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Using a target of PbF2, the thick-target yield from the (19)F(α,n) reaction was measured from E(α)=3.5-10 MeV. From these results, we infer the thick-target neutron yields from targets of F2 and UF6 over this same alpha-particle energy range.

Using a target of PbF2, the thick-target yield from the (19)F(α,n) reaction was measured from E(α)=3.5-10 MeV. From these results, we infer the thick-target neutron yields from targets of F2 and UF6 over this same alpha-particle energy range.

Cardiovascular disease (CVD) remains the main cause of mortality and morbidity in patients with diabetes. Prevention of CVD in diabetes involves a multifactorial approach that aims to treat the cluster of risk factors including hyperglycemia, dyslipidemia, obesity, hypertension, and hypercoagulation associated with this condition. Antiplatelets reduce the prothrombotic environment in diabetes, but complications of this therapeutic approach include a general risk of bleeding, specifically intracranial hemorrhage, the risk of which increases in the presence of hypertension. Current guidelines recommend the use of antiplatelet agents after tight control of blood pressure, which, in clinical practice, is not always possible. In this review, the evidence for antiplatelet use in diabetes with particular emphasis on patients with associated hypertension is examined. Safe levels of blood pressure with antiplatelet therapy, various studies, and general recommendations for diabetes patients, in light of current evidence, are explored. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes is a common and adverse prognostic co-morbidity for patients with heart failure with reduced ejection fraction (HFrEF). The effect of diabetes on long-term outcomes for heart failure with preserved ejection fraction (HFpEF) is less established., Methods: Prospective cohort study of patients referred to a regional HF clinic with newly diagnosed with HFrEF and HFpEF according to the 2016 European Society of Cardiology guidelines. The association between diabetes, all-cause mortality and hospitalisation was quantified using Kaplan-Meier or Cox regression analysis., Results: Between 1st May 2012 and 1st May 2013, of 960 unselected consecutive patients referred with suspected HF, 464 and 314 patients met the criteria for HFpEF and HFrEF respectively. Within HFpEF and HFrEF groups, patients with diabetes were more frequently male and in both groups patients with diabetes were more likely to be treated with β-adrenoceptor antagonists and angiotensin converting enzyme inhibitors. After adjustment for age, sex, medical therapy and co-morbidities, diabetes was associated with increased mortality in individuals with HFrEF (HR 1.46 95% CI: 1.05-2.02; p = .023), but not in those with HFpEF (HR 1.26 95% CI 0.92-1.72; p = .146)., Conclusion: In unselected patients with newly diagnosed HF, diabetes is not an adverse prognostic marker in patients with HFpEF, but is in HFrEF., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: John Gierula has received speaker fees from Abbott and Medtronic and consultancy fees from Microport. Klaus Witte has received speaker fees from Medtronic, Microport, Abbott, Cardiac Dimensions, Pfizer, Bayer, and Bristol-Myers Squibb. Peter Grant has received speaker fees from AstraZenica. Sam Straw has received nonfinancial support from AstraZeneca. Stephen Wheatcroft has received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Lilly and NovNordisk. Mark Kearney has received speaker fees from Merck and Novo Nordisk and unrestricted research awards from Medtronic.

Background A recent randomized trial, the MICHELLE trial, demonstrated improved posthospital outcomes with a 35-day course of prophylactic rivaroxaban for patients hospitalized with COVID-19 at high risk of venous thromboembolism. We explored how often these findings may apply to an unselected clinical population of patients hospitalized with COVID-19. Methods and Results Using a 35-hospital retrospective cohort of patients hospitalized between March 7, 2020, and January 23, 2021, with COVID-19 (MI-COVID19 database), we quantified the percentage of hospitalized patients with COVID-19 who would be eligible for rivaroxaban at discharge per MICHELLE trial criteria and report clinical event rates. The main clinical outcome was derived from the MICHELLE trial and included a composite of symptomatic venous thromboembolism, pulmonary embolus-related death, nonhemorrhagic stroke, and cardiovascular death at 35 days. Multiple sensitivity analyses tested different eligibility and exclusion criteria definitions to determine the effect on eligibility for postdischarge anticoagulation prophylaxis. Of 2016 patients hospitalized with COVID-19 who survived to discharge and did not have another indication for anticoagulation, 25.9% (n=523) would be eligible for postdischarge thromboprophylaxis per the MICHELLE trial criteria (range, 2.9%-39.4% on sensitivity analysis). Of the 416 who had discharge anticoagulant data collected, only 13.2% (55/416) were actually prescribed a new anticoagulant at discharge. Of patients eligible for rivaroxaban per the MICHELLE trial, the composite clinical outcome occurred in 1.2% (6/519); similar outcome rates were 5.7% and 0.63% in the MICHELLE trial's control (no anticoagulation) and intervention (rivaroxaban) groups, respectively. Symptomatic venous thromboembolism events and all-cause mortality were 6.2% (32/519) and 5.66% in the MI-COVID19 and MICHELLE trial control cohorts, respectively. Conclusions Across 35 hospitals in Michigan, ≈1 in 4 patients hospitalized with COVID-19 would qualify for posthospital thromboprophylaxis. With only 13% of patients actually receiving postdischarge prophylaxis, there is a potential opportunity for improvement in care.

Background: The enhanced thrombotic milieu in diabetes contributes to increased risk of vascular events. Aspirin, a key antiplatelet agent, has inconsistent effects on outcomes in diabetes and the best dosing regimen remains unclear. This work investigated effects of aspirin dose and interaction with glycaemia on both the cellular and protein components of thrombosis., Methods: A total of 48 participants with type 1 diabetes and 48 healthy controls were randomised to receive aspirin 75 or 300 mg once-daily (OD) in an open-label crossover study. Light transmittance aggregometry and fibrin clot studies were performed before and at the end of each treatment period., Results: Aspirin demonstrated reduced inhibition of collagen-induced platelet aggregation (PA) in participants with diabetes compared with controls, although the higher dose showed better efficacy. Higher aspirin dose facilitated clot lysis in controls but not individuals with diabetes. Collagen-induced PA correlated with glycaemic control, those in the top HbA1c tertile having a lesser inhibitory effect of aspirin. Threshold analysis suggested HbA1c levels of > 65 mmol/mol and > 70 mmol/mol were associated with poor aspirin response to 75 and 300 mg daily doses, respectively. Higher HbA1c was also associated with longer fibrin clot lysis time., Conclusions: Patients with diabetes respond differently to the antiplatelet and profibrinolytic effects of aspirin compared with controls. In particular, those with elevated HbA1c have reduced inhibition of PA with aspirin. Our findings indicate that reducing glucose levels improves the anti-thrombotic action of aspirin in diabetes, which may have future clinical implications., Trial Registration: EudraCT, 2008-007875-26, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2008-007875-26 ., (© 2021. The Author(s).)

Background This study aimed to assess the effectiveness of sodium-glucose cotransporter 2 inhibitors in reducing the incidence of mortality and cardiovascular outcomes in adults with type 2 diabetes. Methods and Results We conducted a Bayesian meta-analysis of randomized controlled trials comparing sodium-glucose cotransporter 2 inhibitors with placebo. We used meta-regression to examine the association between treatment effects and control group event rates as measures of cardiovascular baseline risk. Fifty-three randomized controlled trials were included in our synthesis. Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63-0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69-1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72-1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61-1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63-1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71-1.08), with a 90.1% to 98.7% probability for the true RR to be <1.00 for both outcomes. There was little evidence for ertugliflozin and sotagliflozin versus placebo for reducing all-cause and cardiovascular mortality. There was no association between treatment effects for all-cause and cardiovascular mortality and the control group event rates. There was evidence for a reduction in the incidence of heart failure for empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin versus placebo (probability RR <1.00 of ≥99.3%) and weaker, albeit positive, evidence for acute myocardial infarction for the first 3 agents (probability RR <1.00 of 89.0%-95.2%). There was little evidence of any agent except canagliflozin for reducing the incidence of stroke. Conclusions Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause and cardiovascular mortality versus placebo. Treatment effects of sodium-glucose cotransporter 2 inhibitors versus placebo do not vary by baseline risk.

The widespread use of complementary products poses a challenge to clinicians in the perioperative period and may increase perioperative risk. Because dietary supplements are regulated differently from traditional pharmaceuticals and guidance is often lacking, the Society for Perioperative Assessment and Quality Improvement convened a group of experts to review available literature and create a set of consensus recommendations for the perioperative management of these supplements. Using a modified Delphi method, the authors developed recommendations for perioperative management of 83 dietary supplements. We have made our recommendations to discontinue or continue a dietary supplement based on the principle that without a demonstrated benefit, or with a demonstrated lack of harm, there is little downside in temporarily discontinuing an herbal supplement before surgery. Discussion with patients in the preoperative visit is a crucial time to educate patients as well as gather vital information. Patients should be specifically asked about use of dietary supplements and cannabinoids, as many will not volunteer this information. The preoperative clinic visit provides the best opportunity to educate patients about the perioperative management of various supplements as this visit is typically scheduled at least 2 weeks before the planned procedure., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objectives: Night shift workers are at cardiometabolic risk due to circadian misalignment. We investigated whether infrequent exercise before each night shift that intentionally would not improve physical performance improves glucose tolerance and 24-h blood pressure profiles and synchronizes circadian rhythms of melatonin and cortisol in rotating night shift workers., Methods: A total of 24 rotating night shift workers (mean age, 35.7 ± 11.8 years) were randomized to exercise or no intervention. Workers in the exercise group performed 15.2 ± 4.5 exercise sessions within 2 h before each night shift. Before and after 12 weeks of exercise intervention and 12 weeks after the intervention, spiroergometry, oral glucose tolerance testing and 24-h blood pressure profiles were performed. Plasma melatonin and cortisol levels were measured in 3-hourly intervals during one 24-h period on each study day., Results: Exercise did not significantly change serum glucose nor insulin levels during oral glucose tolerance testing. Timed physical exercise had no effect on physical performance, nor did it change the circadian rhythms of melatonin and cortisol or influence 24-h blood pressure profiles., Conclusion: Physical exercise before each night shift at a low intensity level that does not improve physical performance does not affect circadian timing, glucose tolerance or 24-h blood pressure profiles in rotating night shift workers.

Obesity-related euglycaemic insulin resistance clusters with cardiometabolic risk factors, contributing to the development of both type 2 diabetes and cardiovascular disease. An increased thrombotic tendency in diabetes stems from platelet hyperactivity, enhanced activity of prothrombotic coagulation factors and impaired fibrinolysis. Furthermore, a low-grade inflammatory response and increased oxidative stress accelerate the atherosclerotic process and, together with an enhanced thrombotic environment, result in premature and more severe cardiovascular disease. The disruption of circadian cycles in man secondary to chronic obesity and loss of circadian cues is implicated in the increased risk of developing diabetes and cardiovascular disease. Levels of melatonin, the endogenous synchronizer of circadian rhythm, are reduced in individuals with vascular disease and those with deranged glucose metabolism. The anti-inflammatory, antihypertensive, antioxidative and antithrombotic activities of melatonin make it a potential therapeutic agent to reduce the risk of vascular occlusive disease in diabetes. The mechanisms behind melatonin-associated reduction in procoagulant response are not fully known. Current evidence suggests that melatonin inhibits platelet aggregation and might affect the coagulation cascade, altering fibrin clot structure and/or resistance to fibrinolysis. Large-scale clinical trials are warranted to investigate the effects of modulating the circadian clock on insulin resistance, glycaemia and cardiovascular outcome.

Background: Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM., Materials and Methods: 56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions., Results: Of the 56 patients, 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention. Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20μmol/L ADP 77.6 ± 8.4% [aspirin] vs. 57.7 ± 17.6% [clopidogrel] vs. 34.1 ± 14.1% [prasugrel], p < 0.001), P-selectin expression (30 μmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 μg/mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001). Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar. Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083)., Conclusions: Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular disease in this population. Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM. Trial registration EudraCT, 2009-011907-22. Registered 15 March 2010, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB.

We performed a MEDLINE search and found 6 studies published February 2018 through January 2019 that should influence perioperative cardiovascular medicine, specifically in preoperative cardiac risk assessment, perioperative medication management, and postoperative cardiac complications., (Copyright © 2019 Cleveland Clinic.)

A MEDLINE search was performed from January 2017 to February 2018, and articles were selected for this update based on their significant influence on the practice of perioperative cardiovascular medicine., (Copyright © 2018 Cleveland Clinic.)

Essentials The roles of β-barrels 1 and 2 in factor XIII (FXIII) are currently unknown. FXIII truncations lacking β-barrel 2, both β-barrels, or full length FXIII, were made. Removing β-barrel 2 caused total loss of activity, removing both β-barrels returned 30% activity. β-barrel 2 is necessary for exposure of the active site cysteine during activation., Summary: Background Factor XIII is composed of an activation peptide segment, a β-sandwich domain, a catalytic core, and, finally, β-barrels 1 and 2. FXIII is activated following cleavage of its A-subunits by thrombin. The resultant transglutaminase activity leads to increased resistance of fibrin clots to fibrinolysis. Objectives To assess the functional roles of β-barrels 1 and 2 in FXIII, we expressed and characterized the full-length FXIII A-subunit (FXIII-A) and variants truncated to residue 628 (truncated to β-barrel 1 [TB1]), residue 515 (truncated to catalytic core [TCC]), and residue 184 (truncated to β-sandwich). Methods Proteins were analyzed by gel electrophoresis, circular dichroism, fluorometric assays, and colorimetric activity assays, clot structure was analyzed by turbidity measurements and confocal microscopy, and clot formation was analyzed with a Chandler loop system. Results and Conclusions Circular dichroism spectroscopy and tryptophan fluorometry indicated that full-length FXIII-A and the truncation variants TCC and TB1 retain their secondary and tertiary structure. Removal of β-barrel 2 (TB1) resulted in total loss of transglutaminase activity, whereas the additional removal of β-barrel 1 (TCC) restored enzymatic activity to ~ 30% of that of full-length FXIII-A. These activity trends were observed with physiological substrates and smaller model substrates. Our data suggest that the β-barrel 1 domain protects the active site cysteine in the FXIII protransglutaminase, whereas the β-barrel 2 domain is necessary for exposure of the active site cysteine during activation. This study demonstrates the importance of individual β-barrel domains in modulating access to the FXIII active site region., (© 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)

Essentials How best to quantify thrombosis risk with peripherally inserted central catheters (PICC) is unknown. Data from a registry were used to develop the Michigan Risk Score (MRS) for PICC thrombosis. Five risk factors were associated with PICC thrombosis and used to develop a risk score. MRS was predictive of the risk of PICC thrombosis and can be useful in clinical practice., Summary: Background Peripherally inserted central catheters (PICCs) are associated with upper extremity deep vein thrombosis (DVT). We developed a score to predict risk of PICC-related thrombosis. Methods Using data from the Michigan Hospital Medicine Safety Consortium, image-confirmed upper-extremity DVT cases were identified. A logistic, mixed-effects model with hospital-specific random intercepts was used to identify factors associated with PICC-DVT. Points were assigned to each predictor, stratifying patients into four classes of risk. Internal validation was performed by bootstrapping with assessment of calibration and discrimination of the model. Results Of 23 010 patients who received PICCs, 475 (2.1%) developed symptomatic PICC-DVT. Risk factors associated with PICC-DVT included: history of DVT; multi-lumen PICC; active cancer; presence of another CVC when the PICC was placed; and white blood cell count greater than 12 000. Four risk classes were created based on thrombosis risk. Thrombosis rates were 0.9% for class I, 1.6% for class II, 2.7% for class III and 4.7% for class IV, with marginal predicted probabilities of 0.9% (0.7, 1.2), 1.5% (1.2, 1.9), 2.6% (2.2, 3.0) and 4.5% (3.7, 5.4) for classes I, II, III, and IV, respectively. The risk classification rule was strongly associated with PICC-DVT, with odds ratios of 1.68 (95% CI, 1.19, 2.37), 2.90 (95% CI, 2.09, 4.01) and 5.20 (95% CI, 3.65, 7.42) for risk classes II, III and IV vs. risk class I, respectively. Conclusion The Michigan PICC-DVT Risk Score offers a novel way to estimate risk of DVT associated with PICCs and can help inform appropriateness of PICC insertion., (© 2017 International Society on Thrombosis and Haemostasis.)

Rationale: In the endothelium, insulin stimulates endothelial NO synthase (eNOS) to generate the antiatherosclerotic signaling radical NO. Insulin-resistant type 2 diabetes mellitus is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear., Objective: To answer this question, we generated a mouse with endothelial cell (EC)-specific overexpression of the human insulin receptor (hIRECO) using the Tie2 promoter-enhancer., Methods and Results: hIRECO demonstrated significant endothelial dysfunction measured by blunted endothelium-dependent vasorelaxation to acetylcholine, which was normalized by a specific Nox2 NADPH oxidase inhibitor. Insulin-stimulated phosphorylation of protein kinase B was increased in hIRECO EC as was Nox2 NADPH oxidase-dependent generation of superoxide, whereas insulin-stimulated and shear stress-stimulated eNOS activations were blunted. Phosphorylation at the inhibitory residue Y657 of eNOS and expression of proline-rich tyrosine kinase 2 that phosphorylates this residue were significantly higher in hIRECO EC. Inhibition of proline-rich tyrosine kinase 2 improved insulin-induced and shear stress-induced eNOS activation in hIRECO EC., Conclusions: Enhancing insulin sensitivity specifically in EC leads to a paradoxical decline in endothelial function, mediated by increased tyrosine phosphorylation of eNOS and excess Nox2-derived superoxide. Increased EC insulin sensitivity leads to a proatherosclerotic imbalance between NO and superoxide. Inhibition of proline-rich tyrosine kinase 2 restores insulin-induced and shear stress-induced NO production. This study demonstrates for the first time that increased endothelial insulin sensitivity leads to a proatherosclerotic imbalance between NO and superoxide., (© 2016 American Heart Association, Inc.)

Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important.

Recent studies have shed light on preoperative risk assessment, medical therapy to reduce postoperative cardiac complications (beta-blockers, statins, and angiotensin II receptor blockers [ARBs]), perioperative management of patients with coronary stents on antiplatelet therapy, and perioperative bridging anticoagulation., (Copyright © 2016 Cleveland Clinic.)

The human circadian system anticipates and adapts to daily environmental changes to optimise behaviour according to time of day and temporally partitions incompatible physiological processes. At the helm of this system is a master clock in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The SCN are primarily synchronised to the 24-h day by the light/dark cycle; however, feeding/fasting cycles are the primary time cues for clocks in peripheral tissues. Aligning feeding/fasting cycles with clock-regulated metabolic changes optimises metabolism, and studies of other animals suggest that feeding at inappropriate times disrupts circadian system organisation, and thereby contributes to adverse metabolic consequences and chronic disease development. 'High-fat diets' (HFD) produce particularly deleterious effects on circadian system organisation in rodents by blunting feeding/fasting cycles. Time-of-day-restricted feeding, where food availability is restricted to a period of several hours, offsets many adverse consequences of HFD in these animals; however, further evidence is required to assess whether the same is true in humans. Several nutritional compounds have robust effects on the circadian system. Caffeine, for example, can speed synchronisation to new time zones after jetlag. An appreciation of the circadian system has many implications for nutritional science and may ultimately help reduce the burden of chronic diseases.

Patients with coronary artery disease and concomitant diabetes mellitus tend to have more extensive vessel disease than non-diabetes mellitus coronary artery disease patients, are at high risk of adverse cardiovascular events and suffer from a great anginal burden. Very few trials have specifically addressed the issue of optimal anti-anginal therapy in coronary artery disease patients who also have diabetes mellitus. Among 'classical' anti-anginal agents, recent guidelines do not specifically recommend any molecule over others; however, European Society of Cardiology guidelines acknowledge that favourable data in patients with concomitant diabetes mellitus and coronary artery disease are available for trimetazidine and ranolazine, two anti-anginal agents with a non-haemodynamic mechanism of action. The aim of this article is to review available evidence supporting the anti-anginal efficacy of these two drugs in the difficult-to-treat population of diabetes mellitus patients, including their effects on glycated haemoglobin (HbA1c), a measure of medium-term glycaemic control. Although direct head-to-head comparisons have not been performed, available evidence favours ranolazine as an effective anti-anginal agent over trimetazidine in this population. In addition, ranolazine lowers HbA1c, indicating that it may improve glycaemic control in patients with diabetes mellitus. Conversely, scanty data are available on the metabolic effects of trimetazidine in this cohort of patients. Thus, ranolazine may represent a valuable therapeutic option in stable coronary artery disease patients with diabetes mellitus., (© The Author(s) 2015.)

Background: Diabetes mellitus (DM) is an established adverse prognostic factor in patients sustaining myocardial infarction (MI). However, its impact on long-term survival remains less clear. The aim of this observational study was to quantify lifetime mortality and years of life lost after MI in patients with and without DM., Methods: In 1995, 2153 individuals with MI were recruited from 20 adjacent hospitals within Yorkshire, UK. Median survival, all-cause mortality at 20 years and lost years of life when compared to actuarial predictions were compared in patients with and without DM. Landmark analyses were conducted to define the ongoing impact of DM beyond specified time points., Results: 13% (279/2153) had known DM. They experienced higher mortality at 30 days (33.1% vs 24.6%; p<0.0001) and at 20 years (84.9% vs 75.7%; p<0.0001). Overall, there was a 48% increased risk of death (p<0.0001), which persisted after adjustment for potential confounders. There was no interaction between DM and prior MI in predicting mortality (p=0.67). Median survival decreased by 3.3 years (p<0.0001). The adverse impact of DM persisted in sequential landmark analyses at 1, 5 and 10 years. Presence of DM conferred 2 extra years of life lost when compared with actuarial predictions (8 vs 6 years; p<0.0001)., Conclusions: DM remains an independent adverse prognostic factor in the long-term after MI. Persistently diverging survival curves support enduring efforts to reduce mortality late after MI., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Computerized provider order entry systems commonly contain alerting mechanisms for patient allergies, incorrect doses, or drug-drug interactions when ordering medications. Providers have the option to override (bypass) these alerts and continue with the order unchanged. This study examines the effect of customizing medication alert override options on the appropriateness of override selection related to patient allergies, drug dosing, and drug-drug interactions when ordering medications in an electronic medical record., Materials and Methods: In this prospective, randomized crossover study, providers were randomized into cohorts that required a reason for overriding a medication alert from a customized or non-customized list of override reasons and/or by free-text entry. The primary outcome was to compare override responses that appropriately correlate with the alert type between the customized and non-customized configurations. The appropriateness of a subset of free-text responses that represented an affirmative and active acknowledgement of the alert without further explanation was classified as "indeterminate." Results were analyzed in three different ways by classifying indeterminate answers as either appropriate, inappropriate, or excluded entirely. Secondary outcomes included the appropriateness of override reasons when comparing cohorts and individual providers, reason selection based on order within the override list, and the determination of the frequency of free-text use, nonsensical responses, and multiple selection responses., Results: Twenty-two clinicians were randomized into 2 cohorts and a total of 1829 alerts with a required response were generated during the study period. The customized configuration had a higher rate of appropriateness when compared to the non-customized configuration regardless of how indeterminate responses were classified (p<0.001). When comparing cohorts, appropriateness was significantly higher in the customized configuration regardless of the classification of indeterminate responses (p<0.001) with one exception: when indeterminate responses were considered inappropriate for the cohort of providers that were first exposed to the non-customized list (p=0.103). Free-text use was higher in the customized configuration overall (p<0.001), and there was no difference in nonsensical response between configurations (p=0.39)., Conclusion: There is a benefit realized by using a customized list for medication override reasons. Poor application design or configuration can negatively affect provider behavior when responding to important medication alerts., (Copyright © 2015. Published by Elsevier Ireland Ltd.)