Dedicated plug based closure for large bore access -The MARVEL prospective registry

Objectives To study safety and performance of the MANTA Vascular closure device (VCD) under real world conditions in 10 centers. Background The MANTA is a novel plug-based device for large bore arteriotomy closure. Methods We included all eligible patients who underwent transfemoral large bore percutaneous procedures. Exclusion criteria were per operator's discretion and included severe calcification or marked tortuosity of the access vessel, presence of marked obesity/cachexia or a systolic blood pressure above 180 mmHg. The primary performance endpoint was time to hemostasis. Primary and secondary safety endpoints were major and minor access site related vascular complications up to 30 days, respectively. Vascular complications were adjudicated by an independent clinical event committee according to VARC-2 criteria. We performed multivariable logistic regression to estimate the effect of baseline and procedural characteristics on any and major vascular complications. Results Between February 2018 and July 2019 500 patients were enrolled undergoing Transcatheter aortic valve replacement (TAVR, N = 496), Balloon aortic valvuloplasty (BAV, N = 2), Mechanical circulatory support (MCS, N = 1) or Endovascular aneurysm repair (EVAR, N = 1). Mean age was 80.8 +/- 6.6 years with a median STS-score of 2.7 [IQR 2.0-4.3] %. MANTA access site complications were major in 20 (4%) and minor in 28 patients (5.6%). Median time to hemostasis was 50 [IQR 20-120] sec. Severe femoral artery calcification, scar presence in groin, longer procedure duration, female gender and history of hypertension were independent predictors for vascular complications. Conclusion In this study, MANTA appeared to be a safe and effective device for large bore access closure under real-world conditions.Peer reviewe

Impact of Rheumatic Musculoskeletal Disease on Psychological Development in Adolescents and Young Adults

Adolescents and young adults (AYAs) undergo significant physiological and psychological transformations. When developmental milestones are combined with additional challenges of growing up with a chronic rheumatic musculoskeletal disease (RMD), it can increase AYA's susceptibility to psychological problems. Emotional issues in adolescence can often persist into adulthood and negatively impact future health, social, and work outcomes. This chapter summarises psychological challenges for AYAs and recommends ways for healthcare professionals (HCPs) to promote mental wellbeing in AYAs with RMD

Loss of viability during freeze-thaw of intact and adherent human embryonic stem cells with conventional slow-cooling protocols is predominantly due to apoptosis rather than cellular necrosis

10.1007/s11373-005-9051-9Journal of Biomedical Science133433-44

Chronic arthritis in children and adolescents in two Indian health service user populations

BACKGROUND: High prevalence rates for rheumatoid arthritis, spondyloarthopathies, and systemic lupus erythematosus have been described in American Indian and Alaskan Native adults. The impact of these diseases on American Indian children has not been investigated. METHODS: We used International Classification of Diseases-9 (ICD-9) codes to search two Indian Health Service (IHS) patient registration databases over the years 1998–2000, searching for individuals 19 years of age or younger with specific ICD-9-specified diagnoses. Crude estimates for disease prevalence were made based on the number of individuals identified with these diagnoses within the database. RESULTS: Rheumatoid arthritis (RA) / juvenile rheumatoid arthritis (JRA) was the most frequent diagnosis given. The prevalence rate for JRA in the Oklahoma City Area was estimated as 53 per 100,000 individuals at risk, while in the Billings Area, the estimated prevalence was nearly twice that, at 115 per 100,000. These rates are considerably higher than those reported in the most recent European studies. CONCLUSION: Chronic arthritis in childhood represents an important, though unrecognized, chronic health challenge within the American Indian population living in the United States

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Raman micro-spectroscopy can be used to investigate the developmental stage of the mouse oocyte

In recent years, the uptake of assisted reproductive techniques such as in vitro fertilisation has risen exponentially. However, there is much that is still not fully understood about the biochemical modifications that take place during the development and maturation of the oocyte. As such, it is essential to further the understanding of how oocyte manipulation during these procedures ultimately affects its developmental potential; yet, there are few methods currently available which are capable of providing a quantitative measure of oocyte quality. Raman spectroscopy enables investigation of the global biochemical profile of intact cells without the need for labelling. Here, Raman spectra were acquired from the ooplasm of mouse oocytes at various stages of development, from late pre-antral follicles, collected after in vitro maturation within their ovarian follicles and from unstimulated and stimulated ovulatory cycles. Using a combination of univariate and multivariate statistical methods, it was found that ooplasm lipid content could be used to discriminate between different stages of oocyte development. Furthermore, the spectral profiles of mature oocytes revealed that oocytes which have developed in vitro are protein-deficient when compared to in vivo grown oocytes. Finally, the ratio of two Raman peak intensities, namely 1605:1447 cm21, used as a proxy for the protein-to-lipid ratio of the ooplasm, was shown to be indicative of the oocyte’s quality. Together, results indicate that Raman spectroscopy may present an alternative analytical tool fo