Publications by authors named "K R S Morgan"

2,086 Publications

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A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer.

PLoS One 2021 21;16(6):e0253021. Epub 2021 Jun 21.

Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

Introduction: Radium-223, abiraterone, and enzalutamide have each been shown to significantly improve survival as monotherapy in patients with metastatic castration-resistant prostate cancer. However, effects of combination radium-223 plus abiraterone or enzalutamide on survival and safety remain unclear.

Patients And Methods: This single-center retrospective cohort study used electronic health record data of patients with metastatic castration-resistant prostate cancer and bone metastases who were treated with radium-223 between April 1, 2014 and February 19, 2019. Patients who received radium-223 monotherapy were compared to patients who received a combination of radium-223 plus either abiraterone or enzalutamide. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, time to symptomatic skeletal event, symptomatic skeletal event-free survival, and incidence of drug-related adverse events. Time-to-event analyses were estimated by log rank tests using Kaplan-Meier curves. Hazard ratios and 95% confidence intervals were derived from Cox proportional hazards models. Chi-square tests evaluated difference in serious adverse events between the two arms.

Results: A total of 60 patients met inclusion criteria (n = 41 in the monotherapy arm, n = 19 in the combination arm). Differences in median overall survival were not observed (12.7 vs. 12.8 months; HR 1.15, 95% CI 0.59-2.23; P = 0.68), but median progression-free survival was significantly longer in the combination arm (7.6 vs. 4.9 months; HR 1.94, 95% CI 1.11-3.40; P = 0.02). Significant differences were not observed in time to first SSE (P = 0.97), SSE-free survival (P = 0.16), or in the overall incidence of serious adverse events (P = 0.45).

Conclusion: Combination radium-223 plus abiraterone or enzalutamide did not improve overall survival, but prolonged progression-free survival without increasing the incidence of serious adverse events in metastatic castration-resistant prostate cancer patients with bone metastases. However, these results are limited by small numbers and patient selection inherent in retrospective analysis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253021PLOS
June 2021

The epidemiology of bacterial zoonoses in pastoral and dairy cattle in Cameroon, Central Africa.

Zoonoses Public Health 2021 Jun 15. Epub 2021 Jun 15.

Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, UK.

Previous work identified that bacterial zoonoses (Brucella species, Coxiella burnetii and Leptospira hardjo) were present in Cameroonian pastoral cattle. To assess the characteristics of this zoonotic risk, we analyse seroprevalence of each pathogen and the associated management, herd and environmental factors in Cameroonian pastoral and dairy cattle. Cross-sectional samples included pastoralist herds in the Northwest Region (NWR n = 750) and Vina Division (VD n = 748) and small holder dairy herds in the NWR (n = 60). Exposure to Brucella spp., C. burnetii and L. hardjo were screened for using commercial ELISAs and population adjusted estimates made. In addition, individual, herd and ecological metadata were collected and used to identify risk factors associated with animal-level seropositivity. In the pastoral cattle, seroprevalence to Brucella spp. was relatively low but was higher in the NWR (4.2%, CI: 2.5%-7.0%) than the VD (1.1%: CI 0.5%-2.4%), while L. hardjo seroprevalence was much higher though similar in the NWR (30.7%, CI 26.3%-35.5%) and VD (35.9%, CI 31.3%-40.7%). No differences were noted in C. burnetii seroprevalence between the two study sites (NWR: 14.6%, CI 11.8%-18.0%. VD: 12.4%, 9.6%-15.9%). Compared to pastoral, dairy cattle had lower seroprevalences for L. hardjo (1.7%, CI: 0.0%-4.9%), C. burnetii (0.0%, CI 0.0%-6.0%) but similar for Brucella spp. (5.0%, CI 0.0%-10.6%). Increased odds of Brucella spp. seropositivity were associated with owning sheep or rearing sheep and fencing cattle in at night. Adult cattle had increased odds of being seropositive for both C. burnetii and L. hardjo. Additionally, exposure to C. burnetii was associated with local ecological conditions and L. hardjo was negatively associated with cattle undertaking transhumance. This work highlights that exposure to these 3 important production diseases and occupational zoonoses are widespread in Cameroonian cattle. Further work is required to understand transmission dynamics between humans and livestock to inform implementation of effective control measures.
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http://dx.doi.org/10.1111/zph.12865DOI Listing
June 2021

The Impact of Virtual Fractional Flow Reserve and Virtual Coronary Intervention Upon Treatment Decisions in the Cardiac Catheter Laboratory.

Can J Cardiol 2021 Jun 11. Epub 2021 Jun 11.

Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.; Department of Cardiology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.; Insigneo Institute for In-silico medicine, Sheffield, UK.

Background: Using fractional flow reserve (FFR) to guide percutaneous coronary intervention for patients with coronary artery disease (CAD) improves clinical decision making but remains under-used. Virtual FFR (vFFR, computed from angiographic images) permits physiological assessment without a pressure wire and can be extended to virtual coronary intervention (VCI) facilitating treatment planning. This study investigated the effect of adding vFFR and VCI to angiography in patient assessment and management.

Methods: Two cardiologists independently reviewed clinical data and angiograms of 50 patients undergoing invasive management of coronary syndromes, and their management plans were recorded. The vFFRs were computed and disclosed, and the cardiologists submitted revised plans. Then, using VCI, the physiological results of various interventional strategies were shown, and further revision was invited.

Results: Disclosure of vFFR led to a change in strategy in 27%. VCI led to a change in stent size in 48%. Disclosure of vFFR and VCI resulted in an increase in operator confidence in their decision. Twelve cases were reviewed by six additional cardiologists. There was limited agreement in the management plans between cardiologists based upon either angiography (kappa=0.31) or vFFR (kappa=0.39).

Conclusions: vFFR has the potential to alter decision making, and VCI can guide stent sizing. However, variability in management strategy remains considerable between operators, even when presented with the same anatomical and physiological data.
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http://dx.doi.org/10.1016/j.cjca.2021.06.004DOI Listing
June 2021

A meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex.

Nat Commun 2021 06 10;12(1):3517. Epub 2021 Jun 10.

University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK.

Epigenome-wide association studies of Alzheimer's disease have highlighted neuropathology-associated DNA methylation differences, although existing studies have been limited in sample size and utilized different brain regions. Here, we combine data from six DNA methylomic studies of Alzheimer's disease (N = 1453 unique individuals) to identify differential methylation associated with Braak stage in different brain regions and across cortex. We identify 236 CpGs in the prefrontal cortex, 95 CpGs in the temporal gyrus and ten CpGs in the entorhinal cortex at Bonferroni significance, with none in the cerebellum. Our cross-cortex meta-analysis (N = 1408 donors) identifies 220 CpGs associated with neuropathology, annotated to 121 genes, of which 84 genes have not been previously reported at this significance threshold. We have replicated our findings using two further DNA methylomic datasets consisting of a further >600 unique donors. The meta-analysis summary statistics are available in our online data resource ( www.epigenomicslab.com/ad-meta-analysis/ ).
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http://dx.doi.org/10.1038/s41467-021-23243-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192929PMC
June 2021