A Double Blind, Placebo-Controlled, Randomized Crossover Study of the Acute Metabolic Effects of Olanzapine in Healthy Volunteers

Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT) along with reduced plasma free fatty acids (FFA) and leptin in animal models. It is unclear whether the same acute effects occur in humans.A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8) and female (7) subjects [18-30 years old, BMI 18.5-25]. Subjects received placebo or olanzapine (10 mg/day) for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA). Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC) by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105) during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203) and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170), whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166) and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184), respectively after olanzapine. Other measures were unchanged.Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics.ClinicalTrials.gov NCT00741026

Prediction of overuse injuries in professional U18-U21 footballers using metrics of training distance and intensity

The most common injury in professional football is an overuse injury to the lower limb. A significant external risk factor of this injury is the mismanagement of training and match loads. The aim of the current study was to examine the predictability of overuse injuries in professional youth soccer players using volume and intensity variables derived from Global Positioning Systems (GPS). A total of 41 players (Age - 17.8 yrs±1.1 yrs) training and match loads were assessed. These external loads were measured over two competitive seasons for every training session and match for each individual. A linear regression was used to test the predictability of the injury based on load, which were grouped using loading groups calculated from squad weekly averages. The load groupings assigned were: Low load = 1 SD below the squad mean score; Normal load = ±1 SD from the squad mean; High load = 1 SD above squad mean. The analysis demonstrated that total distance significantly predicted overuse injury incidence rates (F(1, 39) = 6.482, p = 0.015), whereas high speed running meters could not (F(1, 39) = 1.003, p = 0.323). This study demonstrated that distance covered in training and matches can impact on the incidence of overuse injury in youth soccer players. Coaches should seek to monitor player training loads and incorporate this metric into their decision making for protecting players from overuse injury

Psychosexual development and quality of life outcomes in females with congenital adrenal hyperplasia

BACKGROUND/AIMS: Outcome information regarding females with classical congenital adrenal hyperplasia (CAH) have generally suggested poor quality of life (QoL), general maladjustment, problems regarding sexuality, and decreased fertility. The aim of this study was to assess QoL, psychosocial adaptation, and psychosexual characteristics, includingchildhood gender role behavior, gender identity, and sexual orientation in females with CAH. METHODS: Female patients with 21-hydroxylase deficiency CAH were evaluated using a questionnaire with items relating to knowledge of their condition and its therapy; consistency of medical, surgical, and psychological care; childhood friends and play behavior; and genital, pubertal, and sexual development. The subjects’ perception of outcome was compared with family support and adolescent and adult QoL perspectives, including social relationships, self and body image, and gender and sexual issues. RESULTS: Childhood play and gender characteristics, childhood and adult genital perception, and sexual identity and orientation varied as previously reported. However, most patients indicated good family support, understanding of their condition, good quality medical care, positive self-satisfaction, indices of happiness and body image perception, and satisfaction with their sex lives. CONCLUSION: The data reported here suggest that overall outcome can be very good for females with CAH and that good outcome appears to relate to quality of care and positive social support. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13633-015-0017-z) contains supplementary material, which is available to authorized users

Alpha band oscillations in common synaptic input are explanatory of the complexity of isometric knee extensor muscle torque signals

We investigated whether the strength of oscillations in common synaptic input was explanatory of knee extensor (KE) torque signal complexity during fresh and fatigued submaximal isometric contractions, in adults aged from 18 to 90 years. The discharge times of motor units were derived from the vastus lateralis muscle of 60 participants using high-density surface EMG, during 20 s isometric KE contractions at 20% of maximal voluntary contraction, performed before and after a fatiguing repeated isometric KE contraction protocol at 60% of maximal voluntary contraction. Within-muscle coherence Z-scores were estimated using frequency-domain coherence analysis, and muscle torque complexity was assessed using multiscale entropy analysis and detrended fluctuation analysis. Alpha band (5–15 Hz) coherence was found to predict 23.1% and 31.4% of the variance in the complexity index under 28-scales (CI-28) and detrended fluctuation analysis α complexity metrics, respectively, during the fresh contractions. Delta, alpha and low beta band coherence were significantly increased due to fatigue. Fatigue-related changes in alpha coherence were significantly predictive of the fatigue-related changes in CI-28 and detrended fluctuation analysis α. The fatigue-related increase in sample entropy from scales 11 to 28 of the multiscale entropy analysis curves was significantly predicted by the increase in the alpha band coherence. Age was not a contributory factor to the fatigue-related changes in within-muscle coherence and torque signal complexity. These findings indicate that the strength of alpha band oscillations in common synaptic input can explain, in part, isometric KE torque signal complexity and the fatigue-related changes in torque signal complexity

Test-retest reliability of a 30-minute fixed perceived effort cycling exercise

Purpose: Using exercise protocols at a fixed rating of perceived effort (RPE) is a useful method for exploring the psychophysical influences on exercise performance. However, studies that have employed this protocol have arbitrarily selected RPE values without considering how these values correspond to exercise intensity thresholds and domains. Therefore, aligning RPE intensities with established physiological thresholds seems more appropriate, although the reliability of this method has not been assessed. Methods: Eight recreationally active cyclists completed two identical ramped incremental trials on a cycle ergometer to identify gas exchange threshold (GET). A linear regression model plotted RPE responses during this test alongside gas parameters to establish an RPE corresponding to GET (RPEGET) and 15% above GET (RPE+15%GET). Participants then completed three trials at each intensity, in which performance, physiological, and psychological measures were averaged into five-minute time zone (TZ) intervals and 30-minute ‘overall’ averages. Data were assessed for reliability using intraclass correlation coefficients (ICC) and accompanying standard error measurements (SEM), 95% confidence intervals, and coefficient of variations (CoV). Results: All performance and gas parameters showed excellent levels of test-retest reliability (ICCs = >.900) across both intensities. Performance, gas-related measures, and heart rate averaged over the entire 30-minute exercise demonstrated good intra-individual reliability (CoV = <5%). Conclusion: Recreationally active cyclists can reliably replicate fixed perceived effort exercise across multiple visits when RPE is aligned to physiological thresholds. Some evidence suggests that exercise at RPE+15%GET is more reliable than RPEGET

IS TRAMADOL A PERFORMANCE ENHANCING DRUG? A RANDOMISED CONTROLLED TRIAL

Background: Tramadol is a potent narcotic analgesic that acts on the opioid system. Data from the World Anti-Doping Agency (WADA) Monitoring Programme suggest tramadol is used in several sports to reduce exertional pain and confer a performance advantage. However, it is not included in WADA’s Prohibited List. This study sought to identify whether tramadol enhances performance in time trial cycling. Methods: Twenty-one highly trained cyclists (Age = 32 ± 10 years; Mass = 79.5 ± 11.7 kg; VO2max = 57 ± 7 mL/kg/ min; Peak Power Output = 436 ± 57 W) were screened for tramadol sensitivity through an online interview, and then attended the laboratory across three visits. The first visit identified VO2max, Peak Power Output and Gas Exchange Threshold through a Graded Exercise Test. Between 3-14 days following this visit, participants returned to the laboratory on two further occasions to undertake cycling performance tests following the ingestion of either 100 mg of soluble tramadol (as 2x50 mg Zydol® tablets) or a taste-matched placebo control in a double-blind, randomised, and counter-balanced repeated measures design. The performance tests required participants to complete a 30 min non-exhaustive fixed intensity cycling task at a Heavy exercise intensity, immediately followed by a competitive self-paced 25-mile time trial (TT). Results: Participants completed the TT significantly faster (t20 = 2.87, p = 0.01) in the tramadol condition (63 min 38 s ± 4 min 39 s) compared to the placebo condition (64 min 30 s ± 5 min 12 s). Conclusion: In the current group of cyclists, the 1.3% faster time in the tramadol condition could confer a performance advantage sufficient to take a rider with a TT time in the third quartile, into a medalling position. The data from this study suggests that tramadol is a performance enhancing drug in time trial cycling

Tramadol is a performance enhancing drug in highly trained cyclists. A randomised controlled trial

Tramadol is a potent narcotic analgesic reportedly used in multiple sports to reduce exertional pain and confer a performance advantage. This study sought to identify whether tramadol enhances performance in time trial cycling. Twenty-seven highly trained cyclists were screened for tramadol sensitivity and then attended the laboratory across three visits. Visit 1 identified maximal oxygen uptake, peak power output and gas exchange threshold through a ramp incremental test. Participants returned to the laboratory on two further occasions to undertake cycling performance tests following the ingestion of either 100 mg of soluble tramadol or a taste-matched placebo control in a double-blind, randomised, and crossover design. In the performance tests participants completed a 30 min non-exhaustive fixed intensity cycling task at a Heavy exercise intensity (272 ± 42 W), immediately followed by a competitive self-paced 25-mile time trial (TT). Following removal of two outlier data sets, analysis was completed on n=25. Participants completed the TT significantly faster (d = 0.54, p=0.012) in the tramadol condition (3758 s ± 232 s) compared to the placebo condition (3808 s ± 248 s) and maintained a significantly higher mean power output (+9 W) throughout the TT (ƞp2 = 0.262, p=0.009). Tramadol reduced perception of effort during the fixed intensity trial (p=0.026). The 1.3% faster time in the tramadol condition would be sufficient to change the outcomes of a race and is highly meaningful and pervasive in this cohort of highly trained cyclists. The data from this study suggests that tramadol is a performance enhancing drug