Barcoding of episodic memories in the hippocampus of a food-caching bird.

The hippocampus is critical for episodic memory. Although hippocampal activity represents place and other behaviorally relevant variables, it is unclear how it encodes numerous memories of specific events in life. To study episodic coding, we leveraged the specialized behavior of chickadees-food-caching birds that form memories at well-defined moments in time whenever they cache food for subsequent retrieval. Our recordings during caching revealed very sparse, transient barcode-like patterns of firing across hippocampal neurons. Each "barcode" uniquely represented a caching event and transiently reactivated during the retrieval of that specific cache. Barcodes co-occurred with the conventional activity of place cells but were uncorrelated even for nearby cache locations that had similar place codes. We propose that animals recall episodic memories by reactivating hippocampal barcodes. Similarly to computer hash codes, these patterns assign unique identifiers to different events and could be a mechanism for rapid formation and storage of many non-interfering memories.

Effectiveness and safety of direct oral anticoagulants in patients with venous thromboembolism and creatinine clearance < 30 mL/min.

The few studies that compared direct oral anticoagulants (DOAC) vs. warfarin in the setting of advanced renal insufficiency have focused on patients with atrial fibrillation. The purpose of this observational, matched, cohort study of patients was to assess the effectiveness and safety of DOAC vs. warfarin for the treatment of venous thromboembolism (VTE) among patients with a creatinine clearance (CrCl) < 30 mL/min. This observational, cohort study included patients with VTE and CrCl < 30 mL/min who were newly initiated on a DOAC or warfarin between January 1, 2016 and December 31, 2020. DOAC patients were matched up to 1:2 to warfarin patients. Primary outcome was a composite of recurrent VTE, clinically-relevant bleeding, ischemic stroke, and all-cause mortality. Adjusted conditional, multivariate Cox proportional hazards modeling was used to assess outcomes. 626 DOAC patients were matched to 1071 warfarin patients. DOAC patients had a higher mean age, higher mean baseline CrCl, and were less likely to have been receiving dialysis. There was no statistically significant difference in the composite outcome between groups (adjusted hazard ratio [aHR] 1.13, 95% confidence interval [CI] 0.87-1.47) or in the individual components of the composite (all HR 95% CI crossed 1.00). Identification of statistically non-significant rates of bleeding and thromboembolic outcomes suggest that the use of DOAC or warfarin is reasonable in patients with VTE and CrCl < 30 mL/min.

The Impact of Clinical Pharmacy Services on Direct Oral Anticoagulant Medication Selection and Dosing in the Ambulatory Care Setting.

Background: Off-label dosing of direct oral anticoagulants (DOACs) is both common and associated with adverse patient outcomes. Evidence describing best practices to support optimal direct oral anticoagulant (DOAC) dosing is limited. Objective: To describe the impact of clinical pharmacist intervention on DOAC prescribing. Methods: This retrospective study was a descriptive analysis conducted within an integrated healthcare system with a centralized, pharmacist-led Anticoagulation Management Service (AMS). Patients prescribed a DOAC between January 1, 2020 and December 31, 2020 were included. Pharmacy dispensing reports were generated for pharmacist review and anticoagulant drug therapy changes were recommended to physicians where appropriate. The primary objective was to describe the number and type of recommendations made. Secondary objectives were to determine the provider acceptance rate based on the intervention type and on clinical vs formulary recommendations. Results: Clinical pharmacists made 147 recommendations for 2331 unique patients included in the analysis. Twenty-three recommendations (16%) were to decrease the dose, 46 (31%) were to increase the dose, 14 (10%) were to change the medication due to clinical scenario, 62 (42%) were to change the medication due to cost, and 2 (1%) were another issue. One hundred twenty-three (84%) recommendations were accepted. The provider acceptance rate was similar for clinical and formulary recommendations (85% and 82% respectively). Conclusion: Implementation of report-driven clinical pharmacist intervention led to an improvement in appropriate DOAC medication selection and dosing.

Barcoding of episodic memories in the hippocampus of a food-caching bird.

Episodic memory, or memory of experienced events, is a critical function of the hippocampus1-3. It is therefore important to understand how hippocampal activity represents specific events in an animal's life. We addressed this question in chickadees - specialist food-caching birds that hide food at scattered locations and use memory to find their caches later in time4,5. We performed high-density neural recordings in the hippocampus of chickadees as they cached and retrieved seeds in a laboratory arena. We found that each caching event was represented by a burst of firing in a unique set of hippocampal neurons. These 'barcode-like' patterns of activity were sparse (<10% of neurons active), uncorrelated even for immediately adjacent caches, and different even for separate caches at the same location. The barcode representing a specific caching event was transiently reactivated whenever a bird later interacted with the same cache - for example, to retrieve food. Barcodes co-occurred with conventional place cell activity6,7, as well as location-independent responses to cached seeds. We propose that barcodes are signatures of episodic memories evoked during memory recall. These patterns assign a unique identifier to each event and may be a mechanism for rapid formation and storage of many non-interfering memories.