Assessment of interactions and dosage recommendations of synthetic DMARDs-Evidence-based and consensus-based recommendations based on a systematic literature search.

Conventional synthetic (cs) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) have potential interactions with a multitude of drugs. Furthermore, they sometimes have a lower therapeutic index, particularly in cases of limited organ functions. The aim of this work was to establish evidence-based recommendations on the therapeutic use of DMARDs in the context of drug interactions and dosage recommendations. A systematic literature search was carried out on the issue of drug interactions and dosages in cases of patients with limited kidney function and higher age and suffering from rheumatoid arthritis. A total of 2756 scientific publications were screened and 154 selected of which 68 were scrutinized in detail. Furthermore, the respective product information was also analyzed. A multitude of possible interactions of synthetic DMARDs with different drugs were detected, which were then assessed with respect to the clinical significance and consequences. A consensus process led to making recommendations with which the interactions were classified: A: dangerous combination, B: avoid combination (if possible, pausing DMARD treatment), C: possible combination requiring increased monitoring and potential adjustments in dosage and D: pharmacological interaction without relevance in DMARD standard doses. Apart from that dosage recommendations were established for each csDMARD and tsDMARD depending on kidney function and age. There are 3 primary recommendations and 11 core recommendations on interactions and dosages of csDMARDs and tsDMARDs meant as a practical help for therapeutic decision making and to improve safety in the treatment of rheumatoid arthritis.

Effects of acute exercise and training status on glucocorticoid-induced leucine zipper (GILZ) expression in human skeletal muscle.

Interactions between statin therapy and physical exercise complicate effective cardiovascular prevention. Emerging evidence suggests that muscle strain related changes in the expression of the glucocorticoid-induced leucine zipper (GILZ) may be involved. Therefore, we measured GILZ mRNA expression levels in M. vastus lateralis samples of 32 healthy individuals before and after a standardized bout of strength or endurance exercise. Overall, we found a highly significant downregulation of GILZ after exercise training (p < 0.001). Within-subgroup changes were statistically significant only after strength training, supporting the role of muscle (as opposed to cardiocirculatory) strain. If confirmed, this may help fitting training recommendations and medication.

Evaluating H295R steroidogenesis assay data for robust interpretation.

The in vitro H295R steroidogenesis assay (OECD TG 456) is used to determine a chemical's potential to interfere with steroid hormone synthesis/metabolism. As positive outcomes in this assay can trigger significant higher tiered testing, we compiled a stakeholder database of reference and test item H295R data to characterize assay outcomes. Information concerning whether a Level 5 reproductive toxicity study was triggered due to a positive outcome in the H295R assay was also included. Quality control acceptance criteria were not always achieved, suggesting this assay is challenging to conduct within the guideline specifications. Analysis of test item data demonstrated that pairwise significance testing to controls allowed for overly sensitive statistically significant positive outcomes, which likely contribute to the assay's high positive hit rate. Complementary interpretation criteria (e.g., 1.5-fold change threshold) markedly reduced the rate of equivocal and positive outcomes thus improving identification of robust positive effects in the assay. Finally, a case study (positive H295R outcome and no endocrine adversity in vivo) is presented, which suggests that stricter data interpretation criteria could refine necessary in vivo follow-up testing. Overall, the described additional criteria could improve H295R data interpretation and help inform on how to best leverage this assay for regulatory purposes.

Adenoid hypertrophy-​diagnosis and treatment: the new S2k guideline.

Hyperplasia of the pharyngeal tonsils is to be considered pathologic when nasopharyngeal symptoms of mechanical obstruction and/or chronic inflammation occur. Chronic Eustachian tube dysfunction can result in various middle ear diseases such as conductive hearing loss, cholesteatoma, and recurrent acute otitis media. During examination, attention should be paid to the presence of adenoid facies (long face syndrome), with a permanently open mouth and visible tip of the tongue. In the case of severe symptoms and/or failure of conservative treatment, adenoidectomy is usually performed on an outpatient basis. Conventional curettage remains the established standard treatment in Germany. Histologic evaluation is indicated for clinical evidence of mucopolysaccharidoses. Due to the risk of hemorrhage, the preoperative bleeding questionnaire, which is obligatory before every pediatric surgery, is referred to. Recurrence of adenoids is possible despite correct adenoidectomy. Before discharge home, otorhinolaryngologic inspection of the nasopharynx for secondary bleeding should be performed and anesthesiologic clearance obtained.

[Adenoids-diagnosis and treatment: the new German S2k guideline]. / Adenoide Vegetationen ­ Diagnostik und Therapie ­ die neue S2k-Leitlinie.

Hyperplasia of the pharyngeal tonsils is to be considered pathologic when nasopharyngeal symptoms of mechanical obstruction and/or chronic inflammation occur. Chronic Eustachian tube dysfunction can result in various middle ear diseases such as conductive hearing loss, cholesteatoma, and recurrent acute otitis media. During examination, attention should be paid to the presence of adenoid facies (long face syndrome), with a permanently open mouth and visible tip of the tongue. In the case of severe symptoms and/or failure of conservative treatment, adenoidectomy is usually performed on an outpatient basis. Conventional curettage remains the established standard treatment in Germany. Histologic evaluation is indicated for clinical evidence of mucopolysaccharidoses. Due to the risk of hemorrhage, the preoperative bleeding questionnaire, which is obligatory before every pediatric surgery, is referred to. Recurrence of adenoids is possible despite correct adenoidectomy. Before discharge home, otorhinolaryngologic inspection of the nasopharynx for secondary bleeding should be performed and anesthesiologic clearance obtained.

[Assessment of interactions and dosage recommendations of synthetic DMARDs-Evidence-based and consensus-based recommendations based on a systematic literature search]. / Bewertung von Wechselwirkungen und Dosierungsempfehlungen von synthetischen DMARDs ­ Evidenz- und konsensbasierte Empfehlungen auf Basis einer systematischen Literatursuche.

Conventional synthetic (cs) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) have potential interactions with a multitude of drugs. Furthermore, they sometimes have a lower therapeutic index, particularly in cases of limited organ functions. The aim of this work was to establish evidence-based recommendations on the therapeutic use of DMARDs in the context of drug interactions and dosage recommendations. A systematic literature search was carried out on the issue of drug interactions and dosages in cases of patients with limited kidney function and higher age and suffering from rheumatoid arthritis. A total of 2756 scientific publications were screened and 154 selected of which 68 were scrutinized in detail. Furthermore, the respective specialist subject information was also analyzed. A multitude of possible interactions of synthetic DMARDs with different drugs were detected, which were then assessed with respect to the clinical significance and consequences. A consensus process led to making recommendations with which the interactions were classified: A: dangerous combination, B: avoid combination (if possible, pausing DMARD treatment), C: possible combination requiring increased monitoring and potential adjustments in dosage and D: pharmacological interaction without relevance in DMARD standard doses. Apart from that dosage recommendations were established for each csDMARD and tsDMARD depending on kidney function and age. There are 3 primary recommendations and 11 core recommendations on interactions and dosages of csDMARDs and tsDMARDs meant as a practical help for therapeutic decision making and to improve safety in the treatment of rheumatoid arthritis.

[Development of quality standards for patients with rheumatoid arthritis for use in Germany]. / Entwicklung von Qualitätsstandards für die Versorgung von Patient*innen mit rheumatoider Arthritis zur Anwendung in Deutschland.

Despite a qualitatively and structurally good care of patients with rheumatoid arthritis (RA) in Germany, there are still potentially amendable deficits in the quality of care. For this reason, the German Society for Rheumatology (DGRh) has therefore decided to ask a group of experts including various stakeholders to develop quality standards (QS) for the care of patients with RA in order to improve the quality of care. The QS are used to determine and quantitatively measure the quality of care, subject to relevance and feasibility. The recently published NICE and ASAS standards and a systematic literature search were used as the basis for development. A total of 8 QS, now published for the first time, were approved with the intention to measure and further optimize the quality of care for patients with RA in Germany.

Influence of physical activity on periodontal health in patients with type 2 diabetes mellitus. A blinded, randomized, controlled trial.

OBJECTIVES: The aim was to investigate the effect of physical activity on periodontal health and HbA1c levels in patients with type 2 diabetes mellitus (T2DM) over a period of 6 months. MATERIALS AND METHODS: Thirty-seven patients with non-insulin-dependent T2DM were included in the study. The intervention group (n=20) performed physical activity over a period of 6 months. The control group (n=17) did not receive any intervention. Baseline and final examinations included dental parameters and concentrations of glycosylated hemoglobin (HbA1c) and high-sensitivity C-reactive protein (hsCRP). RESULTS: Physical activity showed a positive effect on periodontal health. Both the BOP (p= 0.005) and the severity of periodontitis (p= 0.001) were significantly reduced in the intervention group compared to the control group. Furthermore, HbA1c levels were reduced (p= 0.010) significantly in the intervention group while hsCRP levels significantly increased in the control group (p= 0.04). CONCLUSIONS: Within the limitations of this randomized, controlled trial, physical activity over a period of 6 months is a health-promoting measure for patients with T2DM and improves both periodontal health and HbA1c concentrations.

Safety management in treatment with antimalarials in rheumatology. Interdisciplinary recommendations on the basis of a systematic literature review.

BACKGROUND: Antimalarial medication (AM) plays an important role in the treatment of rheumatic diseases. OBJECTIVE: Updated evidence-based recommendations on the safety management of rheumatological treatment with AM are presented. METHODS: A systematic literature search in the databases Medline (PubMed) and Cochrane identified 1160 studies on the safety of treatment with AM in rheumatology. In addition, a manual search was carried out and 67 publications considered to be particularly relevant by the authors were analyzed in more detail. These publications served as a basis for consensus-based recommendations. RESULTS: Treatment with AM in rheumatology should be carried out with hydroxychloroquine (HCQ) with a dosage not exceeding 5 mg/kg body weight/day. Patients should undergo a basic ophthalmological examination within the first 6 months of AM treatment. Pre-existing maculopathy, renal insufficiency (glomerular filtration rate, GFR <60 ml/min), tamoxifen comedication, a daily dose of >5 mg/kg HCQ or treatment with chloroquine (CQ) show an increased risk for AM-induced retinopathy. These patients should undergo an annual ophthalmological check from the beginning of the treatment, whereas patients with no risk factors are recommended to start this only after 5 years of taking the medication. The ophthalmological examination should comprise at least both an appropriate subjective and an objective method and these are usually an automated visual field test and optical coherence tomography (OCT). A visual field test revealing a parafoveal sensitivity loss and an OCT showing a parafoveal circumscribed loss of the photoreceptor layer or focal interruptions of the structural line of the outer segment are signs of a possible AM retinopathy. Determination of creatine kinase (CK) and lactate dehydrogenase (LDH) in blood is appropriate to screen for cardiomyopathy and myopathy and should be checked before starting the treatment and then ca. every 3 months. The use of cardiac biomarkers, such as brain natriuretic peptide (BNP) or troponin in serum, electrocardiograph (ECG) or cardiac imaging should be considered depending on the situation. An intake of HCQ is safe during pregnancy and breastfeeding according to the current state of knowledge and is protective for mother and child in patients with systemic lupus erythematosus. CONCLUSION: The updated recommendations on AM treatment in rheumatology in particular include a more rigorous measuring of doses, risk stratification in monitoring and defined ophthalmological examination methods to detect a possible retinopathy.

Musculoskeletal disorders and level of physical activity in welders.

BACKGROUND: Welders demonstrate a high prevalence of musculoskeletal disorders (MSDs), as indicated by high rates of illness-related absenteeism. Leisure time physical activity (LTPA) could be a preventive strategy. However, little is known about LTPA prevalence and its association with MSDs among welders. AIMS: The aim of this study was to analyse the prevalence of MSD and LTPA levels among welders and to identify risk factors for the main disorder of low back pain (LBP). METHODS: The following data were collected from 145 welders from 34 companies in the German steel industry: individual factors (demographics, health behaviour), job-related factors (welding process, welding hours per day, employment years, shift work, ergonomic tools) and MSD (Nordic questionnaire). LTPA (International Physical Activity Questionnaire) was calculated to determine the metabolic equivalent of task (MET) per week as an objective measure of energy expenditure. Prevalence and multivariate regression analysis were calculated to determine odds ratios (ORs). RESULTS: The 12-month prevalence of LBP was 71%, for neck pain 61% and for shoulder pain 55%. Forty-two per cent of the participants accumulated <600 MET/week. The multivariate regression model revealed LTPA <600 MET/week (OR 3.4, 95% CI 1.05-10.85) and neck pain in the previous 12 months (OR 5.2, 95% CI 2.02-13.56) to be significantly associated with LBP. CONCLUSIONS: The results show a high prevalence of MSDs and thus a strong requirement for intervention. Therefore, LTPA should be prioritized and employers should encourage access to regular activity.

[SARS-CoV-2 & rheumatic disease : Consequences of the SARS-CoV-2 pandemic for patients with inflammatory rheumatic diseases. A comparison of the recommendations for action of rheumatological societies and risk assessment of different antirheumatic treatments]. / SARS-CoV-2 & Rheuma : Konsequenzen der SARS-CoV-2-Pandemie für Patienten mit entzündlich rheumatischen Erkrankungen. Ein Vergleich der Handlungsempfehlungen rheumatologischer Fachgesellschaften und Risikobewertung verschiedener antirheumatischer Therapien.

The recommendations of the German Society of Rheumatology (DGRh) update, which update and expand the guidance on the management of patients with inflammatory rheumatic diseases in view of SARS-CoV­2 created at the beginning of the COVID-19 pandemic, correspond in many points with the recommendations for action of the American (ACR) and European (EULAR) societies, but also differ in some points. Therefore, this article discusses the core recommendations of the DGRh update on the prevention of SARS-CoV-2/COVID-19, the risk assessment for inflammatory rheumatic diseases and the use of antirheumatic treatments in the context and in comparison to the ACR and EULAR recommendations, and provides an overview of the risk assessment of individual antirheumatic drugs.

Effects of Escherichia coli strain Nissle 1917 on exercise-induced disruption of gastrointestinal integrity.

PURPOSE: The aim of the current study was to investigate the effects of the probiotic Escherichia coli strain Nissle 1917 (EcN) on the exercise-induced disruption of gastrointestinal (GI) integrity and the associated release of damage and inflammatory markers. METHODS: After a pre-performance test, 19 untrained subjects (aged 18-35 years) passed two identical exhaustive treadmill exercise tests in an intensity corresponding to 60-80% VO2max in a test-retest design. The exercise tests were separated by a time period of 4 weeks. During this period, all subjects ingested 5 ml of an EcN suspension daily. Serum samples were taken before, immediately following and 3 h after both exercise tests. They were analyzed for indicators of GI integrity (zonulin; claudin-3; LPS), various damage and redox markers (I-FABP, GOT; GPT; TBARS) and inflammatory parameters (hsCRP; leucocytes). GI complaints were evaluated by a questionnaire. RESULTS: The intake of EcN resulted in a significantly lower increase in I-FABP and TBARS after exercise (p < 0.05). In contrast, no effect of EcN supplementation was found for hsCRP and leucocyte numbers. Similarly, no differences were found for levels of zonulin and claudin-3. Exercise-associated GI complaints were not affected by the probiotic supplement. CONCLUSION: The probiotic EcN reduced the exercise-associated increase in oxidative stress. This antioxidative mechanism probably leads to a reduction of GI epithelial damage after exhaustive exercise. The lack of EcN effects on other markers of GI permeability and systemic inflammation is most likely due to an inadequate exercise load, with rather small and insignificant exercise effects on these parameters.

[Current guidance of the German Society of Rheumatology for the care of patients with rheumatic diseases during the SARS-CoV-2/Covid 19 pandemic]. / Aktuelle Handlungsempfehlungen der Deutschen Gesellschaft für Rheumatologie für die Betreuung von Patienten mit rheumatischen Erkrankungen während der SARS-CoV­2/Covid 19-Pandemie.

In the current SARS-CoV-2 pandemic there are many questions regarding the safe treatment of patients with inflammatory rheumatic diseases. Many of these questions cannot yet be answered on an evidence-based basis and this does not make patient care easy. The German Society for Rheumatology (DGRh) hopes that these initial recommendations will provide support for specific issues in the care of patients with inflammatory rheumatic diseases in view of the current threat posed by SARS-CoV-2. In order to take advantage of the dynamic worldwide gain in knowledge for our patients, the recommendations will be updated regularly. The updated versions of the recommendations are deposited on the homepage of the DGRh.

[Delegation of medical tasks in rheumatology]. / Delegation ärztlicher Leistungen in der Rheumatologie.

Modern rheumatology enables better and earlier diagnosis and therapy of inflammatory rheumatic system diseases. At the same time, the requirements for the care of rheumatologic patients have risen considerably for non-medical assistant professions and specialists for nursing professions. Since 2006 there has been established an education curriculum "Rheumatological Specialist Assistant DGRh-BDRh" (RFA) with the training to become a "Rheumatological Specialist Assistant (DGRh-BDRh)". In Europe and in parallel in Germany, assistant professions are increasingly involved in the early detection and care of patients with rheumatic diseases and entrusted with tasks.In this work, the overarching principles for delegation of medical tasks to RFA and recommendations for the delegation are published by the Commission for Delegation of the German Society for Rheumatology (DGRh). These recommendations are based on the requirements of the German Medical Association and have been legally evaluated. With the extension of the training of the RFA board certification is aimed for "MFA for Rheumatology". These recommendations enable more transparency and security for delegating doctors and the delegated RFA's.

[Safety management of the treatment with antimalarial drugs in rheumatology. Interdisciplinary recommendations based on a systematic literature search]. / Sicherheitsmanagement der Therapie mit Antimalariamitteln in der Rheumatologie. Interdisziplinäre Empfehlungen auf der Basis einer systematischen Literaturrecherche.

BACKGROUND: Antimalarial medication (AM) plays an important role in the treatment of rheumatic diseases. OBJECTIVE: Updated evidence-based recommendations on the safety management of rheumatological treatment with AM are presented. METHODS: A systematic literature search in the databases Medline (PubMed) and Cochrane identified 1160 studies on the safety of treatment with AM in rheumatology. In addition, a manual search was carried out and 67 publications considered to be particularly relevant by the authors were analyzed in more detail. These publications served as a basis for consensus-based recommendations. RESULTS: Treatment with AM in rheumatology should be carried out with hydroxychloroquine (HCQ) with a dosage not exceeding 5 mg/kg body weight/day. Patients should undergo a basic ophthalmological examination within the first 6 months of AM treatment. Pre-existing maculopathy, renal insufficiency (glomerular filtration rate, GFR <60 ml/min), tamoxifen comedication, a daily dose of >5 mg/kg HCQ or treatment with chloroquine (CQ) show an increased risk for AM-induced retinopathy. These patients should undergo an annual ophthalmological check from the beginning of the treatment, whereas patients with no risk factors are recommended to start this only after 5 years of taking the medication. The ophthalmological examination should comprise at least both an appropriate subjective and an objective method and these are usually an automated visual field test and optical coherence tomography (OCT). A visual field test revealing a parafoveal sensitivity loss and an OCT showing a parafoveal circumscribed loss of the photoreceptor layer or focal interruptions of the structural line of the outer segment are signs of a possible AM retinopathy. Determination of creatine kinase (CK) and lactate dehydrogenase (LDH) in blood is appropriate to screen for cardiomyopathy and myopathy and should be checked before starting the treatment and then ca. every 3 months. The use of cardiac biomarkers, such as brain natriuretic peptide (BNP) or troponin in serum, electrocardiograph (ECG) or cardiac imaging should be considered depending on the situation. An intake of HCQ is safe during pregnancy and breastfeeding according to the current state of knowledge and is protective for mother and child in patients with systemic lupus erythematosus. CONCLUSION: The updated recommendations on AM treatment in rheumatology in particular include a more rigorous measuring of doses, risk stratification in monitoring and defined ophthalmological examination methods to detect a possible retinopathy.