Ljubica Vukelic Andersen

Warfarin for the prevention of systemic embolism in patients with non-valvular atrial fibrillation: a meta-analysis

Background: Warfarin for stroke prevention in patients with atrial fibrillation (AF) is well documented. However, it has not been examined in the prevention of systemic embolism. Objectives: To evaluate the efficacy of warfarin in preventing systemic embolism (embolism to limbs or viscera) in patients with AF. Methods and results: A combined Medline, Embase, Cochrane Library and SveMed+ search were made. Fifteen studies were included. Warfarin was better than antiplatelet agents for preventing systemic embolism with a 50% reduction of risk (odds ratio (OR)u200a=u200a0.50, 95% CI 0.33 to 0.75) without increasing the risk of major bleeding (ORu200a=u200a1.07; 95% CI 0.85 to 1.34). Warfarin compared with placebo resulted in a risk reduction of 71% (ORu200a=u200a0.29; 95% CI 0.08 to 1.07) with higher risk of major bleeding with warfarin (ORu200a=u200a3.01; 95% CI 1.31 to 6.92). Results of a comparison of warfarin with low-dose warfarin (ORu200a=u200a1.52; 95% CI 0.40 to 5.81) or low-dose warfarin with aspirin (ORu200a=u200a1.00; 95% CI 0.17 to 5.81) were inconclusive. Conclusions: Warfarin not only reduces the risk of stroke but is also better than placebo and antiplatelet agents in prevention of systemic embolism in patients with non-valvular AF. Warfarin increases the risk of major bleeding compared with placebo but not compared with antiplatelet agents.

Trends in Risk of Stroke in Patients with a Hospital Diagnosis of Nonvalvular Atrial Fibrillation: National Cohort Study in Denmark, 1980–2002

Aim: We examined trends in incidence of stroke of any nature (ischemic and/or hemorrhagic) in subjects with a hospital diagnosis of nonvalvular atrial fibrillation or flutter in Denmark from 1980 to 2002 by sex, age and conditions of comorbidity. Methods: We identified all individuals, aged 40–89 years, with an incident hospital diagnosis of atrial fibrillation or flutter and no history of stroke or heart valve disease in the Danish National Registry of Patients, and subjects were followed in the Danish National Registry of Patients for occurrence of an incident diagnosis of stroke of any nature (ischemic and/or hemorrhagic) and in the Danish Civil Registration System (emigration and vital status). We used multivariate Cox proportional hazard regression analysis to estimate trends in incidence of stroke. Results: Nonvalvular atrial fibrillation or flutter was diagnosed in 141,493 subjects (75,126 men and 66,367 women), and during follow-up 15,964 subjects had an incident diagnosis of stroke. The hazard ratios for stroke in the last 3-year period compared to the first 5-year period, adjusted for 10-year age group, conditions of comorbidity, and general stroke trend in the Danish population were 0.78 (95% CI 0.70–0.86) in men, and 0.80 (95% CI 0.72–0.88) in women. The reduction in risk of stroke by calendar year was most prominent in patients aged 40–74 years. Conclusion: We observed a modest decrease in risk of stroke in subject with atrial fibrillation in Denmark during calendar years 1980–2002. However, we could not control for any changes in diagnostic performance, admission practice, and medical management of patients with atrial fibrillation.

Seasonal variation in stroke and stroke-associated mortality in patients with a hospital diagnosis of nonvalvular atrial fibrillation or flutter. A population-based study in Denmark.

Aim: There are few data on seasonal variation in stroke and seasonal variation in mortality after stroke in patients with atrial fibrillation. We examined the seasonal pattern in stroke occurrence and the effect of the season on mortality after stroke in patients with a history of nonvalvular atrial fibrillation. Methods:We identified all individuals, aged 40–89 years, with an incident diagnosis of stroke of any nature (ischemic or hemorrhagic) in the 1980–2002 period and no history of heart valve disease and a previous or concomitant diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients. Subjects were followed in the Danish Civil Registration System for emigration and vital status. We used periodic regression models to estimate the peak-trough ratio stratified by sex, age and comorbid medical conditions. Seasonal effect on mortality after stroke was analyzed in a Cox proportional hazards model. Results: The relative incidence of stroke estimated as the ratio of the incidence in the month of the peak (January) to the incidence in the month of the trough (July) was 1.11 (95% confidence interval: 1.07–1.15). The relative incidence of stroke was similar for men and women, did not differ by age (stratified by age 75 years) and was essentially similar for comorbid conditions considered. There was no seasonal effect on mortality after stroke. Conclusions: The occurrence of stroke in patients with atrial fibrillation is modestly higher during the winter. Stroke-associated mortality does not vary by season.

Age and Risk of Stroke in Atrial Fibrillation: Evidence for Guidelines?

Aim: Guidelines for the clinical management of patients with atrial fibrillation suggest that treatment strategies for prescribing oral anticoagulant therapy should implicate change at age 60, 65 and 75 years. We examined if there is any threshold concerning risk of stroke by age. Methods: We identified 141,493 subjects, aged 40–89 years, with an incident hospital diagnosis of nonvalvular atrial fibrillation or flutter and no previous or concomitant diagnosis of stroke in the Danish National Registry of Patients from January 1, 1980, to December 31, 2002. The subjects were followed in the Danish National Registry of Patients for the occurrence of an incident diagnosis of stroke of any nature and in the Danish Civil Registration System for emigration and vital status. We examined the risk of stroke by age in men and women using Cox regression models, which included age categorized in intervals, linear splines of age with cut points at age 60 and 75 years, or at age 65 and 75 years. We also analyzed age as a continuous variable in linear and polynomial regression models. Results: During follow-up 15,964 incident strokes were reported to the Danish National Registry of Patients. The risk of stroke increased by increasing age at baseline. We did not find any evidence for a threshold concerning risk of stroke by age, and the best model fit was obtained in a third-order polynomial regression model. Conclusion: The risk of stroke increased gradually by increasing age, and we could not detect any threshold concerning risk of stroke by age.

Atrial fibrillation and upper limb thromboembolectomy: a national cohort study.

Summary.u2002 Background: The risk factors associated with, and the incidence of systemic embolism in patients with atrial fibrillation (AF) are poorly understood. Objectives: We studied the association between AF and upper limb thromboembolectomy involving brachial, ulnar or radial artery in a national cohort study that included all individuals aged 40–99u2003years with incident AF. Methods: Data were retrieved from the Danish National Vascular Registry, the National Registry of Patients, the Danish Civil Registration System and Statistics Denmark. Results: In total, 131u2003476 patients (68u2003042 men and 63u2003434 women) with AF without previous thromboembolectomy in the upper limb were registered. In the study cohort, 130 men underwent upper limb thromboembolectomy over 220u2003890 person‐years of observation, whilst 275 women underwent thromboembolectomy over 197u2003777 patient‐years. The incidence per 100u2003000 person‐years was 58.9 (95% CI, 49.2–69.8) for men and 139.1 (95% CI, 123.1–156.5) for women. The relative risk of thromboembolectomy among patients with AF compared to the background population was 7.5 (95% CI, 6.3–8.9) for men, and 9.3 (95% CI, 8.3–10.5) for women. Women with AF had a relative thromboembolectomy risk of 1.8 (95% CI, 1.5–2.3) compared to men with AF. Among patients with AF, history of hypertension (HR 2.2–2.9), myocardial infarction (HR 2.9–3.9), heart failure (HR 1.6–1.9) and stroke (HR 2.2–3.8) were significantly associated with increased risk of thromboembolectomy in both men and women. Conclusions: AF substantially increases the risk of upper limb thromboembolectomy. This risk is higher with increasing age, female gender, and associated with hypertension, myocardial infarction, heart failure and stroke.

Upper limb arterial thromboembolism: a systematic review on incidence, risk factors, and prognosis, including a meta-analysis of risk-modifying drugs

The aim of this review is to focus on risk factors, risk‐modifying drugs and prognosis for upper limb arterial thromboembolism, and the relationship between upper limb arterial thromboembolism and atrial fibrillation (AF).

Detection of Patients at High Risk of Medication Errors: Development and Validation of an Algorithm

Medication errors (MEs) are preventable and can result in patient harm and increased expenses in the healthcare system in terms of hospitalization, prolonged hospitalizations and even death. We aimed to develop a screening tool to detect acutely admitted patients at low or high risk of MEs comprised by items found by literature search and the use of theoretical weighting. Predictive variables used for the development of the risk score were found by the literature search. Three retrospective patient populations and one prospective pilot population were used for modelling. The final risk score was evaluated for precision by the use of sensitivity, specificity and area under the ROC (receiver operating characteristic) curves. The variables used in the final risk score were reduced renal function, the total number of drugs and the risk of individual drugs to cause harm and drug–drug interactions. We found a risk score in the prospective population with an area under the ROC curve of 0.76. The final risk score was found to be quite robust as it showed an area under the ROC curve of 0.87 in a recent patient population, 0.74 in a population of internal medicine and 0.66 in an orthopaedic population. We developed a simple and robust score, MERIS, with the ability to detect patients and divide them according to low and high risk of MEs in a general population admitted at acute admissions unit. The accuracy of the risk score was at least as good as other models reported using multiple regression analysis.

Risk of prescribing errors in acutely admitted patients: a pilot study

Background Prescribing errors in emergency settings occur frequently. Knowing which patients have the highest risk of errors could improve patient outcomes. Objective The aim of this study was to test an algorithm designed to assess prescribing error risk in individual patients, and to test the feasibility of medication reviews in high-risk patients. Setting The study was performed at the Acute Admissions Unit at Aarhus University Hospital, Denmark. Methods The study was an interventional pilot study. Patients included were assessed according to risk of prescribing errors with the aid of an algorithm called ‘Medication Risk Score’ (MERIS). Based on the score, high-risk patients were offered a medication review. The clinical relevance of the medication reviews was assessed retrospectively. Main outcome measure The number and nature of prescribing errors during the patients’ hospitalisation. Results The study included 103 patients, all of whom could be risk assessed with the algorithm MERIS. MERIS stratified 38 patients as high-risk patients and 65 as low-risk patients. The 103 patients were prescribed a total of 848 drugs in which 88 prescribing errors were found (10.4xa0%). Sixty-two of these were found in patients in the high-risk group. In general, the medication reviews were found to be clinically relevant and approximately 50xa0% of recommendations were implemented. Conclusion MERIS was found to be applicable in a clinical setting and stratified most patients with prescribing errors into the high-risk group. The medication reviews were feasible and found to be clinically relevant by most raters.

Clinical Pharmacology in Denmark in 2016: 40 Years with the Danish Society of Clinical Pharmacology and 20 Years as a Medical Speciality

The Danish Society of Clinical Pharmacology was founded in 1976, and mainly thanks to the persistent efforts of the society, clinical pharmacology became an independent medical speciality in Denmark in 1996. Since then, clinical pharmacology has gone from strength to strength. In the Danish healthcare system, clinical pharmacology has established itself as an indispensible part of the efforts to promote the rational, safe and economic use of drugs. Clinical pharmacologists are active in drug committees both in hospitals and in the primary sector. All clinical pharmacology centres offer a local medicines information service. Some centres have established an adverse drug effect manager function. Only one centre offers a therapeutic drug monitoring service. Clinical pharmacologists are responsible for the toxicological advice at the Danish Poison Information Centre at Bispebjerg University Hospital in the Capital Region. The Department of Clinical Pharmacology at Aarhus University Hospital works closely together with forensic toxicologists and pathologists, covering issues regarding illicit substances, forensic pharmacology, post-mortem toxicology, expert testimony and research. Therapeutic geriatric and psychiatric teach-inns for specialist and junior doctors are among the newest initiatives organized by clinical pharmacologists. Clinical pharmacologists work also in the Danish Medicines Agency and in the Danish pharmaceutical industry, and the latter has in particular a great growth potential for creating new jobs and career opportunities for clinical pharmacologists. As of July 2016, the Danish Society of Clinical Pharmacology has 175 members, and 70 of these are specialists in clinical pharmacology corresponding to approximately 2.5 specialists per 1000 doctors (Denmark has in total 28,000 doctors) or approximately 12 specialists per one million inhabitants.