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Purpose: Anti-viral and anti-inflammatory therapies were effective in altering virus repletion and immune dysregulation in Coronavirus Disease 2019 (COVID-19) patients. This study aimed to explore the effect of combination therapy on disease progression in a real-world setting.Patients and Methods: A total of 836 patients confirmed with SARS-CoV-2 infection participated in the study from 15 November to 25 December 2022 at Beijing Youan Hospital, Capital Medical University. A prospective cohort study was implemented to investigate the prognostic effect of the combination therapy on virus shedding and clinical recovery.Results: About 78% of patients used nirmatrelvir/ritonavir (N/R, Paxlovid®, Pfizer) negatively, 16% of patients were prescribed nirmatrelvir/ritonavir beyond five days of symptom onset, 4% of patients received N/R monotherapy within five days of symptom onset and 2% of patients received N/R combined with dexamethasone. Compared with untreated patients, N/R monotherapy reduced the median time to 10.0 days from 12.0 days according to the negative conversion of nucleic acid amplification test (NAAT), and combination therapy reduced the time to 7.0 days, and increased to a 1.99 (95% CI 0.92, 4.32) and 14.23-fold (95% CI 4.50, 44.95) probability of negative NAAT, respectively. N/R monotherapy reduced the clinical recovery time to 10.0 days from 13.0 days. Single-use and combined-use non-significantly increased the recovery probability by 61% and 69%, respectively. In mild and moderate patients, the HRs for clinical recovery increased to 1.69 (95% CI 0.73, 3.94) and 2.18 (95% CI 0.29, 16.62), respectively.Conclusion: Combination therapy of N/R and dexamethasone increased negative conversion of NAAT and was associated with a non-significant improvement in clinical recovery. Further studies are warranted to confirm this efficacy. [ABSTRACT FROM AUTHOR]

Purpose/aim: We investigated the regularity changes of the retinal nerve fiber layer (RNFL) and macular ganglion cell complex (mGCC) of the amnestic mild cognitive impairment (aMCI) patients in this prospective cohort study. Materials and methods: Twenty-four aMCI patients and 30 health controls, who are more than 60 years old, were recruited into the study. The RNFL and the mGCC average thickness were measured with Fourier-domain optical coherence tomography (FD-OCT). Results: Compared with that in the controls, the intraocular pressure (IOP) was significantly lower in the aMCI patients. A significant decrease in RNFL thickness in superior temporal, temporal upper (TU), and temporal upper and lower (TL) (TU+TL) quadrants was found in the aMCI patients than in the controls. The average thickness of the mGCC was also significantly thinner in the aMCI patients than in the controls. Conclusions: Retinal degeneration in the aMCI patients detected by OCT together with lower IOP may indicate disease pathological progression. [ABSTRACT FROM AUTHOR]

Background: Functional connectivity in default mode network (DMN) may be changed in Alzheimer’s disease (AD) patients and related risk populations, such as amnestic mild cognitive impairment (aMCI) patients and APOE ε4 carriers. Exploring DMN changes and related behavioral performance of APOE ε4 population might provide valuable evidence for better understanding the development of AD. Methods: Subjects were enrolled from a population-based cohort established in a multi-center study in China. Forty-nine cognitive normal individuals were enrolled after standardized cognitive evaluations, MRI examination and APOE genotyping. Regions of interest (ROI)-based functional connectivity analyses were performed, and voxel-based analyses were used to validate these findings. The correlation between DMN functional connectivity and behavioral performance was further evaluated between APOE ε4ε3 and ε3ε3 carriers. Results: Comparing to ε3ε3 carriers, functional connectivity between left parahippocampal gyrus and right superior frontal cortex (LPHC-R.Sup.F), left parahippocampal gyrus and medial prefrontal cortex (ventral) (LPHC-vMPFC) were significantly increased in ε4ε3 carriers, while connectivity between cerebellar tonsils and retrosplenial was decreased. LPHC-R.Sup.F connectivity was positively correlated with the changes of delay recall from baseline to follow-up (r = 0.768, p = 0.009), while LPHC-vMPFC connectivity had a positive correlation with MMSE at baseline (r = 0.356, p = 0.018), and a negative correlation with long-delayed recognition at follow-up (r = -0.677, p = 0.031). Significantly increased functional connectivity in vMPFC was confirmed in voxel-based analyses by taking LPHC as seed region. Conclusion: APOE ε4 carriers present both increased and decreased functional connectivity in DMN, which is correlated with clinical cognitive performances. DMN changes might be an early sign for cognitive decline. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the usefulness of scleral pneumatonometry as an alternative for corneal measurements of intraocular pressure (IOP) over a broad range of IOPs. Design Prospective, observational cohort study. Participants The study was conducted in the University of California, San Francisco, Retina Clinic between August and November 2013 in 33 adult patients (age range, 34–94 years; mean ± standard deviation, 74.1±13.4 years) receiving anti–vascular endothelial growth factor intravitreal injections, which transiently increase IOP. Methods Corneal pachymetry and serial corneal and temporal scleral pneumatonometry (baseline, immediately after, and 10, 20, and 30 minutes after injection) were collected. One-time baseline corneal and scleral pneumatonometry readings were obtained in the noninjected eye. Main Outcome Measures Correlation analysis and a Bland-Altman plot were used to evaluate reliability and agreement between scleral and corneal measurements of IOP. A linear mixed model was used to determine the relationship between measurements and to perform covariate analyses. Results Scleral and corneal pneumatonometry showed nearly 1:1 linear correlation, although scleral pneumatonometry was biased toward higher values ( r = 0.94; P < 0.001). Scleral pneumatonometry averaged 9.0 mmHg higher than corneal pneumatonometry (95% limits of agreement, −1.5 to 19.5 mmHg). A linear mixed model resulted in the following equation: corneal IOP = 1.04 × scleral IOP − 10.37. Age, central corneal thickness, laterality, and glaucoma and lens status did not impact this relationship. The difference between corneal and scleral pneumotonometry was correlated between the two eyes of individual patients ( r = 0.75; P < 0.001). Conclusions Differences between serial scleral measurements reflect differences between serial corneal measurements. Scleral pneumatonometry should be considered as an alternative to corneal pneumatonometry for following patients in whom corneal measurements are unreliable or unobtainable. [ABSTRACT FROM AUTHOR]