Management of Atrial Fibrillation in Older Patients by Morbidity Burden: Insights From Get With The Guidelines-Atrial Fibrillation.

Background Knowledge is scarce regarding how multimorbidity is associated with therapeutic decisions regarding oral anticoagulants (OACs) in patients with atrial fibrillation. Methods and Results We conducted a cross-sectional study of hospitalized patients with atrial fibrillation using the Get With The Guidelines-Atrial Fibrillation registry from 2013 to 2019. We identified patients ≥65 years and eligible for OAC therapy. Using 16 available comorbidity categories, patients were stratified by morbidity burden. A multivariable logistic regression model was used to determine the odds of receiving OAC prescription at discharge by morbidity burden. We included 34 174 patients with a median (interquartile range) age of 76 (71-83) years, 56.6% women, and 41.9% were not anticoagulated at admission. Of these patients, 38.6% had 0 to 2 comorbidities, 50.7% had 3 to 5 comorbidities, and 10.7% had ≥6 comorbidities. The overall discharge OAC prescription was high (85.6%). The prevalence of patients with multimorbidity increased from 59.7% in 2014 to 64.3% in 2019 (P trend=0.002). Using 0 to 2 comorbidities as the reference, the adjusted odds ratio (95% CI) of OAC prescription were 0.93 (0.82, 1.05) for patients with 3 to 5 comorbidities and 0.72 (0.60, 0.86) for patients with ≥6 comorbidities. In those with ≥6 comorbidities, the most common reason for nonprescription of OACs were frequent falls/frailty (31.0%). Conclusions In a contemporary quality-of-care database of hospitalized patients with atrial fibrillation eligible for OAC therapy, multimorbidity was common. A higher morbidity burden was associated with a lower odds of OAC prescription. This highlights the need for interventions to improve adherence to guideline-recommended anticoagulation in multimorbid patients with atrial fibrillation.

Hybrid optimization of preparative chromatography for a ternary monoclonal antibody mixture.

In the purification of monoclonal antibodies, ion-exchange chromatography is typically used among the polishing steps to reduce the amount of product-related impurities such as aggregates and fragments, whilst simultaneously reducing HCP, residual Protein A and potential toxins and viruses. When the product-related impurities are difficult to separate from the products, the optimization of these chromatographic steps can be complex and laborious. In this paper, we optimize the polishing chromatography of a monoclonal antibody from a challenging ternary feed mixture by introducing a hybrid approach of the simplex method and a form of local optimization. To maximize the productivity of this preparative bind-and-elute cation-exchange chromatography, wide ranges of the three critical operational parameters-column loading, the initial salt concentration, and gradient slope-had to be considered. The hybrid optimization approach is shown to be extremely effective in dealing with this complex separation that was subject to multiple constraints based on yield, purity, and product breakthrough. Furthermore, it enabled the generation of a large knowledge space that was subsequently used to study the sensitivity of the objective function. Increased design space understanding was gained through the application of Monte Carlo simulations. Hence, this work proposes a powerful hybrid optimization method, applied to an industrially relevant process development challenge. The properties of this approach and the results and insights gained, make it perfectly suited for the rapid development of biotechnological unit operations during early-stage bioprocess development.

Pharmacokinetic Assessment of Drug-Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults.

This report summarizes phase 1 studies that evaluated pharmacokinetic interactions between the novel triazole antifungal agent isavuconazole and the immunosuppressants cyclosporine, mycophenolic acid, prednisolone, sirolimus, and tacrolimus in healthy adults. Healthy subjects received single oral doses of cyclosporine (300 mg; n = 24), mycophenolate mofetil (1000 mg; n = 24), prednisone (20 mg; n = 21), sirolimus (2 mg; n = 22), and tacrolimus (5 mg; n = 24) in the presence and absence of clinical doses of oral isavuconazole (200 mg 3 times daily for 2 days; 200 mg once daily thereafter). Coadministration with isavuconazole increased the area under the concentration-time curves (AUC0-∞ ) of tacrolimus, sirolimus, and cyclosporine by 125%, 84%, and 29%, respectively, and the AUCs of mycophenolic acid and prednisolone by 35% and 8%, respectively. Maximum concentrations (Cmax ) of tacrolimus, sirolimus, and cyclosporine were 42%, 65%, and 6% higher, respectively; Cmax of mycophenolic acid and prednisolone were 11% and 4% lower, respectively. Isavuconazole pharmacokinetics were mostly unaffected by the immunosuppressants. Two subjects experienced elevated creatinine levels in the cyclosporine study; most adverse events were not considered to be of clinical concern. These results indicate that isavuconazole is an inhibitor of cyclosporine, mycophenolic acid, sirolimus, and tacrolimus metabolism.

Ablation of atrial fibrillation: what can we tell our patients?

Although catheter-based radiofrequency ablation is no longer experimental, it is not yet the first-line treatment for most patients. The authors describe how this procedure works, its indications, benefits, and limitations, and important points to communicate to potential candidates for this procedure.

Evaluation and development of potentially better practices for the prevention of brain hemorrhage and ischemic brain injury in very low birth weight infants.

OBJECTIVE: Neonatal care providers from 5 institutions formed a multidisciplinary focus group with the purpose of identifying potentially better practices, the implementation of which would lead to a reduction in the incidence of intracranial hemorrhage and periventricular leukomalacia in very low birth weight infants. METHODS: Practices were analyzed, 4 benchmark neonatal intensive care units were identified and evaluated, and the literature was assessed using an evidence-based approach. The work was also reviewed by a nationally respected expert. RESULTS: Ten potentially better clinical practices were identified. In addition, variability in cranial ultrasound practice, related to both procedural process and interpretation, was identified as a confounding problem in evaluating quality. Using the same process, potentially better cranial ultrasound practices were also identified. CONCLUSIONS: Implementation of these practices will improve clinical outcomes as well as the reliability of sonogram interpretation, the basis for evaluating the quality of the team's work.

Cost and speed of locomotion for rotifers.

The hypothesis that the ciliary locomotion of rotifers is size limited and that it accounts of a significant portion of the energy budget was investigated using the genera Brachionus and Asplanchna. Speed of movement was measured among clones of different size in Brachionus, which shows little size variation through development. The same tests were done among individuals of different size within a clone of Asplanchna, which shows significant postembryonic size increase. In both cases, relative speed (body lengths per second) decreased significantly as body size increased. On this basis, and ecologically limiting size for ciliary locomotion is proposed. The actual cost of locomotion was measured for Brachionus; it is 62% of total metabolism, even though the theoretical (calculated) power requirements are well below 1% of total metabolism. Ciliary locomotion in the Rotifera thus appears to be extremely inefficient (low ratio of theoretical to actual power requirements). This hypothesis is supported indirectly by the sensitivity of speed to total metabolic rate in Brachionus: both plateau over the temperature range 20-32°C and decline in parallel outside this range. Unexpectedly high actual cost of locomotion is proposed as an important disadvantage of the Rotifera, partly offsetting the advantages accruing to them from small body size.