Desenvolvimento e aplicação biológica de nanossistemas contendo o fotossensibilizante cloreto de alumínio ftalocianina

Tese (doutorado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Biologia Animal, 2017.Sistemas de liberação de fármacos com base em nanossistemas tornou-se um campo de interesse nas últimas décadas devido à sua capacidade de transporte e entrega de fármacos, proteção contra a degradação do princípio ativo e redução de efeitos colaterais. Entretanto, elucidar como os componentes de nanossistemas se comportam quando expostos a sistemas biológicos, é um passo fundamental a ser dado para que possamos compreender melhor como fazer seu uso clínico. O fotossensibilizante hidrofóbico alumínio-cloro ftalocianina (AlClFt) já foi utilizado no tratamento de câncer de língua, na eliminação de cáries dentárias, câncer de pulmão, entre outros, associada a nanossistemas para superar a hidrofobicidade de AlClFt. Entretanto, pouco se sabe sobre a consequência biológica da exposição à AlClFt, tanto in vitro quanto in vivo. No presente estudo foram realizadas três abordagens visando esclarecer a dinâmica biológica de nanossistemas contendo AlClFt. Na primeira abordagem micelas de Pluronic® F-127 contendo AlClFt (F-127/AlClFt), foram preparadas, caracterizadas fotofísicamente e testadas quanto à geração de oxigênio singleto e sua eficiência terapêutica contra células de adenocarcinoma de pulmão foi confirmada. A segunda abordagem visou estudar por espectrometria de massa a molécula AlClFt antes e após exposição a tecidos biológicos, além de desenvolver e validar método de cromatografia líquida de ultra alta eficiência para detecção de AlClFt em nanossistemas e matrizes biológicas. O método foi validado quanto à seletividade, linearidade, limites de detecção e quantificação, precisão e recuperação. A massa molecular de AlClFt identificada experimentalmente por espectrometria de massa foi menor do que a massa esperada indicando a perda do átomo de cloro quando em solução e a formação de aduto com solvente eluente (metanol) quando associada a cromatografia líquida. O método bioanalítico desenvolvido apresentou aplicabilidade e robustez para uso em estudos de biodistribuição. A terceira abordagem apresentou uma nanoemulsão magnética contendo AlClFt, sua caraterização, efetividade terapêutica in vitro nas linhagens de carcinoma de pulmão de células não pequenas e em macrófagos murinos, assim como sua biodistribuição in vivo avaliada por tomografia computadorizada por emissão de fóton único, fluorescência por imagem e por cromatografia líquida de alta eficiência. A caracterização físico-química de NE-MAG indicou a presença de duas subpopulações compondo o produto final: uma nanoemulsão não-magnética e uma nanoemulsão magnética. A instabilidade decorrente do isolamento das subpopulações, levou à realização do presente trabalho com o nanossistema contendo a mistura das duas subpopulações. A terapia fotodinâmica das células expostas a NE-MAG resultou na identificação de concentração citotóxica que diminui a viabilidade em 50% mais baixa do que já descrito para outras linhagens com o mesmo fotossensibilizante. A biodistribuição de componente magnético por emissão de fóton único indicou captação majoritária pelo fígado e baço em todos os tempos estudados (até 72 horas). A análise de fluorescência por imagem de AlClFt no nanossistema, mostrou intensa captação por fígado e pulmão enquanto que a quantificação analítica de AlClFt por cromatografia líquida indicou maior quantidade de AlClFt recuperado de fígado e rins. A diversidade do encontrado nas diferentes técnicas é justificada pela complexidade do nanossistema utilizado e reforça a importância da associação de técnicas para estudos de biodistribuição devido às diversas vantagens e limitações de cada técnica. Desta forma, as três abordagens utilizadas contribuem para a elucidação da dinâmica biológica de nanossistemas contendo AlClFt.Nanosystem-based drug delivery systems have become a field of interest in recent decades due to their ability to transport and deliver drugs, avoid degradation of the active principle and prevent side effects. However, elucidating how components of a nanosystem behave once exposed to biological systems is a fundamental step to be taken so that we can understand how to use them in living beings. The hydrophobic photosensitizer aluminum-chlorine phthalocyanine (AlClFt) has already been used in the treatment of tongue cancer, against dental caries, lung cancer, among others, associated with nanosystems to overcome the hydrophobicity of AlClFt. However, little is known about the biological consequence of exposure to AlClFt, both in vitro and in vivo. In the present study three approaches were made to clarify the biological dynamics of nanosystems containing AlClFt. In the first approach, Pluronic F-127 micelles containing AlClFt (F-127/AlClFt) were produced, photophysically characterized and tested for singlet oxygen generation and their therapeutic efficacy against lung adenocarcinoma was confirmed. The second approach was to study by mass spectrometry AlClFt molecule before and after exposure to biological tissues and to develop and validate an ultra-high performance liquid chromatography method for detection of AlClFt in nanosystems and in biological matrices. The method was validated for selectivity, linearity, limits of detection and quantification, accuracy and recovery. The mass of AlClFt experimentally identified by mass spectrometry was lower than the predicted mass indicating the loss of the chlorine atom when in solution and the formation of aducts with eluting solvent (methanol) when combined with liquid chromatography. The developed bioanalytical method presented applicability and robustness for use in biodistribution studies. The third approach presented magnetic nanoemulsion containing AlClFt, its characterization, in vitro therapeutic effectiveness in non-small cell lung carcinomas and murine macrophages, as well as its in vivo biodistribution evaluated by single photon emission computed tomography, fluorescence imaging and by high performance liquid chromatography. The physico-chemical characterization indicated the presence of two subpopulations composing the final product: a non-magnetic nanoemulsion and a magnetic nanoemulsion containing AlClFt (NE-MAG-Ft). The instability resulting from the isolation of the subpopulations led to the use in the present work of nanosystem containing the mixture of the two subpopulations. Photodynamic therapy of cells with NE-MAG-Ft yielded a cytotoxic concentration that decreases viability by 50% lower than previously described for other strains with the same photosensitizer. The biodistribution of the magnetic component by single photon emission demonstrated a major uptake by the liver and spleen at all studied times (up to 72 hours). Fluorescence analysis of AlClFt in the nanosystem demonstrated intense liver and lung uptake while analytical quantification of AlClFt by liquid chromatography indicated more AlClFt in liver and kidneys. The diversity of the different techniques is justified by the complexity of the nanosystem used and reinforces the importance of the association of techniques for biodistribution studies due to the different advantages and limitations of each technique. In this way, the three approaches used contribute to the elucidation of the biological dynamics of AlClFtcontaining nanosystems

Structural factors and best practices in implementing a linkage to HIV care program using the ARTAS model

<p>Abstract</p> <p>Background</p> <p>Implementation of linkage to HIV care programs in the U.S. is poorly described in the literature despite the central role of these programs in delivering clients from HIV testing facilities to clinical care sites. Models demonstrating success in linking clients to HIV care from testing locations that do not have co-located medical care are especially needed.</p> <p>Methods</p> <p>Data from the Antiretroviral Treatment Access Studies-II project ('ARTAS-II') as well as site visit and project director reports were used to describe structural factors and best practices found in successful linkage to care programs. Successful programs were able to identify recently diagnosed HIV-positive persons and ensure that a high percentage of persons attended an initial HIV primary care provider visit within six months of enrolling in the linkage program.</p> <p>Results</p> <p>Eight categories of best practices are described, supplemented by examples from 5 of 10 ARTAS-II sites. These five sites highlighted in the best practices enrolled a total of 352 HIV+ clients and averaged 85% linked to care after six months. The other five grantees enrolled 274 clients and averaged 72% linked to care after six months. Sites with co-located HIV primary medical care services had higher linkage to care rates than non-co-located sites (87% vs. 73%). Five grantees continued linkage to care activities in some capacity after project funding ended.</p> <p>Conclusions</p> <p>With the push to expand HIV testing in all U.S. communities, implementation and evaluation of linkage to care programs is needed to maximize the benefits of expanded HIV testing efforts</p

PRIMEIRO REGISTRO DE SPINITECTUS RODOLPHIHERINGI VAZ & PEREIRA, 1934 (SPIRURIDA: CYSTIDICOLIDAE) EM AUCHENIPTERUS NUCHALIS (SPIX & AGASSIZ, 1829) (SILURIFORMES: AUCHENIPTERIDAE) DOS LAGOS DE VÁRZEA DA AMAZÔNIA

Fish are the vertebrates that have the greatest number and diversity of parasitic species. Auchenipterus nuchalis (Spix &amp; Agassiz, 1829) is a small fish that occurs in South America, popularly known as “Peruvian mandi”. It has twilight habits and its diet is basically composed of aquatic insects and microcrustaceans, which are intermediate hosts of several parasitic species. Although fish are the vertebrate group with the highest number of parasitic species, most of these species are still unknown, therefore, the main objective of this study was to know and identify the Nematoda species that parasitize A. nuchalis and calculate the parasitological indices of each species. 38 A. nuchalis were captured in four expeditions in September, October, November and December 2016, in the Catalão lake complex in the municipality of Iranduba, Amazonas, on the left bank of the Solimões river and on the right bank of the Negro river, Brazil. The fish measured, on average, 11.8 - 18 (15.1 ± 1.35) cm in standard length and weighed 30.1 – 71.0 (47 ± 10.66) g. The individuals' digestive tract was preserved in 70% ethanol and transported to the laboratory for analysis. Of the total fish collected and examined, 31 were parasitized. Temporary and permanent slides were mounted to identify the parasitic specimens. The measurements of the individuals were made with the aid of a micrometric eyepiece, coupled to an optical microscope. Eighteen individuals of Spinitectus rodolphiheringi Vaz &amp; Pereira, 1934 parasitizing the intestine and stomach of the hosts were collected. Presenting an infection prevalence rate of 26.3%, which characterizes it as a satellite species. Furthermore, this is an unpublished record of this parasite for A. nuchalis and for the Amazon region.Los peces son los vertebrados que cuentan con mayor número y diversidad de especies parasitarias. Auchenipterus nuchalis (Spix &amp; Agassiz, 1829) es un pequeño pez que se encuentra en América del Sur, conocido popularmente como “mandi peruano”. Tiene hábitos crepusculares y su dieta está compuesta básicamente por insectos acuáticos y microcrustáceos, que son huéspedes intermediarios de varias especies parasitarias. Si bien los peces son el grupo de vertebrados con mayor número de especies parasitarias, la mayoría de estas especies aún se desconocen, por lo que el objetivo principal de este estudio fue conocer e identificar las especies de Nematodos que parasitan A. nuchalis y calcular los índices parasitológicos de cada especie. 38 A. nuchalis fueron capturados en cuatro expediciones en septiembre, octubre, noviembre y diciembre de 2016, en el complejo del lago Catalão en el municipio de Iranduba, Amazonas, en la margen izquierda del río Solimões y en la margen derecha del río Negro, Brasil. Los peces midieron, en promedio, 11,8 - 18 (15,1 ± 1,35) cm de longitud estándar y pesaron 30,1 - 71,0 (47 ± 10,66) g. El tracto digestivo de los individuos se conservó en etanol al 70% y se transportó al laboratorio para su análisis. Del total de peces recolectados y examinados, 31 fueron parasitados. Se montaron portaobjetos temporales y permanentes para identificar los especímenes parásitos. Las medidas de los individuos se realizaron con la ayuda de un ocular micrométrico, acoplado a un microscopio óptico. Se recolectaron dieciocho individuos de Spinitectus rodolphiheringi Vaz &amp; Pereira, 1934 que parasitan el intestino y el estómago de los hospedadores. Presentando una prevalencia de infección del 26,3%, lo que la caracteriza como especie satélite. Además, este es un registro inédito de este parásito para A. nuchalis y para la región amazónica.Os peixes são os vertebrados que apresentam a maior quantidade e diversidade de espécies parasitas. Auchenipterus nuchalis (Spix &amp; Agassiz, 1829) é um peixe de pequeno porte que ocorre na América do Sul, popularmente conhecido como “mandi peruano”. Tem hábitos crepusculares e sua dieta é basicamente composta por insetos aquáticos e microcrustáceos, que são hospedeiros intermediários de várias espécies parasitas. Apesar de os peixes serem o grupo de vertebrados com maior número de espécies parasitas, a maioria dessas espécies ainda é desconhecida, desse modo, o objetivo principal desse estudo foi conhecer e identificar as espécies de Nematoda que parasitam A. nuchalis e calcular os índices parasitológicos de cada espécie. Foram capturados 38 A. nuchalis, em quatro expedições, nos meses de setembro, outubro, novembro e dezembro de 2016, no complexo de lagos do Catalão no município de Iranduba, Amazonas, margem esquerda do rio Solimões e direita do rio Negro, Brasil. Os peixes mediam, em média, 11,8 - 18 (15,1 ± 1,35) cm de comprimento padrão e pesavam 30,1 – 71,0 (47 ± 10,66) g. O trato digestivo dos indivíduos foi conservado em etanol 70% e transportado ao laboratório para análise. Do total de peixes coletados e examinados, 31 estavam parasitados. Lâminas temporárias e permanentes foram montadas para a identificação dos espécimes parasitas. As medidas dos indivíduos foram feitas com o auxílio de ocular micrométrica, acoplada a um microscópio óptico. Foram coletados 18 indivíduos de Spinitectus rodolphiheringi Vaz &amp; Pereira, 1934 parasitando o intestino e estômago dos hospedeiros. Apresentando um índice de prevalência de infecção de 26,3%, o que a caracteriza como uma espécie satélite. Além disso, este é um registro inédito deste parasita para A. nuchalis e para a região Amazônica

Primeiro registro de Procamallanus (Spirocamallanus) inopinatus travassos, Artigas & Pereira, 1928 e contracaecum sp. Para Auchenipterus nuchalis (Spix & Agassiz 1829) (Siluriformes: Auchenipteridae) na Amazônia

Auchenipterus nuchalis (Spix &amp; Agassiz 1829) or Peruvian mandi is a small catfish that occurs in South America, has crepuscular habits and feeds basically on aquatic insects and microcrustaceans. Thirty-eight A. nuchalis were captured in four expeditions during the ebb and dry periods of 2016, in the Catalão lake complex, in the municipality of Iranduba, in the interior of the state of Amazonas, Brazil. Fish averaged 11.8 - 18 (15.1 ± 1.35) cm in standard length and weighed 30.1 - 71.0 (47 ± 10.66) g. The individuals' digestive tract was conserved in 70% ethanol until the analyzes were carried out. Of the total number of fish collected and examined, 21 were parasitized. Temporary and permanent slides were mounted for the identification of parasitic specimens. The measurements of the individuals were made with the aid of a micrometric eyepiece, coupled to an optical microscope. We collected 53 individuals of Procamallanus (S.) inopinatus Travassos, Artigas &amp; Pereira, 1928 with an infection prevalence rate of 52.6% and 17 individuals in the larval stage of Contracaecum sp., with a prevalence of 2.63%. Thus, the species were classified as secondary and satellite species, respectively. Furthermore, this is an unprecedented record of these parasites for A. nuchalis in the Amazon region, Brazil.Auchenipterus nuchalis (Spix &amp; Agassiz 1829) o mandi peruano es un pequeño bagre que se encuentra en América del Sur, tiene hábitos crepusculares y se alimenta básicamente de insectos acuáticos y microcrustáceos. 38 A. nuchalis fueron capturados en cuatro expediciones durante los períodos de vaciante y secos de 2016, en el complejo lacustre de Catalão, municipio de Iranduba, en el interior del estado de Amazonas, Brasil. Los peces medían, en promedio, 11,8 - 18 (15,1 ± 1,35) cm de longitud estándar y pesaban 30,1 - 71,0 (47 ± 10,66) g. El tracto digestivo de los individuos se conservó en etanol al 70% hasta la realización de los análisis. Del total de peces recolectados y examinados, 21 estaban parasitados. Se montaron portaobjetos temporales y permanentes para identificar especímenes parásitos. Las mediciones de los individuos se realizaron con la ayuda de un ocular micrométrico acoplado a un microscopio óptico. Se recolectaron 53 individuos de Procamallanus (S.) inopinatus Travassos, Artigas &amp; Pereira, 1928 con una prevalencia de infección del 52,6% y 17 individuos en estado larvario de Contracaecum sp., con una prevalencia del 2,63%. De esta forma, las especies fueron clasificadas en secundarias y satélites, respectivamente. Además, este es un registro sin precedentes de estos parásitos para A. nuchalis en la región amazónica.Auchenipterus nuchalis (Spix &amp; Agassiz 1829) ou mandi peruano é um pequeno bagre que ocorre na América do Sul, possui hábitos crepusculares e alimenta-se basicamente de insetos aquáticos e microcrustáceos. Foram capturados 38 A. nuchalis, em quatro expedições nos períodos de vazante e seca do ano de 2016, no complexo de lagos do Catalão, município de Iranduba, interior do estado do Amazonas, Brasil. Os peixes mediam, em média, 11,8 - 18 (15,1 ± 1,35) cm de comprimento padrão e pesavam 30,1 – 71,0 (47 ± 10,66) g. O trato digestivo dos indivíduos foi conservado em etanol 70% até a realização das análises. Do total de peixes coletados e examinados, 21 estavam parasitados. Foram montadas lâminas temporárias e permanentes para a identificação dos espécimes parasitas. As medidas dos indivíduos foram feitas com o auxílio de ocular micrométrica, acoplada a um microscópio óptico. Foram coletados 53 indivíduos de Procamallanus (S.) inopinatus Travassos, Artigas &amp; Pereira, 1928 com índice de prevalência de infecção de 52,6% e 17 indivíduos em estágio larval de Contracaecum sp., com prevalência de 2,63%. Dessa forma, as espécies foram classificadas com espécie secundária e satélite, respectivamente. Além disso, este é um registro inédito destes parasitos para A. nuchalis na região Amazônica

HPLC-FLD method for itraconazole quantification in poly lactic-co-glycolic acid nanoparticles, plasma and tissue

Itraconazol, um antifúngico de amplo espectro, possui muitos efeitos colaterais e o uso de nanossistemas para a entrega de fármacos tem sido proposto como um método para otimizar a farmacocinética da droga e reduzir os efeitos colaterais. Um procedimento de cromatografia líquida de alta performance (HPLC) utilizando detecção fluorimétrica foi desenvolvido para a determinação de itraconazol em nanopartículas do copolímero de ácido láctico e glicólico, plasma e tecidos. A linearidade, limites de detecção e quantificação, recuperação, precisão, seletividade e estabilidade do método foram estabelecidas. O método desenvolvido foi testado na detecção e quantificação de itraconazol na biodistribuição de nanopartículas administrados intraperitonealmente em camundongos fêmeas Balb/C. Neste estudo foi desenvolvido um método analítico de HPLC com detecção fluorimétrica para quantificação de itraconazole em nanopartículas poliméricas, tecidos e plasma, sendo ele sensível, de baixo custo, viável para uso de rotina e com potencial para aplicação na biodistribuição e estudos farmacocinéticos de itraconazole em nanossistemas.Itraconazole, a broad-spectrum anti-fungal, has many side effects, and nanosystems for drug delivery have been proposed as a method to optimize the drug's pharmacokinetics and reduce side effects. An high performance liquid chromatography (HPLC) procedure using fluorometric detection was developed for determination of itraconazole in polymeric poly(lactic-co-glycolic acid) nanoparticles, plasma and tissue. Linearity, limits of detection and quantification, recovery, precision, selectivity and stability were established. The developed method was tested in itraconazole detection and quantification of biodistribution of nanoparticles administered intraperitoneally to Balb/C female mice. This study developed an analytical method for HPLC with fluorometric detection for quantification of itraconazole in polymeric nanoparticles, tissue and plasma, which is sensitive, low cost, viable for routine usage and with potential for application in itraconazole biodistribution and pharmacokinetics studies

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24&nbsp;months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500&nbsp;steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30&nbsp;minutes spent performing activities ≥500&nbsp;counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24&nbsp;months), both the number of steps per day (per 500&nbsp;steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500&nbsp;counts per minute (per 30&nbsp;minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score &gt;10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

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)