Can analyses of electronic patient records be independently and externally validated? The effect of statins on the mortality of patients with ischaemic heart disease: a cohort study with nested case-control analysis

Objective To conduct a fully independent and external validation of a research study based on one electronic health record database, using a different electronic database sampling the same population. Design Using the Clinical Practice Research Datalink (CPRD), we replicated a published investigation into the effects of statins in patients with ischaemic heart disease (IHD) by a different research team using QResearch. We replicated the original methods and analysed all-cause mortality using: (1) a cohort analysis and (2) a case-control analysis nested within the full cohort. Setting Electronic health record databases containing longitudinal patient consultation data from large numbers of general practices distributed throughout the UK. Participants CPRD data for 34 925 patients with IHD from 224 general practices, compared to previously published results from QResearch for 13 029 patients from 89 general practices. The study period was from January 1996 to December 2003. Results We successfully replicated the methods of the original study very closely. In a cohort analysis, risk of death was lower by 55% for patients on statins, compared with 53% for QResearch (adjusted HR 0.45, 95% CI 0.40 to 0.50; vs 0.47, 95% CI 0.41 to 0.53). In case-control analyses, patients on statins had a 31% lower odds of death, compared with 39% for QResearch (adjusted OR 0.69, 95% CI 0.63 to 0.75; vs OR 0.61, 95% CI 0.52 to 0.72). Results were also close for individual statins. Conclusions Database differences in population characteristics and in data definitions, recording, quality and completeness had a minimal impact on key statistical outputs. The results uphold the validity of research using CPRD and QResearch by providing independent evidence that both datasets produce very similar estimates of treatment effect, leading to the same clinical and policy decisions. Together with other non-independent replication studies, there is a nascent body of evidence for wider validity

Elevated Baseline Serum Fibrinogen: Effect on 2-Year Major Adverse Cardiovascular Events Following Percutaneous Coronary Intervention.

BackgroundElevated fibrinogen is associated with short-term major adverse cardiovascular events (MACE) after percutaneous coronary intervention, but the relation with late MACE is unknown.Methods and resultsBaseline demographics and 2-year MACE were recorded among subjects undergoing nonemergent percutaneous coronary intervention. A total of 332 subjects (66.6±19.5 years, 69.9% male, 25.3% acute coronary syndrome) were enrolled. Two-year MACE (periprocedural myocardial infarction 9.0%, rehospitalization 6.3%, revascularization 12.7%, non-periprocedural myocardial infarction 4.5%, stent thrombosis 0.9%, stroke 1.8%, and death 0.6%) were associated with higher fibrinogen (352.8±123.4 mg/dL versus 301.6±110.8 mg/dL; P<0.001), longer total stent length (40.1±25.3 mm versus 32.1±19.3 mm; P=0.004), acute coronary syndrome indication (38.7% versus 17.8%; P<0.001), number of bare-metal stents (0.5±1.1 versus 0.2±0.5; P=0.002), and stent diameter ≤2.5 mm (55.8% versus 38.4%, P=0.003). No relation between platelet reactivity and 2-year MACE was observed. Fibrinogen ≥280 mg/dL (odds ratio [OR] 3.0, confidence interval [CI], 1.6-5.4, P<0.001), total stent length ≥32 mm (OR 2.2, CI, 1.3-3.8, P<0.001), acute coronary syndrome indication (OR 4.1, CI, 2.3-7.5, P<0.001), any bare-metal stents (OR 3.2, CI, 1.6-6.1, P<0.001), and stent diameter ≤2.5 mm (OR 2.0, CI, 1.2-3.5, P=0.010) were independently associated with 2-year MACE. Following a landmark analysis excluding periprocedural myocardial infarction, fibrinogen ≥280 mg/dL remained strongly associated with 2-year MACE (37.0% versus 17.4%, log-rank P<0.001).ConclusionsElevated baseline fibrinogen level is associated with 2-year MACE after percutaneous coronary intervention. Acute coronary syndrome indication for percutaneous coronary intervention, total stent length implanted, and use of bare-metal stents or smaller-diameter stents are also independently associated with 2-year MACE, while measures of on-thienopyridine platelet reactivity are not

Origin and evolution of the light nuclides

After a short historical (and highly subjective) introduction to the field, I discuss our current understanding of the origin and evolution of the light nuclides D, He-3, He-4, Li-6, Li-7, Be-9, B-10 and B-11. Despite considerable observational and theoretical progress, important uncertainties still persist for each and every one of those nuclides. The present-day abundance of D in the local interstellar medium is currently uncertain, making it difficult to infer the recent chemical evolution of the solar neighborhood. To account for the observed quasi-constancy of He-3 abundance from the Big Bang to our days, the stellar production of that nuclide must be negligible; however, the scarce observations of its abundance in planetary nebulae seem to contradict this idea. The observed Be and B evolution as primaries suggests that the source composition of cosmic rays has remained quasi-constant since the early days of the Galaxy, a suggestion with far reaching implications for the origin of cosmic rays; however, the main idea proposed to account for that constancy, namely that superbubbles are at the source of cosmic rays, encounters some serious difficulties. The best explanation for the mismatch between primordial Li and the observed "Spite-plateau" in halo stars appears to be depletion of Li in stellar envelopes, by some yet poorly understood mechanism. But this explanation impacts on the level of the recently discovered early ``Li-6 plateau'', which (if confirmed), seriously challenges current ideas of cosmic ray nucleosynthesis.Comment: 18 pages, 9 figs. Invited Review in "Symposium on the Composition of Matter", honoring Johannes Geiss on the occasion of his 80th birthday (Grindelwald, Switzerland, Sept. 2006), to be published in Space Science Series of ISS

The Lantern Vol. 28, No. 2, Spring 1961

• A New Bedlam • A Priori • Germ Warfare • Verse for a Sympathy Card • On Lamartine\u27s Crucifix • On Art • Hope • Hymn to the Morning • An Educator Speaks • Come Out • Insemination • A Day\u27s Hope • Laura • Walking Together • 20 September 1960 • 15 October 1960 • The Governor\u27s Dog • One of the Gang • Poem • Knowledge is Freedom • To Conservative Child • Seventeen American Skating Careers at the Zenithhttps://digitalcommons.ursinus.edu/lantern/1080/thumbnail.jp

Record low Antarctic sea ice cover in February 2022

On 25 February 2022 Antarctic sea ice extent (SIE) dropped to a satellite-era record low level of 1.92 × 106 km2, 0.92 × 106 km2 below the long-term mean. The area of sea ice was also at a record low level of 1.24 × 106 km2. Although no individual sector was at a record low, at the minimum there were negative sea ice anomalies in all sectors of the Southern Ocean, with the largest in the Ross (contributing 46%) and Weddell Seas (26%). The Amundsen Sea Low had a record low depth in October/November 2021, with a series of very deep depressions giving strong offshore winds. These accelerated ice loss during the melt season, creating a 1.00 × 106 km2 coastal polynya in the Ross Sea. In the northern Weddell Sea, westerly winds of record strength led to ice export from the region

Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. METHODS: In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS: In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (-381 accelerometer units; 95% confidence interval [CI], -780 to 17; P=0.06) and a significant decrease in hours of activity per day (-0.30 hours; 95% CI, -0.55 to -0.05; P=0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (-439 accelerometer units; 95% CI, -792 to -86; P=0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels. CONCLUSIONS: Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02053493.)

Optical emission line properties of Narrow Line Seyfert 1s and comparison AGN

Based on a new spectroscopic sample observed using the WHT, we examine the kinematic properties of the various emission line regions in narrow line Seyfert 1 galaxies (NLS1s) by modelling their profiles using multiple component fits. We interpret these results by comparison with velocity components observed for different lines species covered in the same spectrum, and equivalent components measured in the spectra of some broad line Seyfert 1s and a representative Seyfert 2 galaxy. We find that the fits to the Halpha and Hbeta line profiles in NLS1s require an additional broad (~3000km/s) component that might correspond to a suppressed broad line region with similar kinematics to those of typical broad line Seyfert 1s. From the profiles of the forbidden high ionisation lines (FHILs) in NLS1s, we find evidence that they appear to trace an `intermediate' velocity region with kinematics between the standard broad and narrow line regions. Weaker evidence of this region is also present in the profiles of the permitted Balmer lines. Finally, we note that despite having similar ionisation potentials, the relative intensities of the highly ionised lines of [Fe X]6374 and [FeXI]7892 show considerable dispersion from one galaxy to another. The interpretation of this requires further modelling, but suggests the possibility of using the ratio as a diagnostic to constrain the physical conditions of the FHIL emitting region and possibly the shape of the spectral energy distribution in the vicinity of 200eV. This spectral region is very difficult to observe directly due to photoelectric absorption both in our Galaxy and intrinsic to the source.Comment: 24 pages, 13 figures, 5 tables, Accepted for publication in MNRA

A comparative evaluation of the effect of internet-based CME delivery format on satisfaction, knowledge and confidence

<p>Abstract</p> <p>Background</p> <p>Internet-based instruction in continuing medical education (CME) has been associated with favorable outcomes. However, more direct comparative studies of different Internet-based interventions, instructional methods, presentation formats, and approaches to implementation are needed. The purpose of this study was to conduct a comparative evaluation of two Internet-based CME delivery formats and the effect on satisfaction, knowledge and confidence outcomes.</p> <p>Methods</p> <p>Evaluative outcomes of two differing formats of an Internet-based CME course with identical subject matter were compared. A Scheduled Group Learning format involved case-based asynchronous discussions with peers and a facilitator over a scheduled 3-week delivery period. An eCME On Demand format did not include facilitated discussion and was not based on a schedule; participants could start and finish at any time. A retrospective, pre-post evaluation study design comparing identical satisfaction, knowledge and confidence outcome measures was conducted.</p> <p>Results</p> <p>Participants in the Scheduled Group Learning format reported significantly higher mean satisfaction ratings in some areas, performed significantly higher on a post-knowledge assessment and reported significantly higher post-confidence scores than participants in the eCME On Demand format that was not scheduled and did not include facilitated discussion activity.</p> <p>Conclusions</p> <p>The findings support the instructional benefits of a scheduled delivery format and facilitated asynchronous discussion in Internet-based CME.</p