Perioperative Management of Direct Oral Anticoagulants in Cardiac Surgery: Practice Recommendations Based on Current Evidence.

An increasing number of patients on systemic oral anticoagulants present for cardiac surgery, and cardiac anesthesiologists should be well-informed on their management in the perioperative period. Direct oral anticoagulants (DOACs), including factor Xa inhibitors and direct thrombin inhibitors, are an attractive alternative to warfarin due to fewer dietary and drug interactions, less frequent monitoring requirements, and an improved patient adherence. Since the approval of DOACs by the Food and Drug Administration in 2010, the number of patients on these medications only has increased. The guidelines vary on the periprocedural management of DOACs for cardiac surgery. This review evaluated the current evidence for medication cessation before surgery, based on timing as well as plasma drug concentration. The practice recommendations of various monitoring tests and new evolving point-of-care testing are examined herein. The different reversal agents were discussed by the authors for both elective and urgent procedures. The cardiac anesthesiologist needs to be intimately familiar with the management and current best practices of DOACs for safe and appropriate patient care.

A double blind randomized placebo controlled pilot study of single-dose preoperative modafinil for functional recovery after general anesthesia in patients with obstructive sleep apnea.

BACKGROUND: We theorized that modafinil, an atypical psychomotor stimulant, utilized to improve daytime somnolence in patients with obstructive sleep apnea, would improve functional recovery after general anesthesia by improving time to extubation, post-anesthesia care unit (PACU) length of stay and subjective recovery after general anesthesia. METHODS: A double blind, randomized, placebo-controlled pilot study was performed. 102 patients with the diagnosis of obstructive sleep apnea (OSA) were randomized to receive either 200 mg of modafinil or placebo before general anesthesia. The trial was terminated for futility. The primary outcome was PACU length of stay between groups. Secondary functional metrics of improved post-anesthesia recovery were compared between groups. RESULTS: No difference between groups was found on the primary outcome of PACU length of stay (PACULOS). Emergence from general anesthesia was not significantly different when assessed by the time period between termination of volatile anesthetic and extubation. Similarly, no difference between groups was found in intraoperative bispectral index (BIS) values, postoperative pain scores or narcotic consumption (morphine equivalent units). In the post-anesthesia care unit, respiratory rate was increased and mean arterial pressure was lower in the modafinil group. CONCLUSIONS: Our results suggest that the use of single-dose preoperative modafinil may not improve functional recovery after general anesthesia in patients with the diagnosis of OSA. Further research is needed before use of atypical psychomotor stimulants in this surgical population.

The Anticoagulated trauma patient in the age of the direct oral anticoagulants: a Canadian perspective.

BACKGROUND: The anticoagulated trauma patient presents a particular challenge to the critical care physician. Our understanding of these patients is defined and extrapolated by experience with patients on warfarin pre-injury. Today, many patients who would have been on warfarin are now prescribed the Direct Oral Anticoagulants (DOACs) a class of anticoagulants with entirely different mechanisms of action, effects on routine coagulation assays and approach to reversal. METHODS: Trauma registry data from Toronto's (Ontario, Canada) two Level 1 trauma centres were used to identify patients on oral anticoagulation pre-injury from June 1, 2014 to June 1, 2015. The trauma registry and medical records were reviewed and used to extract demographic and clinical data. RESULTS: We found 81 patients were on oral anticoagulants pre-injury representing 3.2% of the total trauma population and 33% of the orally anticoagulated patients were prescribed a DOAC prior to presentation. Comparison between the DOAC and warfarin groups showed similar age, mechanisms of injury, indications for anticoagulation, injury severity score and rate of intracranial hemorrhage. Patients on DOACs had higher initial mean hemoglobin vs warfarin (131 vs 120) and lower serum creatinine (94.8 vs 129.5). The percentage of patients receiving a blood transfusion in the trauma bay and total in-hospital transfusion was similar between the two groups however patients on DOACs were more likely to receive tranexamic acid vs patients on warfarin (32.1% vs 9.1%) and less likely to receive prothrombin concentrates (18.5% vs 60%). Patients on DOACs were found to have higher survival to discharge (92%) vs patients on warfarin (72%). CONCLUSION: Patients on DOACs pre-injury now represent a significant proportion of the anticoagulated trauma population. Although they share demographic and clinical similarities with patients on warfarin, patients on DOACs may have improved outcomes despite lack of established drug reversal protocols and challenging interpretation of coagulation assays. LEVEL OF EVIDENCE: III; Study Type: Retrospective Review.

Giraffe genome sequence reveals clues to its unique morphology and physiology.

The origins of giraffe's imposing stature and associated cardiovascular adaptations are unknown. Okapi, which lacks these unique features, is giraffe's closest relative and provides a useful comparison, to identify genetic variation underlying giraffe's long neck and cardiovascular system. The genomes of giraffe and okapi were sequenced, and through comparative analyses genes and pathways were identified that exhibit unique genetic changes and likely contribute to giraffe's unique features. Some of these genes are in the HOX, NOTCH and FGF signalling pathways, which regulate both skeletal and cardiovascular development, suggesting that giraffe's stature and cardiovascular adaptations evolved in parallel through changes in a small number of genes. Mitochondrial metabolism and volatile fatty acids transport genes are also evolutionarily diverged in giraffe and may be related to its unusual diet that includes toxic plants. Unexpectedly, substantial evolutionary changes have occurred in giraffe and okapi in double-strand break repair and centrosome functions.

Good-quality social care for people with Parkinson's disease: a qualitative study.

OBJECTIVES: The study examines the meaning of good-quality social care for people with Parkinson's disease and their carers. It identifies, from their perspective, the impact of good-quality social care on health and well-being. DESIGN: Qualitative case study methodology, interview and framework analysis techniques were used. SETTING: community locations in the north and midlands of England. PARTICIPANTS: Data were collected from 43 participants including individual interviews with people with Parkinson's disease (n=4), formal and informal social care providers (n=13), 2 focus groups, 1 with people with Parkinson's disease and their carers (n=17), and 1 with professionals (n=8), plus a telephone interview with a former commissioner. FINDINGS: Good-quality social care, delivered in a timely fashion, was reported to have a positive impact on health. Furthermore, there is an indication that good-quality social care can prevent untoward events, such as infections, symptom deterioration and deterioration in mental health. The concept of the 'Impact Gap' developed from the findings, illustrates how the costs of care may be reduced by delivering good-quality social care. Control, choice and maintaining independence emerged as indicators of good-quality social care, irrespective of clinical condition. Participants identified characteristics indicative of good-quality social care specific to Parkinson's disease, including understanding Parkinson's disease, appropriate administration of medication, timing of care and reassessment. 'Parkinson's aware' social care was seen to generate psychological, physical and social benefits that were inter-related. CONCLUSIONS: The findings indicate how maximising quality in social care delivery for people with Parkinson's disease can impact on health and well-being. Long-term or short-term benefits may result in prevented events and reductions in health and social care resource. Health professionals can be instrumental in early detection of and signposting to social care.

Validation of interleukin 28B genotyping assay for clinical use.

OBJECTIVES: The favorable CC genotype at rs12979860 upstream of the interleukin (IL)-28B gene is correlated with a greater post-treatment sustained virologic response rate in chronic hepatitis C infected patients. We report on our validation of a clinical genotyping assay for rs12979860 polymorphisms in the IL28B locus. DESIGN AND METHODS: The rs12979860 genotype was determined using a TaqMan® Real-Time PCR allelic discrimination assay with primers and probes specific for the C and T alleles on the Applied Biosystems 7500 Fast Real-Time PCR System. RESULTS: The rs12979860 genotype determined by our assay was concordant with the genotypes obtained from a reference laboratory. The allelic frequency was similar to that reported in the HapMap project (rs12979860 C=0.65, T=0.35) and did not deviate from Hardy-Weinberg equilibrium. CONCLUSION: Clinical availability of this assay in conjunction with other factors will allow the prediction of the individual patient's response to therapy.