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)

The severity of pandemic H1N1 influenza in the United States, from April to July 2009: A Bayesian analysis

Background: Accurate measures of the severity of pandemic (H1N1) 2009 influenza (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. Methods and Findings: We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data - medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York - were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-96lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5-17 y. sCHR appears to be lowest in persons aged 5-17; our data were too sparse to allow us to determine the group in which it was the highest. Conclusions: These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0-4 and adults 18-64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than assumed.published_or_final_versio

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

Ocena wpływu stanów dynamicznych silnika spalinowego na jego właściwości użytkowe

Internal combustion engines as systems described by non-linear models do not have any properties that would not depend on their current states. The paper presents results of testing an automotive engine in dynamic states determined by the vehicle acceleration sign in vehicle driving tests simulating the real operation of passenger cars. During the tests, pollutant emission rates and fuel flow rates averaged for specific vehicle states were examined. The processes under investigation were found to be highly sensitive both to the dynamic states and to the types of the vehicle driving tests.Silniki spalinowe jako układy opisywane modelami nieliniowymi nie mają właściwości niezależnych od stanów, w jakich się znajdują. W pracy przedstawiono wyniki badań silnika samochodowego w stanach dynamicznych zdeterminowanych znakiem przyspieszenia pojazdu w testach jezdnych symulujących rzeczywistą eksploatację samochodów osobowych. Badano uśrednione w tych stanach: natężenie emisji zanieczyszczeń i natężenie przepływu paliwa. Stwierdzono znaczną wrażliwość badanych procesów zarówno na stany dynamiczne, jak i na rodzaje testów jezdnych

The non- repeatability of the pollutant emission under conditions simulating the traffic of a personal car in cities

W związku z ograniczoną określonością stanów pracy silników spalinowych użytkowanych w samochodach powoduje, że jest celowe traktowanie właściwości użytkowych silników jako wielkości przypadkowych. W artykule przedstawiono wyniki badań empirycznych emisji zanieczyszczeń i zużycia paliwa dla samochodu użytkowanego w warunkach ruchu w miastach. Badania przeprowadzono na hamowni podwoziowej w testach jezdnych, zarówno homologacyjnych, jak i specjalnych. Jako miarę niepowtarzalności wyników badań przyjęto współczynnik zmienności wyników badań. Stwierdzono zróżnicowaną niepowtarzalność wyników badań ze względu na badane wielkości oraz ze względu na warunki ruchu samochodu.Due to uncertain specificity of work states of internal combustion engines used in cars makes it expedient treatment of engines performance as random quantities. The article presents the results of empirical studies of the pollutant emission and fuel consumption for the vehicle operated in traffic conditions in cities. The study was conducted on chassis dynamometer tests, both the approval and special. As a measure of the non-repeatability of research results adopted the variation coefficient of test results. It was found diverse non-repeatability of the test results because the test quantities and due to the conditions of a traffic car

The correlative studies of the pollutant emission and fuel consumption in type-approval tests

Emisji zanieczyszczeń i zużycie paliwa są zależne od stanów pracy samochodowego silnika spalinowego, zdeterminowanych warunkami ruchu pojazdu. W związku z tym wyniki badań emisji zanieczyszczeń i zużycia paliwa w różnych testach homologacyjnych różnią się między sobą. W pracy podjęto się zadania oceny, czy – mimo to – istnieje możliwość porównywania wyników badań emisji zanieczyszczeń i zużycia paliwa w różnych testach homologacyjnych. W wyniku przeprowadzonych analiz stwierdzono, że wyniki badań emisji zanieczyszczeń i zużycia paliwa w testach homologacyjnych: europejskim, amerykańskim i japońskim, są silnie ze sobą skorelowane. Jednocześnie oceniono, że pomiędzy wynikami badań emisji drogowej zanieczyszczeń poszczególnych substancji i eksploatacyjnego zużycia paliwa nie ma znacznej korelacji.The pollutant emission and fuel consumption are dependent on the operating conditions of a internal combustion engine, determined the conditions of the vehicle. Accordingly, the results of the pollutant emis-sion and fuel consumption in various type-approval tests differ from each other. In this paper the task of evaluating whether - despite this - it is possible to compare test results of the pollutant emission and fuel consumption in different type-approval tests. The analyzes found that the test results of the pollutant emission and fuel consumption in type-approval tests: European, American and Japanese, are closely correlated. At the same time it was estimated that between test results of the pollutant emission and fuel consumption is not a significant correlation

Badania porównawcze emisji zanieczyszczeń z samochodowego silnika spalinowego z zastosowaniem testów jezdnych

The pollutant emission from automotive internal combustion (IC) engines is highly susceptible to engine operation states determined by vehicle velocity processes. The article presents results of comparative examinations of specific distance pollutant emission characteristics determined from various vehicle driving tests. The specific distance pollutant emission was determined using vehicle type-approval and special tests as well as tests developed at the Automotive Industry Institute (PIMOT), treated as realizations of the stochastic process of vehicle velocity. The research results confirmed high susceptibility of the IC engine pollutant emission to the engine operation states, which endorses the usefulness of treating the conditions of operation of automotive engines as stochastic processes.Emisja zanieczyszczeń z samochodowych silników spalinowych jest bardzo wrażliwa na stany pracy silników zdeterminowane procesami prędkości samochodów. W niniejszej pracy przedstawiono wyniki badań porównawczych charakterystyk emisji drogowej zanieczyszczeń w różnych testach jezdnych. Do wyznaczania emisji drogowej zanieczyszczeń wykorzystano testy stosowane w procedurach homologacyjnych i testy specjalne oraz opracowane w Przemysłowym Instytucie Motoryzacji, traktowane jako realizacje procesu stochastycznego prędkości samochodu. Wyniki badań potwierdziły znaczną wrażliwość emisji zanieczyszczeń na stany pracy silnika spalinowego, co potwierdza celowość traktowania warunków pracy silników samochodowych jako procesów stochastycznych