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

A 9-year retrospective cohort of patients with lumbar disc herniation: Comparison of patient characteristics and recurrence frequency by smoking status

To evaluate the association between smoking status and patient characteristics and to identify risk factors associated with recurrence in patients who underwent surgery for lumbar disc herniation (LDH). This retrospective study was carried out at Lokman Hekim University, Ankara, Turkey between January 1, 2021 and January 1, 2022. The medical data of patients who underwent microsurgical discectomy for LDH were retrospectively recorded. Patients with any reemergence of LDH within a 6-month period after surgery were defined as having recurrent LDH. A total of 1109 patients were included in the study and mean age was 50.7 +/- 14.3 years. The frequency of hernia at L2-L3 and L3-L4 levels was higher in the nonsmoker group (P < .001). The frequency of cases with Pfirrmann Grade 4 degeneration was higher in the nonsmoker group than in smokers and ex-smokers (P < .001). Protrusion-type hernias were more common in nonsmokers (P = .014), whereas paracentral hernias were more common in smokers (P < .001). The overall frequency of recurrence was 20.4%, and was higher in smokers than in non-smokers and ex-smokers (P < .001). Multivariable logistic regression revealed that current smoking (OR: 2.778, 95% CI [confidence interval]: 1.939-3.980, P < .001), presence of Pfirrmann Grade 4&5 disc degeneration (OR: 4.217, 95% CI: 2.966-5.996, P < .001), and paracentral herniation (OR: 5.040, 95% CI: 2.266-11,207, P < .001) were associated with higher risk of recurrence, whereas presence of sequestrated disc was associated with lower risk of recurrence (OR: 2.262, 95% CI:0.272-0.717, P = .001). Taken together, our data show that smoking, increased degree of degeneration and paracentral hernia increase the risk of LDH recurrence, while sequestrated disc appears to decrease risk. Taking steps to combat smoking in individuals followed for LDH may reduce the risk of recurrence in LDH patients

MİKRO ÇEVRENİN DOKU MÜHENDİSLİĞİ UYGULAMALARINA ETKİSİ

MİKRO ÇEVRENİN DOKU MÜHENDİSLİĞİ UYGULAMALARINA ETKİS

Protein-based materials in load-bearing tissue-engineering applications

Proteins such as collagen and elastin are robust molecules that constitute nanocomponents in the hierarchically organized ultrastructures of bone and tendon as well as in some of the soft tissues that have load-bearing functions. In the present paper, the macromolecular structure and function of the proteins are reviewed and the potential of mammalian and non-mammalian proteins in the engineering of load-bearing tissue substitutes are discussed. Chimeric proteins have become an important structural biomaterial source and their potential in tissue engineering is highlighted. Processing of proteins challenge investigators and in this review rapid prototyping and microfabrication are proposed as methods for obtaining precisely defined custom-built tissue engineered structures with intrinsic microarchitecture

Modeling wastewater discharge at the planning stage of a marine outfall system

The possibility of marine discharge of a negatively buoyant industrial waste was evaluated by a modeling study using Killworth 3-D, which is the first version of the Modular Ocean Model (MOM). The Model was run with the recorded wind direction and speed on the cruise dates and the circulation patterns for surface and subsurface were found to be similar with the current meter measurements. Model scenarios have been set-up in order to estimate the intensity and direction of the currents in the Nemrut Bay under the condition of wind blowing from a definite direction for a long time. MOM model has been run for four major wind directions, each having duration of 10 days and the behavior of the discharge plume in the worst case has been traced. Also, the behavior of the discharge plume in the real case has been estimated by using the wind data of the region. According to the model results, impact of trace elements that compose the discharge effluent is limited both in time and space. It is concluded that trace elements will leave the Bay in a short time due to the short residence times

Osteogenic differentiation of adipose derived stem cells on high and low aspect ratio micropatterns

<div><p>Adipose derived stem cells (ADSCs) were cultured on collagen–silk fibroin films with microchannel and micropillar patterns to investigate the effects of cell morphology changes on osteogenic differentiation. Channel and pillar micropatterned films were prepared from collagen type I and silk fibroin. While higher ADSC proliferation profiles were obtained on micropillar blend film, microchannel blend films, however, caused twice higher aspect ratio and effective orientation of cells. Alkaline phosphatase activity of ADSCs was several times higher on microchannel surface when the measured activities were normalized to cell number. Effective deposition of collagen type I and mineral by the cells were observed for patterned and unpatterned films, and these extracellular matrix components were oriented along the axis of the microchannels. In conclusion, the use of collagen–fibroin blend film with microchannel topography increased the aspect ratio and alignment of cells significantly, and was also effective in the differentiation of ADSCs into osteogenic lineage</p></div

The effect of ACE2 receptor, IFN-?, and TNF-? polymorphisms on the severity and prognosis of the disease in SARS-CoV-2 infection

To investigate the effect of genetic variations in the angiotensin converting enzyme (ACE), interferon (IFNG) and tumor necrosis factor (TNF-alpha) genes on the severity of coronavirus disease (COVID-19). Between September and December 2021, 33 patients with COVID-19 were included in this prospective study. The patients were classified and compared according to disease severity: mild&moderate (n = 26) vs severe&critical (n = 7). These groups were evaluated to assess possible relationships with ACE, TNF-alpha and IFNG gene variations using univariate and multivariable analyses. The median age of the mild&moderate group was 45.5 (22-73), and that of the severe&critical group was 58 (49-80) years (p = 0.014). Seventeen (65.4%) of the mild&moderate patients and 3 (42.9%) of severe&critical patients were female (p = 0.393). According to results of univariate analysis, the percentage of patients with the c.418-70C>G variant of the ACE gene was significantly higher in the mild&moderate group (p = 0.027). The ACE gene polymorphisms, c.2312C>T, c.3490G>A, c.3801C>T, and c.731A>G, were each only seen in separate patients with critical disease. The following variants were observed more frequently in the mild&moderate group: c.582C>T, c.3836G>A, c.511+66A>G, c.1488-58T>C, c.3281+25C>T, c.1710-90G>C, c.2193A> G, c.3387T>C for ACE; c.115-3delT for IFNG; and c.27C>T for TNF. It can be expected that patients carrying the ACE gene c.418-70C>G variant may present with a mild clinical manifestation of COVID-19. Several genetic polymorphisms may be associated with pathophysiology, as they appear to help predict COVID-19 severity and enable early identification of the patients requiring aggressive treatment.Turkiye Modern Cerrahi Egitim ve Arasxtirma Dernegi; Turkiye Solunum Arasxtirmalari Dernegi [ADF/17]The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research received support from two organizations(Turkiye Modern Cerrahi Egitim ve Arasxtirma Dernegi, Turkiye Solunum Arasxtirmalari Dernegi (ADF/17)