In atrial fibrillation epilepsy risk differs between oral anticoagulants: active comparator, nested case-control study

AIMS: Atrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC). METHODS AND RESULTS: We performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004. In 2011-17, 227 707 AF patients initiated treatment with a DOAC or PPC, of which 1828 cases developed epilepsy on current treatment with an oral anticoagulant. They were matched to 19 084 controls without epilepsy. Patients with DOAC treatment for AF had an overall higher risk of epilepsy with an odds ratio of 1.39, 95% CI (1.24; 1.55) compared to current PPC treatment. Cases had higher baseline CHA2DS2-VASc scores and more frequently a history of stroke than controls. After excluding patients with ischaemic stroke prior to the diagnosis of epilepsy, the risk of epilepsy was still higher on DOACs than on PPC. In contrast, within a cohort of patients with venous thromboembolism, the risk of epilepsy on treatment with DOACs was less elevated [adjusted odds ratio 1.15, 95% CI (0.98; 1.34)]. CONCLUSION: In patients with AF initiating oral anticoagulation, treatment with a DOAC was associated with an increased risk of epilepsy compared to the vitamin K antagonist PPC. Covert brain infarction may explain the observed elevated risk of epilepsy

The influence of Lucretius' De rerum natura on Alexander Pope's An essay on man

The Influence of Lucretius' De Rertun Natura and of its English translations by Thomas Creech and John Dryden on Alexander Pope's Essay on Man has not previously been adequately explored. As this thesis demonstrates, comparative analysis shows (1) that the Lucretiun poem is a model for Pope's manner of addressing the audience, for the pose of his speaker, and for his satiric and didactic style; (2) that the English translations of Creech and Dryden are sources of many verbal echoes and allusions and of a few rhymes; (3) that De Rerum Natura is the source of several controlling metaphors for the Essay on Man; (4) that similarities exist between the Lucretiun concept of order arising from disorder and Pope's concept of "discordia concors" and between the recognition of the cycle as the outer aspect of Nature in both poems; (5) that one of Pope's purposes is to refute the Epicurean religious beliefs professed by Lucretius; and (6) that a remarkable similarity exists between the ethical beliefs of Lucretius and those of Pope. The evidence suggests that De Reruzn Natura, and its translations by Creech and Dryden, should be considered major influences on Pope's An Essay on Man.Thesis (M.A.

Different Risk Profiles of European Patients Using Direct Oral Anticoagulants or Vitamin K Antagonists: a Rapid Review

PURPOSE OF REVIEW: We investigated the risk profiles of patients using direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA) in European cohort studies to estimate the importance of potential (measured or unmeasured) confounding factors in analyses comparing these drugs. We searched MEDLINE and EMBASE (2008–2018) for relevant studies and extracted information on age, sex, comorbidity, Charlson comorbidity index, HAS-BLED score (assessing risk of bleeding) and CHA2DS2-VASc score (assessing risk of stroke). RECENT FINDINGS: Overall, 66 studies with 2,808,757 patients were included. Most patients were from France (37%), Denmark (24%) and Germany (23%). In 56 studies (85%), the focus was on patients with atrial fibrillation. Of the 43 studies comparing DOAC with VKA users, 33% reported a higher and 16% a lower age of DOAC compared with VKA users. The mean age varied by about 1 year in most of these studies. Rivaroxaban was used in the widest age range. Patients with DOAC more often had a history of stroke or bleedings, and patients with VKA more often had a history of diabetes, renal failure, cancer, heart failure or other heart diseases. Most studies did not observe differences regarding the HAS-BLED score or the CHA2DS2-VASc score between groups. SUMMARY: Our review suggests that there are relevant differences in the risk profiles of DOAC versus VKA users and between users of individual DOACs. Reported HAS-BLED or CHA2DS2-VASc scores did not reflect these differences. These patterns require careful consideration in the interpretation of observational studies comparing the effectiveness and the risks of these drugs, also when comparing the results of studies conducted in different countries

Opsoclonus-myoclonus syndrome associated with pancreatic neuroendocrine tumor: a case report

Abstract Background Opsoclonus-myoclonus syndrome (OMS) is a rare, immune-mediated neurological disorder. In adults, the pathogenesis can be idiopathic, post-infectious or paraneoplastic, the latter etiology belonging to the ever-expanding group of defined paraneoplastic neurological syndromes (PNS). In contrast to other phenotypes of PNS, OMS cannot be ascribed to a single pathogenic autoantibody. Here, we report the first detailed case of paraneoplastic, antibody-negative OMS occurring in association with a pancreatic neuroendocrine tumor (pNET). Case presentation A 33-year-old female presented with a two-week history of severe ataxia of stance and gait, dysarthria, head tremor, myoclonus of the extremities and opsoclonus. Her past medical history was notable for a metastatic pancreatic neuroendocrine tumor, and she was subsequently diagnosed with paraneoplastic opsoclonus-myoclonus syndrome. Further workup did not reveal a paraneoplastic autoantibody. She responded well to plasmapheresis, as she was refractory to the first-line therapy with corticosteroids. Conclusions This case expands current knowledge on tumors associated with paraneoplastic opsoclonus-myoclonus syndrome and the age group in which it can occur. It further adds evidence to the effectiveness of plasmapheresis in severe cases of opsoclonus-myoclonus syndrome with a lack of response to first-line therapy

Validation of Algorithms to Identify Acute Myocardial Infarction, Stroke, and Cardiovascular Death in German Health Insurance Data

PURPOSE: Validation of outcomes allows measurement of and correction for potential misclassification and targeted adjustment of algorithms for case definition. The purpose of our study was to validate algorithms for identifying cases of acute myocardial infarction (AMI), stroke, and cardiovascular (CV) death using patient profiles, ie, chronological tabular summaries of relevant available information on a patient, extracted from pseudonymized German claims data. PATIENTS AND METHODS: Based on the German Pharmacoepidemiological Research Database (GePaRD), 250 cases were randomly selected (50% males) for each outcome between 2016 and 2017 based on the inclusion criteria age ≥50 years and continuous insurance ≥1 year and applying the following algorithms: hospitalization with a main diagnosis of AMI (ICD-10-GM codes I21.- and I22.-) or stroke (I63, I61, I64) or death with a hospitalization in the 60 days before with a main diagnosis of CV disease. Patient profiles were built including (i) age and sex, (ii) hospitalizations incl. diagnoses, procedures, discharge reasons, (iii) outpatient diagnoses incl. diagnostic certainty, physician specialty, (iv) outpatient encounters, and (v) outpatient dispensings. Using adjudication criteria based on clinical guidelines and risk factors, two trained physicians independently classified cases as “certain”, “probable”, “unlikely” or “not assessable”. Positive predictive values (PPVs) were calculated as percentage of confirmed cases among all assessable cases. RESULTS: For AMI, the overall PPV was 97.6% [95% confidence interval 94.8–99.1]. The PPV for any stroke was 94.8% [91.3–97.2] and higher for ischemic (98.3% [95.0–99.6]) than for hemorrhagic stroke (86.5% [76.5–93.3]). The PPV for CV death was 79.9% [74.4–84.4]. It increased to 91.7% [87.2–95.0] after excluding 32 cases with data insufficient for a decision. CONCLUSION: Algorithms based on hospital diagnoses can identify AMI, stroke, and CV death from German claims data with high PPV. This was the first study to show that German claims data contain information suitable for outcome validation

Safety and effectiveness of rivaroxaban for prevention of stroke in patients with nonvalvular atrial fibrillation: analysis of routine clinical data from four countries

BACKGROUND: The safety and effectiveness of rivaroxaban versus vitamin K antagonists (standard of care [SOC]) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) was evaluated in Europe. RESEARCH DESIGN AND METHODS: Observational studies were conducted in the UK, the Netherlands, Germany, and Sweden. Primary safety outcomes were hospitalization for intracranial hemorrhage, gastrointestinal bleeding, or urogenital bleeding among new users of rivaroxaban and SOC with NVAF; outcomes were analyzed using cohort (rivaroxaban or SOC use) and nested case–control designs (current vs nonuse). Statistical analyses comparing rivaroxaban and SOC cohorts were not performed. RESULTS: Overall, 162,919 rivaroxaban users and 177,758 SOC users were identified. In the cohort analysis, incidence ranges for rivaroxaban users were 0.25–0.63 events per 100 person-years for intracranial bleeding, 0.49–1.72 for gastrointestinal bleeding, and 0.27–0.54 for urogenital bleeding. Corresponding ranges for SOC users were 0.30–0.80, 0.30–1.42, and 0.24–0.42, respectively. In the nested case–control analysis, current SOC use generally presented a greater risk of bleeding outcomes than nonuse. Rivaroxaban use (vs nonuse) was associated with a higher risk of gastrointestinal bleeding, but a similar risk of intracranial or urogenital bleeding, in most countries. Ischemic stroke incidence ranged from 0.31 to 1.52 events per 100 person-years for rivaroxaban users. CONCLUSION: Incidences of intracranial bleeding were generally lower with rivaroxaban than with SOC, whereas incidences of gastrointestinal and urogenital bleeding were generally higher. The safety profile of rivaroxaban for NVAF in routine practice is consistent with findings from randomized controlled trials and other studies