No abstract

The X-ray crystal structures of two superfolder green fluorescent protein (sfGFP) constructs containing a genetically incorporated spectroscopic reporter unnatural amino acid, 4-nitro-l-phenylalanine (pNO 2 F), at two unique sites in the protein have been determined. Amber codon-suppression methodology was used to site-specifically incorporate pNO 2 F at a solvent-accessible (Asp133) and a partially buried (Asn149) site in sfGFP. The Asp133pNO 2 F sfGFP construct crystallized with two molecules per asymmetric unit in space group P3 2 21 and the crystal structure was refined to 2.05 Å resolution. Crystals of Asn149pNO 2 F sfGFP contained one molecule of sfGFP per asymmetric unit in space group P4 1 22 and the structure was refined to 1.60 Å resolution. The alignment of Asp133pNO 2 F or Asn149pNO 2 F sfGFP with wild-type sfGFP resulted in small root-mean-square deviations, illustrating that these residues do not significantly alter the protein structure and supporting the use of pNO 2 F as an effective spectroscopic reporter of local protein structure and dynamics.

Background Vaso‐occlusive crises (VOCs) are the hallmark of sickle cell disease (SCD), with higher severity among hospitalized patients. Clustering hospitalizations with similar pain trajectories could identify vulnerable patient subgroups. Aims were to (a) identify clusters of hospitalizations based on pain trajectories; (b) identify factors associated with these clusters; and (c) determine the association between these clusters and 30‐day readmissions. Methods We retrospectively included 350 VOC hospitalizations from 2013 to 2016 among 59 patients. Finite mixture modeling identified clusters of hospitalizations from intercepts and slopes of pain trajectories during the hospitalization. Generalized estimating equations for multinomial and logistic models were used to identify factors associated with clusters of hospitalizations and 30‐day readmissions, respectively, while accounting for multiple hospitalizations per patient. Results Three clusters of hospitalizations based on pain trajectories were identified: slow (n = 99), moderate (n = 207), and rapid (n = 44) decrease in pain scores. In multivariable analysis, SCD complications, female gender, and affective disorders were associated with clusters with slow or moderate decrease in pain scores (compared to rapid decrease). Although univariate analysis found that the cluster with moderate decrease in pain scores was associated with lower odds of 30‐day readmissions compared to the cluster with slow decrease, it was nonsignificant in multivariable analysis. SCD complications were associated with higher odds of 30‐day readmissions and older age was associated with lower odds of 30‐day readmissions. Conclusions Our results highlight variability in pain trajectories among patients with SCD experiencing VOC and provide a novel approach for identifying subgroups of patients that could benefit from more intensive follow‐up.

Background Vaso‐occlusive crises (VOC) are the hallmark of sickle cell disease (SCD). Adults experiencing VOC often have high rates of unexpected healthcare utilization. We characterized prior and future healthcare utilization among adults hospitalized with VOC at an urban, academic medical center. Methods We identified 449 VOC hospitalizations among 63 patients from 2013 to 2016. Patients were categorized based on receiving established care at the medical center and prior utilization: (a) not established (n = 21); (b) newly established (n = 10); (c) established with low utilization in past 12 months (<4 VOC hospitalizations) (n = 22); and (d) established with high utilization in past 12 months (≥4 VOC hospitalizations) (n = 10). Patient and hospitalization characteristics and future utilization were compared across categories. Results Median age was 26 years (Q1 = 22, Q3 = 29) and 55.6% were female. Established patients with high prior utilization tended to have higher median pain scores at admission (10, P = .08). Thirty‐day readmissions were highest in established patients with high prior utilization (P = .06), but 30‐day clinic visits were highest in established patients with low prior utilization (P = .08). Adjusted linear regression found that newly established patients (β = −4.6, P < .01) and established patients with low prior utilization (β = −5.6, P < .01) had fewer VOC hospitalizations in the ensuing 12 months than established patients with high prior utilization. Conclusion Among patients with SCD hospitalized for VOC, there was heterogeneity in healthcare utilization, with persistence in utilization over time for some patients. Efforts are needed to shift care from the acute setting to the outpatient clinic, which may lead to improved outcomes.

Background Although oral anticancer medications (OAM) provide opportunity for treatment at home, challenges include prescription filling, monitoring side effects, safe handling, and adherence. We assessed understanding of and adherence to OAM in vulnerable patients. Methods This 2018 pilot study defined vulnerable patients based on Chinese language, older age (≥65 years), and subsidized insurance. All participants had a cancer diagnosis and were taking an OAM filled through the hospital’s specialty pharmacy. Participants reported on OAM taking (days per week, times per day, special instructions) and handling (handling, storage, disposal). The specialty pharmacist classified patient-reported responses about OAM taking and handling as adequate or inadequate. OAM regimens were classified by complexity. Results Of 61 eligible patients, 55 participated. Mean age was 68 years (standard deviation [SD] = 12) and 53% were female. Patient subgroups were: 27% Chinese, 64% ≥65 years, and 9% subsidized insurance. Forty-nine percent were on frontline therapy and median time on OAM was 1 year (Quartile 1 = 0.4, Quartile 3 = 1.7). Adequacy of OAM taking (30%) and handling (15%) were low; 15% had adequacy in both. Adequacy of OAM taking and handling did not vary by patient subgroup or regimen complexity. Mean patient-reported adherence was high (5.4, SD = 1, possible range 1–6) and did not vary by adequacy of OAM taking or handling. Conclusions Understanding of OAM taking and handling in this group of vulnerable patients was low and did not align with patient-reported adherence. Future interventions should ensure that patients understand how to safely take and handle OAM, thereby optimizing their therapeutic potential.