Persistence with opioid treatment in Germany in patients suffering from chronic non-malignant or cancer pain.

BACKGROUND: The aim of the present study was to assess factors influencing opioid persistence in a large patient cohort of 32,158 patients receiving opioid treatment for either chronic non-malignant or cancer pain. METHODS: Data from 32,158 patients with first-time prescription of an opioid in the timeframe from January 2009 until December 2013 treated in 115 orthopedic, 104 neurological and 1129 general practitioner practices were retrospectively analyzed (Disease Analyzer database Germany). A Cox proportional hazards regression model was used to estimate the relationship between non-persistence and the demographic and clinical variables described previously for a maximum follow-up period of 1 year. RESULTS: After 1 year of follow-up, 69% of patients treated with opioids had stopped medication intake (refill gap of 90 days). There was a significantly increased risk of treatment discontinuation for younger patients (<40 years HR: 1.45; 41-50 years HR: 1.37; 51-60 years HR: 1.23; 61-70 years HR: 1.22) as compared with patients aged >70. Cancer pain was associated with a significantly lower risk of therapy discontinuation (HR: 0.69), whereas persistence was considerably less probable for diagnoses such as various kinds of back pain (HR: 1.26), osteoarthritis (HR: 1.14) and spondylarthritis (HR: 1.09). Chronic comorbidities such as diabetes, hypertension, heart insufficiency, and dementia were associated with a decreased risk of treatment discontinuation. CONCLUSION: Our study showed that persistence with opioid treatment is associated with cancer pain, chronic comorbidities and depression, while younger age and chronic non-malignant pain (especially due to back pain) increase the possibility of opioid discontinuation. It will be the task of future studies to assess reasons for opioid discontinuation in more detail, which is an important step towards improving patient care and health outcomes.

Homing in virtual environments: effects of field of view and path layout.

Triangle completion (ie homing to the starting point after completing two legs of a triangle) is a widely used method for examining path-integration abilities in animals and humans. Two experiments are reported in which homing was used to examine the efficiency of purely visual mechanisms (eg optical flow) for spatial-information coding and integration. Adult observers had to complete triangles in an interactively simulated three-dimensional environment which consisted of two critical objects and a homogeneous set of white cylinders serving as background. Each participant completed twenty-seven triangles corresponding to a factorial combination of three geometrical fields of view (40 degrees, 60 degrees, or 80 degrees) and nine triangle layouts (with variations of the first turning angle and the second leg). Homing performances revealed strong effects of triangle layout, but no effect of geometrical fields of view: variations in the amount of simultaneous visible spatial information did not influence the acquisition of spatial knowledge in the environments used. Applying the encoding-error model to the data revealed severe systematic errors of picking up directional information while moving through visually simulated environments. These results are discussed with respect to informational differences between situations of purely visual and nonvisual navigations in space.

Actin-sequestering ability of thymosin beta 4, thymosin beta 4 fragments, and thymosin beta 4-like peptides as assessed by the DNase I inhibition assay.

Thymosin beta 4 containing 43 amino-acid residues belongs to a family of highly homologous peptides present at high concentrations in various species, cells, and tissues. Safer et al. [J. Biol. Chem. 266, 4029-4032 (1991)] have shown that thymosin beta 4 is an actin-sequestering peptide. Because DNase I is inhibited by G-actin and not by F-actin we employed this enzymatic assay to determine the actin sequestering properties of 4 other thymosin beta 4-like peptides and fragments of thymosin beta 4 generated by enzymatic digestions. Thymosin beta 4 sequesters G-actin at a 1 to 1 ratio an thereby inhibits its polymerisation to F-actin in high salt solution. The oxidation of the single methionine residue at position 6 does not abolish its actin-sequestering properties. However neither thymosin beta 4 24-43 nor thymosin beta 4 13-43 inhibit the polymerisation of G-actin. We conclude from this that some structural features in the amino-acid sequence of thymosin beta 4 before position 13 are obligatory for its biological function. Oxidized thymosin beta 4 (beta 4-sulfoxide) as well as four other thymosin beta 4-like peptides were shown to be actin-sequestering peptides like thymosin beta 4.

Isolation and characterization of thymosin beta 9 Met from pork spleen.

We have identified a new thymosin beta 4-like peptide in pork spleen. The new peptide (12 mg) and thymosin beta 4 (33 mg) were isolated from 230 g of spleen by solid phase extraction, preparative isoelectric focusing, and HPLC. The new peptide was termed thymosin beta 9 Met to indicate its close relationship to thymosin beta 9 from calf. The only difference from thymosin beta 9 is the substitution of leucine by methionine at position 6. This peptide replaces thymosin beta 10 which is the minor thymosin beta 4-like peptide in most mammals, e.g., in man, rat, mouse, cat, and rabbit. The structure was determined by amino acid analysis, tryptic digestion, and carboxypeptidase digestion. Pork spleen contains 192 micrograms of thymosin beta 4 and 117 micrograms of thymosin beta 9 Met per gram of tissue.