Vestergaardwilhelmsen9333

The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial.

To estimate the effect of remdesivir in blocking viral replication.

We analysed nasopharyngeal normalized viral loads from 665 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020-000936-23), randomized to either standard of care (SoC) or SoC + remdesivir. We used a mathematical model to reconstruct viral kinetic profiles and estimate the antiviral efficacy of remdesivir in blocking viral replication. Additional analyses were conducted stratified on time of treatment initiation (≤7 or >7 days since symptom onset) or viral load at randomization (< or ≥3.5 log10 copies/104 cells).

In our model, remdesivir reduced viral production by infected cells by 2-fold on average (95% CI 1.5-3.2-fold). Model-based simulations predict that remdesivir reduced time to viral clearance by 0.7 days compared with SoC, with large inter-individual variabilities (IQR 0.0-1.3 days). Remdesivir had a larger impact in patients with high viral load at randomization, reducing viral production by 5-fold on average (95% CI 2.8-25-fold) and the median time to viral clearance by 2.4 days (IQR 0.9-4.5 days).

Remdesivir halved viral production, leading to a median reduction of 0.7 days in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.

Remdesivir halved viral production, leading to a median reduction of 0.7 days in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.

Pediatric patients with immunocompromising or certain chronic medical conditions have an increased risk of acquiring invasive pneumococcal disease (IPD). The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for patients ≥2 years at high risk for IPDs. The aim of this project was to improve PPSV23 vaccination rates for children at high risk for IPD who were seen in 3 specialty clinics from ∼20% to 50% over a 12-month period.

The project team included quality improvement champions from the divisions of rheumatology, infectious diseases, and pulmonology in addition to leaders from our population health management subsidiary. Several initiatives were implemented, starting with review of patient inclusion criteria per the vaccination recommendations, that led to the design and deployment of an automated weekly previsit planning report. Additionally, we implemented a process to stock pneumococcal vaccines and shared best practices among the divisions. We monitored improvement through times series and run charts of PPSV23 vaccination rates.

The initial PPSV23 vaccination rate for applicable high-risk patients was ∼20%. There was an increase in vaccination rate to ∼60%. All 3 divisions showed improvements in their individual PPSV23 vaccination rates.

Using quality improvement methodology, we increased PPSV23 vaccination rates in 3 pediatric specialty clinics, and this improvement was sustained. We will continue to identify best practices and actively recruit additional divisions because we have the opportunity to reach >9000 high-risk patients.

9000 high-risk patients.The human orbitofrontal cortex, ventromedial prefrontal cortex (vmPFC), and anterior cingulate cortex are involved in reward processing and thereby in emotion but are also implicated in episodic memory. To understand these regions better, the effective connectivity between 360 cortical regions and 24 subcortical regions was measured in 172 humans from the Human Connectome Project and complemented with functional connectivity and diffusion tractography. The orbitofrontal cortex has effective connectivity from gustatory, olfactory, and temporal visual, auditory, and pole cortical areas. The orbitofrontal cortex has connectivity to the pregenual anterior and posterior cingulate cortex and hippocampal system and provides for rewards to be used in memory and navigation to goals. The orbitofrontal and pregenual anterior cortex have connectivity to the supracallosal anterior cingulate cortex, which projects to midcingulate and other premotor cortical areas and provides for action-outcome learning including limb withdrawal or flight or fight to aversive and nonreward stimuli. The lateral orbitofrontal cortex has outputs to language systems in the inferior frontal gyrus. The medial orbitofrontal cortex connects to the nucleus basalis of Meynert and the pregenual cingulate to the septum, and damage to these cortical regions may contribute to memory impairments by disrupting cholinergic influences on the neocortex and hippocampus.Explosively emerging SARS-CoV-2 variants challenge current nomenclature schemes based on genetic diversity and biological significance. Genomic composition-based machine learning methods have recently performed well in identifying phenotype-genotype relationships. We introduced a framework involving dinucleotide (DNT) composition representation (DCR) to parse the general human adaptation of RNA viruses and applied a three-dimensional convolutional neural network (3D CNN) analysis to learn the human adaptation of other existing coronaviruses (CoVs) and predict the adaptation of SARS-CoV-2 variants of concern (VOCs). A markedly separable, linear DCR distribution was observed in two major genes-receptor-binding glycoprotein and RNA-dependent RNA polymerase (RdRp)-of six families of single-stranded (ssRNA) viruses. Additionally, there was a general host-specific distribution of both the spike proteins and RdRps of CoVs. Selleck PF-8380 The 3D CNN based on spike DCR predicted a dominant type II adaptation of most Beta, Delta and Omicron VOCs, with high transmissibility and low pathogenicity. Type I adaptation with opposite transmissibility and pathogenicity was predicted for SARS-CoV-2 Alpha VOCs (77%) and Kappa variants of interest (58%). The identified adaptive determinants included D1118H and A570D mutations and local DNTs. Thus, the 3D CNN model based on DCR features predicts SARS-CoV-2, a major type II human adaptation and is qualified to predict variant adaptation in real time, facilitating the risk-assessment of emerging SARS-CoV-2 variants and COVID-19 control.

To assess the impact of gestational antibiotics on the risk of preterm birth, since a healthy maternal microbiome may be protective.

Population-based cohort study including all first pregnancies in Sweden (2006-16). The association between gestational and recent pre-conception systemic antibiotics and preterm birth was assessed by multivariable logistic regression presented as ORs and 95% CIs, adjusted for comorbidities (hypo- and hyperthyroidism, hypertension, or diabetes mellitus pre-gestation), trimester, antibiotic class and treatment duration.

Compared with non-users, antibiotic exposure was associated with increased risks of preterm birth in mothers with comorbidities (OR = 1.32, 95% CI 1.18-1.48) and without (OR = 1.09, 95% CI 1.06-1.13). Pre-conception use showed no association, while risk was increased for first and second trimester use and decreased for third trimester use. The increased risks were seen for the following antibiotic groups in mothers without and with comorbidities, respectively macrolides, lincosamides and streptogramins (OR = 1.63, 95% CI 1.45-1.83; OR = 2.48, 95% CI 1.72-3.56); quinolones (OR = 1.60, 95% CI 1.32-1.94; OR = 2.11, 95% CI 1.12-4.03); non-penicillin β-lactams (OR = 1.15, 95% CI 1.07-1.24; OR = 1.39, 95% CI 1.07-1.83); other antibacterials (OR = 1.09, 95% CI 1.03-1.14; 1.38, 95% CI 1.16-1.63); and penicillins (OR = 1.04, 95% CI 1.01-1.08; 1.23, 95% CI 1.09-1.40). Antibiotic indications were not available, which could also affect preterm birth.

Antibiotic use during pregnancy was associated with an increased risk of preterm birth, especially in mothers with chronic diseases.

Antibiotic use during pregnancy was associated with an increased risk of preterm birth, especially in mothers with chronic diseases.

The primary objective of this study was to identify the occurrence and factors associated with intensive care unit (ICU)-acquired weakness (ICUAW) in patients with COVID-19. Secondarily, we monitored the evolution of muscle strength and mobility among individuals with ICUAW and those without ICUAW and the association of these variables with length of stay, mechanical ventilation (MV), and other clinical variables.

In this prospective observational study, individuals admitted to the ICU for >72hours with COVID-19 were evaluated for muscle strength and mobility at 3 times when being weaned from ventilatory support, discharged from the ICU, and discharged from the hospital. Risk factors for ICUAW were monitored.

The occurrences of ICUAW at the 3 times evaluated among the 75 patients included were 52%, 38%, and 13%. The length of the ICU stay (29.5 [IQR = 16.3-42.5] vs 11 [IQR = 6.5-16] days), the length of the hospital stay (43.5 [IQR = 22.8-55.3] vs 16 [IQR = 12.5-24] days), and time on MV (25.5 [IQR = those who required MV) were factors independently associated with ICUAW.

Patients who had COVID-19 and developed ICUAW had longer periods of ICU stay, hospital stay, and MV. Bed rest time and use of corticosteroids (for those who required MV) were factors independently associated with ICUAW.

There has been increasing evidence that physicians in gynaecology are not routinely enquiring about work during consultations.

To explore the effect gynaecological conditions can have on work functioning, the importance of work outcomes among patients and whether work considerations are discussed during clinical consultations.

A cross-sectional survey was administered to employed patients attending a gynaecological clinic at Guy's Hospital. The survey assessed four areas demographics, gynaecological condition (including self-assessed severity), work status and perceived impact of the condition on work functioning and job satisfaction. Simple descriptive analysis and statistical techniques were used to interpret the data.

One hundred and six participants participated (mean age 37.49 ± 9.09). About 95% found it important to be able to work whilst receiving treatment and 82% of patients had reported at least a slight impact on their working ability due to their condition. Of the 31 patients for whom it was their first appointment, 77% said it would be useful to discuss the possible impacts their gynaecological condition could have on their work. About 66% (19/29) of the participants attending a follow-up appointment reported that their doctor had not discussed their work with them.

The symptoms of gynaecological conditions can impact patients' ability to work. There is a lack of useful discussion from doctors about the perceived impact gynaecological conditions can have on a patient's ability to work, despite patients finding it important to be able to remain or return to work.

The symptoms of gynaecological conditions can impact patients' ability to work. There is a lack of useful discussion from doctors about the perceived impact gynaecological conditions can have on a patient's ability to work, despite patients finding it important to be able to remain or return to work.