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Background: There is still no clinical evidence available to support or to oppose corticosteroid treatment for coronavirus disease 2019 (COVID-19) pneumonia. Objective: To investigate the efficacy and safety of corticosteroid given to the hospitalized patients with COVID-19 pneumonia. Methods: This was a prospective, multicenter, single-blind, randomized control trial. Adult patients with COVID-19 pneumonia who were admitted to the general ward were randomly assigned to either receive methylprednisolone or not for 7 days. The primary end point was the incidence of clinical deterioration 14 days after randomization. Results: We terminated this trial early because the number of patients with COVID-19 pneumonia in all the centers decreased in late March. Finally, a total of 86 COVID-19 patients underwent randomization. There was no difference of the incidence of clinical deterioration between the methylprednisolone group and control group (4.8 vs. 4.8%, p = 1.000). The duration of throat viral RNA detectability in the methylprednisolone group was 11 days (interquartile range, 6–16 days), which was significantly longer than that in the control group (8 days [2–12 days], p = 0.030). There were no significant differences between the 2 groups in other secondary outcomes. Mass cytometry discovered CD3 + T cells, CD8 + T cells, and NK cells in the methylprednisolone group which were significantly lower than those in the control group after randomization (p < 0.05). Conclusions: From this prematurely closed trial, we found that the short-term early use of corticosteroid could suppress the immune cells, which may prolong severe acute respiratory syndrome coronavirus 2 shedding in patients with COVID-19 pneumonia. Trial Registration: ClinicalTrials.gov, NCT04273321.

The authors report results of an analysis of nasal and throat swabs from 17 patients in Zhuhai, China, who had received a diagnosis of Covid-19. Higher viral loads soon after symptom onset indicate the need for isolation strategies different from those used for the earlier SARS epidemic.

Oropharyngeal dysphagia is prevalent in age-related neurological disorders presenting with impaired efficacy and safety of swallowing due to a loss of muscle force and sensory deficits. Stimulating the oropharynx with capsaicin that mediates Substance P release is an emerging pharmacological treatment option which needs further scientific evidence. Our aim was to comprehensively evaluate the effect of capsaicin on biochemical, neurophysiological, and biomechanical parameters of swallowing function. In a randomized study on healthy individuals, the impact of orally administered capsaicinoids at different dosages and application durations in comparison to non-carbonated water was evaluated. Time course and magnitude of salivary Substance P increase were monitored. Magnetoencephalography was used to detect cortical swallowing network alterations. Modifications in swallowing biomechanics were measured applying high-resolution pharyngeal manometry. Capsaicinoids at 10 μmol/L improved swallowing efficacy as seen by a significant increase of pharyngeal contractile integral and upper esophageal sphincter activation and relaxation times in manometry. Significant improvement of precision in a challenging swallow task accompanied by a reduction in swallowing-related submental electromyographic power was observed with capsaicinoids preconditioning at 10 μmol/L over 5 min, but not with continuous stimulation. The cortical activation pattern remained unchanged after any intervention. A significant increase of salivary Substance P was not detected with 10 μmol/L but with 50 μmol/L and lasted for 15 min after application. Capsaicinoids mediate dose-dependent Substance P release and positively alter swallowing biomechanics in healthy subjects. The results provide supportive evidence for the value of natural capsaicinoids to improve swallowing function.

Abstract Study Objectives The Sleep Apnea Multilevel Surgery (SAMS) trial found that modified uvulopalatopharyngoplasty with tonsillectomy (if tonsils present) combined with radiofrequency tongue ablation reduced obstructive sleep apnea (OSA) severity and daytime sleepiness in moderate-severe OSA. This study aimed to investigate mechanisms of effect on apnea-hypopnea index (AHI) reduction by assessing changes in upper airway volumes (airway space, soft palate, tongue, and intra-tongue fat). Methods This is a case series analysis of 43 participants of 51 randomized to the surgical arm of the SAMS trial who underwent repeat magnetic resonance imaging (MRI). Upper airway volume, length, and cross-sectional area, soft palate and tongue volumes, and tongue fat were measured. Relationships between changes in anatomical structures and AHI were assessed. Results The participant sample was predominantly male (79%); mean ± SD age 42.7 ± 13.3 years, body mass index 30.8 ± 4.1 kg/m2, and AHI 47.0 ± 22.3 events/hour. There were no, or minor, overall volumetric changes in the airway, soft palate, total tongue, or tongue fat volume. Post-surgery there was an increase in the minimum cross-sectional area by 0.1 cm2 (95% confidence interval 0.04–0.2 cm2) in the pharyngeal airway, but not statistically significant on corrected analysis. There was no association between anatomical changes and AHI improvement. Conclusions This contemporary multilevel upper airway surgery has been shown to be an effective OSA treatment. The current anatomical investigation suggests there are not significant post-operative volumetric changes associated with OSA improvement 6-month post-surgery. This suggests that effect on OSA improvement is achieved without notable deformation of airway volume. Reduced need for neuromuscular compensation during wake following anatomical improvement via surgery could explain the lack of measurable volume change. Further research to understand the mechanisms of action of multilevel surgery is required. Clinical Trial This manuscript presents a planned image analysis of participants randomized to the surgical arm or the clinical trial multilevel airway surgery in patients with moderate-severe obstructive sleep apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=266019&isReview=true%20Australian%20New%20Zealand%20Clinical%20Trials%20Registry%20ACTRN12514000338662, prospectively registered on March 31, 2014.

Abstract Rationale Oral appliances (OAs) are commonly used as an alternative treatment to continuous positive airway pressure for patients with obstructive sleep apnea (OSA). However, OAs have variable success at reducing the apnea–hypopnea index (AHI), and predicting responders is challenging. Understanding this variability may lie with the recognition that OSA is a multifactorial disorder and that OAs may affect more than just upper-airway anatomy/collapsibility. Objectives The objectives of this study were to determine how OA alters AHI and four phenotypic traits (upper-airway anatomy/collapsibility and muscle function, loop gain, and arousal threshold), and baseline predictors of which patients gain the greatest benefit from therapy. Methods In a randomized crossover study, 14 patients with OSA attended two sleep studies with and without their OA. Under each condition, AHI and the phenotypic traits were assessed. Multiple linear regression was used to determine independent predictors of the reduction in AHI. Measurements and Main Results OA therapy reduced the AHI (30 ± 5 vs. 11 ± 2 events/h; P < 0.05), which was driven by improvements in upper-airway anatomy/collapsibility under passive (1.9 ± 0.7 vs. 4.7 ± 0.6 L/min; P < 0.005) and active conditions (2.4 ± 0.9 vs. 6.2 ± 0.4 L/min; P < 0.001). No changes were seen in muscle function, loop gain, or the arousal threshold. Using multivariate analysis, baseline passive upper-airway collapsibility and loop gain were independent predictors of the reduction in AHI (r2 = 0.70; P = 0.001). Conclusions Our findings suggest that OA therapy improves the upper-airway collapsibility under passive and active conditions. Importantly, a greater response to therapy occurred in those patients with a mild anatomic compromise and a lower loop gain.

Antibiotic administration is the standard treatment for the bacterium Helicobacter pylori, the main causative agent of peptic ulcer disease and gastric cancer. However, the long-term consequences of this treatment on the human indigenous microbiota are relatively unexplored. Here we studied short- and long-term effects of clarithromycin and metronidazole treatment, a commonly used therapy regimen against H. pylori, on the indigenous microbiota in the throat and in the lower intestine. The bacterial compositions in samples collected over a four-year period were monitored by analyzing the 16S rRNA gene using 454-based pyrosequencing and terminal-restriction fragment length polymorphism (T-RFLP). While the microbial communities of untreated control subjects were relatively stable over time, dramatic shifts were observed one week after antibiotic treatment with reduced bacterial diversity in all treated subjects in both locations. While the microbiota of the different subjects responded uniquely to the antibiotic treatment some general trends could be observed; such as a dramatic decline in Actinobacteria in both throat and feces immediately after treatment. Although the diversity of the microbiota subsequently recovered to resemble the pre treatment states, the microbiota remained perturbed in some cases for up to four years post treatment. In addition, four years after treatment high levels of the macrolide resistance gene erm(B) were found, indicating that antibiotic resistance, once selected for, can persist for longer periods of time than previously recognized. This highlights the importance of a restrictive antibiotic usage in order to prevent subsequent treatment failure and potential spread of antibiotic resistance.

Resistance to antibiotics is a major public-health problem, and studies that link antibiotic use and resistance have shown an association but not a causal effect. We used the macrolides azithromycin and clarithromycin to investigate the direct effect of antibiotic exposure on resistance in the oral streptococcal flora of healthy volunteers. Volunteers were treated with azithromycin (n=74), clarithromycin (74), or placebo (76) in a randomised, double-blind trial. Pharyngeal swabs were obtained before and after administration of study treatment through 180 days. The proportion of streptococci that were macrolide resistant was assessed and the molecular basis of any change in resistance investigated. Analyses were done on an intent-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00354952. The number of dropouts (n=20) was much the same in all groups until day 42; dropouts increased substantially at day 180 (105). Both macrolides significantly increased the proportion of macrolide-resistant streptococci compared with the placebo at all points studied, peaking at day 8 in the clarithromycin group (mean increase 50·0%, 95% CI 41·7–58·2; p<0·0001) and at day 4 in the azithromycin group (53·4%, 43·4–63·5; p<0·0001). The proportion of macrolide-resistant streptococci was higher after azithromycin treatment than after clarithromycin use, with the largest difference between the two groups at day 28 (17·4% difference, 9·2–25·6; p<0·0001). Use of clarithromycin, but not of azithromycin, selected for the erm(B) gene, which confers high-level macrolide resistance. This study shows that, notwithstanding the different outcomes of resistance selection, macrolide use is the single most important driver of the emergence of macrolide resistance in vivo. Physicians prescribing antibiotics should take into account the striking ecological side-effects of such antibiotics.

This study investigated the association between tongue and hyoid position, tongue volume, and pharyngeal airway dimensions with craniofacial growth patterns in the sagittal, vertical, and transverse planes. Cone beam computed tomography was used to assess 185 non-growing subjects (mean age, 28.7 ± 9.5 years). Multivariate linear regression analyses evaluated relationships between tongue and airway variables, and cephalometric/dental arch measurements. Class III skeletal patterns-reflected by lower ANB and higher APDI-were significantly correlated with anteriorly positioned hyoids (ANB: β = 0.249; APDI: β = -0.291), and lower tongue positions at the tongue tip (ANB: β = -0.231; APDI: β = 0.166) and in the posterior area (ANB: β = -0.186; APDI: β = 0.196), and greater tongue volume (APDI: β = 0.174). Hyperdivergent vertical patterns-indicated by a lower ODI-were significantly correlated with a lower tongue tip position (β = -0.311) and posterior tongue position (β = -0.230). Regarding transverse dimensions, tongue volume showed positive correlations with upper intermolar width (β = 0.349), lower intercanine width (β = 0.130), lower intermolar width (β = 0.311), and a negative correlation with upper intercanine width (β = -0.299). Sagittal and vertical craniofacial patterns are interrelated and show associations with tongue and hyoid position, as well as tongue volume. Transverse dental arch dimensions are correlated not only with tongue position and volume but also with pharyngeal airway volume.

The comparative performance of different clinical sampling methods for diagnosis of SARS-CoV-2 infection by RT-PCR among populations with suspected infection remains unclear. This meta-analysis aims to systematically compare the diagnostic performance of different clinical specimen collection methods. In this systematic review and meta-analysis, we systematically searched PubMed, Embase, MEDLINE, Web of Science, medRxiv, bioRxiv, SSRN, and Research Square from Jan 1, 2000, to Nov 16, 2020. We included original clinical studies that examined the performance of nasopharyngeal swabs and any additional respiratory specimens for the diagnosis of SARS-CoV-2 infection among individuals presenting in ambulatory care. Studies without data on paired samples, or those that only examined different samples from confirmed SARS-CoV-2 cases were not useful for examining diagnostic performance of a test and were excluded. Diagnostic performance, including sensitivity, specificity, positive predictive value, and negative predictive value, was examined using random effects models and double arcsine transformation. Of the 5577 studies identified in our search, 23 studies including 7973 participants with 16 762 respiratory samples were included. Respiratory specimens examined in these studies included 7973 nasopharyngeal swabs, 1622 nasal swabs, 6110 saliva samples, 338 throat swabs, and 719 pooled nasal and throat swabs. Using nasopharyngeal swabs as the gold standard, pooled nasal and throat swabs gave the highest sensitivity of 97% (95% CI 93–100), whereas lower sensitivities were achieved by saliva (85%, 75–93) and nasal swabs (86%, 77–93) and a much lower sensitivity by throat swabs (68%, 35–94). A comparably high positive predictive value was obtained by pooled nasal and throat (97%, 90–100) and nasal swabs (96%, 87–100) and a slightly lower positive predictive value by saliva (93%, 88–97). Throat swabs have the lowest positive predictive value of 75% (95% CI 45–96). Comparably high specificities (range 97–99%) and negative predictive value (range 95–99%) were observed among different clinical specimens. Comparison between health-care-worker collection and self-collection for pooled nasal and throat swabs and nasal swabs showed comparable diagnostic performance. No significant heterogeneity was observed in the analysis of pooled nasal and throat swabs and throat swabs, whereas moderate to substantial heterogeneity (I2 ≥30%) was observed in studies on saliva and nasal swabs. Our review suggests that, compared with the gold standard of nasopharyngeal swabs, pooled nasal and throat swabs offered the best diagnostic performance of the alternative sampling approaches for diagnosis of SARS-CoV-2 infection in ambulatory care. Saliva and nasal swabs gave comparable and very good diagnostic performance and are clinically acceptable alternative specimen collection methods. Throat swabs gave a much lower sensitivity and positive predictive value and should not be recommended. Self-collection for pooled nasal and throat swabs and nasal swabs was not associated with any significant impairment of diagnostic accuracy. Our results also provide a useful reference framework for the proper interpretation of SARS-CoV-2 testing results using different clinical specimens. Hong Kong Research Grants Council.