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)

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

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

On the roughness measurement on knee prostheses

The majority of total knee replacements currently implanted present an articulation composed of two metal parts, femoral and tibial components, between which there is a polyethylene insert serving as a bearing surface. The finishing surface of the metal components is a very important factor in minimizing the polyethylene wear rate and, later, the gradual production of metal and plastic debris. Considering the role of surface roughness on volumetric wear rates, the purpose of this study is to develop a protocol for the roughness characterization of total knee prosthesis (TKP) metal components, taking into consideration a limited number of points on each surface. Six mobile TKP of different sizes (three size 2 and three size 6) were tested on a knee joint simulator to compare the wear behavior of each group. After 2 million cycles the weight loss by the polyethylene inserts was measured with gravimetric method and the surface roughness of the metallic components was assessed in terms of average surface roughness, Ra, skewness, Rsk, and total roughness, Rt. Roughness measurement involved 29 points on each femoral condyle and 26 points on each metal tibial plate. The data collected has shown an increased roughness upon wear testing for both the investigated TKP sizes. No statistical differences were observed between the two groups for both the parameters Ra, Rsk, and Rt. The surface of all metallic components became more negatively skewed, indicating diminishing peaks. The various parameters were correlated to the volumetric loss using a linear regression analysis

Wear Behaviours and Oxidation Effects on Different UHMWPE Acetabular Cups Using a Hip Joint Simulator

Given the long-term problem of polyethylene wear, medical interest in the new improved cross-linked polyethylene (XLPE), with or without the adding of vitamin E, has risen. The main aim of this study is to gain further insights into the mutual effects of radiation cross-linking and addition of vitamin E on the wear performance of ultra-high-molecular-weight polyethylene (UHMWPE). We tested four different batches of polyethylene (namely, a standard one, a vitamin E-stabilized, and two cross-linked) in a hip joint simulator for five million cycles where bovine calf serum was used as lubricant. The acetabular cups were then analyzed using a confocal profilometer to characterize the surface topography. Moreover; the cups were analyzed by using Fourier Transformed Infrared Spectroscopy and Differential Scanning Calorimetry in order to assess the chemical characteristics of the pristine materials. Comparing the different cups’ configuration, mass loss was found to be higher for standard polyethylene than for the other combinations. Mass loss negatively correlated to the cross-link density of the polyethylenes. None of the tested formulations showed evidence of oxidative degradation. We found no correlation between roughness parameters and wear. Furthermore, we found significantly differences in the wear behavior of all the acetabular cups. XLPEs exhibited lower weight loss, which has potential for reduced wear and decreased osteolysis. However, surface topography revealed smoother surfaces of the standard and vitamin E stabilized polyethylene than on the cross-linked samples. This observation suggests incipient crack generations on the rough and scratched surfaces of the cross-linked polyethylene liners

Pfizer-BioNTech and Sinopharm: A Comparative Study on Post-Vaccination Antibody Titers

COVID-19 (coronavirus disease 2019) vaccines induce immunity through different mechanisms. The aim of this study is to compare the titers of specific antibodies in subjects vaccinated with either the Pfizer-BioNTech COVID-19 vaccine or the Sinopharm vaccine. This prospective observational cohort included Jordanian adults vaccinated with two doses, 21 days apart, of either of the two aforementioned vaccines. Titers were collected 6 weeks after the administration of the second dose. Overall, 288 participants were included, of which 141 were administered the Pfizer-BioNTech vaccine, while 147 were administered the Sinopharm vaccine. Remarkably, 140 (99.3%) of the Pfizer-BioNTech vaccine recipients had positive IgG titers, while 126 (85.7%) of Sinopharm recipients had positive IgG (p p p = 0.002), compared with a negative effect of cardiovascular diseases (OR: 0.33; 95% CI: 0.11–0.99; p = 0.48) on IgG titers. In conclusion, fully vaccinated recipients of the Pfizer-BioNTech vaccine had superior quantitative efficiency compared to Sinopharm recipients. A booster dose is supported for Sinopharm recipients, or those with chronic immunosuppressive diseases

Pfizer-BioNTech and Sinopharm: A Comparative Study on Post-Vaccination Antibody Titers

COVID-19 (coronavirus disease 2019) vaccines induce immunity through different mechanisms. The aim of this study is to compare the titers of specific antibodies in subjects vaccinated with either the Pfizer-BioNTech COVID-19 vaccine or the Sinopharm vaccine. This prospective observational cohort included Jordanian adults vaccinated with two doses, 21 days apart, of either of the two aforementioned vaccines. Titers were collected 6 weeks after the administration of the second dose. Overall, 288 participants were included, of which 141 were administered the Pfizer-BioNTech vaccine, while 147 were administered the Sinopharm vaccine. Remarkably, 140 (99.3%) of the Pfizer-BioNTech vaccine recipients had positive IgG titers, while 126 (85.7%) of Sinopharm recipients had positive IgG (p &lt; 0.001). The mean titer for IgG among Pfizer-BioNTech recipients was 515.5 ± 1143.5 BAU/mL, compared to 170.0 ± 230.0 BAU/mL among Sinopharm subjects (p &lt; 0.001). Multivariable regression analysis showed that the Pfizer-BioNTech vaccine positively correlated with positive IgG titers (OR: 25.25; 95% CI: 3.25–196.15; p = 0.002), compared with a negative effect of cardiovascular diseases (OR: 0.33; 95% CI: 0.11–0.99; p = 0.48) on IgG titers. In conclusion, fully vaccinated recipients of the Pfizer-BioNTech vaccine had superior quantitative efficiency compared to Sinopharm recipients. A booster dose is supported for Sinopharm recipients, or those with chronic immunosuppressive diseases