[Disease-related knowledge acquisition through structured patient information in rheumatoid arthritis (StruPI-RA) : First results of the StruPI-RA study in Germany]. / Krankheitsbezogener Wissenserwerb durch strukturierte Patienteninformation bei Rheumatoider Arthritis (StruPI-RA) : Erste Ergebnisse der StruPI-RA-Studie in Deutschland.

BACKGROUND/OBJECTIVE: The structured patient information for rheumatoid arthritis (StruPi-RA) program was the first standardized outpatient education program in rheumatoid arthritis (RA) in Germany. The main objective of the study was to determine the efficacy of the StruPi-RA program concerning disease-specific knowledge acquisition in patients with early stage RA or after changing the treatment regimen. METHODS: A total of 61 patients were included in a control group design, 32 in the intervention group (IG) and 29 in the control group (CG). Patients of the IG attended 3 modules of 90 min in a structured patient information program (StruPI-RA) including the topics of diagnostics, treatment and living with RA. Patients in the CG only received information material from the German Rheumatism League. The primary target criterion was the disease-related acquisition of knowledge, measured with the patient knowledge questionnaire (PKQ). Data were collected before and after participation in StruPI-RA. RESULTS: The improvement in knowledge in the IG attending the StruPI-RA compared to the CG was significant in time and group comparisons. No influence of disease duration or educational level was observed. The subscale treatment alone showed a significant difference in the group and time comparison. CONCLUSION: Participation in the StruPI-RA program in early RA was associated with a significant increase in disease-specific knowledge compared to the control group of patients. This leads to better decision-making in terms of treatment, a more beneficial doctor-patient communication and better self-management. In the long term an improvement in treatment adherence and quality of life is expected.

COMPARISON OF WEARABLES FOR SELF-MONITORING OF HEART RATE IN CORONARY REHABILITATION PATIENTS.

The leading cause of morbidity and mortality in the world is ischemic heart disease. Physical activity is a major approach in prevention and therapy of cardiac diseases. Self-heart-rate-monitoring in daily life is an important point for health awareness of cardiac patients. Aim of this study was validation of measurement accuracy of seven different devices against ECG-monitoring during cardiac rehabilitation training on a bicycle ergometer. Tested devices were: Garmin Forerunner 35 (Garmin), Mio Fuse (Mio), Fitbit Charge HR (FitbitHR), Fitbit Surge (FitbitS), Withings Pulse™ Ox (Withings), Apple Watch Series 1 (Apple) and Pearl Fitness-Tracker (FBT-50.HR PRO.V4). All devices were tested on 35 participants with six timed measurements during 20 minutes constant load bicycle ergometer workout for each. Simultaneousely, ECG measurements were recorded. Pearson´s correlations were assessed. Apple, Mio, and Garmin showed excellent accuracy with close correlation to ECG for self-monitoring of heart rate (HR) during cycling. FitbitHR, Pearl and FitbitS presented reasonable results. In contrast, Withings showed poor correlation to ECG with significant differences. We found significant differences between the tested devices. Since accuracy is of major importance for cardiac patients, only Apple, Mio and Garmin could be recommended. However, further research within distinct clinical and non-clinical settings is necessary and should take different types of physical activities into account.

Whole-body vibration training as a workplace-based sports activity for employees with chronic low-back pain.

The goal of this randomized and controlled study was to examine whether whole-body vibration (WBV) training is able to reduce back pain and physical disability in seated working office employees with chronic low-back pain in a real-world setting. A total of 41 subjects (68.3% female/mean age 45.5±9.1 years/mean BMI 26.6±5.2) were randomly allocated to an intervention group (INT [n=21]) or a control group (CON [n=20]). The INT participated in WBV training 2.5 times per week for 3 months. The primary outcome was the change in the Roland and Morris disability questionnaire (RMQ) score over the study period. In addition, secondary outcomes included changes in the Oswestry Disability Index (ODI), the Work Ability Index Questionnaire, the quality of life questionnaire SF-36, the Freiburger activity questionnaire, and an isokinetic test of the musculature of the trunk. Compliance with the intervention in the INT reached a mean of 81.1%±31.2% with no long-lasting unwanted side effects. We found significant positive effects of 3 months of WBV training in the INT compared to the CON regarding the RMQ (P=.027), the ODI (P=.002), the SF-36 (P=.013), the Freiburger activity questionnaire (P=.022), the post-interventional sick-leave in the INT (P=.008), and trends regarding a positive effect of the intervention on the muscular capacity of the muscles of the trunk in flexion. WBV training seems to be an effective, safe, and suitable intervention for seated working employees with chronic low-back pain.

Alzheimer's Disease and (Phyto) Estrogen Treatment: Modification of Effects by Age, Type of Treatment, and Duration of Use.

Background: There is a continued debate on whether menopausal hormone therapy (MHT) protects women against Alzheimer's disease (AD). It is also unclear whether phytoestrogen could be an alternative treatment for AD. Objective: To investigate whether mixed study findings may be due to differences in age at initiation of MHT and duration of prescription of different types of MHT using meta-analyses. Methods: After a systematic literature search, meta-analyses were carried out using Cochrane Revman 5.4.1.software including data from large nationwide studies of registered medically diagnosed AD and prescribed MHT. These analyses were stratified for duration and type of treatment, by age at start of prescription of therapy. Insufficient quality data were available for phytoestrogen treatment and AD meta-analyses. Results: A total of 912,157 women were included from five registries, of whom 278,495 had developed AD during follow-up. Meta-analyses suggested a small increased AD risk after 5-10 years prescription of combination MHT regardless of age, and over 10 years only in women younger than 60 years of age. No association was seen for estrogen alone for women younger than 60 years of age, but AD risk did increase for women over 60 years of age for up to 5 years of MHT prescriptions. Conclusions: Combination MHT should probably be prescribed for less than 5 years after menopause to reduce risk for AD, while estrogen alone should not be prescribed to women over 60. For phytoestrogen, small treatment trials suggested some benefit of tempeh (fermented soy), which should be investigated further.

Exercise increases serum brain-derived neurotrophic factor in patients with major depressive disorder.

BACKGROUND: Brain derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of major depressive disorder (MDD). Existing data on exercise treatment in people with MDD are inconsistent concerning the effect of exercise on BDNF pointing either to increased or unaltered BDNF concentrations. However, studies in non-depressed persons demonstrated a significant effect on resting peripheral BDNF concentrations in aerobic training interventions. Given the lack of clarity mentioned above, the current study aimed at examining the effect of adjunctive exercise on serum BDNF levels in guideline based treated patients with MDD. METHODS: 42 depressed inpatients were included, and randomized either to a 6 week structured and supervised exercise intervention plus treatment as usual (EXERCISE, n=22), or to treatment as usual (TAU, n=20). BDNF serum concentrations were assessed before and after the intervention in both study groups with established immunoassays. RESULTS: Serum BDNF slightly decreased in the TAU group, whilst there was an increase in BDNF levels in the exercise group. There was a significant time x group effect concerning sBDNF (p=0.030) with repeated ANOVA measures with age and BMI as covariates, suggesting an increase in BDNF concentrations in the EXERCISE group compared to TAU. LIMITATIONS: Though there was no statistic difference in the antidepressant medication between EXERCISE and TAU potential interactions between exercise and medication on the effects of exercise in BDNF cannot be excluded. Gender was not considered as a covariate in ANOVA due to the small number of objects. CONCLUSIONS: Exercise training given as adjunct to standard guideline based treatment appears to have additional effects on BDNF serum concentrations in people with MDD. Our results add further evidence to the beneficial effects of exercise in the treatment of MDD.

Differences in intrinsic efficacy of benzodiazepines are reflected in their concentration-EEG effect relationship.

1. The relevance of EEG effect parameters as a measure of the central nervous system effects of benzodiazepines was evaluated. The concentration-EEG effect relationships of the benzodiazepine agonist midazolam, partial agonist bretazenil, antagonist flumazenil and inverse agonist Ro 19-4603 were quantified and compared with the intrinsic efficacy and affinity of these compounds at the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex. 2. The pharmacokinetics and pharmacodynamics of the compounds were determined after a single intravenous bolus administration of 5 mg kg-1 midazolam, 2.5 mg kg-1 bretazenil, 10 mg kg-1 flumazenil or 2.5 mg kg-1 Ro 19-4603 to male Wistar derived rats. In a separate experiment the distribution between blood, cerebrospinal fluid and brain concentrations of these compounds was determined. A sensitive assay was developed to measure bretazenil and Ro 19-4603 concentrations in small samples of biological fluids. 3. The benzodiazepine-induced changes in amplitudes in the 11.5-30 Hz frequency band, as determined by aperiodic analysis, was used as EEG effect measure. Concentration-EEG effect relationships were derived by a pharmacokinetic-pharmacodynamic modelling procedure and in the case of midazolam, bretazenil and Ro 19-4603 successfully quantified by the sigmoidal Emax model. Large differences in maximal effect of midazolam (Emax = 73 +/- 2 microVs-1), bretazenil (Emax = 19 +/- 1 microVs-1) and Ro 19-4603 (Emax = -6.5 +/- 0.4 microVs-1) were observed, reflecting their differences in intrinsic efficacy. A close correlation was found between the EC50 values based on free drug concentration and receptor affinity as determined by displacement of [3H]-flumazenil in a washed brain homogenate at 37 degrees C. In the concentration range of receptor saturation flumazenil did not produce any changes in the EEG effect measure.4. The study demonstrated that the change in amplitudes in the 11.5-30 Hz frequency band of the EEG is a relevant measure of the pharmacological effect intensity of benzodiazepines, because it seems to reflect their affinity and intrinsic efficacy at the central GABA-benzodiazepine receptor complex.

Unchanged pharmacokinetics of etoposide given by intra-arterial hepatic infusion as compared with i.v. infusion.

We investigated the pharmacokinetics of etoposide given to a patient suffering from multifocal liver metastases from an unknown primary tumor. The drug was given either by i.v. infusion or by hepatic arterial infusion (HAI). The calculated pharmacokinetic parameters (mean values +/- SD) were similar after i.v. infusion and HAI, viz., 6.4 +/- 0.7 versus 6.5 +/- 0.2 h for the terminal elimination half-life (t1/2 beta), 98.5 +/- 1.3 versus 101.3 +/- 5.9 mg l(-1) h for the area under the plasma concentration-time curve (AUC), 21.2 +/- 0.3 versus 20.6 +/- 1.2 ml min-1 m-2 for clearance (Cl), 17.7 +/- 1.9 versus 18.1 +/- 2.6 mg/l for the peak concentration, and 11.7 +/- 1.3 versus 11.6 +/- 1.01/m2 for the volume of distribution (Vd), respectively. We therefore conclude that administration of etoposide by HAI does not result in a significantly higher liver extraction. Hepatic extraction of etoposide is determined by the fraction of non-protein-bound (free) drug present. The lack of a difference between the two administration routes suggests that under in vivo conditions the equilibrium between free and bound drug is established before the drug reaches the hepatic arterioles. Consequently, administration by HAI does not lead to an increased exposure of the tumor in the liver to free (active) etoposide. Furthermore, the overall exposure of the liver to total (bound + free) etoposide is increased only from about 100 to 120 mg l-1 h. These results do not favor the use of this more complex route of drug administration in the treatment of (metastatic) cancer located in the liver.

Physical capacity and quality of life in patients with multiple sclerosis.

BACKGROUND: Physical capacity (PC) and quality of life (QoL) are both reduced in multiple sclerosis (MS). OBJECTIVE: Aim of our study was to investigate limitations in PC and QoL in response to the severity of MS. METHODS: The study involved 60 patients (PG) (Expanded Disability Status Scale EDSS 0-3:38, EDSS 3.5-6:22) and 48 healthy controls (CG). Endurance capacity was assessed as peak oxygen uptake (VO2peak) and ventilatory anaerobic threshold (VAT). Maximum force was measured in isokinetic testing. QoL was assessed using the SF-36-questionnaire and HALEMS. RESULTS: Patients with MS showed reduced VO2peak and QoL in comparison with CG. Patients with an EDSS >3 showed reduced VO2peak, and maximum force, however at the VAT there was no significant difference independent of the EDSS. The MS-specific QoL HALEMS and subscales 1, 4, 6, 8 and the physical sum score of the SF-36-questionnaire were evaluated to be better in patients with an EDSS ≤3. CONCLUSIONS: There are limitations within PC in patients with MS in comparison with a healthy CG; within the PG there are notes on a similar aerobic capacity but worsened anaerobic capacity in patients with an EDSS >3. This should be taken into account in future treatment strategies for training therapy.

In vivo modeling of the pharmacodynamic interaction between benzodiazepines which differ in intrinsic efficacy.

The pharmacokinetic and pharmacodynamic interactions between the benzodiazepine agonist midazolam, on one hand, and the partial agonist bretazenil and inverse agonist Ro 19-4603, on the other, were characterized in vivo in rats using effect parameters derived from quantitative EEG analysis. Male Wistar-derived rats received an i.v. infusion of 3 mg/kg bretazenil or 3 mg/kg Ro 19-4603 in 5 min during a steady-state infusion of midazolam at a rate of 2.8 mg/kg/hr. EEG signals were continuously measured and quantified by aperiodic EEG analysis and the change in amplitudes in the 11.5 to 30 Hz (beta) frequency band was used as measure of drug effect on the central nervous system. Frequent arterial blood samples were taken to determine the pharmacokinetics of the drugs. Both bretazenil and Ro 19-4603 did not influence the steady-state plasma concentrations of midazolam, but markedly antagonized the midazolam-induced increase in EEG effect measure to the extent of their own intrinsic maximal effects. The changes in EEG effect as a function of drug concentrations were described by a competitive interaction model, allowing the estimation of the pharmacodynamic parameters (means +/- S.E.) of the partial agonist, Emax = 15 +/- 5 microV/sec and EC50 = 19 +/- 5 ng/ml, and inverse agonist, Emax = -5.8 +/- 1.6 microV/sec and EC50 = 7.8 +/- 2.5 ng/ml. Similar values of the pharmacodynamic parameters were obtained after a single i.v. administration of these drugs, which provides evidence for the validity of the proposed interaction model.(ABSTRACT TRUNCATED AT 250 WORDS)