Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency

BACKGROUND

Low molecular weight heparins (LMWHs) have been cautiously used in patients with chronic kidney disease (CKD) due to fear of accumulation. Dalteparin, however, has shown minimal tendency to accumulate in patients with CKD and may be safe to use in this patient population.

OBJECTIVE

We compared the incidence of clinically significant bleeding in patients with CKD receiving therapeutic doses of dalteparin to that of patients with CKD receiving therapeutic doses of UFH.

DESIGN

This was a retrospective cohort study.

SUBJECTS

Inpatients with CKD (GFR?<?60 ml/min) who were treated with therapeutic dalteparin or UFH were included in the study

MAIN MEASURES

Primary outcome was major bleeding within 10 days of anticoagulation, identified by ICD-9 code and confirmed by chart review. Demographic characteristics, laboratory values, comorbidities, prior bleeding history and inpatient medications were extracted for each admission from the electronic medical record. Logistic regression models were created to examine the association between choice of anticoagulant and bleeding rates, after adjustment for demographic and clinical characteristics.

KEY RESULTS

Dalteparin-treated patients were significantly less likely to experience a major bleed than patients treated with UFH (1.14 % vs. 3.49 %, p?<?0.001). The reduced likelihood of bleeding associated with dalteparin treatment remained significant after adjustment for patient characteristics (HR 0.39, 95 % CI: 0.21–0.70, p?<?0.0001). A stratified analysis for subgroups with GFR< 30 mL/min and with GFR between 30 and 60 mL/min showed that dalteparin was still associated with lower odds of bleeding compared to treatment with unfractionated heparin, but the difference was nonsignificant for GFR< 30 (HR 0.35, 95 % CI: 0.11–1.15), even after adjustment (OR 0.37, 95 % CI: 0.11–1.22).

CONCLUSION

In patients with CKD, treatment with therapeutic dose dalteparin was associated with lower rates of bleeding than treatment with unfractionated heparin. For patients with severe CKD (GFR< 30), dalteparin was shown to be at least as safe as unfractionated heparin.

     

The man who feels two hearts: the different pathways of interoception

Recent advances in neuroscience have provided new insights into the understanding of heart–brain interaction and communication. Cardiac information to the brain relies on two pathways, terminating in the insular cortex (IC) and anterior cingulate cortex (ACC), along with the somatosensory cortex (S1-S2). Interoception relying on these neuroanatomical pathways has been shown to modulate social cognition. We report the case study of C.S., a patient with an ‘external heart’ (an extracorporeal left-univentricular cardiac assist device, LVAD). The patient was assessed with neural/behavioral measures of cardiac interoception complemented by neuropsychological and social cognition measures. The patient’s performance on the interoception task (heartbeat detection) seemed to be guided by signals from the artificial LVAD, which provides a somatosensory beat rather than by his endogenous heart. Cortical activity (HEP, heartbeat-evoked potential) was found decreased in comparison with normal volunteers, particularly during interoceptive states. The patient accurately performed several cognitive tasks, except for interoception-related social cognition domains (empathy, theory of mind and decision making). This evidence suggests an imbalance in the patient’s cardiac interoceptive pathways that enhances sensation driven by the artificial pump over that from the cardiac vagal-IC/ACC pathway. A patient with two hearts, one endogenous and one artificial, presents a unique opportunity to explore models of interoception and heart–brain interaction.     

Effects of Perinatal Stress and Maternal Traumatic Stress on the Cortisol Regulation of Preterm Infants

Preterm infants experience intense stress during the perinatal period because they endure painful and intense medical procedures. Repeated activation of the hypothalamic–pituitary–adrenal (HPA) axis during this period may have long‐term effects on subsequent cortisol regulation. A premature delivery may also be intensely stressful for the parents, and they may develop symptoms of posttraumatic stress disorder (PTSD). Usable saliva samples were collected (4 times per day over 2 days, in the morning at awakening, at midday, in the afternoon, and in the evening before going to bed) to assess the diurnal cortisol regulation from 46 preterm infants when the infants were 12 months of corrected age (～ 14 months after birth). Mothers reported their level of PTSD symptoms. The results showed an interaction between perinatal stress and maternal traumatic stress on the diurnal cortisol slope of preterm infants (R² = .32). This suggests that the HPA axis of preterm infants exposed to high perinatal stress may be more sensitive to subsequent environmental stress.     

Efficacy and safety of treatment with biologicals (benralizumab,dupilumab, mepolizumab,omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma

Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV₁, without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV₁. More data on long-term safety are needed together with more efficacy data in the paediatric population.