Several placebo-controlled trials have been recently published evaluating novel therapies targeting the defective CFTR protein. This systematic review examines the clinical efficacy and safety of CFTR modulators in individuals with cystic fibrosis (CF) with specific genetic mutations. Online sources were searched for placebo-controlled, parallel-design clinical trials investigating CFTR modulators from January 1, 2005 to March 31, 2018. The primary outcome of interest was FEV 1 % predicted (ppFEV 1 ). Fourteen RCTs met our eligibility criteria. The largest improvement in ppFEV 1 favouring treatment was observed for ivacaftor (IVA) in G551D individuals (≥6 years old). Both tezacaftor-ivacaftor (TEZ-IVA) and lumacaftor-ivacaftor (LUM-IVA) also improved ppFEV 1 in F508del homozygous individuals but there was increased reporting of respiratory adverse events with LUM-IVA compared to placebo. IVA also significantly improved ppFEV 1 in a sub-group of individuals ≥18 years old with an R117H mutation. No significant improvements in ppFEV 1 were observed for IVA, LUM, or TEZ in F508del homozygous individuals, LUM or LUM-IVA in F508del heterozygous individuals, or ataluren in individuals with a nonsense mutation. Significant improvements in ppFEV 1 and other clinical outcomes were observed for IVA in G551D individuals, TEV-IVA and LUM-IVA in F508del homozygous individuals, and IVA in adults with a R117H mutation.
This pilot study showed that IF therapy is safe, noninvasive, and effective modality to improve constipation symptoms and anorectal manometry parameters in children with history of myelomeningocele.
Animated biofeedback effectively treats bowel and voiding dysfunction in children with dysfunctional voiding. Pelvic floor muscle exercises coordinate breathing and pelvic floor muscle contractions, and are beneficial in improving bowel dysfunction.
Objectives:To summarise the accuracy of artificial intelligence (AI) computer vision algorithms to classify ear disease from otoscopy.Design:Systematic review and meta-analysis.Methods:Using the PRISMA guidelines, nine online databases were searched for articles that used AI computer vision algorithms developed from various methods (convolutional neural networks, artificial neural networks, support vector machines, decision trees and k-nearest neighbours) to classify otoscopic images. Diagnostic classes of interest: normal tympanic membrane, acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with or without perforation, cholesteatoma and canal obstruction.Mainoutcomemeasures:Accuracy to correctly classify otoscopic images compared to otolaryngologists (ground truth). The Quality Assessment of Diagnostic Accuracy Studies Version 2 tool was used to assess the quality of methodology and risk of bias.Results: Thirty-nine articles were included. Algorithms achieved 90.7% (95%CI: 90.1-91.3%) accuracy to difference between normal or abnormal otoscopy images in 14 studies. The most common multiclassification algorithm (3 or more diagnostic classes) achieved 97.6% (95%CI: 97.3-97.9%) accuracy to differentiate between normal, AOM and OME in three studies. AI algorithms outperformed human assessors to classify otoscopy images achieving 93.4% (95%CI: 90.5-96.4%) versus 73.2% (95%CI: 67.9-78.5%) accuracy in three studies. Convolutional neural networks achieved the highest accuracy compared to other classification methods. Conclusion:AI can classify ear disease from otoscopy. A concerted effort is requiredto establish a comprehensive and reliable otoscopy database for algorithm training.An AI-supported otoscopy system may assist health care workers, trainees and primary care practitioners with less otology experience identify ear disease.
The aim of the present study was to demonstrate the regaining histological characteristics of bioengineered external anal sphincters (EAS) in rabbit fecal incontinence model. The EAS of 16 rabbits were resected and decellularized. The decellularized scaffolds were transplanted to the terminal rectum following a period of 6 months of fecal incontinency (5 days after sterilization). The rabbits were divided into two groups: in group 1 (n = 8), myogenic satellite cells were injected into the transplanted sphincters. In group 2 (n = 8), the transplanted scaffolds remained in situ without cellular injection. The histological evaluation was performed with desmin, myosin, smooth muscle actin, CD31, and CD34 at 3-month intervals. The rabbits were followed for 2 years. Electromyography (EMG) with needle and electrical stimulation, pudendal and muscle electrical stimulation were also performed after 2 years of transplantation. At the time of biopsy, no evidence of inflammation or rejection was observed and the transplanted EAS appeared histologically and anatomically normal. The immunohistochemistry staining validated that the histological features of EAS was more satisfactory in group 1 in short-term follow-up. However, no statistically significant difference was detected between two groups in long-term follow-ups (p value > 0.05). In both groups, grafted EAS contracted in response to electrical signals delivered to the muscle and the pudendal nerve. However, more signals were detected in group 1 in EMG evaluation. In conclusion, bioengineered EAS with myogenic satellite cells can gain more satisfactory histological outcomes in short-term follow-ups with better muscle electrical stimulation outcomes.
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