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  • Oxford University Press (OUP)  (12)
  • 2020-2024  (12)
  • 1
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 71, No. 7 ( 2020-10-23), p. e115-e124
    Abstract: This study investigated adherence and associated factors among people with recent injection drug use (IDU) or current opioid agonist therapy (OAT) and compared once-daily to twice-daily hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy. Methods SIMPLIFY and D3FEAT are international, multicenter studies that recruited participants with recent IDU (previous 6 months; SIMPLIFY, D3FEAT) or current OAT (D3FEAT) between March 2016 and February 2017 in 8 countries. Participants received sofosbuvir/velpatasvir (once daily; SIMPLIFY) or paritaprevir/ritonavir/ombitasvir, dasabuvir (twice daily) ± ribavirin (D3FEAT) for 12 weeks administered in electronic blister packs. We evaluated overall adherence (proportion of prescribed doses taken) and nonadherence ( & lt;90% adherent) between dosing patterns. Results Of 190 participants, 184 (97%) completed treatment. Median adherence was 92%, with higher adherence among those receiving once-daily vs twice-daily therapy (94% vs 87%, P = .005). Overall, 40% of participants (n = 76) were nonadherent ( & lt;90% adherent). Recent stimulant injecting (odds ratio [OR], 2.48 [95% confidence interval {CI}, 1.28–4.82] ), unstable housing (OR, 2.18 [95% CI, 1.01–4.70]), and twice-daily dosing (OR, 2.81 [95% CI, 1.47–5.36] ) were associated with nonadherence. Adherence decreased during therapy. Sustained virologic response was high in nonadherent (89%) and adherent populations (95%, P = .174), with no difference in SVR between those who did and did not miss 7 consecutive doses (92% vs 93%, P = .897). Conclusions This study demonstrated high adherence to once- and twice-daily DAA therapy among people with recent IDU or currently receiving OAT. Nonadherence described did not impact treatment outcomes, suggesting forgiveness to nonadherence.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 2
    In: Clinical Infectious Diseases, Oxford University Press (OUP), ( 2023-08-08)
    Abstract: Scarce data are available comparing infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This study aimed to compare the clinical presentation, microbiological profile, management, and outcomes of IE after SAVR versus TAVR. Methods Data were collected from the “Infectious Endocarditis after TAVR International” (enrollment from 2005 to 2020) and the “International Collaboration on Endocarditis” (enrollment from 2000 to 2012) registries. Only patients with an IE affecting the aortic valve prosthesis were included. A 1:1 paired matching approach was used to compare patients with TAVR and SAVR. Results A total of 1688 patients were included. Of them, 602 (35.7%) had a surgical bioprosthesis (SB), 666 (39.5%) a mechanical prosthesis, 70 (4.2%) a homograft, and 350 (20.7%) a transcatheter heart valve. In the SAVR versus TAVR matched population, the rate of new moderate or severe aortic regurgitation was higher in the SB group (43.4% vs 13.5%; P & lt; .001), and fewer vegetations were diagnosed in the SB group (62.5% vs 82%; P & lt; .001). Patients with an SB had a higher rate of perivalvular extension (47.9% vs 27%; P & lt; .001) and Staphylococcus aureus was less common in this group (13.4% vs 22%; P = .033). Despite a higher rate of surgery in patients with SB (44.4% vs 27.3%; P & lt; .001), 1-year mortality was similar (SB: 46.5%; TAVR: 44.8%; log-rank P = .697). Conclusions Clinical presentation, type of causative microorganism, and treatment differed between patients with an IE located on SB compared with TAVR. Despite these differences, both groups exhibited high and similar mortality at 1-year follow-up.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2002229-3
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  • 3
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 17, No. 1 ( 2023-01-26), p. 37-48
    Abstract: There are concerns regarding the potential impact of the COVID-19 outbreak on patients with inflammatory bowel disease [IBD]. We report on the impact of the COVID-19 outbreak in a European prospective cohort study of patients with IBD Patients and Methods We prospectively collected data from 5457 patients with IBD nested in the ongoing I-CARE project and still followed up in April 2020, with monthly online monitoring of clinical activity, treatment, imaging and endoscopy. Investigators were also contacted to report incidental cases. Results In total, 233 [4.3%] reported COVID-19 and 12 [0.2%] severe COVID-19, with no COVID-19 deaths. The risk of COVID-19 in patients with IBD was not increased compared to the general population (standardized incidence ratio [SIR]: 1.18, 95% confidence interval [CI] [1.03–1.34], p = 0.009), as well as the risk of severe COVID-19 (SIR: 0.69, 95% CI [0.35–1.20] , p = 0.93). We did not observe any negative impact of the different IBD-related medication on the risk of either COVID-19 or severe COVID-19. In 2020, the COVID-19 outbreak resulted in a drastic decrease in endoscopic and imaging procedures from March to May 2020 compared to 2018 and 2019. No impacts on clinical IBD disease activity as well as ongoing treatment were noted. Conclusion No increases in either COVID-19 or severe COVID-19 incidences were observed in patients with IBD. There was no impact of COVID-19 on IBD-related medication and clinical activity. Access to endoscopy and imaging was restricted during the first months of the first COVID-19 outbreak.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2389631-0
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  • 4
    In: NAR Cancer, Oxford University Press (OUP), Vol. 4, No. 2 ( 2022-04-08)
    Abstract: Sequencing of cell-free DNA (cfDNA) in cancer patients’ plasma offers a minimally-invasive solution to detect tumor cell genomic alterations to aid real-time clinical decision-making. The reliability of copy number detection decreases at lower cfDNA tumor fractions, limiting utility at earlier stages of the disease. To test a novel strategy for detection of allelic imbalance, we developed a prostate cancer bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency SNPs and tailored analytical solutions to enable allele-informed evaluation. First, we assessed it on plasma samples from 50 advanced prostate cancer patients. We then confirmed improved detection of genomic alterations in samples with & lt;10% tumor fractions when compared against an independent assay. Finally, we applied PCF_SELECT to serial plasma samples intensively collected from three patients previously characterized as harboring alterations involving DNA repair genes and consequently offered PARP inhibition. We identified more extensive pan-genome allelic imbalance than previously recognized in prostate cancer. We confirmed high sensitivity detection of BRCA2 allelic imbalance with decreasing tumor fractions resultant from treatment and identified complex ATM genomic states that may be incongruent with protein losses. Overall, we present a framework for sensitive detection of allele-specific copy number changes in cfDNA.
    Type of Medium: Online Resource
    ISSN: 2632-8674
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 3025038-9
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  • 5
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 48, No. 4 ( 2020-02-28), p. 2173-2188
    Abstract: The XPA protein functions together with the single-stranded DNA (ssDNA) binding protein RPA as the central scaffold to ensure proper positioning of repair factors in multi-protein nucleotide excision repair (NER) machinery. We previously determined the structure of a short motif in the disordered XPA N-terminus bound to the RPA32C domain. However, a second contact between the XPA DNA-binding domain (XPA DBD) and the RPA70AB tandem ssDNA-binding domains, which is likely to influence the orientation of XPA and RPA on the damaged DNA substrate, remains poorly characterized. NMR was used to map the binding interfaces of XPA DBD and RPA70AB. Combining NMR and X-ray scattering data with comprehensive docking and refinement revealed how XPA DBD and RPA70AB orient on model NER DNA substrates. The structural model enabled design of XPA mutations that inhibit the interaction with RPA70AB. These mutations decreased activity in cell-based NER assays, demonstrating the functional importance of XPA DBD–RPA70AB interaction. Our results inform ongoing controversy about where XPA is bound within the NER bubble, provide structural insights into the molecular basis for malfunction of disease-associated XPA missense mutations, and contribute to understanding of the structure and mechanical action of the NER machinery.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 6
    In: European Heart Journal - Cardiovascular Imaging, Oxford University Press (OUP), Vol. 22, No. 5 ( 2021-04-28), p. 518-527
    Abstract: Non-invasive assessment and risk stratification of coronary artery disease in patients with large body habitus is challenging. We aim to examine whether body mass index (BMI) modifies the prognostic value and diagnostic utility of stress cardiac magnetic resonance imaging (CMR) in a multicentre registry. Methods and results The SPINS Registry enrolled consecutive intermediate-risk patients who presented with a clinical indication for stress CMR in the USA between 2008 and 2013. Baseline demographic data including BMI, CMR indices, and ratings of study quality were collected. Primary outcome was defined by a composite of cardiovascular death and non-fatal myocardial infarction. Of the 2345 patients with available BMI included in the SPINS cohort, 1177 (50%) met criteria for obesity (BMI ≥ 30) with 531 (23%) at or above Class 2 obesity (BMI ≥ 35). In all BMI categories, & gt;95% of studies were of diagnostic quality for cine, perfusion, and late gadolinium enhancement (LGE) sequences. At a median follow-up of 5.4 years, those without ischaemia and LGE experienced a low annual rate of hard events ( & lt;1%), across all BMI strata. In patients with obesity, both ischaemia [hazard ratio (HR): 2.14; 95% confidence interval (CI): 1.30–3.50; P = 0.003] and LGE (HR: 3.09; 95% CI: 1.83–5.22; P  & lt; 0.001) maintained strong adjusted association with the primary outcome in a multivariable Cox regression model. Downstream referral rates to coronary angiography, revascularization, and cost of care spent on ischaemia testing did not significantly differ within the BMI categories. Conclusion In this large multicentre registry, elevated BMI did not negatively impact the diagnostic quality and the effectiveness of risk stratification of patients referred for stress CMR.
    Type of Medium: Online Resource
    ISSN: 2047-2404 , 2047-2412
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2042482-6
    detail.hit.zdb_id: 2647943-6
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  • 7
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. 1 ( 2022-01-01)
    Abstract: The relationship between postvaccination symptoms and strength of antibody responses is unclear. The goal of this study was to determine whether adverse effects caused by vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine-induced antibody levels. Methods We conducted a single-center, observational cohort study consisting of generally healthy adult participants that were not severely immunocompromised, had no history of coronavirus disease 2019, and were seronegative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein before vaccination. Severity of vaccine-associated symptoms was obtained through participant-completed questionnaires. Testing for immunoglobulin G antibodies against SARS-CoV-2 spike protein and receptor-binding domain was conducted using microsphere-based multiplex immunoassays performed on serum samples collected at monthly visits. Neutralizing antibody titers were determined by microneutralization assays. Results Two hundred six participants were evaluated (69.4% female, median age 41.5 years old). We found no correlation between vaccine-associated symptom severity scores and vaccine-induced antibody titers 1 month after vaccination. We also observed that (1) postvaccination symptoms were inversely correlated with age and weight and more common in women, (2) systemic symptoms were more frequent after the second vaccination, (3) high symptom scores after first vaccination were predictive of high symptom scores after second vaccination, and (4) older age was associated with lower titers. Conclusions Lack of postvaccination symptoms after receipt of the BNT162b2 vaccine does not equate to lack of vaccine-induced antibodies 1 month after vaccination.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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  • 8
    In: Virus Evolution, Oxford University Press (OUP), Vol. 7, No. 2 ( 2021-12-16)
    Abstract: Characterisation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic diversity through space and time can reveal trends in virus importation and domestic circulation and permit the exploration of questions regarding the early transmission dynamics. Here, we present a detailed description of SARS-CoV-2 genomic epidemiology in Ecuador, one of the hardest hit countries during the early stages of the coronavirus-19 pandemic. We generated and analysed 160 whole genome sequences sampled from all provinces of Ecuador in 2020. Molecular clock and phylogeographic analysis of these sequences in the context of global SARS-CoV-2 diversity enable us to identify and characterise individual transmission lineages within Ecuador, explore their spatiotemporal distributions, and consider their introduction and domestic circulation. Our results reveal a pattern of multiple international importations across the country, with apparent differences between key provinces. Transmission lineages were mostly introduced before the implementation of non-pharmaceutical interventions, with differential degrees of persistence and national dissemination.
    Type of Medium: Online Resource
    ISSN: 2057-1577
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2818949-8
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  • 9
    In: European Heart Journal, Oxford University Press (OUP), Vol. 44, No. 13 ( 2023-04-01), p. 1157-1166
    Abstract: Chronic kidney disease (CKD) increases risk of cardiovascular disease (CVD). Less is known about how CVD associates with future risk of kidney failure with replacement therapy (KFRT). Methods and results The study included 25 903 761 individuals from the CKD Prognosis Consortium with known baseline estimated glomerular filtration rate (eGFR) and evaluated the impact of prevalent and incident coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) events as time-varying exposures on KFRT outcomes. Mean age was 53 (standard deviation 17) years and mean eGFR was 89 mL/min/1.73 m2, 15% had diabetes and 8.4% had urinary albumin-to-creatinine ratio (ACR) available (median 13 mg/g); 9.5% had prevalent CHD, 3.2% prior stroke, 3.3% HF, and 4.4% prior AF. During follow-up, there were 269 142 CHD, 311 021 stroke, 712 556 HF, and 605 596 AF incident events and 101 044 (0.4%) patients experienced KFRT. Both prevalent and incident CVD were associated with subsequent KFRT with adjusted hazard ratios (HRs) of 3.1 [95% confidence interval (CI): 2.9–3.3], 2.0 (1.9–2.1), 4.5 (4.2–4.9), 2.8 (2.7–3.1) after incident CHD, stroke, HF and AF, respectively. HRs were highest in first 3 months post-CVD incidence declining to baseline after 3 years. Incident HF hospitalizations showed the strongest association with KFRT [HR 46 (95% CI: 43–50) within 3 months] after adjustment for other CVD subtype incidence. Conclusion Incident CVD events strongly and independently associate with future KFRT risk, most notably after HF, then CHD, stroke, and AF. Optimal strategies for addressing the dramatic risk of KFRT following CVD events are needed.
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2001908-7
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  • 10
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: We sought to determine the frequency of asymptomatic SARS-CoV-2 infections, the BNT162b2 mRNA COVID 19 vaccine-related symptoms, and the correlates of immunity in post-vaccination breakthrough infections in a prospective cohort of healthcare workers. Methods We have been conducting a single-center, observational cohort study of healthcare workers. 271 participants were enrolled since August 25, 2020. Testing for SARS-CoV-2 spike (S)-specific IgG antibodies is conducted using a microsphere-based multiplex immunoassay interpolated against an internal standard curve for binding antibody (bAb) units (BAU) and has been performed on serum samples collected at monthly visits between September 2020 to August of 2021, and quarterly since then. Neutralizing antibody titers against wild-type (WT) virus are determined by microneutralization assays and against Delta and Omicron variants by lentiviral pseudovirus neutralization assays. For the first 6 months, participants completed a symptoms questionnaire every day they had any symptoms. Results 12 participants were diagnosed with SARS-CoV-2, with at least mild symptoms. Of 206 participants evaluated for adverse effects after 1st and 2nd vaccine doses, no relationship was observed between vaccine-associated symptom scores and antibody titers 1 month after the 2nd dose. Longitudinal studies demonstrate that anti-S IgG bAbs decrease from a geometric mean (GM) of 1929 BAU/mL at 1 month post-vaccination to a GM of 442 BAU/mL at 6 months post-vaccination (P & lt; 0.001, n=187), and that boosting increases S-specific IgG BAU. While only 5 of 39 participants had detectable anti-Omicron neutralizing activity 1 month after 2 vaccinations, booster vaccination resulted in detectable neutralizing activity for all participants. Conclusion Asymptomatic infection is likely rare, that there is no relationship between vaccine-associated symptom severity and antibody titers 1 month after the 2nd vaccination, and that booster results in better protection against the Omicron variant. Ongoing studies are evaluating serological and cellular immune responses immediately prior to 38 breakthrough infections in an attempt to identify immune correlates of protection and will be reported at the conference. Disclosures John H. Powers, III, MD, Arrevus: Advisor/Consultant|Eicos: Advisor/Consultant|Evofem: Advisor/Consultant|Eyecheck: Advisor/Consultant|Gilead: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|OPKO: Advisor/Consultant|Resolve: Advisor/Consultant|Romark: Advisor/Consultant|SpineBioPharma: Advisor/Consultant|UTIlity: Advisor/Consultant|Vir: Advisor/Consultant David Tribble, MD, DrPH, Astra Zeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Simon Pollett, MBBS, Astra Zeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Timothy Burgess, MD, MPH, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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