurements showed decreased erythema (p = 0.0001) and hyperpigmentation (p = 0.002) underneath Hydrofilm. Hydrofilm also completely prevented moist desquamation, and significantly reduced patients’ treatment-related symptoms of itching, burning, pain, and limitations of day-to-day-activities. Significant beneficial effects were observed in terms of radiation dermatitis severity, erythema, hyperpigmentation as well as subjective treatment-related symptom experiences, while adverse reactions were rare and minor. Therefore, a prophylactic application of Hydrofilm polyurethane films can be suggested in hypofractionated WBI