The Percentage of Mature Height as a Morphometric Index of Somatic Growth: A Formal Scrutiny of Conventional Simple Ratio Scaling Assumptions.

PURPOSE: To assess conventional assumptions that underpin the percentage of mature height index as the simple ratio of screening height (numerator) divided by actual or predicted adult height (denominator). METHODS: We examined cross-sectional data from 99 academy youth soccer players (chronological age range, 11.5 to 17.7 y) skeletally immature at the screening time and with adult height measurements available at follow-up. RESULTS: The y-intercept value of -60 cm (95% confidence interval, -115 to -6 cm) from linear regression between screening height and adult height indicated the failure to meet the zero y-intercept assumption. The correlation coefficient between present height and adult height of .64 (95% confidence interval, .50 to .74) was not equal to the ratio of coefficient of variations between these variables (CVx/CVy = 0.46) suggesting Tanner's special circumstance was violated. The non-zero correlation between the ratio and the denominator of .21 (95% confidence interval, .01 to .39) indicated that the percentage of mature height was biased low for players with generally shorter adult height, and vice versa. CONCLUSION: For the first time, we have demonstrated that the percentage of mature height is an inconsistent statistic for determining the extent of completed growth, leading to potentially biased inferences for research and applied purposes.

Elite North American soccer performance in thermally challenging environments: An explorative approach to tracking outcomes.

AIMS: The physiologic challenges related to performances in hot conditions calls for dedicated consideration when planning athlete training, although complete amelioration of the effects of heat may not be possible. We aimed to quantify within-subject correlations between different measures of environmental temperature and performance changes over multiple elite soccer competitions. METHODS: Thirty-seven elite male soccer players (age: 26 ± 3.4 years, height: 171 ± 2 cm, body mass: 78 ± 7.1 kg) competed in North America over four seasons (range: 3 to 98 matches). Players wore global positioning system devices during games and reported differential-RPE immediately post game. Temperatures at kick-off, week average temperature, the difference between game-day and week average (DiffTemp), and heat index at kick-off were obtained. Within-player correlations were calculated using general linear models to quantify associations between fluctuations in temperature measures and physical and perceived outputs. RESULTS: Correlations between total distance and the various temperature measures were trivial to small (range: -0.08 to 0.13, p=<0.001-0.02). Small negative correlations were found between all temperature measures except DiffTemp and high-speed running (HSR) (range: -0.17 to -0.14, p=<0.001). Most correlations between differential-RPE and temperature measures were trivial to small and not significant (r = 0.06 to 0.18 p = 0.03-0.92) although breathlessness-RPE and heat index showed a small significant association (P = 0.018). CONCLUSION: Decrements in HSR appear to be associated with increased environmental temperature, however, these associations are small in magnitude.

Influence of Lumbar Mobilizations During the Nordic Hamstring Exercise on Hamstring Measures of Knee Flexor Strength, Failure Point, and Muscle Activity: A Randomized Crossover Trial.

OBJECTIVE: The aims of this study were to quantify the effects of spinal mobilization on force production, failure point, and muscle activity of the hamstrings during the Nordic hamstring exercise (NHE), and to explore individual differences in responses. METHODS: In a replicated randomized crossover trial, 24 asymptomatic, recreationally active men (age [mean ± standard deviation]: 27 ± 6 years; body mass: 82 ± 17 kg; height: 181 ± 8 cm) completed 2 standardized intervention trials (L4/5 zygapophyseal mobilizations) and 2 control trials. The failure point of the NHE was determined with 3D motion capture. Peak force, knee flexor torque, and electromyography (EMG) of the biceps femoris were measured. Data analyses were undertaken to quantify mean intervention response and explore any individual response heterogeneity. RESULTS: Mean (95% confidence interval) left-limb force was higher in intervention than in control trials by 18.7 (4.6-32) N. Similarly, right-limb force was higher by 22.0 (3.4-40.6) N, left peak torque by 0.14 (0.06-0.22) N • m, and right peak torque by 0.14 (0.05-0.23) N • m/kg. Downward force angle was decreased in intervention vs control trials by 4.1° (0.5°-7.6°) on the side of application. Both peak EMG activity (P = .002), and EMG at the downward force (right; P = .020) increased in the intervention condition by 16.8 (7.1-26.4) and 8.8 (1.5-16.1) mV, respectively. Mean downward acceleration angle changed by only 0.3° (-8.9° to 9.4°) in intervention vs control trials. A clear response heterogeneity was indicated only for right force (Participant × Intervention interaction: P = .044; response heterogeneity standard deviation = 34.5 [5.7-48.4] N). Individual response heterogeneity was small for all other outcomes. CONCLUSION: After spinal mobilization, immediate changes in bilateral hamstring force production and peak torque occurred during the NHE. The effect on the NHE failure point was unclear. Electromyographic activity increased on the ipsilateral side. Response heterogeneity was generally similar to the random trial-to-trial variability inherent in the measurement of the outcomes.

Balance impairment in individuals with COPD: a systematic review with meta-analysis.

BACKGROUND: People with chronic obstructive pulmonary disease (COPD) are four times more likely to fall than healthy peers, leading to increased morbidity and mortality. Poor balance is a major risk factor for falls. This review aims to quantify the extent of balance impairment in COPD, and establish contributing clinical factors, which at present are sparse. METHODS: Five electronic databases were searched, in July 2017 and updated searches were performed in March 2019, for studies comparing balance in COPD with healthy controls. Meta-analyses were conducted on sample mean differences (MD) and reported correlations between balance and clinical factors. Meta-regression was used to quantify the association between mean difference in percentage predicted forced expiratory volume in 1 s (FEV1) and mean balance impairment. Narrative summaries were provided where data were insufficient for meta-analysis. RESULTS: Twenty-three studies were included (n=2751). Meta-analysis indicated COPD patients performed worse than healthy controls on timed up and go (MD=2.77 s, 95% CI 1.46 s to 4.089 s, p=<0.005), single leg stance (MD=-11.75 s, 95% CI -15.12 s to -8.38 s, p=<0.005) and berg balance scale (MD=-6.66, 95% CI -8.95 to -4.37, p=<0.005). The pooled correlation coefficient between balance and reduced quadriceps strength was weak-moderate (r=0.37, 95% CI 0.23 to 0.45, p=<0.005). The relationship between differences in percentage predicted FEV1 and balance were negligible (r2 =<0.04). CONCLUSIONS: Compared with healthy controls, people with COPD have a clinically meaningful balance reduction, which may be related to reduced muscle strength, physical activity and exercise capacity. Our findings support a need to expand the focus of pulmonary rehabilitation to include balance assessment and training, and further exploration of balance impairment in COPD. PROSPERO registration number CRD4201769041.

A Tool to Explore Discrete-Time Data: The Time Series Response Analyser.

The analysis of time series data is common in nutrition and metabolism research for quantifying the physiological responses to various stimuli. The reduction of many data from a time series into a summary statistic(s) can help quantify and communicate the overall response in a more straightforward way and in line with a specific hypothesis. Nevertheless, many summary statistics have been selected by various researchers, and some approaches are still complex. The time-intensive nature of such calculations can be a burden for especially large data sets and may, therefore, introduce computational errors, which are difficult to recognize and correct. In this short commentary, the authors introduce a newly developed tool that automates many of the processes commonly used by researchers for discrete time series analysis, with particular emphasis on how the tool may be implemented within nutrition and exercise science research.

True Interindividual Variability Exists in Postprandial Appetite Responses in Healthy Men But Is Not Moderated by the FTO Genotype.

BACKGROUND: After meal ingestion, a series of coordinated hormone responses occur concomitantly with changes in perceived appetite. It is not known whether interindividual variability in appetite exists in response to a meal. OBJECTIVES: The aim of this study was to 1) assess the reproducibility of appetite responses to a meal; 2) quantify individual differences in responses; and 3) explore any moderating influence of the fat mass and obesity associated (FTO) gene. METHODS: Using a replicated crossover design, 18 healthy men (mean ± SD age: 28.5 ± 9.8 y; BMI: 27.0 ± 5.0 kg/m2) recruited according to FTO genotype (9 AA, 9 TT) completed 2 identical control and 2 identical standardized meal conditions (5025 kJ) in randomized sequences. Perceived appetite and plasma acylated ghrelin, total peptide YY (PYY), insulin, and glucose concentrations were measured before and after interventions as primary outcomes. Interindividual differences were explored using Pearson's product-moment correlations between the first and second replicates of the control-adjusted meal response. Within-participant covariate-adjusted linear mixed models were used to quantify participant-by-condition and genotype-by-condition interactions. RESULTS: The meal suppressed acylated ghrelin and appetite perceptions [standardized effect size (ES): 0.18-4.26] and elevated total PYY, insulin, and glucose (ES: 1.96-21.60). For all variables, SD of change scores was greater in the meal than in the control conditions. Moderate-to-large positive correlations were observed between the 2 replicates of control-adjusted meal responses for all variables (r = 0.44-0.86, P ≤ 0.070). Participant-by-condition interactions were present for all variables (P ≤ 0.056). FTO genotype-by-condition interactions were nonsignificant (P ≥ 0.19) and treatment effect differences between genotype groups were small (ES ≤ 0.27) for all appetite parameters. CONCLUSIONS: Reproducibility of postprandial appetite responses is generally good. True interindividual variability is present beyond any random within-subject variation in healthy men but we detected no moderation by the FTO genotype. These findings highlight the importance of exploring individual differences in appetite for the prevention and treatment of obesity. This trial was registered at clinicaltrials.gov as NCT03771690.

Issues in the determination of 'responders' and 'non-responders' in physiological research.

NEW FINDINGS: What is the topic for this review? We discuss the dichotomization of continuous-level physiological measurements into 'responders' and 'non-responders' when interventions/treatments are examined in robust parallel-group studies. What advances does it highlight? Sample responder counts are biased by pre-to-post within-subject variability. Sample differences in counts may be explained wholly by differences in mean response, even without individual response heterogeneity and even if test-retest measurement error informs the choice of response threshold. A less biased and more informative approach uses the SD of individual responses to estimate the chance a new person from the population of interest will be a responder. ABSTRACT: As a follow-up to our 2015 review, we cover more issues on the topic of 'response heterogeneity', which we define as clinically important individual differences in the physiological responses to the same treatment/intervention that cannot be attributed to random within-subject variability. We highlight various pitfalls with the common practice of counting the number of 'responders', 'non-responders' and 'adverse responders' in samples that have been given certain treatments or interventions for research purposes. We focus on the classical parallel-group randomized controlled trial and assume typical good practice in trial design. We show that sample responder counts are biased because individuals differ in terms of pre-to-post within-subject random variability in the study outcome(s) and not necessarily treatment response. Ironically, sample differences in responder counts may be explained wholly by sample differences in mean response, even if there is no response heterogeneity at all. Sample comparisons of responder counts also have relatively low statistical precision. These problems do not depend on how the response threshold has been selected, e.g. on the basis of a measurement error statistic, and are not rectified fully by the use of confidence intervals for individual responses in the sample. The dichotomization of individual responses in a research sample is fraught with pitfalls. Less biased approaches for estimating the proportion of responders in a population of interest are now available. Importantly, these approaches are based on the SD for true individual responses, directly incorporating information from the control group.

Exploration of associations between the FTO rs9939609 genotype, fasting and postprandial appetite-related hormones and perceived appetite in healthy men and women.

BACKGROUND: The fat mass and obesity-associated gene (FTO) rs9939609 A-allele has been associated with obesity risk. Although the exact mechanisms involved remain unknown, the FTO rs9939609 A-allele has been associated with an impaired postprandial suppression of appetite. OBJECTIVES: To explore the influence of FTO rs9939609 genotype on fasting and postprandial appetite-related hormones and perceived appetite in a heterogeneous sample of men and women. DESIGN: 112 healthy men and women aged 18-50-years-old completed three laboratory visits for the assessment of FTO rs9939609 genotype, body composition, aerobic fitness, resting metabolic rate, visceral adipose tissue, liver fat, fasting leptin, and fasting and postprandial acylated ghrelin, total PYY, insulin, glucose and perceived appetite. Participants wore accelerometers for seven consecutive days for the assessment of physical activity and sedentary behaviour. Multivariable general linear models quantified differences between FTO rs9939609 groups for fasting and postprandial appetite outcomes, with and without the addition of a priori selected physiological and behavioural covariates. Sex-specific univariable Pearson's correlation coefficients were quantified between the appetite-related outcomes and individual characteristics. RESULTS: 95% confidence intervals for mean differences between FTO rs9939609 groups overlapped zero in unadjusted and adjusted general linear models for all fasting (P ≥ 0.28) and postprandial (P ≥ 0.19) appetite-related outcomes. Eta2 values for explained variance attributable to FTO rs9939609 were <5% for all outcomes. An exploratory correlation matrix indicated that associations between fasting and postprandial acylated ghrelin, total PYY and general or abdominal adiposity were also small (r = -0.23 to 0.15, P ≥ 0.09). Fasting leptin, glucose and insulin and postprandial insulin concentrations were associated with adiposity outcomes (r = 0.29 to 0.81, P ≤ 0.033). CONCLUSIONS: Associations between the FTO rs9939609 genotype and fasting or postprandial appetite-related outcomes were weak in healthy men and women.

Peak Oxygen Uptake in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Meta-Analysis.

To evaluate the magnitude of the difference in VO2peak between patients with Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) and apparently healthy controls, 7 databases (Cochrane, PubMed, PsycINFO, Web of Knowledge, Embase, Scopus, Medline) were searched for articles published up to March 2018. Search terms included "chronic fatigue syndrom*"AND ("peak" OR "maxim*" OR "max") AND ("oxygen uptake" OR "oxygen consumption" OR "VO2peak" or "VO2max". Eligibility criteria were adults>18 y with clinically diagnosed CFS/ME, with VO2peak measured in a maximal test and compared against an apparently healthy control group. The methodological quality of included studies was assessed using a modified Systematic Appraisal of Quality for Observational Research critical appraisal framework. A random effects meta-analysis was conducted on 32 cross-sectional studies (effects). Pooled mean VO2peak was 5.2 (95% CI: 3.8-6.6) ml.kg-1min-1 lower in CFS/ME patients vs. healthy controls. Between-study variability (Tau) was 3.4 (1.5-4.5) ml.kg-1min-1 indicating substantial heterogeneity. The 95% prediction interval was -1.9 to 12.2 ml.kg-1min-1. The probability that the effect in a future study would be>the minimum clinically important difference of 1.1 ml.kg-1min-1 (in favour of controls) was 0.88 - likely to be clinically relevant. Synthesis of the available evidence indicates that CFS/ME patients have a substantially reduced VO2peak compared to controls.

The impact of venepuncture training on the reduction of pre-analytical blood sample haemolysis rates: A systematic review.

BACKGROUND: Venepuncture involves the introduction of a needle into a vein to collect a representative blood sample for laboratory testing. In the pre-analytical phase, haemolysis (the rupturing of erythrocytes and release of their contents into the extracellular compartment) has safety, quality and cost implications. Training in correct venepuncture practice has the potential to reduce in vitro haemolysis rates, but the evidence for this notion has yet to be synthesised. DESIGN: Systematic review (PRISMA Checklist). METHODS: Published studies on the effectiveness of venepuncture training on haemolysis rates were searched in relevant databases. The McMaster critical appraisal tool was used to assess methodological quality. The GRADE tool was used to evaluate the body of evidence in relation to the research questions. Implementation fidelity was also scrutinised in each study. RESULTS: Eight out of 437 retrieved studies met the inclusion criteria. None were randomised controlled trials (RCT). Between-study heterogeneity in design, intervention characteristics and the biochemical threshold for haemolysis precluded a meta-analysis. Post-training reductions in haemolysis rates of between 0.4%-19.8% were reported in four of the studies, which developed their intervention according to a clear evidence base and included mentoring in the intervention. Rises in haemolysis rates of between 1.3%-1.9% were reported in two studies, while the intervention effect was inconsistent within two other studies. CONCLUSION: There are no RCTS on the effectiveness of venepuncture training for reducing haemolysis rates, and findings from the existing uncontrolled studies are unclear. For a more robust evidence base, we recommend more RCTs with standardisation of haemolysis thresholds and training-related factors. RELEVANCE TO CLINICAL PRACTICE: While venepuncture training is an important factor influencing quality of blood sample in clinical practice, more robust evidence is needed to make specific recommendations about training content for reduction of haemolysis rates. Standardisation of haemolysis thresholds would also enable future meta-analyses.

Changes in Sprint-Related Outcomes During a Period of Systematic Training in a Girls' Soccer Academy.

Wright, MD and Atkinson, G. Changes in sprint-related outcomes during a period of systematic training in a girls' soccer academy. J Strength Cond Res 33(3): 793-800, 2019-The longitudinal tracking of performance indicators is lacking during the training of young female soccer players. Therefore, changes in 5-m acceleration, 20-m speed, change-of-direction (COD) speed, and repeated-sprint ability (RSA) were quantified during a 3-year period in an English Football Association Center of Excellence. Fourteen players (mean age = 12.1 years, SD = ±0.9) were recruited, and their best performance scores from preseason and in-season testing were averaged. Players were typically exposed to soccer (2 × 90 minutes per week) and strength and conditioning training (1 × 70 minutes per week) and played 20 soccer matches (50-80 minutes) during 35-week seasons. Mean (±90% confidence limits (CL)) overall improvements over the 3 years were 5.9% (1.3) (most likely large) for speed, 4.0% (1.0) (most likely large) for RSA, 8.8% (1.1) for acceleration, and 8.3% (1.4) for COD speed (both most likely very large). Improvements between years one and 2 ranged from most likely moderate to very large. Further small improvements in COD speed and 20-m speed (both likely) were observed between years 2 and 3. Individual differences in response were apparent only for COD speed, which were moderate and small between years 2 and 3. Most likely very large to near-perfect within-player correlations were observed between maturation and sprint measures. These data from a single-arm longitudinal study indicate that systematic exposure to training, which includes one dedicated strength and conditioning session each week, is associated with improvements in sprint-related physical qualities in girls.

Storage after gamma irradiation affects in vivo oxygen delivery capacity of transfused red blood cells in preterm infants.

BACKGROUND: Gamma irradiation of red blood cells (RBCs) is well recognized to exacerbate storage lesion formation, but the effect of storage after irradiation on in vivo oxygen delivery capacity of transfused RBCs is currently not known. STUDY DESIGN AND METHODS: In 24 preterm infants with anemia receiving nonurgent transfusion of irradiated RBCs, we examined cerebral regional tissue oxygenation (crSO2 ) and time spent with peripheral arterial saturation (SpO2 ) less than 88%. Physiologic data were obtained immediately before, immediately after, and 5 days after transfusion. RESULTS: We observed linear negative moderate correlations between time since irradiation and the magnitude of change in crSO2 (r = -0.60; 95% CI, -0.81 to -0.27; p = 0.0018) and time spent with SpO2 of less than 88% (r = -0.42; 95% CI, -0.71 to 0.003; p = 0.04) immediately after transfusion. In infants (n = 9) who received fresher RBCs (irradiated <10 days before transfusion), there was a sustained increase in mean crSO2 up to 5 days after transfusion (3.0%; 95% CI, 0.3% to 5.7%; p = 0.04). Conversely, in infants (n = 15) who received older RBCs (irradiated ≥10 days before transfusion), there were negligible changes in crSO2 after transfusion at any time point. CONCLUSION: Our findings indicate that storage after gamma irradiation may have a detrimental effect on the oxygen delivery capacity of RBCs given to anemic preterm infants.

A comprehensive allometric analysis of 2nd digit length to 4th digit length in humans.

It has been widely reported that men have a lower ratio of the 2nd and 4th human finger lengths (2D : 4D). Size-scaling ratios, however, have the seldom-appreciated potential for providing biased estimates. Using an information-theoretic approach, we compared 12 candidate models, with different assumptions and error structures, for scaling untransformed 2D to 4D lengths from 154 men and 262 women. In each hand, the two-parameter power function and the straight line with intercept models, both with normal, homoscedastic error, were superior to the other models and essentially equivalent to each other for normalizing 2D to 4D lengths. The conventional 2D : 4D ratio biased relative 2D length low for the generally bigger hands of men, and vice versa for women, thereby leading to an artefactual indication that mean relative 2D length is lower in men than women. Conversely, use of the more appropriate allometric or linear regression models revealed that mean relative 2D length was, in fact, greater in men than women. We conclude that 2D does not vary in direct proportion to 4D for both men and women, rendering the use of the simple 2D : 4D ratio inappropriate for size-scaling purposes and intergroup comparisons.

Exercise training reduces the acute physiological severity of post-menopausal hot flushes.

KEY POINTS: A post-menopausal hot flush consists of profuse physiological elevations in cutaneous vasodilatation and sweating that are accompanied by reduced brain blood flow. These responses can be used to objectively quantify hot flush severity. The impact of an exercise training intervention on the physiological responses occurring during a hot flush is currently unknown. In a preference-controlled trial involving 21 post-menopausal women, 16 weeks of supervised moderate intensity exercise training was found to improve cardiorespiratory fitness and attenuate cutaneous vasodilatation, sweating and the reductions in cerebral blood flow during a hot flush. It is concluded that the improvements in fitness that are mediated by 16 weeks of exercise training reduce the severity of physiological symptoms that occur during a post-menopausal hot flush. A hot flush is characterised by feelings of intense heat, profuse elevations in cutaneous vasodilatation and sweating, and reduced brain blood flow. Exercise training reduces self-reported hot flush severity, but underpinning physiological data are lacking. We hypothesised that exercise training attenuates the changes in cutaneous vasodilatation, sweat rate and cerebral blood flow during a hot flush. In a preference trial, 18 symptomatic post-menopausal women underwent a passive heat stress to induce hot flushes at baseline and follow-up. Fourteen participants opted for a 16 week moderate intensity supervised exercise intervention, while seven participants opted for control. Sweat rate, cutaneous vasodilatation, blood pressure, heart rate and middle cerebral artery velocity (MCAv) were measured during the hot flushes. Data were binned into eight equal segments, each representing 12.5% of hot flush duration. Weekly self-reported frequency and severity of hot flushes were also recorded at baseline and follow-up. Following training, mean hot flush sweat rate decreased by 0.04 mg cm(2) min(-1) at the chest (95% confidence interval 0.02-0.06, P = 0.01) and by 0.03 mg cm(2) min(-1) (0.02-0.05, P = 0.03) at the forearm, compared with negligible changes in control. Training also mediated reductions in cutaneous vasodilatation by 9% (6-12%) at the chest and by 7% (4-9%) at forearm (P ≤ 0.05). Training attenuated hot flush MCAv by 3.4 cm s(-1) (0.7-5.1 cm s(-1) , P = 0.04) compared with negligible changes in control. Exercise training reduced the self-reported severity of hot flushes by 109 arbitrary units (80-121, P < 0.001). These data indicate that exercise training leads to parallel reductions in hot flush severity and within-flush changes in cutaneous vasodilatation, sweating and cerebral blood flow.

Drug interventions for the treatment of obesity in children and adolescents.

BACKGROUND: Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences. OBJECTIVES: To assess the efficacy of drug interventions for the treatment of obesity in children and adolescents. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed (subsets not available on Ovid), LILACS as well as the trial registers ICTRP (WHO) and ClinicalTrials.gov. Searches were undertaken from inception to March 2016. We checked references and applied no language restrictions. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of pharmacological interventions for treating obesity (licensed and unlicensed for this indication) in children and adolescents (mean age under 18 years) with or without support of family members, with a minimum of three months' pharmacological intervention and six months' follow-up from baseline. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity. In addition, we excluded trials which included growth hormone therapies and pregnant participants. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data following standard Cochrane methodology. Where necessary we contacted authors for additional information. MAIN RESULTS: We included 21 trials and identified eight ongoing trials. The included trials evaluated metformin (11 trials), sibutramine (six trials), orlistat (four trials), and one trial arm investigated the combination of metformin and fluoxetine. The ongoing trials evaluated metformin (four trials), topiramate (two trials) and exenatide (two trials). A total of 2484 people participated in the included trials, 1478 participants were randomised to drug intervention and 904 to comparator groups (91 participants took part in two cross-over trials; 11 participants not specified). Eighteen trials used a placebo in the comparator group. Two trials had a cross-over design while the remaining 19 trials were parallel RCTs. The length of the intervention period ranged from 12 weeks to 48 weeks, and the length of follow-up from baseline ranged from six months to 100 weeks.Trials generally had a low risk of bias for random sequence generation, allocation concealment and blinding (participants, personnel and assessors) for subjective and objective outcomes. We judged approximately half of the trials as having a high risk of bias in one or more domain such as selective reporting.The primary outcomes of this review were change in body mass index (BMI), change in weight and adverse events. All 21 trials measured these outcomes. The secondary outcomes were health-related quality of life (only one trial reported results showing no marked differences; very low certainty evidence), body fat distribution (measured in 18 trials), behaviour change (measured in six trials), participants' views of the intervention (not reported), morbidity associated with the intervention (measured in one orlistat trial only reporting more new gallstones following the intervention; very low certainty evidence), all-cause mortality (one suicide in the orlistat intervention group; low certainty evidence) and socioeconomic effects (not reported).Intervention versus comparator for mean difference (MD) in BMI change was -1.3 kg/m2 (95% confidence interval (CI) -1.9 to -0.8; P < 0.00001; 16 trials; 1884 participants; low certainty evidence). When split by drug type, sibutramine, metformin and orlistat all showed reductions in BMI in favour of the intervention.Intervention versus comparator for change in weight showed a MD of -3.9 kg (95% CI -5.9 to -1.9; P < 0.00001; 11 trials; 1180 participants; low certainty evidence). As with BMI, when the trials were split by drug type, sibutramine, metformin and orlistat all showed reductions in weight in favour of the intervention.Five trials reported serious adverse events: 24/878 (2.7%) participants in the intervention groups versus 8/469 (1.7%) participants in the comparator groups (risk ratio (RR) 1.43, 95% CI 0.63 to 3.25; 1347 participants; low certainty evidence). A total 52/1043 (5.0%) participants in the intervention groups versus 17/621 (2.7%) in the comparator groups discontinued the trial because of adverse events (RR 1.45, 95% CI 0.83 to 2.52; 10 trials; 1664 participants; low certainty evidence). The most common adverse events in orlistat and metformin trials were gastrointestinal (such as diarrhoea, mild abdominal pain or discomfort, fatty stools). The most frequent adverse events in sibutramine trials included tachycardia, constipation and hypertension. The single fluoxetine trial reported dry mouth and loose stools. No trial investigated drug treatment for overweight children. AUTHORS' CONCLUSIONS: This systematic review is part of a series of associated Cochrane reviews on interventions for obese children and adolescents and has shown that pharmacological interventions (metformin, sibutramine, orlistat and fluoxetine) may have small effects in reduction in BMI and bodyweight in obese children and adolescents. However, many of these drugs are not licensed for the treatment of obesity in children and adolescents, or have been withdrawn. Trials were generally of low quality with many having a short or no post-intervention follow-up period and high dropout rates (overall dropout of 25%). Future research should focus on conducting trials with sufficient power and long-term follow-up, to ensure the long-term effects of any pharmacological intervention are comprehensively assessed. Adverse events should be reported in a more standardised manner specifying amongst other things the number of participants experiencing at least one adverse event. The requirement of regulatory authorities (US Food and Drug Administration and European Medicines Agency) for trials of all new medications to be used in children and adolescents should drive an increase in the number of high quality trials.

The within-participant correlation between perception of effort and heart rate-based estimations of training load in elite soccer players.

The measurement of relative physiological stress during training is important because this is the stimulus for the long-term adaptive response. Measurements of perceived exertion (RPE) have been reported to correlate with the heart rate during field-based training sessions. Nevertheless, there are few studies on how well RPE tracks with the heart rate over repeated training sessions in elite soccer players. Therefore, we aimed to quantify the within-participant correlations between variability in session-RPE (sRPE) and the heart rate in elite male soccer players, and to determine whether the playing position moderated these correlations. The field-based training of four central defenders, four wide defenders, six central midfielders, two wide midfielders and three attackers from an elite English Premier League squad were monitored over an entire in-season competitive period, giving a total of 1010 individual training sessions for study. Correlations between session-RPE and heart rates were quantified using a within-participant model. The correlation between changes in sRPE and heart rates was r = 0.75 (95% CI: 0.71-0.78). This correlation remained high across the various player positions (wide-defender, r = 0.81; central-defender, r = 0.74; wide midfielder, r = 0.70; central midfielder, r = 0.70; attacker, r = 0.84; P < 0.001). The correlation between changes in RPE and heart rates, measured during a season-long period of field-based training, is high in a sample of elite soccer players.

True and false interindividual differences in the physiological response to an intervention.

NEW FINDINGS: What is the topic of this review? In 'personalized medicine', various plots and analyses are purported to quantify individual differences in intervention response, identify responders/non-responders and explore response moderators or mediators. What advances does it highlight? We highlight the impact of within-subject random variation, which is inevitable even with 'gold-standard' measurement tools/protocols and sometimes so substantial that it explains all apparent individual response differences. True individual response differences are quantified only by comparing the SDs of changes between intervention and comparator arms. When these SDs are similar, true individual response differences are clinically unimportant and further analysis unwarranted. Within the 'hot topic' of personalized medicine, we scrutinize common approaches for presenting and quantifying individual differences in the physiological response to an intervention. First, we explain how popular plots used to present individual differences in response are contaminated by random within-subject variation and the regression to the mean artefact. Using a simulated data set of blood pressure measurements, we show that large individual differences in physiological response can be suggested by some plots and analyses, even when the true magnitude of response is exactly the same in all individuals. Second, we present the appropriate designs and analysis approaches for quantifying the true interindividual variation in physiological response. It is imperative to include a comparator arm/condition (or derive information from a prior relevant repeatability study) to quantify true interindividual differences in response. The most important statistic is the SD of changes in the intervention arm, which should be compared with the same SD in the comparator arm or from a prior repeatability study in the same population conducted over the same duration as the particular intervention. Only if the difference between these SDs is clinically relevant is it logical to go on to explore any moderators or mediators of the intervention effect that might explain the individual response. To date, very few researchers have compared these SDs before making claims about individual differences in physiological response and their importance to personalized medicine.

The clinical relevance of the percentage flow-mediated dilation index.

In 2010, the American College of Cardiology Foundation and American Heart Association could not recommend brachial artery percentage flow-mediated dilation (FMD%) for risk assessment of coronary artery disease (CAD) in asymptomatic adults. We aimed to scrutinise past and recently published findings regarding FMD% in this same context of clinical utility and conclude that (1) the question of whether brachial FMD% is a suitable substitute for coronary vasodilation is addressed by method agreement statistics rather than the correlation coefficients that have been reported in past studies. Also, the much-repeated view that brachial FMD% and coronary vasodilation are "closely related" is not entirely justified, even before the influence of baseline lumen diameters on this relationship is accounted for; (2) along with the specialist training and the considerable time (≥1 h) that is required for the FMD% protocol, the error in individual measurements and population reference ranges is too large for clinical decisions to be robust on individual patients; (3) many interventions that are proposed to change FMD% also change baseline artery diameter, which can bias estimates of any intervention effects on the flow-mediated response per se, and (4) the FMD% index generates spurious correlations between shear rate, artery diameter and endothelial function, which may help to explain the apparent paradoxes of FMD% being higher in obese people and lower in athletes. In conclusion, the clinical relevance of brachial artery flow-mediated dilation is unclear at present. The dependence of the chosen index, FMD%, on initial artery size has contributed to this lack of clarity.

Surgery for the treatment of obesity in children and adolescents.

BACKGROUND: Child and adolescent overweight and obesity have increased globally, and are associated with significant short and long term health consequences. OBJECTIVES: To assess the effects of surgical interventions for treating obesity in childhood and adolescence. SEARCH METHODS: We searched the Cochrane Library, MEDLINE, PubMed, EMBASE as well as LILACS, ICTRP Search Portal and ClinicalTrials.gov (all from database inception to March 2015). References of identified studies and systematic reviews were checked. No language restrictions were applied. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of surgical interventions for treating obesity in children and adolescents (age < 18 years) with a minimum of six months follow-up. Interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity were excluded. Pregnant females were also excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias and extracted data. Where necessary authors were contacted for additional information. MAIN RESULTS: We included one RCT (a total of 50 participants, 25 in both the intervention and comparator group). The intervention focused on laparoscopic adjustable gastric banding surgery, which was compared to a control group receiving a multi component lifestyle programme. The participating population consisted of Australian adolescents (a higher proportion of girls than boys) aged 14 to 18 years, with a mean age of 16.5 and 16.6 years in the gastric banding and lifestyle group, respectively which was conducted in a private hospital, receiving funding from the gastric banding manufacturer. The study authors were unable to blind participants, personnel and outcome assessors which may have resulted in a high risk of performance and detection bias. Attrition bias was noted as well. The study authors reported a mean reduction in weight of 34.6 kg (95% confidence interval (CI) 30.2 to 39.0) at two years, representing a change in body mass index (BMI) of 12.7 (95% CI 11.3 to 14.2) for the surgery intervention; and a mean reduction in weight of 3.0 kg (95% CI 2.1 to 8.1) representing a change in BMI of 1.3 (95% CI 0.4 to 2.9) for the lifestyle intervention. The differences between groups were statistically significant for all weight measures at 24 months (P < 0.001). The overall quality of the evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was low. Adverse events were reported in 12/25 (48%) participants in the intervention group compared to 11/25 (44%) in the control group (low quality evidence). A total of 28% of the adolescents undergoing gastric banding required revisional surgery. No data were reported for all-cause mortality, behaviour change, participants views of the intervention and socioeconomic effects. At two years, the gastric banding group performed better than the lifestyle group in two of eight health-related quality of life concepts (very low quality evidence) as measured by the Child Health Questionnaire (physical functioning score (94 versus 78, community norm 95) and change in health score (4.4 versus 3.6, community norm 3.5)). AUTHORS' CONCLUSIONS: Laparoscopic gastric banding led to greater body weight loss compared to a multi component lifestyle program in one small study with 50 patients. These results do not provide enough data to assess efficacy across populations from different countries, socioeconomic and ethnic backgrounds, who may respond differently. This systematic review highlights the lack of RCTs in this field. Future studies should assess the impact of the surgical procedure and post operative care to minimise adverse events, including the need for post operative adjustments and revisional surgery. Long-term follow-up is also critical to comprehensively assess the impact of surgery as participants enter adulthood.