Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer’s disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD.
This study examined outcomes of antireflux and antacid treatment for the signs and symptoms of chronic laryngitis. Patients from a referral institutional practice with chronic laryngitis symptoms, without other apparent causes of laryngeal inflammation, were followed up and examined at progressive stages of antireflux treatment as a case series outcome study. The cases included unselected individuals with a diagnosis of chronic (> 3 months' duration) laryngitis. Patients with chronic throat complaints were treated with nocturnal antireflux precautions, with addition of famotidine 20 mg or omeprazole 20 mg at bedtime for patients who did not respond to antireflux precautions alone. The outcome measures were resolution of symptoms, and change in findings on telescopic laryngoscopy. Chronic throat symptoms of 93 of 182 patients (51%) responded to nocturnal antireflux precautions alone. The complaints of an additional 48 patients resolved with the addition of famotidine 20mg at bedtime to antireflux precautions (77% response). The symptoms of 34 of the remaining 41 patients responded to treatment with omeprazole 20 mg at bedtime. Therefore, symptoms of 96% of patients responded to treatment aimed at preventing reflux of gastric acid. The remaining patients with refractory symptoms had a partial response or no response or chose fundoplication. Erythema and granular mucositis were the most common laryngoscopic findings. Ulceration and granuloma formation were less common, but also responded to antireflux treatment. Some (7) patients required high doses of omeprazole or fundoplication to achieve symptomatic relief and healing of chronic inflammatory changes of the posterior larynx. Relapse of symptoms was common when treatment was stopped.(ABSTRACT TRUNCATED AT 250 WORDS)
The successful use of the tracheoesophageal voice prosthesis for speech rehabilitation of the total laryngectomy patient has lead to common application of this device. Although the creation of a tracheoesophageal fistula is a simple procedure, it is not without complications. A review of 104 patients who underwent this procedure indicated a complication rate of 25%. Complications were related primarily to the fistula and included migration and progressive enlargement of the puncture, persistent or recurring infection of the fistula site, aspiration pneumonia, and death. Other problems included aspiration of the prosthesis, vertebral osteomyelitis, and tracheal stomal and esophageal stenosis. Many of these patients required hospitalization, intravenous antibiotics, and major surgical procedures to treat these complications. Guidelines for early identification and management of these problems as well as methods to prevent complications are discussed.
The signs and symptoms of posterior laryngitis improve with the administration of omeprazole and symptoms recur after discontinuation of therapy, suggesting that reflux is the underlying etiology. Patients with refractory symptoms, but intolerant of omeprazole, may benefit from antireflux surgery. Laryngoscopic findings of posterior laryngitis are often subtle, and many patients with posterior laryngitis do not have esophagitis.
This study examined charts and 16-mm pictures or videotapes of 138 patients with carcinoma of the larynx treated during the last 10 years. Among these patients, 19 were nonsmokers and nondrinkers or only light social drinkers with moderate to severe gastroesophageal reflux (GER). Serial cinephotographs are presented with follow-up of up to 10 years. The common presence of GER in these nonsmoking, nondrinking patients and the probable role of this chronic irritative disorder as a causative agent in carcinoma of the laryngopharynx are discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.