Osteoarthritis of the knee – clinical assessments and inflammatory markers11Supported by a grant from the Robert Bosch Stiftung, Stuttgart, Germany.

AbstractObjective: The present cross sectional study was performed to test the hypothesis that in osteoarthritis (OA) of the knee severity of this disease is related to local levels of inflammatory metabolites and their corresponding enzymes.Methods: From 41 patients with OA of the knee (age range 45–79 years) undergoing arthroscopy blood, synovial fluid (SF) and synovial membrane (SM) were collected. Clinical conditions were primarily assessed by the WOMAC-index and radiographic grading (K&L-grade). Concentrations of PGE2, TxB2and NO2/3and that of IL-6, IL-1α, IL-1β, TNFα, COX-2 and iNOS were determined in SF and SM, respectively.Results: With advancing age K&L-grade and COX-2 in SM increased significantly (P=0.005 and P=0.01, respectively). TNFα and IL-1α were not detectable in SM samples. Apart from a correlation between PGE2and WOMAC-index (r=0.36, P=0.035) no significant relationships could be found between the various inflammatory parameters and any of the assessed clinical signs.Conclusions: Apparently no direct relationships exist between the measured markers of inflammation (e.g. PGE2, NO2/3) or the involved enzymes (e.g. COX-2, iNOS) and the severity of OA of the knee. The degenerative condition of this disease might be due to the more local, mainly mechanical injury with little systemic upset. However, further longitudinal studies are needed to clarify whether the assessed biochemical markers could serve as predictors for the progression of OA

The Use of Placebo and Non-Specific Therapies and Their Relation to Basic Professional Attitudes and the Use of Complementary Therapies among German Physicians - A Cross-Sectional Survey

We aimed to investigate the use of placebos ( e. g. saline injections) and non-specific treatments ( e. g. vitamin supplements in individuals without a relevant deficiency) among physicians working in private practices in Germany, and how such use is associated with the belief in and the use of complementary and alternative treatments, and basic professional attitudes. A four-page questionnaire was sent to nationwide random samples of general practitioners ( GP),internists and orthopaedists working in private practices. The response rate was 46% ( 935 of 2018). 24% of GPs, 44% of internists and 57% of orthopaedists had neither used pure placebos nor non-specific therapies in the previous 12 months. 11% percent of GPs, 12% of internists and 7% of orthopaedists had exclusively used pure placebos;30%,33% and 26%,respectively, had exclusively used non-specific therapies;35%,12% and 9% had used both. Age, sex and agreement to the statement that physicians should harness placebo effects were not significantly associated with any pattern of use. Exclusive use of pure placebos was associated with being a GP, being an internist, and having unorthodox professional views. In addition to these three factors, a lower use of CAM therapies and a wish for having more time was associated with the exclusive use of nonspecific therapies. Among physicians using both pure placebo and non-specific therapies, heterodox views were also somewhat more pronounced. However, associations were particularly strong for being a GP ( Odds ratio 11.6 ( 95%CI 6.41;21.3)) and having orthodox views ( Odds ratio 0.10 ( 95%CI 0.06;0.18)) among this group. In conclusion, the use of placebos and non-specific treatments varies strongly between medical specialties and is associated with basic professional attitudes. The findings support the view that the use of placebos and, in particular, of non-specific therapies is primarily a coping behaviour for difficult and uncertain situations

Use of Placebos and Nonspecific and Complementary Treatments by German Physicians - Rationale and Development of a Questionnaire for a Nationwide Survey

Background: We are performing a nationwide survey in a random sample ofGerman general practitioners (GPs), orthopedists, and internists on theuse of placebos and nonspecific as well as complementary treatments andtheir association with basic professional attitudes. In this article weexplain the theoretical considerations behind the study approach and thedevelopment of the questionnaire. Methods: Based on a systematic reviewof published surveys, own surveys on the topic, and on theoreticalconsiderations we developed a preliminary version of a 4-pagequestionnaire that was tested for feasibility in a convenience sample of80 participants of a general medical education event. We also performedcognitive interviews with 8 physicians to investigate whether thequestions were understood adequately. Results: The questions on typicalplacebos and complementary treatments were well understood and easy toanswer for participants. Discussions about the phrasing of questions onnonspecific treatments during interview reflected the vagueness of thisconcept; but this did not seem to create major problems when answeringthe related questions. The original questions regarding basicprofessional attitudes partly were not understood in the mannerintended. The relevant questions were modified but the interviewssuggest that these issues are difficult to grasp in a quantitativesurvey. Conclusion: Our testing procedures suggest that ourquestionnaire is well-suited to investigate our questions with somelimitations regarding the issue of basic professional attitudes

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Use of Placebos and Nonspecific and Complementary Treatments by German Physicians - Rationale and Development of a Questionnaire for a Nationwide Survey

Background: We are performing a nationwide survey in a random sample ofGerman general practitioners (GPs), orthopedists, and internists on theuse of placebos and nonspecific as well as complementary treatments andtheir association with basic professional attitudes. In this article weexplain the theoretical considerations behind the study approach and thedevelopment of the questionnaire. Methods: Based on a systematic reviewof published surveys, own surveys on the topic, and on theoreticalconsiderations we developed a preliminary version of a 4-pagequestionnaire that was tested for feasibility in a convenience sample of80 participants of a general medical education event. We also performedcognitive interviews with 8 physicians to investigate whether thequestions were understood adequately. Results: The questions on typicalplacebos and complementary treatments were well understood and easy toanswer for participants. Discussions about the phrasing of questions onnonspecific treatments during interview reflected the vagueness of thisconcept; but this did not seem to create major problems when answeringthe related questions. The original questions regarding basicprofessional attitudes partly were not understood in the mannerintended. The relevant questions were modified but the interviewssuggest that these issues are difficult to grasp in a quantitativesurvey. Conclusion: Our testing procedures suggest that ourquestionnaire is well-suited to investigate our questions with somelimitations regarding the issue of basic professional attitudes

Use of pure placebos and non-specific therapies among respondents.

<p>Numbers are absolute frequencies (percentages; 95%-CI) unless otherwise indicated.</p

Basic professional attitudes, belief in and use of CAM therapies.

<p>Values are means (95%-CI) or absolute frequencies (percentages; 95%CI).</p

Factors associated with the pattern of the use of placebos and non-specific treatments in multivariate multinomial regression (n = 796, r² = 0.30 (Nagelkerke)).

<p>Odds ratios (OR) >1 indicate more frequent use compared to physicians using neither placebos nor non-specific treatments.</p