Left atrial dyssynchrony in veteran endurance athletes with and without paroxysmal atrial fibrillation.

BACKGROUND: Prolonged endurance exercise increase the risk of atrial fibrillation (AF) in men. Functional parameters may help separate physiological from pathological atrial remodeling in athletes. LA mechanical dispersion (LA MD) is associated with AF in the general population, but the associations between prolonged exercise, LA MD and AF are not known. PURPOSE: To describe LA MD in veteran athletes with and without paroxysmal AF (pAF) and to investigate LA MD's ability to identify veteran athletes with pAF. METHODS: Two hundred and ninety-three men, skiers with (n = 57) and without (n = 87) pAF, and controls with (n = 61) and without pAF (n = 88) underwent an echocardiographic exam in sinus rhythm. LA reservoir strain (LASr) was measured, and LA MD defined as the standard deviation of time-to-peak strain (SD-TPS). RESULTS: Skiers (mean age 70.7 ± 6.7 years) reported an average of 40-50 years of endurance exercise. LA volumes were associated with pAF and athletic status (p < .001). SD-TPS was associated with pAF (p < .001) but not athletic status (p = .173). We found no significant trend between years of exercise and SD-TPS in individuals without AF (p = .893). SD-TPS did not add incremental value in identifying athletes with pAF in addition to clinical markers, QRS width, LA volume, and LASr (p = .056). CONCLUSION: LA MD was associated with pAF regardless of athletic status but not related to years of endurance exercise, suggesting LA MD could be a promising marker of pathological atrial remodeling in athletes. However, we found no incremental value of LA MD identifying athletes with pAF when LASr was included in the model.

Hypokalemia Promotes Arrhythmia by Distinct Mechanisms in Atrial and Ventricular Myocytes.

RATIONALE: Hypokalemia occurs in up to 20% of hospitalized patients and is associated with increased incidence of ventricular and atrial fibrillation. It is unclear whether these differing types of arrhythmia result from direct and perhaps distinct effects of hypokalemia on cardiomyocytes. OBJECTIVE: To investigate proarrhythmic mechanisms of hypokalemia in ventricular and atrial myocytes. METHODS AND RESULTS: Experiments were performed in isolated rat myocytes exposed to simulated hypokalemia conditions (reduction of extracellular [K+] from 5.0 to 2.7 mmol/L) and supported by mathematical modeling studies. Ventricular cells subjected to hypokalemia exhibited Ca2+ overload and increased generation of both spontaneous Ca2+ waves and delayed afterdepolarizations. However, similar Ca2+-dependent spontaneous activity during hypokalemia was only observed in a minority of atrial cells that were observed to contain t-tubules. This effect was attributed to close functional pairing of the Na+-K+ ATPase and Na+-Ca2+ exchanger proteins within these structures, as reduction in Na+ pump activity locally inhibited Ca2+ extrusion. Ventricular myocytes and tubulated atrial myocytes additionally exhibited early afterdepolarizations during hypokalemia, associated with Ca2+ overload. However, early afterdepolarizations also occurred in untubulated atrial cells, despite Ca2+ quiescence. These phase-3 early afterdepolarizations were rather linked to reactivation of nonequilibrium Na+ current, as they were rapidly blocked by tetrodotoxin. Na+ current-driven early afterdepolarizations in untubulated atrial cells were enabled by membrane hyperpolarization during hypokalemia and short action potential configurations. Brief action potentials were in turn maintained by ultra-rapid K+ current (IKur); a current which was found to be absent in tubulated atrial myocytes and ventricular myocytes. CONCLUSIONS: Distinct mechanisms underlie hypokalemia-induced arrhythmia in the ventricle and atrium but also vary between atrial myocytes depending on subcellular structure and electrophysiology.

Impact of neighbourhood-level socioeconomic status, traditional coronary risk factors, and ancestry on age at myocardial infarction onset: A population-based register study.

BACKGROUND: There is consensus that low socioeconomic status (SES) is associated with an increased risk of acute myocardial infarction (AMI), but the extent to which traditional coronary risk factors and other characteristics of low SES mediate this effect remains uncertain. This study examined AMI patients residing in neighbouring city districts with the same local hospital despite having among the most considerable differences in mean SES in Norway. Our purpose was to assess low SES as a coronary risk factor and examine whether traditional coronary risk factors or ancestry mediate this effect. METHODS: Six hundred six patients (215 and 391 with a low and high neighbourhood-level SES, respectively) admitted to Diakonhjemmet Hospital with non-ST-elevation myocardial infarction (NSTEMI) between 2014 and 2017, entered analysis. Data from the Norwegian Myocardial Infarction Register were used to identify patient characteristics, and the STATA/SE 15.1 software was used to perform the statistical analyses. RESULTS: Patients from socioeconomically disadvantaged city-districts had a 4.9 years earlier onset of AMI (68.99 vs. 73.89 years; p < 0.001) and a higher prevalence of previous AMI, known diabetes, and current smokers (36% vs. 27%, 25% vs. 12%, and 33% vs. 17%, respectively; all p ≤ 0.05). When only comparing patients with a first time AMI, an even greater difference in the age at AMI onset was found (6.1 yrs; p < 0.001). The difference in age at AMI onset remained statistically significant when adjusting for traditional coronary risk factors (3.28 yrs; 95% confidence interval (CI) 1.11-5.44; p = 0.003), but not when adjusting for presumed non-Northwest-European ancestry (1.81 yrs; 95% CI -0.55 to 4.17; p = 0.132). CONCLUSION: This study supports earlier research showing an increased risk of AMI in socioeconomically disadvantaged individuals. In our population, presumed non-Northwest-European ancestry could entirely explain the increased risk, whereas traditional coronary risk factors could only partly explain the increased risk.

Potassium infusion increases the likelihood of conversion of recent-onset atrial fibrillation-A single-blinded, randomized clinical trial.

BACKGROUND: The optimal antiarrhythmic management of recent-onset atrial fibrillation (ROAF) or atrial flutter is controversial and there is a considerable variability in clinical treatment strategies. It is not known if potassium infusion has the potential to convert ROAF or atrial flutter to sinus rhythm (SR). Therefore, we aimed to investigate if patients with ROAF or atrial flutter and plasma-potassium levels ≤4.0 mmol/L have increased probability to convert to SR if the plasma-potassium level is increased towards the upper reference range (4.1-5.0 mmol/L). METHODS: In a placebo-controlled, single-blinded trial, patients with ROAF or atrial flutter and plasma-potassium ≤4.0 mmol/L presenting between April 2013 and November 2017 were randomized to receive potassium chloride (KCl) infusion (n = 60) or placebo (n = 53). Patients in the KCl group received infusions at one of three different rates: 9.4 mmol/h (n = 11), 12 mmol/h (n = 19), or 15 mmol/h (n = 30). RESULTS: There was no statistical difference in the number of conversions to SR between the KCl group and placebo [logrank test, P = .29; hazard ratio (HR) 1.20 (CI 0.72-1.98)]. However, KCl-infused patients who achieved an above-median hourly increase in plasma-potassium (>0.047 mmol/h) exhibited a significantly higher conversion rate compared with placebo [logrank P = .002; HR 2.40 (CI 1.36-4.21)] and KCl patients with below-median change in plasma-potassium [logrank P < .001; HR 4.41 (CI 2.07-9.40)]. Due to pain at the infusion site, the infusion was prematurely terminated in 10 patients (17%). CONCLUSIONS: Although increasing plasma-potassium levels did not significantly augment conversion of ROAF or atrial flutter to SR in patients with potassium levels in the lower-normal range, our results indicate that this treatment may be effective when a rapid increase in potassium concentration is tolerated and achieved.

Impact of genotype-predicted CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction - a prospective observational study.

PURPOSE: The ß-1 adrenergic receptor blocker metoprolol is primarily metabolized by the polymorphic enzyme cytochrome P 450 2D6 (CYP2D6), an enzyme with substantial genetic heterogeneity. Our purpose was to investigate the impact of CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction (MI). METHODS: We included 136 patients with MI discharged on treatment with metoprolol with a recommendation to the general practitioner (GP) to increase the metoprolol dose up to 200 mg/day within 2 months if possible. At follow-up, metoprolol dosage after up-titration, metoprolol steady-state trough plasma concentrations, hemodynamic parameters, potential metoprolol-induced adverse drug reactions and number of visits to the GP were measured. CYP2D6 genotyping including the reduced-function variant alleles CYP2D6*9, CYP2D6*10 and CYP2D6*41 was performed after end of follow-up. RESULTS: According to the genotype-defined CYP2D6 phenotypes, 30% of the patients were metoprolol extensive metabolizers (EMs), 55% intermediate metabolizers (IMs) and 13% poor metabolizers (PMs; carriers of non-coding and reduced-function variant included). Dose-adjusted metoprolol trough concentrations were significantly higher in IM (2-fold) and PM (6.2-fold) groups vs. the EM group (p < 0.001). Only 35% of patients in the PM group achieved the primary end point, i.e. reaching at least 85% of the expected maximum heart rate (HR) during exercise, compared with 78% in the EM group (p < 0.01), and maximum observed HR at exercise was significantly lower in the PM group vs. the EM group (129 ± 5 vs. 142 ± 2 bpm, p < 0.007). In contrast, metoprolol maintenance dose, blood pressure, exercise capacity, number of visits at the GP and frequency and severity of self-reported potential metoprolol-related adverse drug reactions were not significantly different between the groups. CONCLUSION: Using a comprehensive CYP2D6 genotyping panel, the present study demonstrates a > 6-fold increase of dose-adjusted plasma metoprolol trough concentration in CYP2D6 PMs vs. EMs with a parallel lower increase in achieved maximum HR during exercise but without association between genotype and frequency or severity of self-reported adverse drug effects. This may indicate that CYP2D6 PMs potentially could benefit of the increased plasma concentration per dose in a naturalistic setting.

Screening for symptoms of depression and anxiety in a cardiology department. / Screening for symptomer på depresjon og angst ved en hjertemedisinsk avdeling.

BACKGROUND: Depression and anxiety are common in patients with cardiac disease and predict a poorer prognosis, increased mortality and reduced compliance with treatment. National and international guidelines recommend procedures for screening, but there is a lack of studies of such practices in Norwegian hospitals. The objective of this study was to implement a simple screening method for symptoms of depression and anxiety in patients with cardiac disease. MATERIAL AND METHOD: Patients in the Department of Cardiology at Diakonhjemmet Hospital who had valvular heart disease, tachyarrhythmia, myocardial infarction or heart failure were screened for symptoms of depression, anxiety and panic attacks with the aid of five questions from the Patient Health Questionnaire-2 (PHQ-2), Generalized Anxiety Disorder Scale-2 (GAD-2) and Patient Health Questionnaire - Somatic, Anxiety, and Depressive Symptom Scales (PHQ-SADS). The patients were recruited from the outpatient clinic or ward at least one month after acute heart disease. RESULTS: A total of 57 of 232 patients reported symptoms of depression or anxiety when screened. The screening method was easy to implement, but time constraints and uncertainty regarding procedures for follow-up and the effect of following up the patients were reported. INTERPRETATION: Good tools and methods are available for screening for symptoms of depression and anxiety and anxiety in patients with cardiac disease. More studies are needed regarding the benefits of screening, at what stage of the disease it should be performed, and whether it should be performed by the primary and/or the specialist health services.

Prescribing of NOACs has outnumbered warfarin: exploring how physicians choose anticoagulant treatments.

PURPOSE: The development of non-vitamin K-dependent oral anticoagulants (NOACs) is a new alternative to treatment with warfarin. The purpose of this study was to explore drug prescription decisions of NOACs or warfarin from hospital physicians in cardiovascular departments. METHODS: A qualitative study with focus group interviews was conducted in three different hospitals. The interview guide explored the background of prescribing anticoagulants (warfarin, dabigatran, rivaroxaban, and apixaban) and experiences with effect and side-effects they had observed in patients. RESULTS: The systematic text condensation eluded four main themes: when to prescribe NOACs, concern about side-effects, pharmaceutical properties and patient adherence, and prescribing policy and intra-professional communication. All available anticoagulants were prescribed. However, no specific NOAC was preferred. Factors perceived as contraindications for NOACs varied among the doctors. Most had observed side-effects of NOACs; however, these rarely influenced prescribing decisions due to small differences in safety profiles. Few drug-drug interactions and fixed daily doses made NOACs easy to prescribe; but some doctors had experienced lack of drug effect for some patients. Non-adherence with NOACs was harder to spot. Some different prescribing cultures had evolved between the different hospitals and between general practitioners. CONCLUSION: The hospital physicians chose anticoagulants based on patient conditions as renal function, bleeding risks, and drug interactions being the most common taken into account. They could not say which NOAC was best, and wish that future studies could compare the different NOACs, and not just compare with warfarin.

Initiation of and long-term adherence to secondary preventive drugs after acute myocardial infarction.

BACKGROUND: Secondary preventive drug therapy following acute myocardial infarction (AMI) is recommended to reduce the risk of new cardiovascular events. The aim of this nationwide cohort study was to examine the initiation and long-term use of secondary preventive drugs after AMI. METHODS: The prescription of drugs in 42,707 patients < 85 years discharged alive from hospital after AMI in 2009-2013 was retrieved by linkage of the Norwegian Patient Register, the Norwegian Prescription Database, and the Norwegian Cause of Death Registry. Patients were followed for up to 24 months. RESULTS: The majority of patients were discharged on single or dual antiplatelet therapy (91 %), statins (90 %), beta-blockers (82 %), and angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor II blockers (ARB) (60 %). Patients not undergoing percutaneous coronary intervention (PCI) (42 %) were less likely to be prescribed secondary preventive drugs compared with patients undergoing PCI. This was particular the case for dual antiplatelet therapy (43 % vs. 87 %). The adherence to prescribed drugs was high: 12 months after index AMI, 84 % of patients were still on aspirin, 84 % on statins, 77 % on beta-blockers and 57 % on ACEI/ARB. Few drug and dose adjustments were made during follow-up. CONCLUSION: Guideline-recommended secondary preventive drugs were prescribed to most patients discharged from hospital after AMI, but the percentage receiving such therapy was significantly lower in non-PCI patients. The long-time adherence was high, but few drug adjustments were performed during follow-up. More attention is needed to secondary preventive drug therapy in AMI patients not undergoing PCI.

Altered Levels of Fatty Acids and Inflammatory and Metabolic Mediators in Epicardial Adipose Tissue in Patients With Systolic Heart Failure.

BACKGROUND: Adipose tissue has endocrine properties, secreting a wide range of mediators into the circulation, including factors involved in cardiovascular disease. However, little is known about the potential role of adipose tissue in heart failure (HF), and the aim of this study was to investigate epicardial (EAT) and subcutaneous (SAT) adipose tissue in HF patients. METHODS AND RESULTS: Thirty patients with systolic HF and 30 patients with normal systolic function undergoing thoracic surgery were included in the study. Plasma was sampled and examined with the use of enzyme-linked immunosorbent assays, whereas SAT and EAT biopsies were collected and examined by means of reverse-transcription polymerase chain reaction and gas chromatography. Significantly higher expressions of mRNA encoding interleukin-6, adrenomedullin, peroxisome proliferator-activated receptor α, and fatty acid (FA)-binding protein 3, as well as higher levels of monounsaturated FA and palmitoleic acid, were seen in the EAT of HF patients, whereas the levels of docosahexaenoic acid were lower. Palmitoleic acid levels in EAT were correlated with 2 parameters of cardiac remodeling: increasing left ventricular end-diastolic diameter and N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: Our results demonstrate adipose tissue depot-specific alterations of synthesis of FA and inflammatory and metabolic mediators in systolic HF patients. EAT may be a source of increased circulatory and myocardial levels of these mediators through endocrine actions.

Drug-related emergency department visits: external validation of an assessment tool in a general emergency department population.

BACKGROUND: The process of identifying drug-related hospitalisations is subjective and time-consuming. Assessment tool for identifying hospital admissions related to medications (AT-HARM10) was developed to simplify and objectify this process. AT-HARM10 has not previously been externally validated, thus the predictive precision of the tool is uncertain. AIM: To externally validate AT-HARM10 in adult patients admitted to the emergency department (ED). METHOD: This retrospective cross-sectional study investigated 402 patients admitted to the ED, Diakonhjemmet Hospital, Oslo, Norway. A trained 5th-year pharmacy student used AT-HARM10 to assess all patients and to classify their ED visits as possibly or unlikely drug-related. Assessment of the same patients by an interdisciplinary expert panel acted as the gold standard. The external validation was conducted by comparing AT-HARM10 classifications with the gold standard. RESULTS: According to AT-HARM10 assessments, 169 (42%) patients had a possible drug-related ED visit. Calculated sensitivity and specificity values were 95% and 71%, respectively. Further, positive and negative predictive values were 46% and 98%, respectively. Adverse effects/over-treatment and suboptimal treatment were the issues most frequently overestimated by AT-HARM10 compared with the gold standard. CONCLUSION: AT-HARM10 identifies drug-related ED visits with high sensitivity. However, the low positive predictive value indicates that further review of ED visits classified as possible drug-related by AT-HARM10 is necessary. AT-HARM10 can serve as a useful first-step screening that efficiently identifies unlikely drug-related ED visits, thus only a smaller proportion of the patients need to be reviewed by an interdisciplinary expert panel.

Case report: First case of Borrelia miyamotoi meningitis in an immunocompromised patient in Norway.

Background: Tick-borne disease caused by B. miyamotoi (BMD) usually manifest as a febrile illness in humans. Complications include relapsing fever and in rare occasions involvement of the central nervous system. Only a few cases of meningoencephalitis have been described, mostly in immunosuppressed patients. Case presentation: A 70-year-old female receiving immunosuppressive rituximab therapy presented with frontal headache, dizziness, nausea, vomiting and chills. Clinical laboratory blood analyses were normal. Cerebrospinal fluid (CSF) was translucent and analysis showed increased leucocyte count (187 106/L) and elevated level of protein (1056 mg/L). Empiric antibiotic treatment was initiated. The patient showed an early symptomatic relief and 24 h after admission she was discharged from the hospital and antibiotic treatment was discontinued. Two weeks after hospitalisation the B. miyamotoi specific PCR turned out positive in both CSF and serum. At the time, the patient was recovered with mild residual headache. She was treated with high dose doxycycline and her subtle symptoms disappeared. Conclusions: To our knowledge, we present the first patient with BMD-associated meningitis in Norway, one of eight cases reported worldwide. The patient had mild symptoms and received an early diagnosis. A more severe progression or relapse of disease may have been prevented by antibiotic treatment. BMD should be considered as causes of aseptic meningitis, especially in immunosuppressed patients living in endemic areas.

Long-Term Outcomes of Invasive vs Conservative Strategies for Older Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is a frequent cause of hospital admission in older people, but clinical trials targeting this population are scarce. OBJECTIVES: The After Eighty Study assessed the effect of an invasive vs a conservative treatment strategy in a very old population with NSTE-ACS. METHODS: Between 2010 and 2014, the investigators randomized 457 patients with NSTE-ACS aged ≥80 years (mean age 85 years) to an invasive strategy involving early coronary angiography with immediate evaluation for revascularization and optimal medical therapy or to a conservative strategy (ie, optimal medical therapy). The primary endpoint was a composite of myocardial infarction, need for urgent revascularization, stroke, and death. The long-term outcomes are presented. RESULTS: After a median follow up of 5.3 years, the invasive strategy was superior to the conservative strategy in the reduction of the primary endpoint (incidence rate ratio: 0.76; 95% CI: 0.63-0.93; P = 0.0057). The invasive strategy demonstrated a significant gain in event-free survival of 276 days (95% CI: 151-400 days; P = 0.0001) at 5 years and 337 days (95% CI: 123-550 days; P = 0.0001) at 10 years. These results were consistent across subgroups of patients with respect to major cardiovascular prognostic factors. CONCLUSIONS: In patients aged ≥80 years with NSTE-ACS, the invasive strategy was superior to the conservative strategy in the reduction of composite events and demonstrated a significant gain in event-free survival. (The After Eighty Study: a randomized controlled trial; NCT01255540).

Right Heart Structure and Function in Lifelong Recreational Endurance Athletes with and without Paroxysmal Atrial Fibrillation.

BACKGROUND: Healthy young athletes adapt to the increased demands of endurance exercise with symmetric cardiac remodeling. Male veteran endurance athletes have an increased risk for atrial fibrillation (AF), and some athletes seem susceptible to changes mimicking arrhythmogenic cardiomyopathy. Intense exercise puts a disproportionate hemodynamic load on the right-sided heart chambers. Despite this, data describing right heart structure and function in older veteran athletes are scarce. The aim of this study was to investigate structural and functional characteristics of the right heart in veteran athletes with and without AF to contribute to the understanding of exercise-induced cardiac remodeling in this group. METHODS: Three hundred two male participants, of whom 151 were veteran skiers (62 with paroxysmal AF) and 151 were control subjects from the general population (62 with paroxysmal AF), underwent echocardiographic examinations in sinus rhythm to evaluate right atrial (RA) and right ventricular (RV) structure and function. While 87 of the participants had never exercised regularly, 50, 43, and 122 men had practiced regular endurance exercise for 1 to 20, 20 to 40, and >40 years, respectively. RESULTS: RA volume and RV size increased with cumulative years of exercise (P < .001), with a disproportionate increase in RV size compared with left ventricular (LV) size, regardless of AF status (P < .001). RA and RV function assessed by strain remained similar despite lifelong exposure to endurance exercise. AF was associated with reduced RA strain irrespective of exposure to exercise (P < .001). CONCLUSIONS: RA and RV sizes and RV/LV ratio showed a dose-response relationship with cumulative years of endurance exercise, whereas RA and RV function did not, indicating that increasing RV/LV ratio may represent a physiologic adaptation to prolonged endurance exercise. AF was associated with reduced RA function, regardless of exposure to exercise, suggesting that RA functional parameters are more closely linked to AF than RA size in veteran athletes.

Impact of systematic medication review in emergency department on patients' post-discharge outcomes-A randomized controlled clinical trial.

INTRODUCTION: The main objective of this study was to investigate whether systematic medication review conducted by clinical pharmacists can impact clinical outcomes and post-discharge outcomes for patients admitted to the emergency department. METHOD: This parallel group, non-blinded, randomized controlled trial was conducted in the emergency department, Diakonhjemmet Hospital, Oslo, Norway. The study was registered in ClinicalTrials.gov, Identifier: NCT03123640 in April 2017. From April 2017 to May 2018, patients ≥18 years were included and randomized (1:1) to intervention- or control group. The control group received standard care from emergency department physicians and nurses. In addition to standard care, the intervention group received systematic medication review including medication reconciliation conducted by pharmacists, during the emergency department stay. The primary outcome was proportion of patients with an unplanned contact with hospital within 12 months from inclusion stay discharge. RESULTS: In total, 807 patients were included and randomized, 1:1, to intervention or control group. After excluding 8 patients dying during hospital stay and 10 patients lacking Norwegian personal identification number, the primary analysis comprised 789 patients: 394 intervention group patients and 395 control group patients. Regarding the primary outcome, there was no significant difference in proportion of patients with an unplanned contact with hospital within 12 months after inclusion stay discharge between groups (51.0% of intervention group patients vs. 53.2% of control group patients, p = 0.546). CONCLUSION: As currently designed, emergency department pharmacist-led medication review did not significantly influence clinical- or post-discharge outcomes. This study did, however pinpoint important practical implementations, which can be used to design tailored pharmacist-led interventions and workflow regarding drug-related issues in the emergency department setting.

Drug-related emergency department visits: prevalence and risk factors.

The study aimed to investigate the prevalence of drug-related emergency department (ED) visits and associated risk factors. This retrospective cohort study was conducted in the ED, Diakonhjemmet Hospital, Oslo, Norway. From April 2017 to May 2018, 402 patients allocated to the intervention group in a randomized controlled trial were included in this sub-study. During their ED visit, these patients received medication reconciliation and medication review conducted by study pharmacists, in addition to standard care. Retrospectively, an interdisciplinary team assessed the reconciled drug list and identified drug-related issues alongside demographics, final diagnosis, and laboratory tests for all patients to determine whether their ED visit was drug-related. The study population's median age was 67 years (IQR 27, range 19-96), and patients used a median of 4 regular drugs (IQR 6, range 0-19). In total, 79 (19.7%) patients had a drug-related ED visits, and identified risk factors were increasing age, increasing number of regular drugs and medical referral reason. Adverse effects (72.2%) and non-adherence (16.5%) were the most common causes of drug-related ED visits. Antithrombotic agents were most frequently involved in drug-related ED visits, while immunosuppressants had the highest relative frequency. Only 11.4% of the identified drug-related ED visits were documented by physicians during ED/hospital stay. In the investigated population, 19.7% had a drug-related ED visit, indicating that drug-related ED visits are a major concern. If not recognized and handled, this could be a threat against patient safety. Identified risk factors can be used to identify patients in need of additional attention regarding their drug list during the ED visit.

Emergency department physicians' distribution of time in the fast paced-workflow-a novel time-motion study of drug-related activities.

Background In the emergency department physicians are forced to distribute their time to ensure that all admitted patients receive appropriate emergency care. Previous studies have raised concerns about medication discrepancies in patient's drug lists at admission to the emergency department. Thus, it is important to study how emergency department physicians distribute their time, to highlight where workflow redesign can be needed.Aim to quantify how emergency department physicians distribute their time between various task categories, with particular focus on drug-related tasks.Method Direct observation, time-motion study of emergency department physicians at Diakonhjemmet Hospital, Oslo, Norway. Physicians' activities were categorized in discrete categories and data were collected with the validated method of Work Observation Method By Activity Timing between October 2018 to January 2019. Bootstrap analysis determined 95% confidence intervals for proportions and interruption rates.Results During the observation time of 91.4 h, 31 emergency department physicians were observed. In total, physicians spent majority of their time gathering information (36.5%), communicating (26.3%), and documenting (24.2%). Further, physicians spent 17.8% (95% CI 16.8%, 19.3%) of their time on drug-related tasks. On average, physicians spent 7.8 min (95% CI 7.2, 8.6) per hour to obtain and document patients' drug lists.Conclusion Emergency department physicians are required to conduct numerous essential tasks and distributes a minor proportion of their time on drug-related tasks. More efficient information flow regarding drugs should be facilitated at transitions of care. The presence of healthcare personnel dedicated to obtaining drug lists in the emergency department should be considered.

Mechanisms of novel cardioprotective functions of CCN2/CTGF in myocardial ischemia-reperfusion injury.

CCN2/connective tissue growth factor (CTGF), a CCN family matricellular protein repressed in healthy hearts after birth, is induced in heart failure of various etiologies. Multiple cellular and biological functions have been assigned to CCN2/CTGF depending on cellular context. However, the functions and mechanisms of action of CCN2/CTGF in the heart as well as its roles in cardiac physiology and pathophysiology remain unknown. Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) were generated and compared with nontransgenic littermate control (NLC) mice. Tg-CTGF mice displayed slightly lower cardiac mass and inconspicuous increase of myocardial collagen compared with NLC mice but no evidence of contractile dysfunction. Analysis of the myocardial transcriptome by DNA microarray revealed activation of several distinct gene programs in Tg-CTGF hearts involved in cardioprotection and growth inhibition. Indeed, Tg-CTGF mice subjected to ischemia-reperfusion injury by in situ transient occlusion of the left anterior descending coronary artery in vivo displayed reduced vulnerability with markedly diminished infarct size. These findings were recapitulated in isolated hearts perfused with recombinant human (h)CTGF before the ischemia-reperfusion procedure. Consistently, Tg-CTGF hearts, as well as isolated adult cardiac myocytes exposed to recombinant hCTGF, displayed enhanced phosphorylation and activity of the Akt/p70S6 kinase/GSK-3ß salvage kinase pathway and induction of several genes with reported cardioprotective functions. Inhibition of Akt activities also prevented the cardioprotective phenotype of hearts from Tg-CTGF mice. This report provides novel evidence that CTGF confers cardioprotection by salvage phosphokinase signaling leading to inhibition of GSK-3ß activities, activation of phospho-SMAD2, and reprogramming of gene expression.

Inflammatory interaction between LIGHT and proteinase-activated receptor-2 in endothelial cells: potential role in atherogenesis.

The interaction between inflammatory cytokines and endothelial cells is a critical step in atherogenesis leading to endothelial dysfunction and inflammation. We have previously reported that the tumor necrosis factor superfamily member LIGHT could be involved in atherogenesis through its ability to promote vascular inflammation. In the present study we identified proteinase-activated receptor (PAR)-2 as an inflammatory mediator that was markedly enhanced by LIGHT in endothelial cells. We also found that LIGHT acted synergistically with PAR-2 activation to promote enhanced release of the proatherogenic chemokines interleukin-8 and monocyte chemoattractant protein-1, underscoring that the interaction between LIGHT and PAR-2 is biologically active, promoting potent inflammatory effects. We showed that the LIGHT-mediated upregulation of PAR-2 in endothelial cells is mediated through the HVEM receptor, involving Jun N-terminal kinase signaling pathways. A LIGHT-mediated upregulation of PAR-2 mRNA levels was also found in human monocytes when these cells were preactivated by tumor necrosis factor alpha. We have previously demonstrated increased plasma levels of LIGHT in unstable angina patients, and here we show a similar pattern for PAR-2 expression in peripheral blood monocytes. We also found that LIGHT, LIGHT receptors, and PAR-2 showed enhanced expression, and, to some degree, colocalization in endothelial cells and macrophages, in the atherosclerotic plaques of ApoE(-/-) mice, suggesting that the inflammatory interaction between LIGHT and PAR-2 also may be operating in vivo within an atherosclerotic lesion. Our findings suggest that LIGHT/PAR-2-driven inflammation could be a pathogenic loop in atherogenesis potentially representing a target for therapy in this disorder.