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)

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Nannoliths and paleobiogeographic census from DSDP Site 56-435

Calcareous nannofossils were encountered at only one of the sites (435) drilled during DSDP Leg 56. Cores from Hole 435A yield fairly diverse early and late Pliocene assemblages. The section shows considerable reworking, however. Three to five biostratigraphic datum events provide a reasonable biochronology. The datums range from about 3.3 Ma in Core 11 to about 1.8 Ma in Core 3. Paleobiogeographic data indicate relatively stable and warm climatic conditions in this area in the early Pliocene, becoming more unstable in the late Pliocene when the cosmopolitan species become dominant

Inherited landscapes and sea level change

Enabled by recently gained understanding of deep-seated and surficial Earth processes, a convergence of views between geophysics and sedimentary geology has been quietly taking place over the past several decades. Surface topography resulting from lithospheric memory, retained at various temporal and spatial scales, has become the connective link between these two methodologically diverse geoscience disciplines. Ideas leading to the hypothesis of plate tectonics originated largely with an oceanic focus, where dynamic and mostly horizontal movements of the crust could be envisioned. But when these notions were applied to the landscapes of the supposedly rigid plate interiors, there was less success in explaining the observed anomalies in terrestrial topography. Solid-Earth geophysics has now reached a developmental stage where vertical movements can be measured and modeled at meaningful scales and the deep-seated structures can be imaged with increasing resolution. Concurrently, there have been advances in quantifying mechanical properties of the lithosphere (the solid outer skin of Earth, usually defined to include both the crust and the solid but elastic upper mantle above the asthenosphere). The lithosphere acts as the intermediary that transfers the effects of mantle dynamics to the surface. These developments have allowed us to better understand the previously puzzling topographic features of plate interiors and continental margins. On the sedimentary geology side, new quantitative modeling techniques and holistic approaches to integrating source-to-sink sedimentary systems have led to clearer understanding of basin evolution and sediment budgets that allow the reconstruction of missing sedimentary records and past geological landscapes

Long-Term Cyclicities in Phanerozoic Sea-Level Sedimentary Record and their Potential Drivers

Cyclic sedimentation has varied at several timescales and this variability has been geologically well documented at Milankovitch timescales, controlled in part by climatically (insolation) driven sea-level changes. At the longer (tens of Myr) timescales connection between astronomical parameters and sedimentation via cyclic solar-system motions within the Milky Way has also been proposed, but this hypothesis remains controversial because of the lack of long geological records. The absence of a physical mechanism that could explain the connection between climate and astronomy at these longer timescales led to the explanation of plate motions as the main driver of climate on Earth. Here we statistically show a prominent and persistent ~36 Myr sedimentary cyclicity superimposed on two megacycles (~250 Myr) in a relatively well-constrained sea-level (SL) record of the past 542 Myr (Phanerozoic eon). Given the possible link between amplitudes of the ~36 and ~250 Myr cyclicities in SL record and the potential that these periodicities fall into the frequency band of solar system motions, we suggest an astronomical origin, and model these periodicities as originating from the path of the solar system in the Milky Way as vertical and radial periods that modulate the flux of cosmic rays on Earth. Our finding of the ~36 Myr SL cyclicity lends credibility to the existing hypothesis about the imprint of solar-system vertical period on the geological record. The ~250 Myr megacycles are tentatively attributed to a radial period. However, the tectonic drivers also remain potentially plausible. The potential existence of a correlation between the modeled astronomical signal and the geological record may offer an indirect proxy to understand the structure and history of the Milky Way by providing a 542 Myr long record of the path of the Sun in our Galaxy