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Purpose of reviewIncretin-based therapy with glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors is considered a promising therapeutic option for type 2 diabetes mellitus. Cumulative evidence, mainly from preclinical animal studies, reveals that incretin-based therapies also may elicit beneficial effects on kidney function. This review gives an overview of the physiology, pathophysiology, and pharmacology of the renal incretin system.Recent findingsActivation of GLP-1R in the kidney leads to diuretic and natriuretic effects, possibly through direct actions on renal tubular cells and sodium transporters. Moreover, there is evidence that incretin-based therapy reduces albuminuria, glomerulosclerosis, oxidative stress, and fibrosis in the kidney, partially through GLP-1R-independent pathways. Molecular mechanisms by which incretins exert their renal effects are understood incompletely, thus further studies are needed.SummaryThe GLP-1R and DPP-4 are expressed in the kidney in various species. The kidney plays an important role in the excretion of incretin metabolites and most GLP-1R agonists and DPP-4 inhibitors, thus special attention is required when applying incretin-based therapy in renal impairment. Preclinical observations suggest direct renoprotective effects of incretin-based therapies in the setting of hypertension and other disorders of sodium retention, as well as in diabetic and nondiabetic nephropathy. Clinical studies are needed in order to confirm translational relevance from preclinical findings for treatment options of renal diseases.
Background:
Given the rising number of strokes worldwide, and the large number of individuals left with disabilities after stroke, novel strategies to reduce disability, increase functions in the motor and the cognitive domains, and improve quality of life are of major importance. Physical activity is a promising intervention to address these challenges but, as yet, there is no study demonstrating definite outcomes. Our objective is to assess whether additional treatment in the form of physical fitness-based training for patients early after stroke will provide benefits in terms of functional outcomes, in particular gait speed and the Barthel Index (co-primary outcome measures) reflecting activities of daily living (ADL). We will gather secondary functional outcomes as well as mechanistic parameters in an exploratory approach.
Methods/Design: Our phase III randomised controlled trial will recruit 215 adults with moderate to severe limitations of walking and ADL 5 to 45 days after stroke onset. Participants will be stratified for the prognostic variables of "centre", "age", and "stroke severity", and randomly assigned to one of two groups. The interventional group receives physical fitness training delivered as supported or unsupported treadmill training (cardiovascular active aerobic training; five times per week, over 4 weeks; each session 50 minutes; total of 20 additional physical fitness training sessions) in addition to standard rehabilitation treatment. The control intervention consists of relaxation sessions (non-cardiovascular active; five times per week week, over 4 weeks; each session 50 minutes) in addition to standard rehabilitation treatment. Co-primary efficacy endpoints will be gait speed (in m/s, 10 m walk) and the Barthel Index (100 points total) at 3 months post-stroke, compared to baseline measurements. Secondary outcomes include standard measures of quality of life, sleep and mood, cognition, arm function, maximal oxygen uptake, and cardiovascular risk factors including blood pressure, pulse, waist-to-hip ratio, markers of inflammation, immunity and the insulin-glucose pathway, lipid profile, and others.
Discussion: The goal of this endpoint-blinded, phase III randomised controlled trial is to provide evidence to guide post-stroke physical fitness-based rehabilitation programmes, and to elucidate the mechanisms underlying this intervention.
Potential cost-effectiveness of therapeutic drug monitoring in patients with resistant hypertension
(2014)
Background: Nonadherence to drug therapy poses a significant problem in the treatment of patients with presumed resistant hypertension. It has been shown that therapeutic drug monitoring (TDM) is a useful tool for detecting nonadherence and identifying barriers to treatment adherence, leading to effective blood pressure (BP) control. However, the cost-effectiveness of TDM in the management of resistant hypertension has not been investigated.
Results: In the age group of 60-year olds, TDM gained 1.07 QALYs in men and 0.97 QALYs in women at additional costs of (sic)3854 and (sic)3922, respectively. Given a willingness-to-pay threshold of (sic)35 000 per QALY gained, the probability of TDM being cost-effective was 95% or more in all age groups from 30 to 90 years. Results were influenced mostly by the frequency of TDM testing, the rate of nonresponders to TDM, and the magnitude of effect of TDM on BP.
Conclusion: Therapeutic drug monitoring presents a potential cost-effective healthcare intervention in patients diagnosed with resistant hypertension. Importantly, this finding is valid for a wide range of patients, independent of sex and age.
Background
It has been demonstrated that core strength training is an effective means to enhance trunk muscle strength (TMS) and proxies of physical fitness in youth. Of note, cross-sectional studies revealed that the inclusion of unstable elements in core strengthening exercises produced increases in trunk muscle activity and thus provide potential extra training stimuli for performance enhancement. Thus, utilizing unstable surfaces during core strength training may even produce larger performance gains. However, the effects of core strength training using unstable surfaces are unresolved in youth. This randomized controlled study specifically investigated the effects of core strength training performed on stable surfaces (CSTS) compared to unstable surfaces (CSTU) on physical fitness in school-aged children.
Methods
Twenty-seven (14 girls, 13 boys) healthy subjects (mean age: 14 ± 1 years, age range: 13–15 years) were randomly assigned to a CSTS (n = 13) or a CSTU (n = 14) group. Both training programs lasted 6 weeks (2 sessions/week) and included frontal, dorsal, and lateral core exercises. During CSTU, these exercises were conducted on unstable surfaces (e.g., TOGU© DYNAIR CUSSIONS, THERA-BAND© STABILITY TRAINER).
Results
Significant main effects of Time (pre vs. post) were observed for the TMS tests (8-22%, f = 0.47-0.76), the jumping sideways test (4-5%, f = 1.07), and the Y balance test (2-3%, f = 0.46-0.49). Trends towards significance were found for the standing long jump test (1-3%, f = 0.39) and the stand-and-reach test (0-2%, f = 0.39). We could not detect any significant main effects of Group. Significant Time x Group interactions were detected for the stand-and-reach test in favour of the CSTU group (2%, f = 0.54).
Conclusions
Core strength training resulted in significant increases in proxies of physical fitness in adolescents. However, CSTU as compared to CSTS had only limited additional effects (i.e., stand-and-reach test). Consequently, if the goal of training is to enhance physical fitness, then CSTU has limited advantages over CSTS.
Background: Cross-sectional studies detected associations between physical fitness, living area, and sports participation in children. Yet, their scientific value is limited because the identification of cause-and-effect relationships is not possible. In a longitudinal approach, we examined the effects of living area and sports club participation on physical fitness development in primary school children from classes 3 to 6.
Methods: One-hundred and seventy-two children (age: 9-12 years; sex: 69 girls, 103 boys) were tested for their physical fitness (i.e., endurance [9-min run], speed [50-m sprint], lower- [triple hop] and upper-extremity muscle strength [1-kg ball push], flexibility [stand-and-reach], and coordination [star coordination run]). Living area (i.e., urban or rural) and sports club participation were assessed using parent questionnaire.
Results: Over the 4 year study period, urban compared to rural children showed significantly better performance development for upper- (p = 0.009, ES = 0.16) and lower-extremity strength (p < 0.001, ES = 0.22). Further, significantly better performance development were found for endurance (p = 0.08, ES = 0.19) and lower-extremity strength (p = 0.024, ES = 0.23) for children continuously participating in sports clubs compared to their non-participating peers.
Conclusions: Our findings suggest that sport club programs with appealing arrangements appear to represent a good means to promote physical fitness in children living in rural areas.
The purpose of this study was to assess intrasession and intersession reliability of maximal and explosive isometric torque production of the elbow flexors and its respective neuromuscular activation pattern. Subjects (13 men, age: 24.8 +/- 3.1 years, height: 1.9 +/- 0.1 m, body mass: 83.7 +/- 12.7 kg; and 6 women, age: 26.5 +/- 1.4 years, height: 1.7 +/- 0.1 m, body mass: 62.7 +/- 7.0 kg) were tested and retested 2-7 days later performing unilateral maximal isometric elbow flexions. Absolute (coefficient of variation[CV], test-retest variability[TRV], Bland-Altman plots with 95% limits of agreement) and relative reliability statistics (intraclass correlation coefficient) were calculated for various mechanical (i.e., maximal isometric torque, rate of torque development, impulse) and electromyographical measures (i.e., mean average voltage) at different time intervals relative to onset of torque (i. e., 30, 50, 100, 200, 300, 400, 100-200 ms). Intraclass correlation coefficient values were >= 0.61 for all mechanical and electromyographical measures and time intervals indicating good to excellent intrasession and intersession reliability. BlandAltman plots confirmed these findings by showing that only 0-2 (<= 3.3%) data points were beyond the limits of agreement. Regarding torque and electromyographic measures, CV (11.9-32.3%) and TRV (18.4-53.8%) values were high during the early intervals of torque development (<= 100 ms) indicating high variability. During the later intervals (>100 ms), lower CV (i. e., 5.0-29.9%) and TRV values (i.e., 5.4-34.6%) were observed indicating lower variability. The present study revealed that neuromuscular performance during explosive torque production of the elbow flexors is reproducible in time intervals >100 ms after onset of isometric actions, whereas during earlier time intervals variability is high.