The Children's Anti-inflammatory Reliever (CARE) study: a protocol for a randomised controlled trial of budesonide-formoterol as sole reliever therapy in children with mild asthma.

BACKGROUND: Asthma is the most common chronic disease in children, many of whom are managed solely with a short-acting ß2-agonist (SABA). In adults, the evidence that budesonide-formoterol as sole reliever therapy markedly reduces the risk of severe exacerbations compared with SABA alone has contributed to the Global Initiative for Asthma recommending against SABA monotherapy in this population. The current lack of evidence in children means it is unknown whether these findings are also relevant to this demographic. High-quality randomised controlled trials (RCTs) are needed. OBJECTIVE: The aim of this study is to determine the efficacy and safety of as-needed budesonide-formoterol therapy compared with as-needed salbutamol in children aged 5 to 15 years with mild asthma, who only use a SABA. METHODS: A 52-week, open-label, parallel group, phase III RCT will recruit 380 children aged 5 to 15 years with mild asthma. Participants will be randomised 1:1 to either budesonide-formoterol (Symbicort Rapihaler®) 50/3 µg, two actuations as needed, or salbutamol (Ventolin®) 100  µg, two actuations as needed. The primary outcome is asthma attacks as rate per participant per year. Secondary outcomes assess asthma control, lung function, exhaled nitric oxide and treatment step change. A cost-effectiveness analysis is also planned. CONCLUSION: This is the first RCT to assess the safety and efficacy of as-needed budesonide-formoterol in children with mild asthma. The results will provide a much-needed evidence base for the treatment of mild asthma in children.

Tips and Tricks to Optimize Surgical Outcomes After ACL Repair Using Dynamic Intraligamentary Stabilization.

PURPOSE: This paper describes technical difficulties and outcomes for the first 15 patients treated with Dynamic Intraligamentary Stabilization (DIS) for anterior cruciate ligament (ACL) repair. METHODS: The first 15 patients treated with DIS were included. To optimize the inclusion process, a new pre-operative pathway was developed. All intra-operative technical problems were recorded. During the 2-year follow-up period, patient-related outcome measures, return to work, anterior-posterior knee laxity using a Rolimeter and ACL healing as revealed by MRI follow-up scans were recorded. RESULTS: During 11 DIS procedures, 15 technical problems were encountered. Six were surgeon-related and 9 were material-related. All problems were resolved intra-operatively. Repeat surgery was performed in 4 patients due to arthrofibrosis and in 1 due to a cyclops lesion. The DIS implant was removed in all 5 patients. According to the Tegner score, 7 of 10 (70%) patients returned to the pre-injury level of sporting activity within 6 months. The mean return to work time was 5.4 (SD 3.6) weeks. On MRI, 10 patients showed normal ACL healing (Grade 1) and 3 showed a high repair signal intensity (Grade 2). Although 2 patients showed no signs of ACL healing on MRI (Grade 3), no instability was reported or measured post-operatively or after the DIS implant was removed. CONCLUSION: All intra-operative technical problems were resolved and did not lead to conversion to ACL reconstruction. We share tips and tricks that could assist surgeons who are just starting to use the DIS technique.

Study protocol: a single-blind, multi-center, randomized controlled trial comparing dynamic intraligamentary stabilization, internal brace ligament augmentation and reconstruction in individuals with an acute anterior cruciate ligament rupture: LIBRƎ study.

BACKGROUND: The current gold standard for the treatment of an anterior cruciate ligament (ACL) rupture is reconstruction with tendon graft. Recently, two surgical ACL repair techniques have been developed for treating an acute ACL rupture: Dynamic Intraligamentary Stabilization (DIS, Ligamys®) and Internal Brace Ligament Augmentation (IBLA, InternalBrace™). We will conduct a single-blind, multi-center, randomized controlled trial which compares DIS, IBLA and reconstruction for relative clinical efficacy and economic benefit. METHODS: Subjects, aged 18-50 years, with a proximal, primary and repairable ACL rupture will be included. DIS is preferably performed within 4 weeks post-rupture, IBLA within 12 weeks and reconstruction after 4 weeks post-rupture. Patients are included in study 1 if they present within 0-4 weeks post-rupture and surgery is feasible within 4 weeks post-rupture. Patients of study 1 will be randomized to either DIS or IBLA. Patients are included in study 2 if they present after 4 weeks post-rupture and surgery is feasible between 5 and 12 weeks post-rupture. Patients of study 2 will be randomized to either IBLA or reconstruction. A total of 96 patients will be included, with 48 patients per study and 24 patients per study arm. Patients will be followed-up for 2 years. The primary outcome is change from baseline (pre-rupture) in International Knee Documentation Committee score to 6 months post-operatively. The main secondary outcomes are the EQ-5D-5 L, Tegner score, Lysholm score, Lachman test, isokinetic and proprioceptive measurements, magnetic resonance imaging outcome, return to work and sports, and re-rupture/failure rates. The statistical analysis will be based on the intention-to-treat principle. The economic impact of the surgery techniques will be evaluated by the cost-utility analysis. The LIBRƎ study is to be conducted between 2018 and 2022. DISCUSSION: This LIBRƎ study protocol is the first study to compare DIS, IBLA and ACL reconstruction for relative clinical efficacy and economic benefit. The outcomes of this study will provide data which could aid orthopaedic surgeons to choose between the different treatment options for the surgical treatment of an acute ACL rupture. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov; NCT03441295. Date registered 13.02.2018.

Assessment of Anterior Cruciate Ligament Graft Maturity With Conventional Magnetic Resonance Imaging: A Systematic Literature Review.

BACKGROUND: Magnetic resonance imaging (MRI) signal intensity (SI) measurements are being used increasingly in both clinical and research studies to assess the maturity of anterior cruciate ligament (ACL) grafts in humans. However, SI in conventional MRI with weighted images is a nonquantitative measure dependent on hardware and software. PURPOSE: To conduct a systematic review of studies that have used MRI SI as a proxy for ACL graft maturity and to identify potential confounding factors in assessing the ACL graft in conventional MRI studies. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review was conducted by searching the MEDLINE/PubMed, Scopus, and Cochrane Library electronic databases according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify studies that examined the healing of the intra-articular portion of the ACL graft by assessing SI on MRIs. RESULTS: A total of 34 studies were selected for inclusion in this systematic review. The MRI acquisition techniques and methods to evaluate the ACL graft SI differed greatly across the studies. No agreement was found regarding the time frames of SI changes in MRI reflecting normal healing of the ACL tendon graft, and the graft SI and clinical outcomes after ACL reconstruction were found to be poorly correlated. CONCLUSION: The MRI acquisition and evaluation methods used to assess ACL grafts are very heterogeneous, impeding comparisons of SI between successive scans and between independent studies. Therefore, quantitative MRI-based biomarkers of ACL graft healing are greatly needed to guide the appropriate time of returning to sports after ACL reconstruction.