Factor replacement therapy for the treatment of moderate to severe haemophilia A and B can be complicated by the production of inhibitory alloantibodies to factor VIII (FVIII) or factor IX. Treatment with the nanofiltered anti-inhibitor coagulant complex, Factor Eight Inhibitor Bypassing Activity (FEIBA NF), is a key therapeutic option for controlling acute haemorrhages in patients with high-titre inhibitors or low-titre inhibitors refractory to replacement therapy. Given the high risk for morbidity and mortality in haemophilia patients with inhibitors to FVIII or FIX, we conducted this Phase 3 prospective study to evaluate whether prophylaxis with FEIBA NF is a safe and effective treatment option. Over a 1-year period, 17 subjects were treated prophylactically (85 ± 15 U kg−1 every other day) while 19 subjects were treated on demand. The median (IQR) annualized bleeding rate (ABR) during prophylaxis was 7.9 (8.1), compared to 28.7 (32.3) during on-demand treatment, which amounts to a 72.5% reduction and a statistically significant difference in ABRs between arms (P = 0.0003). Three (17.6%) subjects (ITT) on prophylaxis experienced no bleeding episodes, whereas none treated on demand were bleeding episode-free. Total utilization of FEIBA NF for the treatment of bleeding episodes was significantly higher during on-demand therapy than prophylaxis (P = 0.0067). There were no differences in the rates of related adverse events between arms. This study demonstrates that FEIBA prophylaxis significantly reduces all types of bleeding compared with on-demand treatment, and the safety of prophylaxis is comparable to that of on-demand treatment.

Gel entrapment retains suspension cells in a bioreactor for high-density operations without the difficulties of cell separation. To achieve and sustain high cell densities in animal cell culture, beads under 1 mm in diameter are desirable to minimize diffusional limitations. The challenge is to develop a controllable, scaleable process to produce small, monodispersed beads for cell immobilization. In this work, alginate bead populations were produced in the 0.5-1 mm size range with less than 10% standard deviation by destabilizing a viscous jet with a controlled disturbance. Systematic study of the drop formation with this "vibration" method demonstrated that Weber's theory for the instability of viscous jets qualitatively applies to the alginate system and provides a predictive tool for selecting the wavelength of disturbance for controlled bead formation. Nonlinear theory also provided guidance in establishing proper operating conditions to avoid satellite drop formation which decreases bead uniformity. A viscosity range 150-500 cp was found to be optimum for bead formation and served to rapidly establish the appropriate alginate concentration for the wide variety of commercial alginates. Through an understanding of the interaction of viscosity, linear velocity, nozzle diameter, and frequency of disturbance used to destabilize the jet, the predictable formation of small, uniform alginate beads was demonstrated with this method. As an example of scaleup, a 10-nozzle manifold can process 3-50 L of alginate/h, depending on the desired bead size.

A diamond composition ATR probe was used in situ to obtain IR spectra on replicate Escherichia coli fermentations involving a complex medium. The probe showed excellent stability over a 6-month operating period and was unaffected by either agitation or aeration. The formation of an unknown was observed from IR spectra obtained during the sterilization; subsequent experiments proved this to be a reaction product between yeast extract and the phosphates used as buffer salts. Partial-least-squares-based calibration/prediction models were developed for both glucose and acetate using in-process samples. The resulting models had prediction errors of +/-0.26 and +/-0.75 g/L for glucose and acetic acid, respectively, errors which were statistically equivalent to the estimated experimental errors in the reference measurements. Relative concentration profiles for the unknown formed during sterilization could be generated either by tracking peak height at an independent wavelength or by self-modeling curve resolution of the spectral region overlapping that of glucose. These profiles indicated that this compound was metabolized simultaneously with glucose; upon depletion of the glucose, when the microorganism switched to consumption of acetic acid, utilization continued but at a lower rate. The data presented provide an extensive characterization of the performance characteristics of this in situ analysis and clearly demonstrate its utility not just in the quantitative measurement of multiple known species but in the qualitative evaluation of unknown species.

Purpose The purpose of this study was to assess nurses’ knowledge, perceived self‐efficacy, and intended behaviors relative to integrating the social determinants of health (SDoH) into clinical practice. Design and Methods A cross‐sectional study was completed with 768 nurses working in three hospitals within a large regional healthcare system located in the Midwest. Data were collected using an adapted 71‐item SDoH Survey, which measured nurses’ confidence in and frequency of discussing the SDoH with patients, general knowledge of the SDoH, familiarity with patients’ social and economic conditions, and awareness of their institution’s health equity strategic plan to achieve health equity. The institution’s health equity strategic plan reflects the organization’s commitment to improving the health of individuals and neighborhoods by addressing the SDoH known to influence health status and life expectancy. Finally, participants were asked to describe barriers to incorporating the SDoH into practice along with completing five demographic items. Descriptive statistics were used to describe the findings. Findings Of the 768 respondents, 63% had a baccalaureate degree in nursing and 33.1% reported more than 20 years in nursing. Fifty percent of respondents reported feeling more knowledgeable or confident in their ability to discuss access to care issues with patients compared to the other SDoH. Identified barriers to discussing the SDoH included insufficient time to address identified needs and unfamiliarity with internal and external resources. Respondents stressed the need for interdisciplinary education and collaboration along with more information on the role of social workers. Conclusions Nurses are more confident in discussing certain determinants of health and could benefit from more skill development in discussing SDoH issues and stronger collaborative partnerships to address identified needs. Clinical Relevance Findings from the study have implications for supporting the educational and resource needs of front‐line nurses employed in hospitals and health systems seeking to address broader societal issues influencing the health status and outcomes of patients and communities.

A novel gel entrapment method has been developed where macropores are created within alginate beads to provide an environment for high-density growth of mammalian cells. The method takes advantage of an interaction between poly(ethylene glycol) (PEG) and alginate to provide a network of pores within the bead for growth while the surrounding alginate matrix retains the integrity of the bead and minimizes cell leakage. Hybridomas were grown to a density approaching 10(8) cells/mL of beads in this system, while conventional alginate restricted growth to a maximum of 2 x 10(7) cells/mL of beads. In addition, cell leakage was minimal even at high cell densities, which was not the case with the conventional alginate system. Study of the conventional system determined that cell growth was limited by the alginate matrix; increasing the alginate concentrations resulted in lower final cell densities. In contrast, the PEG-alginate system permits growth in pores so the alginate matrix serves only as a structural matrix for cells. The pore size can be varied as a function of PEG concentration (10-20 wt % PEG) to provide radially defined areas for cell growth and radial diffusion pathways for nutrients/products in the adjacent alginate matrix. Because the PEG-alginate entrapment process does not require additional chemical reactions or temperature changes, the system offers a simple alternative to attain high cell densities in an immobilized bead system. As an illustration of the concept, cells entrapped in this system were grown to high density in both batch and perfusion modes for the production of monoclonal antibodies. Using the suspension batch culture as the base case, the specific monoclonal antibody production rate increased 1.6-fold for the slower growing batch-immobilized culture and 3-fold for the immobilized perfusion culture.