Alogliptin and Heart Failure Outcomes in Patients With Type 2 Diabetes.

Background: In 2016, the FDA issued a warning for saxagliptin and alogliptin regarding an increased risk of heart failure (HF), potentially limiting the use of effective medications in type 2 diabetes. Current data and guideline recommendations regarding HF risk are conflicting, especially with alogliptin. In March 2019, the Memphis Veterans Affairs Medical Center made a formulary change from saxagliptin to alogliptin, creating an opportunity to evaluate a large number of patients receiving alogliptin. Objective: To evaluate the risk of HF with alogliptin use in type 2 diabetes patients. Methods: A retrospective chart review of patients prescribed alogliptin was performed. The primary outcome was the composite number of HF hospital admissions and ED visits. Secondary outcomes included exacerbation rates among established HF patients, incidence of new-onset HF, incidence of alogliptin discontinuation due to HF, comparison of HF exacerbations between saxagliptin and alogliptin in patients with prior saxagliptin use, and evaluation of concomitant cardiotoxic medications. Results: 455 patients were included. A composite of 28 hospital admissions and ED visits occurred for a HF exacerbation. Fourteen patients (26.4%) of 53 patients with established HF had an exacerbation, whereas 5 patients (1.2%) of 402 patients with no history of HF had an exacerbation. Eight patients (2%) developed new-onset HF. Alogliptin was discontinued in 4 patients (0.9%) due to HF. No statistically significant difference in HF exacerbations was found between patients on alogliptin who previously received saxagliptin (4.8% vs 4.2%, P = 0.726). Conclusions: Alogliptin may increase the risk of HF exacerbation in patients with established HF.

Implementation of a pharmacist-led transitional care clinic.

PURPOSE: To describe a pharmacist-led transitional care clinic (TCC) for high-risk patients who were recently hospitalized or seen in the emergency department (ED). SUMMARY: The Memphis Veterans Affairs Medical Center (VAMC) established a pharmacist-led face-to-face and telephone follow-up TCC to improve posthospitalization follow-up care through medication optimization and disease state management, particularly for veterans with high-risk disease states such as chronic obstructive pulmonary disease (COPD) and heart failure (HF). The clinic's clinical pharmacy specialists (CPSs) ordered diagnostic and laboratory tests, performed physical assessments, and consulted other providers and specialty services in addition to performing medication reconciliation, compliance assessment, and evaluation of adverse drug events. TCC patients were typically seen within 2 weeks of discharge and subsequently referred back to their primary care provider or a specialty care provider for continued management. A retrospective review of 2016 TCC data found that 7.8% of patients seen in the TCC were readmitted within 30 days of discharge; readmission rates for COPD and HF were reduced to 13% and 10%, respectively, compared to hospital-wide readmission rates of 17% and 24%. A separate observational analysis found that 30-day readmissions for COPD and HF were reduced in TCC patients, with pharmacists documenting an average of 6.2 interventions and 3.3 medication-related problems per patient. To reduce clinic appointment no-shows, the CPSs worked with inpatient providers and schedulers to emphasize to patients the importance of clinic attendance; also, TCC services were expanded to include telehealth appointments to increase access for rural and/or homebound patients. CONCLUSION: A pharmacist-led TCC effectively reduced readmissions and prevented medication-related problems for high-risk patients who were hospitalized or seen in the ED.

Low-Dose Alteplase for the Treatment of Submassive Pulmonary Embolism: A Case Series.

PURPOSE: Pulmonary embolism (PE) can lead to significant morbidity and mortality. Thrombolytics are currently approved for the treatment of massive PE; however, the CHEST guidelines recommend against systemic thrombolytic use in acute PE patients without hypotension, unless these patients deteriorate on anticoagulation alone. Several studies have demonstrated the effectiveness of thrombolysis in submassive PE; however, the full thrombolytic dose resulted in significantly increased risk of non-intracranial bleeding and hemorrhagic stroke. The MOPETT trial demonstrated that low-dose tissue plasminogen activator (tPA) significantly reduced the risk of pulmonary hypertension and recurrent PE compared to anticoagulation alone in submassive PE patients without any bleeding events. SUMMARY: This case series highlights 5 patient cases utilizing low-dose tPA for submassive PE. All patients had successful resolution of their symptoms and improvement in vitals and laboratory values. Furthermore, no patient had any bleeding during or after tPA administration. Three patients showed improved right ventricle function and reduced or normal right ventricle size on echocardiogram after tPA administration. CONCLUSION: The potential for low-dose tPA as a safe and efficacious treatment option for submassive PE is illustrated by this case series. However, larger, randomized controlled trials are needed to establish low-dose tPA as an accepted treatment modality.

Essential role of copper in the activity and regular periodicity of a recombinant, tumor-associated, cell surface, growth-related and time-keeping hydroquinone (NADH) oxidase with protein disulfide-thiol interchange activity (ENOX2).

ECTO-NOX proteins are growth-related cell surface proteins that catalyze both hydroquinone or NADH oxidation and protein disulfide interchange and exhibit time-keeping and prion-like properties. A bacterially expressed truncated recombinant 46 kDa ENOX2 with full ENOX2 activity bound ca 2 moles copper and 2 moles of zinc per mole of protein. Unfolding of the protein in trifluoroacetic acid in the presence of the copper chelator bathocuproine resulted in reversible loss of both enzymatic activities and of a characteristic pattern in the Amide I to Amide II ratios determined by FTIR with restoration by added copper. The H546-V-H together with His 562 form one copper binding site and H582 represents a second copper site as determined from site-directed mutagenesis. Bound copper emerges as having an essential role in ENOX2 both for enzymatic activity and for the structural changes that underly the periodic alternations in activity that define the time-keeping cycle of the protein.

Structural changes revealed by Fourier transform infrared and circular dichroism spectroscopic analyses underlie tNOX periodic oscillations.

A recurring pattern of spectral changes indicative of periodic changes in the proportion of beta-structure and a-helix of a recombinant ECTO-NOX fusion protein of tNOX, with a cellulose binding domain peptide, was demonstrated by Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopic analyses. The pattern of structural changes correlated with oscillatory patterns of enzymatic activities exhibited by the protein previously interpreted as indicative of a clock function. The pattern consisted of a repeating pattern of oscillations with a period length of 21 min with five maxima (two separated by 5 min and 3 separated by 4 to 4.5 min) within each 21 min repeat. Oscillatory patterns were not obvious in comparable FTIR or CD spectra of albumin, ribonuclease or concanavalin A. The period length was constant at 5, 15, 25, 35 and 45 degrees C (temperature compensated) and oscillations occurred independently of substrate presence. Spectra obtained in deuterium oxide yielded a longer period length of 26 min both for oscillations in enzymatic activity and absorbance ratios determined by FTIR. Taken together the findings suggest that the regular patterns of oscillations exhibited by the ECTO-NOX proteins are accompanied by recurrent global changes in the conformation of the protein backbone that directly modulate enzymatic activity.