A qualitative study of recruitment strategies: Perspectives from older adults living with diabetes.

AIMS: There is a need to increase representation of diverse older adults in health-related qualitative research to better understand and improve chronic disease care over the lifespan. Our aim was to elicit perspectives about research recruitment among a diverse sample of older adults with diabetes participating in a qualitative study. METHODS: Older adults with diabetes and caregivers were recruited through purposive sampling for semi-structured interviews focused on diabetes self care. Six questions were used to explore recruitment strategies and recommendations for engaging older adults in research. We analysed interview transcripts using descriptive analysis to identify themes related to engaging older adults in research studies. RESULTS: Seventeen older adults with diabetes and three caregivers participated (N = 20). Descriptive analysis revealed four themes: (1) Recruitment of older adults requires varied strategies to overcome barriers to engagement and participation; (2) Building and leveraging personal relationships is central to successful recruitment; (3) Transparent communication about the research process and value of the study is needed to inform and motivate older adults to participate; and (4) Research offers a connection to a broader community: sharing, learning and helping others. CONCLUSIONS: We found four main themes related to the complexity of recruiting older adults for research studies. These insights may inform more effective, equitable and inclusive recruitment efforts targeted at older adults in the future.

Use of systems thinking and adapted group model building methods to understand patterns of technology use among older adults with type 1 diabetes: a preliminary process evaluation.

BACKGROUND: A growing number of older adults (ages 65+) live with Type 1 diabetes. Simultaneously, technologies such as continuous glucose monitoring (CGM) have become standard of care. There is thus a need to understand better the complex dynamics that promote use of CGM (and other care innovations) over time in this age group. Our aim was to adapt methods from systems thinking, specifically a participatory approach to system dynamics modeling called group model building (GMB), to model the complex experiences that may underlie different trajectories of CGM use among this population. Herein, we report on the feasibility, strengths, and limitations of this methodology. METHODS: We conducted a series of GMB workshops and validation interviews to collect data in the form of questionnaires, diagrams, and recordings of group discussion. Data were integrated into a conceptual diagram of the "system" of factors associated with uptake and use of CGM over time. We evaluate the feasibility of each aspect of the study, including the teaching of systems thinking to older adult participants. We collected participant feedback on positive aspects of their experiences and areas for improvement. RESULTS: We completed nine GMB workshops with older adults and their caregivers (N = 33). Each three-hour in-person workshop comprised: (1) questionnaires; (2) the GMB session, including both didactic components and structured activities; and (3) a brief focus group discussion. Within the GMB session, individual drawing activities proved to be the most challenging for participants, while group activities and discussion of relevant dynamics over time for illustrative (i.e., realistic but not real) patients yielded rich engagement and sufficient information for system diagramming. Study participants liked the opportunity to share experiences with peers, learning and enhancing their knowledge, peer support, age-specific discussions, the workshop pace and structure, and the systems thinking framework. Participants gave mixed feedback on the workshop duration. CONCLUSIONS: The study demonstrates preliminary feasibility, acceptability, and the value of GMB for engaging older adults about key determinants of complex health behaviors over time. To our knowledge, few studies have extended participatory systems science methods to older adult stakeholders. Future studies may utilize this methodology to inform novel approaches for supporting health across the lifespan.

Receipt of Diabetes Specialty Care and Management Services by Older Adults With Diabetes in the U.S., 2015-2019: An Analysis of Medicare Fee-for-Service Claims.

OBJECTIVE: We characterized the receipt of diabetes specialty care and management services among older adults with diabetes. RESEARCH DESIGN AND METHODS: Using a 20% random sample of fee-for-service Medicare beneficiaries aged ≥65 years, we analyzed cohorts of type 1 diabetes (T1D) or type 2 diabetes (T2D) with history of severe hypoglycemia (HoH), and all other T2D annually from 2015 to 2019. Outcomes were receipt of office-based endocrinology care, diabetes education, outpatient diabetes health services, excluding those provided in primary care, and any of the aforementioned services. RESULTS: In the T1D cohort, receipt of endocrinology care and any service increased from 25.9% and 29.2% in 2015 to 32.7% and 37.4% in 2019, respectively. In the T2D with HoH cohort, receipt of endocrinology care and any service was 13.9% and 16.4% in 2015, with minimal increases. Age, race/ethnicity, residential setting, and income were associated with receiving care. CONCLUSIONS: These findings suggest that many older adults may not receive specialty diabetes care and underscore health disparities.

Ranolazine in chronic total occlusion percutaneous coronary intervention.

Ranolazine is an anti-anginal medication given to patients with chronic angina and persistent symptoms despite medical therapy. We examined 11 491 chronic total occlusion (CTO) percutaneous coronary interventions (PCI) that were performed at 41 US and non-US centers between 2012 and 2023 in the PROGRESS-CTO Registry. Patients on ranolazine at baseline had more comorbidities, more complex lesions, lower procedural and technical success (based on univariable but not multivariable analysis), and higher incidence of major adverse cardiac events (MACE) (on both univariable and multivariable analysis).

Validation of the BCIS CHIP Score in chronic total occlusion percutaneous coronary intervention.

BACKGROUND: The complex high-risk indicated percutaneous coronary intervention (CHIP) score is a tool developed using the British Cardiovascular Intervention Society (BCIS) database to define CHIP cases and predict in-hospital major adverse cardiac or cerebrovascular events (MACCE). AIM: To assess the validity of the CHIP score in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We evaluated the performance of the CHIP score on 8341 CTO PCIs from the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) performed at 44 centers between 2012 and 2023. RESULTS: In our cohort, 7.8% (n = 647) of patients had a CHIP score of 0, 50.2% (n = 4192) had a CHIP score of 1-2, 26.2% (n = 2187) had a CHIP score of 3-4, 11.7% (n = 972) had a CHIP score of 5-6, 3.3% (n = 276) had a CHIP score of 7-8, and 0.8% (n = 67) had a CHIP score of 9+. The incidence of MACCE for a CHIP score of 0 was 0.6%, reaching as high as 8.7% for a CHIP score of 9+, confirming that a higher CHIP score is associated with a higher risk of MACCE. The estimated increase in the risk of MACCE per one score unit increase was 100% (95% confidence interval [CI]: 65%-141%). The AUC of the CHIP score model for predicting MACCE in our cohort was 0.63 (95% CI: 0.58-0.67). There was a positive correlation between the CHIP score and the PROGRESS-CTO MACE score (Spearman's correlation: 0.37; 95% CI: 0.35-0.39; p < 0.001). CONCLUSIONS: The CHIP score has modest predictive capacity for MACCE in CTO PCI.

Predictors of successful primary antegrade wiring in chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Antegrade wiring is the most commonly used chronic total occlusion (CTO) crossing technique. METHODS: Using data from the PROGRESS CTO registry (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; Clinicaltrials.gov identifier: NCT02061436), we examined the clinical and angiographic characteristics and procedural outcomes of CTO percutaneous coronary interventions (PCIs) performed using a primary antegrade wiring strategy. RESULTS: Of the 13 563 CTO PCIs performed at 46 centers between 2012 and 2023, a primary antegrade wiring strategy was used in 11 332 (83.6%). Upon multivariable logistic regression analysis, proximal cap ambiguity (odds ratio [OR]: 0.52; 95% CI, 0.46-0.59), side branch at the proximal cap (OR: 0.85; 95% CI, 0.77-0.95), blunt/no stump (OR: 0.52; 95% CI: 0.47-0.59), increasing lesion length (OR [per 10 mm increase]: 0.79; 95% CI, 0.76-0.81), moderate to severe calcification (OR: 0.73; 95% CI, 0.66-0.81), moderate to severe proximal tortuosity (OR: 0.67; 95% CI, 0.59-0.75), bifurcation at the distal cap (OR: 0.66; 95% CI, 0.59-0.73), left anterior descending artery CTO (OR [vs right coronary artery]: 1.44; 95% CI, 1.28-1.62) and left circumflex CTO (OR [vs right coronary artery]: 1.22; 95% CI, 1.07-1.40), non-in-stent restenosis lesion (OR: 0.56; 95% CI, 0.49-0.65), and good distal landing zone (OR: 1.18; 95% CI, 1.06-1.32) were independently associated with primary antegrade wiring crossing success. CONCLUSIONS: The use of antegrade wiring as the initial strategy was high (83.6%) in our registry. We identified several parameters associated with primary antegrade wiring success.

Use of plaque modification microcatheters during percutaneous coronary interventions for chronic total occlusion: insights from the PROGRESS-CTO Registry.

Plaque modification microcatheters (PM) (Tornus [Asahi] and Turnpike Gold [Teleflex]) are devices that are mainly used to modify the cap or lesion and maintain good support in chronic total occlusion (CTO) percutaneous coronary artery intervention (PCI). We evaluated the frequency of use and outcomes of plaque modification microcatheters in an international multicenter registry. Plaque modification microcatheters were utilized in 242 cases (1.6%: Tornus in 51% and Turnpike Gold in 49%) with decreasing frequency over time (P-for-trend: 0.007 and 0.035, respectively). Technical and procedural success and the incidence of major cardiac adverse events were similar with Tornus and Turnpike Gold use. PM are infrequently utilized in CTO-PCI and are associated with high success and acceptable complication rates.

Geographic Variation and Environmental Predictors of Nontuberculous Mycobacteria in Laboratory Surveillance, Virginia, USA, 2021-20231.

Because epidemiologic and environmental risk factors for nontuberculous mycobacteria (NTM) have been reported only infrequently, little information exists about those factors. The state of Virginia, USA, requires certain ecologic features to be included in reports to the Virginia Department of Health, presenting a unique opportunity to study those variables. We analyzed laboratory reports of Mycobacterium avium complex (MAC) and M. abscessus infections in Virginia during 2021-2023. MAC/M. abscessus was isolated from 6.19/100,000 persons, and 2.37/100,000 persons had MAC/M. abscessus lung disease. M. abscessus accounted for 17.4% and MAC for 82.6% of cases. Saturated vapor pressure was associated with MAC/M. abscessus prevalence (prevalence ratio 1.414, 95% CI 1.011-1.980; p = 0.043). Self-supplied water use was a protective factor (incidence rate ratio 0.304, 95% CI 0.098-0.950; p = 0.041). Our findings suggest that a better understanding of geographic clustering and environmental water exposures could help develop future targeted prevention and control efforts.

Second Nationwide Tuberculosis Outbreak Caused by Bone Allografts Containing Live Cells - United States, 2023.

During July 7-11, 2023, CDC received reports of two patients in different states with a tuberculosis (TB) diagnosis following spinal surgical procedures that used bone allografts containing live cells from the same deceased donor. An outbreak associated with a similar product manufactured by the same tissue establishment (i.e., manufacturer) occurred in 2021. Because of concern that these cases represented a second outbreak, CDC and the Food and Drug Administration worked with the tissue establishment to determine that this product was obtained from a donor different from the one implicated in the 2021 outbreak and learned that the bone allograft product was distributed to 13 health care facilities in seven states. Notifications to all seven states occurred on July 12. As of December 20, 2023, five of 36 surgical bone allograft recipients received laboratory-confirmed TB disease diagnoses; two patients died of TB. Whole-genome sequencing demonstrated close genetic relatedness between positive Mycobacterium tuberculosis cultures from surgical recipients and unused product. Although the bone product had tested negative by nucleic acid amplification testing before distribution, M. tuberculosis culture of unused product was not performed until after the outbreak was recognized. The public health response prevented up to 53 additional surgical procedures using allografts from that donor; additional measures to protect patients from tissue-transmitted M. tuberculosis are urgently needed.

Supporting the 'lived expertise' of older adults with type 1 diabetes: An applied focus group analysis to characterize barriers, facilitators, and strategies for self-management in a growing and understudied population.

INTRODUCTION: There is a growing number of older adults (≥65 years) who live with type 1 diabetes. We qualitatively explored experiences and perspectives regarding type 1 diabetes self-management and treatment decisions among older adults, focusing on adopting care advances such as continuous glucose monitoring (CGM). METHODS: Among a clinic-based sample of older adults ≥65 years with type 1 diabetes, we conducted a series of literature and expert informed focus groups with structured discussion activities. Groups were transcribed followed by inductive coding, theme identification, and inference verification. Medical records and surveys added clinical information. RESULTS: Twenty nine older adults (age 73.4 ± 4.5 years; 86% CGM users) and four caregivers (age 73.3 ± 2.9 years) participated. Participants were 58% female and 82% non-Hispanic White. Analysis revealed themes related to attitudes, behaviours, and experiences, as well as interpersonal and contextual factors that shape self-management and outcomes. These factors and their interactions drive variability in diabetes outcomes and optimal treatment strategies between individuals as well as within individuals over time (i.e. with ageing). Participants proposed strategies to address these factors: regular, holistic needs assessments to match people with effective self-care approaches and adapt them over the lifespan; longitudinal support (e.g., education, tactical help, sharing and validating experiences); tailored education and skills training; and leveraging of caregivers, family, and peers as resources. CONCLUSIONS: Our study of what influences self-management decisions and technology adoption among older adults with type 1 diabetes underscores the importance of ongoing assessments to address dynamic age-specific needs, as well as individualized multi-faceted support that integrates peers and caregivers.

A conceptual model of the continuous glucose monitoring integration process for older adults with diabetes developed using participatory systems science methods.

AIMS: Continuous glucose monitoring (CGM) use remains low in older adults. We aimed to develop a conceptual model of CGM integration among older adults with type 1 and type 2 diabetes. METHODS: We previously engaged older adults with type 1 diabetes using participatory system science methods to develop a model of the system of factors that shape CGM integration. To validate and expand the model, we conducted semi-structured interviews with 17 older adults with type 1 and type 2 diabetes and 3 caregivers. Vignettes representing each integration phase were used to elicit outcomes and strategies to support CGM use. Data were analyzed using team-based causal loop diagraming. RESULTS: The model includes six phases spanning (1) CGM uptake; (2) device set-up; acquisition of (3) belief in oneself to use CGM effectively; (4) belief that CGM is preferable to blood glucose monitoring; (5) belief in future CGM benefits CGM; and (6) development of a sense of reliance on CGM. Causal loop diagrams visualize factors and feedback loops shaping outcomes at each phase. Participants proposed support strategies spanning clinical, educational, and behavioral interventions. CONCLUSIONS: The model underscores the complex transition of learning new technology and provides opportunities for tailored support for older adults.

Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

A Cost Analysis of Rethink the Strip: De-implementing a Low-value Practice in Primary Care.

BACKGROUND: Routine self-monitoring of blood glucose is a low-value practice that provides limited benefit for patients with non-insulin-treated type 2 diabetes mellitus. OBJECTIVES: We estimated the costs of Rethink the Strip (RTS), a multistrategy approach to the de-implementation of self-monitoring of blood glucose in primary care. RESEARCH DESIGN: RTS was conducted among 20 primary care clinics in North Carolina. We estimated the non-site-based and site-based costs of the 5 RTS strategies (practice facilitation, audit and feedback, provider champions, educational meetings, and educational materials) from the analytic perspective of an integrated health care system for 12 and 27-month time horizons. Material costs were tracked through project records, and personnel costs were assessed using activity-based costing. We used nationally based wage estimates. RESULTS: Total RTS costs equaled $68,941 for 12 months. Specifically, non-site-based costs comprised $16,560. Most non-site-based costs ($11,822) were from the foundational programming and coding updates to the electronic health record data to develop the audit and feedback reports. The non-site-based costs of educational meetings, practice facilitation, and educational materials were substantially lower, ranging between ~$400 and $1000. Total 12-month site-based costs equaled $2569 for a single clinic (or $52,381 for 20 clinics). Educational meetings were the most expensive strategy, averaging $1401 per clinic. The site-based costs for the 4 other implementation strategies were markedly lower, ranging between $51 for educational materials and $555 for practice facilitation per clinic. CONCLUSIONS: This study provides detailed cost information for implementation strategies used to support evidence-based programs in primary care clinics.

Atrial fibrillation and chronic total occlusion percutaneous coronary intervention outcomes: insights from the Progress-CTO registry.

BACKGROUND: We examined the effect of atrial fibrillation on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We examined the baseline characteristics and procedural outcomes of 9,166 CTO PCIs performed at 39 US and non-US centers between 2012 and 2023. RESULTS: Atrial fibrillation was present in 1122 (12%) patients. These patients were older and had a higher incidence of comorbidities, such as hypertension, dyslipidemia, heart failure, cerebrovascular disease, and peripheral arterial disease, lower left ventricular ejection fraction, and lower eGFR. Their CTOs were more likely to have moderate to severe calcification and longer lesion length. They also had higher mean J-CTO and PROGRESS-CTO complications (Acute MI, MACE, Mortality, Perforation, and Pericardiocentesis) scores. Patients with atrial fibrillation had higher prevalence of uncrossable and undilatable CTO lesions and required longer procedure (107 vs 119 min; P less than .001) and fluoroscopy (40 vs 43 min; P=.005) time. Technical success and MACE, including procedural/in-hospital bleeding, were similar in patients with and without atrial fibrillation. Although the crude incidence of MACE on follow-up (median 61 days) was significantly higher in patients with atrial fibrillation, the latter was not independently associated with adverse events on Cox proportional hazards analysis. CONCLUSIONS: Patients with atrial fibrillation undergoing CTO PCI are older, have more comorbidities, higher lesion complexity, and longer procedure time, but similar technical success and in-hospital MACE. They have higher MACE and mortality during follow-up, but the difference is not significant after adjusting for potential confounding variables.

Simplified urine-based method to detect rifampin underexposure in adults with tuberculosis: a prospective diagnostic accuracy study.

Variable pharmacokinetics of rifampin in tuberculosis (TB) treatment can lead to poor outcomes. Urine spectrophotometry is simpler and more accessible than recommended serum-based drug monitoring, but its optimal efficacy in predicting serum rifampin underexposure in adults with TB remains uncertain. Adult TB patients in New Jersey and Virginia receiving rifampin-containing regimens were enrolled. Serum and urine samples were collected over 24 h. Rifampin serum concentrations were measured using validated liquid chromatography-tandem mass spectrometry, and total exposure (area under the concentration-time curve) over 24 h (AUC0-24) was determined through noncompartmental analysis. The Sunahara method was used to extract total rifamycins, and rifampin urine excretion was measured by spectrophotometry. An analysis of 58 eligible participants, including 15 (26%) with type 2 diabetes mellitus, demonstrated that urine spectrophotometry accurately identified subtarget rifampin AUC0-24 at 0-4, 0-8, and 0-24 h. The area under the receiver operator characteristic curve (AUC ROC) values were 0.80 (95% CI 0.67-0.90), 0.84 (95% CI 0.72-0.94), and 0.83 (95% CI 0.72-0.93), respectively. These values were comparable to the AUC ROC of 2 h serum concentrations commonly used for therapeutic monitoring (0.82 [95% CI 0.71-0.92], P = 0.6). Diabetes status did not significantly affect the AUC ROCs for urine in predicting subtarget rifampin serum exposure (P = 0.67-0.92). Spectrophotometric measurement of urine rifampin excretion within the first 4 or 8 h after dosing is a simple and cost-effective test that accurately predicts rifampin underexposure. This test provides critical information for optimizing tuberculosis treatment outcomes by facilitating appropriate dose adjustments.

Impact of preprocedural anemia on in-hospital and follow-up outcomes of chronic total occlusion percutaneous coronary intervention.

BACKGROUND: The impact of preprocedural anemia on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We examined the clinical and angiographic characteristics and procedural outcomes of 8633 CTO PCIs performed at 39 US and non-US centers between 2012 and 2023. Anemia was defined as a hemoglobin level of <13 g/dL in men and <12 g/dL in women. RESULTS: Anemia was present in 1652 (19%) patients undergoing CTO PCI. Anemic patients had a higher incidence of comorbidities, such as diabetes mellitus, hypertension, dyslipidemia, heart failure, cerebrovascular disease, and peripheral arterial disease. CTOs in anemic patients were more likely to have complex angiographic characteristics, including smaller diameter, longer length, moderate to severe calcification, and moderate to severe proximal tortuosity. Anemic patients required longer procedure (119 vs. 107 min; p < 0.001) and fluoroscopy (45 vs. 40 min; p < 0.001) times but received similar contrast volumes. Technical success was similar between the two groups. In-hospital major adverse cardiac events (MACE) rates were higher in patients with anemia; however, this association was no longer significant after adjusting for confounding factors. Baseline anemia was independently associated with follow-up MACE (adjusted hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.07-2.49; p = 0.023) and all-cause mortality (adjusted HR: 3.03; 95% CI: 1.41-6.49; p = 0.004). CONCLUSIONS: Preprocedural anemia is associated with more comorbidities, higher lesion complexity, longer procedure times, and higher follow-up MACE and mortality after CTO PCI.

Growth Factors Released from Advanced Platelet-Rich Fibrin in the Presence of Calcium-Based Silicate Materials and Their Impact on the Viability and Migration of Stem Cells of Apical Papilla.

Advanced platelet-rich fibrin (A-PRF) provides the scaffold and growth factors necessary for stem cells to proliferate and differentiate in successful regenerative endodontic procedures. This study investigates the release of transforming growth factor-ß1 (TGF-ß1), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) from A-PRF in cell culture media in the presence and absence of mineral trioxide aggregate (MTA) or Biodentine. Additionally, this research assesses the viability and migration of stem cells of the apical papilla (SCAP) in previously conditioned media. A-PRF obtained from 14 participants were incubated for 7 days in cell culture media alone or via layering with MTA or Biodentine discs and the release of selected growth factors in the media was evaluated using ELISA. The viability of SCAP grown in conditioned media was measured using the CCK8 assay, while SCAP migration was assessed via a transwell assay by counting migrated cells. The release of TGF-ß1, PDGF, and VEGF was significantly higher in media with A-PRF alone than in the presence of either calcium-based silicate material (p < 0.05), which showed no difference from the no-A-PRF control (p < 0.05). None of the tested growth factors released in the A-PRF-conditioned media correlated with clot weight. A-PRF-conditioned media, both with and without calcium-based silicate materials, did not impact SCAP viability and migration (p > 0.05). This study shows that SCAP behavior is not impacted by the decrease in growth factor released in the presence of calcium-based silicate materials and that their role in REPs warrants further investigation.

Evaluation of cataract formation in fish exposed to environmental radiation at Chernobyl and Fukushima.

Recent studies apparently finding deleterious effects of radiation exposure on cataract formation in birds and voles living near Chernobyl represent a major challenge to current radiation protection regulations. This study conducted an integrated assessment of radiation exposure on cataractogenesis using the most advanced technologies available to assess the cataract status of lenses extracted from fish caught at both Chernobyl in Ukraine and Fukushima in Japan. It was hypothesised that these novel data would reveal positive correlations between radiation dose and early indicators of cataract formation. The structure, function and optical properties of lenses were analysed from atomic to millimetre length scales. We measured the short-range order of the lens crystallin proteins using Small Angle X-Ray Scattering (SAXS) at both the SPring-8 and DIAMOND synchrotrons, the profile of the graded refractive index generated by these proteins, the epithelial cell density and organisation and finally the focal length of each lens. The results showed no evidence of a difference between the focal length, the epithelial cell densities, the refractive indices, the interference functions and the short-range order of crystallin proteins (X-ray diffraction patterns) in lens from fish exposed to different radiation doses. It could be argued that animals in the natural environment which developed cataract would be more likely, for example, to suffer predation leading to survivor bias. But the cross-length scale study presented here, by evaluating small scale molecular and cellular changes in the lens (pre-cataract formation) significantly mitigates against this issue.

Direct oral anticoagulants or vitamin K antagonists in emergencies: comparison of management in an observational study.

Background: Restoring hemostasis in patients on oral anticoagulants presenting with major hemorrhage (MH) or before surgical intervention has changed, with the replacement of vitamin K antagonist (VKA) with direct oral anticoagulants (DOACs). Objectives: To observe the difference in urgent hemostatic management between patients on VKA and those on DOACs. Methods: A multicenter observational study evaluated the variation in laboratory testing, hemostatic management, mortality, and hospital length of stay (LOS) in patients on VKA or DOACs presenting with MH or urgent hemostatic restoration. Results: Of the 1194 patients analyzed, 783 had MH (61% VKA) and 411 required urgent hemostatic restoration before surgery (56% VKA). Compared to the international normalized ratio (97.6%), plasma DOAC levels were measured less frequently (<45%), and the time taken from admission for the coagulation sample to reach the laboratory varied widely (median, 52.3 minutes; IQR, 24.8-206.7). No significant plasma DOAC level (<50 ng/mL) was found in up to 19% of patients. There was a poor relationship between plasma DOAC level and the usage of a hemostatic agent. When compared with patients receiving VKA (96.5%) or dabigatran (93.7%), fewer patients prescribed a factor Xa inhibitor (75.5%) received a prohemostatic reversal agent. The overall 30-day mortality for MH (mean: 17.8%) and length of stay (LOS) (median: 8.7 days) was similar between VKA and DOAC patients. Conclusion: In DOAC patients, when compared to those receiving VKA, plasma DOAC levels were measured less frequently than the international normalized ratio and had a poor relationship with administering a hemostatic reversal agent. In addition, following MH, mortality and LOS were similar between VKA and DOAC patients.