A Computable Algorithm for Medication Optimization in Heart Failure With Reduced Ejection Fraction.

Background: Guideline-directed medical therapy (GDMT) optimization can improve outcomes in heart failure with reduced ejection fraction. Objectives: The objective of this study was to determine if a novel computable algorithm appropriately recommended GDMT. Methods: Clinical trial data from the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure) and HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trials were evaluated with a computable medication optimization algorithm that outputs GDMT recommendations and a medication optimization score (MOS). Algorithm-based recommendations were compared to medication changes. A Cox proportional-hazards model was used to estimate the associations between MOS and the composite primary end point for both trials. Results: The algorithm recommended initiation of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blockers, and mineralocorticoid receptor antagonists in 52.8%, 34.9%, and 68.1% of GUIDE-IT visits, respectively, when not prescribed the drug. Initiation only occurred in 20.8%, 56.9%, and 15.8% of subsequent visits. The algorithm also identified dose titration in 48.8% of visits for angiotensin-converting enzyme inhibitor/angiotensin receptor blockers and 39.4% of visits for beta-blockers. Those increases only occurred in 24.3% and 36.8% of subsequent visits. A higher baseline MOS was associated with a lower risk of cardiovascular death or heart failure hospitalization (HR: 0.41; 95% CI: 0.21-0.80; P = 0.009) in GUIDE-IT and all-cause death and hospitalization (HR: 0.61; 95% CI: 0.44-0.84; P = 0.003) in HF-ACTION. Conclusions: The algorithm accurately identified patients for GDMT optimization. Even in a clinical trial with robust protocols, GDMT could have been further optimized in a meaningful number of visits. The algorithm-generated MOS was associated with a lower risk of clinical outcomes. Implementation into clinical care may identify and address suboptimal GDMT in patients with heart failure with reduced ejection fraction.

Clinician Perception of the Effectiveness of an Automated Early Warning and Response System for Sepsis in an Academic Medical Center.

RATIONALE: We implemented an electronic early warning and response system (EWRS) to improve detection of and response to severe sepsis. Sustainability of such a system requires stakeholder acceptance. We hypothesized that clinicians receiving such alerts perceive them to be useful and effective. OBJECTIVES: To survey clinicians after EWRS notification about perceptions of the system. METHODS: For a 6-week study period 1 month after EWRS implementation in a large tertiary referral medical center, bedside clinicians, including providers (physicians, advanced practice providers) and registered nurses (RNs), were surveyed confidentially within 2 hours of an alert. MEASUREMENTS AND MAIN RESULTS: For the 247 alerts that triggered, 127 providers (51%) and 105 RNs (43%) completed the survey. Clinicians perceived most patients as stable before and after the alert. Approximately half (39% providers, 48% RNs) felt the alert provided new information, and about half (44% providers, 56% RNs) reported changes in management as a result of the alert, including closer monitoring and additional interventions. Over half (54% providers, 65% RNs) felt the alert was appropriately timed. Approximately one-third found the alert helpful (33% providers, 40% RNs) and fewer felt it improved patient care (24% providers, 35% RNs). CONCLUSIONS: A minority of responders perceived the EWRS to be useful, likely related to the perception that most patients identified were stable. However, management was altered half the time after an alert. These results suggest further improvements to the system are needed to enhance clinician perception of the system's utility.

Risk of otitis externa following manual cerumen removal.

OBJECTIVES: Based on an interpretation of a recent Joint Commission protocol to sterilize instruments coming into contact with mucous membranes, there has been institutional interest in sterile packaging of cerumen curettes used for manual cerumen removal. To date, there are no studies that have assessed the risk of otitis externa (OE) following cerumen removal and the utility of sterile packaging is questionable. The objective of this study is to assess the incidence of OE following cerumen disimpaction prior to the implementation of sterile packaging at our institution. METHODS: This was a retrospective chart review. Over a I-year period, 1457 episodes of manual cerumen removal took place in the otolaryngology clinic. Charts were assessed for signs or symptoms of OE within 2 weeks of the procedure through follow-up phone calls and clinic visits in the otolaryngology division. RESULTS: There were no patients who followed up with symptoms or signs suggestive of OE in the 2-week postprocedure period. CONCLUSION: There is no evidence that OE is a complication of manual cerumen removal when performed by otolaryngologists using clean technique. Unnecessary sterilization of tools leads to increased cost and time for this common outpatient procedure performed by the otolaryngologist.

Comparison of activated caspase detection methods in the gentamicin-treated chick cochlea.

Aminoglycoside antibiotics induce caspase-dependent apoptotic death in cochlear hair cells. Apoptosis, a regulated form of cell death, can be induced by many stressors, which activate signaling pathways that result in the controlled dismantling of the affected cell. The caspase family of proteases is activated in the apoptotic signaling pathway and is responsible for cellular destruction. The initiator caspase-9 and the effector caspase-3 are both activated in chick cochlear hair cells following aminoglycoside exposure. We have analyzed caspase activation in the avian cochlea during gentamicin-induced hair cell death to compare two different methods of caspase detection: caspase antibodies and CaspaTag kits. Caspase antibodies bind to the cleaved activated form of caspase-9 or caspase-3 in specific locations in fixed tissue. CaspaTag is a fluorescent inhibitor that binds to a reactive cysteine residue on the large subunit of the caspase heterodimer in unfixed tissue. To induce cochlear hair cell loss, 1-2 week-old chickens received a single injection of gentamicin (300 mg/kg). Chicks were sacrificed 24, 30, 42, 48, 72, or 96 h after injection. Cochleae were dissected and labeled for activated caspase-9 or caspase-3 using either caspase-directed antibodies or CaspaTag kits. Ears were co-labeled with either phalloidin or myosin VI to visualize hair cells and to determine the progression of cochlear damage. The timing of caspase activation was similar for both assays; however, caspase-9 and caspase-3 antibodies labeled only those cells currently undergoing apoptotic cell death. Conversely, CaspaTag-labeled all the cells that have undergone apoptotic cell death and ejection from the sensory epithelium, in addition to those that are currently in the cell death process. This makes CaspaTag ideal for showing an overall pattern or level of cell death over a period of time, while caspase antibodies provide a snapshot of cell death at a specific time point.