To describe the gender trends in ophthalmology primary practice areas using the American Board of Ophthalmology (ABO) diplomates.
A trend study plus a cross-sectional study of the ABO's database.
The ...de-identified records of all (N = 12,844) ABO-certified ophthalmologists between 1992 and 2020 were obtained. The year of certification, gender, and self-reported primary practice for each ophthalmologist was recorded. Subspecialty was defined as the self-reported primary practice emphasis. Practice trends of the entire population and the subpopulation of subspecialists were explored based on gender and were then visualized using tables and graphs and analyzed using the χ2 or Fisher exact test.
A total of 12,844 board-certified ophthalmologists were included. Nearly half (47%) reported a subspecialty as their primary practice area (n = 6042), of whom the majority were male (65%, n = 3940). In the first decade, men outnumbered women reporting subspecialty practices by more than 2:1. Over time, the number of women subspecialists increased whereas the number of men remained stable, such that by 2020 women comprised almost half of new ABO diplomates reporting subspecialty practice. When all subspecialists were compared within gender, there was not a significant difference (P = .15) between the percentage of male (46%) and female (48%) ophthalmologist reporting a subspecialty practice. However, a significantly greater proportion of women than men reported primary practice in pediatrics (20.1% vs 7.9%, P < .001) and glaucoma (21.8% vs 16.0%, P < .0001). Alternatively, a significantly greater proportion of men reported primary practice in vitreoretinal surgery (47.2% vs 22.0%, P < .0001). There was no significant difference between the proportion of men and women reporting cornea (P = .15) or oculoplastics (P = .31).
The number of women in ophthalmology subspecialty practice has increased steadily over the past 30 years. Men and women subspecialize at the same rate, but significant differences exist between the types of ophthalmology practiced by each gender.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Aims
To consolidate evidence to determine (i) the association between cardiovascular risk factors and health outcomes with coronavirus 2019 (COVID-19); and (ii) the impact of COVID-19 on ...cardiovascular health.
Methods and results
An umbrella review of systematic reviews was conducted. Fourteen medical databases and pre-print servers were searched from 1 January 2020 to 5 November 2020. The review focused on reviews rated as moderate or high-quality using the AMSTAR 2 tool. Eighty-four reviews were identified; 31 reviews were assessed as moderate quality and one was high-quality. The following risk factors were associated with higher mortality and severe COVID-19: renal disease odds ratio (OR) (95% confidence interval) for mortality 3.07 (2.43–3.88), diabetes mellitus OR 2.09 (1.80–2.42), hypertension OR 2.50 (2.02–3.11), smoking history risk ratio (RR) 1.26 (1.20–1.32), cerebrovascular disease RR 2.75 (1.54–4.89), and cardiovascular disease OR 2.65 (1.86–3.78). Liver disease was associated with higher odds of mortality OR 2.81 (1.31–6.01), but not severe COVID-19. Current smoking was associated with a higher risk of severe COVID-19 RR 1.80 (1.14–2.85), but not mortality. Obesity associated with higher odds of mortality OR 2.18 (1.10–4.34), but there was an absence of evidence for severe COVID-19. In patients hospitalized with COVID-19, the following incident cardiovascular complications were identified: acute heart failure (2%), myocardial infarction (4%), deep vein thrombosis (7%), myocardial injury (10%), angina (10%), arrhythmias (18%), pulmonary embolism (19%), and venous thromboembolism (25%).
Conclusion
Many of the risk factors identified as associated with adverse outcomes with COVID-19 are potentially modifiable. Primary and secondary prevention strategies that target cardiovascular risk factors may improve outcomes for people following COVID-19.
It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes ...30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis.
A study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis.
2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03-1.98; Log-Rank test p = 0.029).
In COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting ...multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding domain (RBD) of the spike protein. Administered in combinations, these mAbs provided low-dose protection against SARS-CoV-2 infection in the K18-human angiotensin-converting enzyme 2 mouse model, using both neutralization and Fc effector antibody functions. The RBD mAb WRAIR-2125, which targets residue F486 through a unique heavy-chain and light-chain pairing, demonstrated potent neutralizing activity against all major SARS-CoV-2 variants of concern. In combination with NTD and other RBD mAbs, WRAIR-2125 also prevented viral escape. These data demonstrate that NTD/RBD mAb combinations confer potent protection, likely leveraging complementary mechanisms of viral inactivation and clearance.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Our understanding of the formation and evolution of the corona and the heliosphere is linked to our capability of properly interpret the data from remote sensing and
in-situ
observations. In this ...respect, being able to correctly connect
in-situ
observations with their source regions on the Sun is the key for solving this problem. In this work we aim at testing a diagnostics method for this connectivity.
This paper makes use of a coronal jet observed on 2010 August 2nd in active region 11092 as a test for our connectivity method. This combines solar EUV and
in-situ
data together with magnetic field extrapolation, large scale MHD modeling and FIP (First Ionization Potential) bias modeling to provide a global picture from the source region of the jet to its possible signatures at 1 AU.
Our data analysis reveals the presence of outflow areas near the jet which are within open magnetic flux regions and which present FIP bias consistent with the FIP model results. In our picture, one of these open areas is the candidate jet source. Using a back-mapping technique we identified the arrival time of this solar plasma at the ACE spacecraft. The
in-situ
data show signatures of changes in the plasma and magnetic field parameters, with FIP bias consistent with the possible passage of the jet material.
Our results highlight the importance of remote sensing and
in-situ
coordinated observations as a key to solve the connectivity problem. We discuss our results in view of the recent Solar Orbiter launch which is currently providing such unique data.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The interaction of RB with chromatin is key to understanding its molecular functions. Here, for first time, we identify the full spectrum of chromatin-bound RB. Rather than exclusively binding ...promoters, as is often described, RB targets three fundamentally different types of loci (promoters, enhancers, and insulators), which are largely distinguishable by the mutually exclusive presence of E2F1, c-Jun, and CTCF. While E2F/DP facilitates RB association with promoters, AP-1 recruits RB to enhancers. Although phosphorylation in CDK sites is often portrayed as releasing RB from chromatin, we show that the cell cycle redistributes RB so that it enriches at promoters in G1 and at non-promoter sites in cycling cells. RB-bound promoters include the classic E2F-targets and are similar between lineages, but RB-bound enhancers associate with different categories of genes and vary between cell types. Thus, RB has a well-preserved role controlling E2F in G1, and it targets cell-type-specific enhancers and CTCF sites when cells enter S-phase.
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•RB associates with E2F-promoters, AP-1 enhancers, and CTCF-insulators•RB-bound promoters and enhancers target different sets of genes•Cell-cycle progression redistributes chromatin-bound RB toward enhancers•RB-bound promoters are conserved while enhancers are cell-type specific
Sanidas et al. show that, rather than exclusively targeting E2F-promoters, RB associates with specific groups of promoters, enhancers, and insulators to target different sets of genes. Cell-cycle progression redistributes RB toward cell-type-specific enhancers. PanChIP software confirms that RB associates with distinct transcription factors at different types of loci.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Atrial fibrillation (AF) associates with higher Alzheimer's disease (AD) and vascular dementia risks but the clinical implications have been scarcely investigated. We examined the ...association between AD or vascular dementia and adverse outcomes in AF patients.
Methods
Cohort study between January 2000 and 2017. AF patients were divided into two groups according to vascular dementia or AD, and balanced using propensity score matching (PSM). During 4‐years of follow‐up, incident intracranial hemorrhages (ICH), the composite of ischemic stroke/transient ischemic attack (TIA), hospitalizations, and all‐cause deaths, were recorded.
Results
Two thousand three hundred seventy‐seven AF patients with dementia (1225 with vascular dementia, and 1152 with AD) were identified. Following a PSM, 615 patients were included in each cohort (i.e., 1:1) and all variables were well‐matched. After PSM, 22 (3.6%) patients with vascular dementia and 55 (8.1%) patients with AD had incident ICH during follow‐up (hazard ratio HR: 2.22, 95% confidence interval CI: 1.33−3.70, log‐rank p = 0.002). Overall, 237 (38.5%) patients with vascular dementia and 193 (31.4%) patients with AD, developed an ischemic stroke/TIA. The risk of ischemic stroke/TIA was 1.32‐fold higher in vascular dementia (HR: 1.32, 95% CI: 1.09−1.59, log‐rank p = 0.003). The risk of rehospitalization (HR: 1.14, 95% CI: 1.01−1.31), and mortality (HR: 1.25, 95% CI: 1.01−1.58) were also higher among AF patients with vascular dementia compared to AD.
Conclusions
The two forms of dementia in AF patients are associated with different prognosis, with AD being associated with a higher risk of ICH, and vascular dementia with a higher risk of stroke/TIA, hospitalization, and mortality.
AF means atrial fibrillation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
It is unclear if direct-acting oral anticoagulants (DOACs) use before hospitalization due to COVID-19 diagnosis would potentially impact the severity and clinical outcomes thereafter. We compared ...30-day hospitalization/re-hospitalization and clinical outcomes between patients on chronic DOAC therapy and patients not on oral anticoagulation (OAC) therapy at time of COVID-19 diagnosis.
We used data from TriNetX, a global federated health research network. Patients aged ≥18 years who were treated with DOACs at time of COVID-19 diagnosis between 20 January 2020 and 28 February 2021 were included, and matched with patients not on OAC therapy from the same period. All patients were followed-up at 30-days after COVID-19 diagnosis. The primary outcomes were all-cause mortality, hospitalization/re-hospitalization, venous thromboembolism (VTE) and intracranial hemorrhage (ICH).
738,423 patients were included. After propensity score matching (PSM), 26,006 patients remained in the study (13,003 on DOACs; 13,003 not on OAC). DOAC-treated patients (mean age 67.1 ± 15.4 years, 52.2% male) had higher relative risks (RRs) and lower 30-days event-free survival as compared to patients not on OAC for all-cause mortality (RR 1.27, 95% CI 1.12–1.44; Log-Rank test p = 0.010), hospitalization/re-hospitalization (RR 1.72, 95% CI 1.64–1.82; Log-Rank test p < 0.001) and VTE (RR 4.51, 95% CI 3.91–5.82; Log-Rank test p < 0.001), but not for ICH (RR 0.90, 95% CI 0.54–1.51; Log-Rank test p = 0.513).
In COVID-19 patients, previous DOAC therapy at time of diagnosis was not associated with improved clinical outcomes or lower hospitalization/re-hospitalization rate compared to patients not taking OAC therapy.
•It is unclear if chronic DOAC therapy has some impact on COVID-19 prognosis.•Prior DOAC users before COVID-19 were matched with patients non on anticoagulants.•All-cause mortality, hospitalization and VTE were higher in DOAC-treated patients.•Chronic DOAC therapy at time of COVID-19 diagnosis did not improve clinical outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Several anthropometric measurements are used to assess cardiovascular risk and progress during clinical treatment. Most commonly used anthropometric measurements include total body weight and body ...mass index (BMI), with several other simple anthropometric measures typically underused in clinical practice. Herein, we review the evidence on the relationship between different anthropometric measurements and cardiovascular risk in patients with and without cardiovascular disease (CVD).BackgroundSeveral anthropometric measurements are used to assess cardiovascular risk and progress during clinical treatment. Most commonly used anthropometric measurements include total body weight and body mass index (BMI), with several other simple anthropometric measures typically underused in clinical practice. Herein, we review the evidence on the relationship between different anthropometric measurements and cardiovascular risk in patients with and without cardiovascular disease (CVD).Data for this review were identified by searches in PubMed, the Web of Science, Google Scholar, and references from relevant articles by using appropriate and related terms. The last search was performed on June 22, 2022. Articles published in English and Spanish were reviewed and included, if appropriate. We included studies detailing the relationship between skinfolds thickness, waist-to-hip ratio (WHR) and Conicity index with cardiovascular risk in adults with/without CVD.MethodsData for this review were identified by searches in PubMed, the Web of Science, Google Scholar, and references from relevant articles by using appropriate and related terms. The last search was performed on June 22, 2022. Articles published in English and Spanish were reviewed and included, if appropriate. We included studies detailing the relationship between skinfolds thickness, waist-to-hip ratio (WHR) and Conicity index with cardiovascular risk in adults with/without CVD.In patients from the general population, elevated subscapular and triceps skinfolds showed a positive relationship with the development of hypertension, diabetes mellitus, hypercholesterolemia, cardiovascular mortality, and all-cause mortality. A higher subscapular skinfold was also associated with increased risk of coronary artery disease and stroke. A higher WHR, as well as other less common anthropometric measurements such as the Conicity index, was associated with an increased risk of myocardial infarction, incident CVD, major adverse cardiovascular events, and mortality in both patients with and without previous CVD.ResultsIn patients from the general population, elevated subscapular and triceps skinfolds showed a positive relationship with the development of hypertension, diabetes mellitus, hypercholesterolemia, cardiovascular mortality, and all-cause mortality. A higher subscapular skinfold was also associated with increased risk of coronary artery disease and stroke. A higher WHR, as well as other less common anthropometric measurements such as the Conicity index, was associated with an increased risk of myocardial infarction, incident CVD, major adverse cardiovascular events, and mortality in both patients with and without previous CVD.Non-traditional anthropometric measurements including skinfolds and WHR seem to improve the prediction of cardiovascular risk in the general population, and recurrent events in patients with previous CVD. Use of additional anthropometric techniques according to an objective and standardized method, may aid cardiovascular risk stratification in patients from the general population and the evaluation of therapeutic interventions for patients with CVD.ConclusionsNon-traditional anthropometric measurements including skinfolds and WHR seem to improve the prediction of cardiovascular risk in the general population, and recurrent events in patients with previous CVD. Use of additional anthropometric techniques according to an objective and standardized method, may aid cardiovascular risk stratification in patients from the general population and the evaluation of therapeutic interventions for patients with CVD.
The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer ...broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.
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