2 Minute Medicine Rewind March 8, 2021

Rates of rebleeding, thrombosis and mortality associated with resumption of anticoagulant therapy after anticoagulant-related bleeding

1. Resuming oral anticoagulant (OAC) therapy after an OAC-related bleed was associated with higher rates of subsequent bleeding, but lower rates of thrombosis and all-cause mortality.  

Evidence Rating Level: 2 (Good)

While oral anticoagulants (OACs) are used to prevent thrombosis, a common adverse side effect with OAC usage is bleeding. A clinical dilemma occurs when deciding whether or not to resume OACs after a bleed. Past research has shown that 50% and 64% of patients permanently stopped OAC usage after a gastrointestinal (GI) and intracranial bleed respectively. As well, previous studies have focused more on warfarin use after bleeding, and not so much on direct OACs (DOACs), which are the primary preventative measure for stroke due to atrial fibrillation. Therefore, the current study aimed to compare bleeding, thrombosis, and all-cause mortality outcomes between patients who did or did not resume OACs, after a bleeding event related to OAC use. Data was gathered between 2012 and 2017 from patients aged 66 years and older, who had a hospital admission related to bleeding, and a prescription for an OAC within 100 days prior to admission. Of the 6793 patients in the study, 70.5% of patients resumed using an OAC within a year of admission (71.6% for GI bleed, and 45.6% for intracranial hemorrhage). For all categories of bleed, there was a lower rate of thrombosis for those who resumed OACs (10.0% vs 14.9%, adjusted hazards ratio 0.60, 95% CI 0.50-0.72). However, the rates of bleeding were higher in those who resumed OACs (35.2% vs 16.4%, adjusted HR 1.88, 95% CI 0.48-0.60). Additionally, there was a lower rate of mortality for those who resumed OACs (31% vs 54%, adjusted HR 0.54, 95% CI 0.48-0.60). These findings were generally consistent across GI bleeds, intracranial hemorrhage, and extracranial non-GI bleeds, although the rate of thrombosis for intracranial hemorrhage patients resuming OACs was no different from those who did not resume (HR 0.73, 95% CI 0.44-1.23). Overall, resumption of OACs after an OAC-related bleed was shown to reduce thrombosis and all-cause mortality rates significantly.


Identifying at‐risk patients for sustained atrial high‐rate episodes using the C2HEST Score: The West Birmingham Atrial Fibrillation Project

1. The C2HEST score had moderate accuracy in predicting sustained atrial high-rate episodes (SAHREs) for patients with cardiac implantable electronic devices, but no atrial fibrillation.

2. A 1-point increase in the C2HEST score was associated with a 39% increased risk of SAHREs).

Evidence Rating Level: 2 (Good)

In patients without atrial fibrillation (AF) but having cardiac implantable electronic devices (CIEDs), there is an estimated 30% prevalence for experiencing atrial high-rate episodes (AHREs). In particular, when these episodes last greater than 24 hours, they are classified as sustained AHREs (SASHREs), a form of subclinical AF, which are associated with greater risk of thromboembolic events. However, there has not been a model to assess risk of these events in CIED patients without AF, and so the study aimed to examine the predictive value of a recently developed evaluation tool, known as the C2HEST. This stands for coronary artery disease or chronic obstructive pulmonary disease, hypertension, elderly age (≥75 years), systolic heart failure, and thyroid disease. The E and S are worth 2 points each, whereas the other letters are worth 1 point. The data set for this study came from the West Birmingham Atrial Fibrillation Project, with patients from 1999 to 2017. Among the 500 patient sample, the mean age was 69.9 years, and 57.0% were male. Over a mean follow-up of 53.1 months, 44 patients experienced SAHREs, with an incident rate of 2.09% per year (95% CI, 1.47-2.71% per year). The patients with SAHREs had a mean±SD C2HEST score of 3.4±1.5, versus a score of 2.4±1.6 in those without SAHREs (p < 0.001). For those with a score of 0 or 1, 2 or 3, and greater than 4, the incident rates were 0.85 (95% CI 0.27-1.94), 1.87. (95% CI 1.06-2.91), and 3.62 (95% CI 2.14-5.16) respectively. With the 0 or 1 score as the reference, the p-values were 0.159 for the 2-3 score and 0.004 for the greater than 4 score. Furthermore, there was a 39% higher risk of SAHREs with every point increase on the C2HEST criteria (hazards ratio 1.39, 95% CI 1.16-1.68). Overall, the C2HEST evaluation tool was determined to have a moderately accurate predictive value for SAHREs in CIED patients with no AF. In particular, patients with a C2HEST score of greater than 4 are at particularly high risk, which has implications for more frequent monitoring and device examination for this population.


Safety of combined division vs separate division of the splenic vein in patients undergoing distal pancreatectomy

1. In distal pancreatectomy procedures, combined division of the splenic vein with the pancreatic parenchyma had no difference in safety compared to the conventional, separated division method.

Evidence Rating Level: 1 (Excellent)

In a distal pancreatectomy (DP) procedure, apart from dissecting the pancreas, surgeons conventionally dissect the splenic artery and vein after isolating them from the pancreas parenchyma. The logic of this isolation was to prevent potential pancreatic fistulas (PFs) and intra-abdominal hemorrhage, which is reported in 1-8% of DP patients. However, a simpler method is dissecting the splenic vein and pancreatic parenchyma together, although the safety of this technique has not previously been investigated. Therefore, the aim of this multicentre, phase 3 randomized controlled trial, was to establish the non-inferiority of the combined resection versus separated resection of the splenic vein in DP procedures. There were 316 patients overall (159 in the intent-to-treat separate division, 157 in the intent-to-treat combined division), with procedures done in 45 institutions in Japan between 2016 and 2019. The primary outcome measured was the incidence of grade B/C PF. In the separate division group, the incidence was 27.1% (42 patients), compared to 28.6% (44 patients) in the combined division (odds ratio 1.108, 95% CI 0.847-1.225, p = 0.047). Additionally, there were no differences in operative time, blood loss, or incidence of postoperative intra-abdominal hemorrhage (only 2 patients in each group experienced this). Although there was a higher incidence of pancreatic injury, such as laceration, in the combined group, the difference was not statistically significant (5.9% versus 2.0%, p = 0.14). Overall, the study demonstrated non-inferiority of the technique involving dissection of the pancreatic parenchyma combined with the splenic vein, compared to the technique involving separate dissection, for distal pancreatectomy procedures.


Neurologic involvement in children and adolescents with COVID-19 or multisystem inflammatory syndrome

1. 22% of children and adolescents hospitalized for COVID-19 related reasons developed neurologic symptoms, with 10% of these cases being life-threatening, with conditions such as encephalopathy, stroke, and CNS infection.

Evidence Rating Level: 4 (Below Average)

Although COVID-19 affects the respiratory system primarily, there have also been neurological disorders associated with the disease. In one early report from Wuhan, 36% of adults hospitalized with COVID-19 had neurologic symptoms. In children and adolescents with COVID-19, a rare illness known as multisystem inflammatory syndrome in children (MIS-C) has been identified, with case series studies n 2020 reporting 6-58% of MIS-C patients having central or peripheral nervous system issues. The aim of the current case series study was to characterize the type and severity of neurologic conditions for patients under 21 years of age, who were hospitalized for COVID-19 related reasons. Data was collected from 61 hospitals in 31 states across the United States, between March and December 2020. In total, 1695 patients (54% male) were included in the study, with a median age of 9.1 (interquartile range 2.4-15.3 years). Out of these, 365 patients (22%) had some form of neurologic involvement, which was more likely in patients with underlying neurologic disorders (22% versus 8%). The most common neurologic signs were seizures in children younger than 5, and anosmia/ageusia in patients between 13 and 20. In terms of survival, 96% and 99% of patients with and without neurologic involvement respectively were discharged alive. 43 of the 365 patients (12%) had life-threatening neurological involvement, with 79% not having had major underlying conditions, and 47% meeting the MIS-C criteria. The life-threatening conditions included severe encephalopathy (n=15), ischemic or hemorrhagic stroke (n=12), CNS infection (n=8), and cerebral edema (n=4). Out of these 43 patients, 11 passed away and 17 were discharged with neurologic deficits. Overall, the study found neurologic symptoms in about 1/5 of children and adolescents hospitalized for COVID-19 related reasons, which included some life-threatening and fatal cases.


Relationships between depression and anxiety symptoms and adipocyte-derived proteins in postmenopausal women

1. High adiponectin and low leptin levels were associated with greater anxiety and depression symptoms in postmenopausal women.

Evidence Rating Level: 2 (Good)

Rates of depression and anxiety are nearly 2 times higher during and after menopause, with some prevalence estimates ranging from 18-41.8% and 7-25% for peri- and postmenopausal periods respectively. Although there is no clear causative link, past studies have shown a correlation between depression and obesity or metabolic syndrome. As well, anxiety symptoms and obesity were found to be correlated with increased inflammation and insulin resistance. The hormones adiponectin and leptin have been proposed as potential markers for greater risk and lower risk of mental illness respectively: Both are secreted by adipocytes, with adiponectin having anti-inflammatory and insulin-sensitizing action, and leptin having pro-inflammatory and metabolic regulatory effects. The current study investigated the association between adiponectin and leptin levels with anxiety and depression in postmenopausal women. The study consisted of 190 postmenopausal women with a median age of 53 (interquartile range 50-56 years). Hormone levels were measured from blood tests after an 8-hour fast, and the psychological tests administered were the Center for Epidemiologic Studies Depression Scale (CES-D) and the Hamilton Anxiety Rating Scale (HAM-A). Higher scores on these psychological tests indicated more severe mental illness. Overall, the study found significant correlations between both psychological tests, and adiponectin and leptin levels. Higher adiponectin levels were associated with higher CES-D scores (p = 0.009) and HAM-A scores (p = 0.01), whereas lower leptin levels were associated with higher CES-D scores (p = 0.015) and HAM-A scores (p = 0.001). In particular, patients with a CES-D score greater than 16 and HAM-A greater than 18 had higher adiponectin levels than those with lower scores.  In conclusion, high adiponectin and low leptin levels were found to be potential indicators of anxiety and depression symptoms in postmenopausal women.

Image: PD

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