Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

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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

Robotic assessment of the influence of age on upper-limb sensorimotor function

Ana LLinares, Francisco Javier Badesa, Ricardo Morales, Nicolas Garcia-Aracil, JM Sabater, Eduardo Fernandez Biomedical Neuroengineering, Universidad Miguel Hern&aacute;ndez de Elche, Elche, Spain Purpose: This paper examines the influence of age on several attributes of sensorimotor performance while performing a reaching task. Our hypothesis, based on previous studies, is that aged persons will show differences in one or more of the attributes of sensorimotor performance. Patients and methods: Fifty-one subjects (aged 20&ndash;80 years) with no known neuromotor disorders of the upper limbs participated in the study. Subjects were asked to grasp the end-effector of a pneumatic robotic device with two degrees of freedom in order to reach peripheral targets (1.0 cm radius), &quot;quickly and accurately&quot;, from a centrally located target (1.0 cm radius). Subjects began each trial by holding the hand within the central target for 2000 milliseconds. Afterwards, a peripheral target was illuminated. Then participants were given 3000 milliseconds to complete the movement. When a target was reached, the participant had to return to the central target in order to start a new trial. A total of 64 trials were completed and each peripheral target was illuminated in a random block design. Results: Subjects were divided into three groups according to age: group 1 (age 20&ndash;40 years), group 2 (age 41&ndash;60 years), and group 3 (age 61&ndash;80 years). The Kruskal&ndash;Wallis test showed significant differences (P &lt; 0.05) between groups, except for the variables postural speed in the dominant arm, and postural speed and initial deviation in the non-dominant arm (P &gt; 0.05). These results suggest that age introduces significant differences in upper-limb motor function. Conclusion: Our findings show that there are objective differences in sensorimotor function due to age, and that these differences are greater for the dominant arm. Therefore for the assessment of upper-limb function, we should take into account the influence of age. Moreover, these results suggest that robotic systems can provide a new and effective approach in the assessment of sensorimotor function. Keywords: aging, sensorimotor function, robotics, rehabilitatio

A four-state Markov model of sleep-wakefulness dynamics along light/dark cycle in mice

<div><p>Behavioral states alternate between wakefulness (wk), rapid eye movement (rem) and non-rem (nrem) sleep at time scale of hours <i>i.e</i>., light and dark cycle rhythms and from several tens of minutes to seconds (<i>i.e</i>., brief awakenings during sleep). Using statistical analysis of bout duration, Markov chains of sleep-wk dynamics and quantitative EEG analysis, we evaluated the influence of light/dark (ld) changes on brain function along the sleep-wk cycle. Bout duration (bd) histograms and Kaplan-Meier (km) survival curves of wk showed a bimodal statistical distribution, suggesting that two types of wk do exist: brief-wk (wkb) and long-wk (wkl). Light changes modulated specifically wkl bouts, increasing its duration during active/dark period. In contrast, wkb, nrem and rem bd histograms and km curves did not change significantly along ld cycle. Hippocampal eeg of both types of wk were different: in comparison wkb showed a lower spectral power in fast gamma and fast theta bands and less emg tone. After fitting a four-states Markov chain to mice hypnograms, moreover in states transition probabilities matrix was found that: in dark/active period, state-maintenance probability of wkl increased, and probability of wkl to nrem transition decreased; the opposite was found in light period, favoring the hypothesis of the participation of brief wk into nrem-rem intrinsic sleep cycle, and the role of wkl in SWS homeostasis. In conclusion, we propose an extended Markov model of sleep using four stages (wkl, nrem, rem, wkb) as a fully adequate model accounting for both modulation of sleep-wake dynamics based on the differential regulation of long-wk (high gamma/theta) epochs during dark and light phases.</p></div

Spectral analysis of sleep stages normalized to the total spectrum of the signal in 24 hours.

<p>A) Hippocampal spectral content of long and brief wake is different (in red; cortex in blue); i and ii, long wake epochs had an augmented theta band with a characteristic 8 Hz peak (<i>θ</i>₂ band; arrow a), whereas in the brief wake a lower frequency theta peak activity was at 6 Hz (<i>θ</i>₁ band; arrow b); in addition, the power of fast gamma hippocampal frequencies in long wake epochs is significantly increased compared to brief wake. During nrem sleep a predominance of delta and beta power, and a reduction of gamma band were observed (iii) and in rem there was a predominance of theta (iv; arrow a) with low delta and beta, and an increased gamma band with respect to nrem. B) Long vs. brief wake spectrums; hippocampal, but not cortical, fast gamma and theta power (<i>θ</i>₂) and EMG tone were decreased in brief-wk (<i>p</i> < 0.001).</p

Diagram of four-state Markov model accounting for the wk-sleep dynamics across dark/light cycle.

<p>Circular arrows correspond to the probability of maintaining a state (i.e., the time spent in the corresponding state or bout duration), and straight arrows to transitions between states; arrows thickness are proportional to the corresponding probabilities (from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189931#pone.0189931.t001" target="_blank">Table 1</a>), and the dark and light periods are represented in black and grey. The sleep-wake model of four states comprises of two wk states (with spectral differences, see text): a long-wk (wkl) and a brief-wk (wkb); and of nrem and rem sleep states. States of wkl and nrem were more stable than rem and wkb, while state transitions wkb to nrem and rem to nrem were the most probable. Circadian modulation increased the stability of wkl mainly by reducing the transitions from wkl to nrem during dark active period (*, <i>p</i> < 0.05; and **, <i>p</i> < 0.01).</p

Statistics of wk, nrem and rem bout duration as a function of dark/light periods.

<p>A) Bouts duration histogram showed a clear bimodal density distribution of wake (brief- and long-wk) while nrem and rem distribution was unimodal; only the density of long-wk varied during circadian rhythm, lasting longer in the dark (active) than light (inactive) phase. B) Cumulative wk showed by Kaplan-Meyer survival curves exhibited a biexponential distribution (wkb and wkl, vertical bar) with a significant increment of wkl duration in dark phase. C) Mean bout durations of wkl nrem rem and wkb; duration increased in wkl during dark in comparison with light phase. Clear differences in duration distribution during light and dark period are shown (*, Anova and Log-Rank Test for Kaplan-Meier analysis <i>p</i> < 0.05).</p

Representative data illustrating dark/light modulation of sleep-wake behavior in C57Bl/6 mouse.

<p>A i-ii) Hypnogram was generated by automatic sleep scoring of wk, nrem and rem sleep states. B) Long (-) and brief (*) wk bouts were identified based on the frequency pattern of cortex and hippocampal eeg activity (i-ii). iii) raw eeg during brief wk.</p