Analysis of complex mixtures with benchtop nuclear magnetic resonance: Solvent suppression with T2 and diffusion filters.

Benchtop nuclear magnetic resonance (NMR) spectrometers are being employed in a wide variety of applications from undergraduate teaching and research in academia to quality control and process monitoring in industrial settings. Incorporating benchtop NMR in some of these applications presents opportunities for new practical uses of the technology and challenges that truly test the capabilities of compact NMR spectrometers. For instance, the use of protonated solvents in manufacturing or process monitoring requires separating and quantitating the analyte signals of interest from the strong (overwhelming) response from the solvents. Furthermore, due to the lower field strength available with permanent magnet spectrometers, the NMR spectra of complex mixtures can be more difficult to analyze due to partial or complete signal overlap. To address some of these challenges and to extend the range of applications of benchtop NMR, we investigate NMR techniques that enable quantitative analysis of different components in mixtures. These pulse sequences can be used to suppress one or multiple solvent peaks, to filter out signals by spin-spin relaxation time (T2), or to separate signal components by a molecule's diffusion coefficient (NMR diffusometry). In this paper, we discuss quantitative analysis of excipients in buffers for therapeutic proteins to highlight the usefulness of these NMR pulse sequences in the analysis of complex samples with benchtop NMR spectrometers.

Surgery in degenerative spondylolisthesis: does fusion improve outcome in subgroups? A secondary analysis from a randomized trial (NORDSTEN trial).

BACKGROUND CONTEXT: Patients with spinal stenosis and degenerative spondylolisthesis are treated surgically with decompression alone or decompression with fusion. However, there is debate regarding which subgroups of patients may benefit from additional fusion. PURPOSE: To investigate possible treatment effect modifiers and prognostic variables among patients operated for spinal stenosis and degenerative spondylolisthesis. DESIGN: A secondary exploratory study using data from the Norwegian Degenerative Spondylolisthesis and Spinal Stenosis (NORDSTEN-DS) trial. Patients were randomized to decompression alone or decompression with instrumented fusion. PATIENT SAMPLE: The sample in this study consists of 267 patients from a randomized multicenter trial involving 16 hospitals in Norway. Patients were enrolled from February 12, 2014, to December 18, 2017. The study did not include patients with degenerative scoliosis, severe foraminal stenosis, multilevel spondylolisthesis, or previous surgery. OUTCOME MEASURES: The primary outcome was an improvement of ≥ 30% on the Oswestry Disability Index score (ODI) from baseline to 2-year follow-up. METHODS: When investigating possible variables that could modify the treatment effect, we analyzed the treatment arms separately. When testing for prognostic factors we analyzed the whole cohort (both treatment groups). We used univariate and multiple regression analyses. The selection of variables was done a priori, according to the published trial protocol. RESULTS: Of the 267 patients included in the trial (183 female [67%]; mean [SD] age, 66 [7.6] years), complete baseline data for the variables required for the present analysis were available for 205 of the 267 individuals. We did not find any clinical or radiological variables at baseline that modified the treatment effect. Thus, none of the commonly used criteria for selecting patients for fusion surgery influenced the chosen primary outcome in the two treatment arms. For the whole cohort, less comorbidity (American Society of Anesthesiologists Classification [ASA], OR = 4.35; 95% confidence interval (CI [1.16-16.67]) and more preoperative leg pain (OR = 1.23; CI [1.02-1.50]) were significantly associated with an improved primary outcome. CONCLUSIONS: In this study on patients with degenerative spondylolisthesis, neither previously defined instability criteria nor other pre-specified baseline variables were associated with better clinical outcome if fusion surgery was performed. None of the analyzed variables can be applied to guide the decision for fusion surgery in patients with degenerative spondylolisthesis. For both treatment groups, less comorbidity and more leg pain were associated with improved outcome 2 years after surgery. TRIAL REGISTRATION: NORDSTEN-DS ClinicalTrials.gov, NCT02051374.

14N nuclear quadrupole resonance of some sulfa drugs.

The 14N nuclear quadrupole double resonance spectra of different polymorphs of sulfanilamide, sulfadiazine, sulfamerazine and sulfamethazine have been measured and the 14N quadrupole coupling tensors have been determined. The obtained 14N spectra are compared with those of other sulfa drugs like sulfathiazole. It is shown that different polymorphs can be easily discriminated. The application of this technique for non-destructive analysis, polymorph determination and quality control in the production of pharmaceuticals is stressed.