A comparison of opioid dose between home palliative care and hospital palliative care

Abstract Objective While opioids are a key part of palliative care, few studies have evaluated opioid demand in the home care context. This study aims to compare opioid usage in home care and hospital care settings. Methods This cross-sectional study retrospectively recruited patients receiving palliative care in home care and hospital settings, between November 2018 and October 2020. Opioid prescriptions were standardized to oral morphine equivalent (OME) doses at 7 and 14 days prior to death and analyzed. Additional analysis performed multivariable linear regression on the outcome of OME at 7 days, adjusting for medical setting and confounders in patients with opioid prescriptions. Results After 21 exclusions, 209 patients (48 home care and 161 hospital care) were eligible for analysis. The home care group had a higher mean age (74.8 years) and Palliative Prognosis Score (50), than the hospital group (70.1 and 40, respectively). Mean OME at 7 and 14 days before death was numerically higher in the home care group (72.8 mg/day and 53.0 mg/day, respectively) than the hospital care group (57.7 mg/day and 35.7 mg/day). Student’s t-test produced p-values of 0.49 and 0.32, and the Wilcoxon rank sum test found p-values of 0.24 and 0.11 at 7 and 14 days, respectively. Multivariable regression analysis of the home care group found mean OME of 40.7 mg/day; 95% confidence interval [-0.62, 82.0 (mg/day)], p = 0.06. Additional analysis found a p-value of 0.06 for medical setting. Conclusions We did not find a statistically significant difference in opioid use between home care and hospital care. However, the numerically higher rate of use in the home care group suggests that further research is warranted

High-resolution neutron crystallography visualizes an OH-bound resting state of a copper-containing nitrite reductase

Copper-containing nitrite reductases (CuNIRs) transform nitrite to gaseous nitric oxide,which is a key process in the global nitrogen cycle. The catalytic mechanism has been extensively studied to ultimately achieve rational control of this important geobiochemical reaction. However, accumulated structural biology data show discrepancies with spectroscopic and computational studies; hence, the reaction mechanism is still controversial. In particular, the details of the proton transfer involved in it are largely unknown. This situation arises fromthe failure of determining positions of hydrogen atoms and protons, which play essential roles at the catalytic site of CuNIRs, even with atomic resolution X-ray crystallography. Here, we determined the 1.50 Å resolution neutron structure of a CuNIR from Geobacillus thermodenitrificans (trimer molecular mass of ∼106 kDa) in its resting state at low pH. Our neutron structure reveals the protonationstates of catalytic residues (deprotonated aspartate and protonated histidine), thus providing insights into the catalytic mechanism. We found that a hydroxide ion can exist as a ligand to the catalytic Cu atom in the resting state even at a low pH. This OH-bound Cu site is unexpected from previously given X-ray structures but consistent with a reaction intermediate suggested by computational chemistry. Furthermore, the hydrogen-deuterium exchange ratio in our neutron structure suggests that the intramolecular electron transfer pathway has a hydrogen-bond jump, which is proposed by quantum chemistry. Our study can seamlessly link the structural biology to the computational chemistry of CuNIRs, boosting our understanding of the enzymes at the atomic and electronic levels

Reevaluation of protein neutron crystallography with and without X-ray/neutron joint refinement

Protein neutron crystallography is a powerful technique to determine the positions of hydrogen atoms, providing crucial biochemical information such as the protonation states of catalytic groups and the geometry of hydrogen bonds. Recently, we determined the crystal structure of a bacterial copper amine oxidase by joint refinement using X-ray and neutron diffraction data sets at resolutions of 1.14 A and 1.72 A, respectively (Murakawa, T. et al. (2020). Proc. Natl Acad. Sci. USA, 117, 10818?10824). While the joint refinement is effective for determination of the accurate positions of heavy atoms on the basis of the electron density, the structural information of light atoms (hydrogen and deuterium) derived from the neutron diffraction data might be affected by the X-ray data. To unravel the information included in the neutron diffraction data, we conducted the structure determination again using only the neutron diffraction data at a 1.72 A resolution and compared the results with those obtained by the previous study. Most hydrogen and deuterium atoms were identified at essentially the same positions in both the neutron-only and X-ray/neutron joint refinements. Nevertheless, the neutron-only refinement was found to be less effective than the joint refinement in providing very accurate heavy atom coordinates that lead to significant improvement of the neutron scattering length density map, especially for the active-site cofactor. Consequently, we have confirmed that the X-ray/neutron joint refinement is crucial for determination of the real chemical structure of the catalytic site of the enzyme

Revisiting the concept of peptide bond planarity in an iron-sulfur protein by neutron structure analysis

The planarity of the peptide bond is important for the stability and structure formation of proteins. However, substantial distortion of peptide bonds has been reported in several high-resolution structures and computational analyses. To investigate the peptide bond planarity, including hydrogen atoms, we report a 1.2 Å resolution neutron structure of the oxidized form of high-potential iron-sulfur protein. This high-resolution neutron structure shows that the nucleus positions of the amide protons deviate from the peptide plane and shift toward the acceptors. The planarity of the H-N-C=O plane depends strongly on the pyramidalization of the nitrogen atom. Moreover, the orientation of the amide proton of Cys75 is different in the reduced and oxidized states possibly due to the electron storage capacity of the iron-sulfur cluster

Hybridization of Wide-Angle X-ray and Neutron Diffraction Techniques in the Crystal Structure Analyses of Synthetic Polymers

The development in the crystal structure analysis of synthetic polymers using the hybridized combination of wide-angle X-ray and neutron diffraction (WAXD and WAND, respectively) techniques has been reviewed with many case studies performed by the authors. At first, the technical development was reviewed, in which the usage of high-energy synchrotron X-ray source was emphasized for increasing the total number of the observable diffraction peaks, and several examples were introduced. Secondly, the usage of the WAND method was introduced, in which the successful extraction of hydrogen atomic positions was described. The third example is to show the importance for the hybrid combination of these two diffraction methods. The quantitative WAXD data analysis gave the crystal structures of at-poly(vinyl alcohol) (at-PVA) and at-PVA-iodine complex. However, the thus-proposed structure models were found not to reproduce the observed WAND data very much. The reason came from the remarkable difference in the atomic scattering powers of the constituting atomic species between WAXD and WAND phenomena. The introduction of statistical disorder solved this serious problem, which reproduced both of the observed WAXD and WAND data consistently. The more systematic combination of WAXD and WAND methods, or the so-called X-N method, was applied also to the quantitative evaluation of the bonded electron density distribution along the skeletal chains, where the results about polydiacetylene single crystals were presented as the first successful study. Finally, the application of WAND technique in the trace of structural changes induced under the application of external stress or temperature was described. The future perspective is described for the development of structural science of synthetic polymers on the basis of the combined WAXD/WAND techniques