A study protocol for a randomised crossover study evaluating the effect of diets differing in carbohydrate quality on ileal content and appetite regulation in healthy humans

A major component of the digesta reaching the colon from the distal ileum is carbohydrate. This carbohydrate is subject to microbial fermentation and can radically change bacterial populations in the colon and the metabolites they produce, particularly short-chain fatty acids (SCFA). However, very little is currently known about the forms and levels of carbohydrate in the ileum and the composition of the ileal microbiota in humans. Most of our current understanding of carbohydrate that is not absorbed by the small intestine comes from ileostomy models, which may not reflect the physiology of an intact gastrointestinal tract. We will investigate how ileal content changes depending on diet using a randomised crossover study in healthy humans. Participants will be inpatients at the research facility for three separate 4-day visits. During each visit, participants will consume one of three diets, which differ in carbohydrate quality: 1) low-fibre refined diet; 2) high-fibre diet with intact cellular structures; 3) high-fibre diet where the cellular structures have been disrupted (e.g. milling, blending). On day 1, a nasoenteric tube will be placed into the distal ileum and its position confirmed under fluoroscopy. Ileal samples will be collected via the nasoenteric tube and metabolically profiled, which will determine the amount and type of carbohydrate present, and the composition of the ileal microbiota will be measured. Blood samples will be collected to assess circulating hormones and metabolites. Stool samples will be collected to assess faecal microbiota composition. Subjective appetite measures will be collected using visual analogue scales. Breath hydrogen will be measured in real-time as a marker of intestinal fermentation. Finally, an continuous fermentation model will be inoculated with ileal fluid in order to understand the shift in microbial composition and SCFA produced in the colon following the different diets. ISRCTN11327221. [Abstract copyright: Copyright: © 2019 Byrne CS et al.

Analysis of repeated high-intensity running performance in professional soccer

The aims of this study conducted in a professional soccer team were two-fold: to characterise repeated high-intensity movement activity profiles in official match-play; b) to inform and verify the construct validity of tests commonly used to determine repeated-sprint ability in soccer by investigating the relationship between the results from a test of repeated-sprint ability and repeated high-intensity performance in competition. High-intensity running performance (movement at velocities >19.8 km/h for a minimum of 1-s duration) in 20 players was measured using computerised time motion analysis. Performance in 80 French League 1 matches was analysed. In addition, 12 out of the 20 players performed a repeated-sprint test on a non-motorized treadmill consisting of 6 consecutive 6s sprints separated by 20s passive recovery intervals. In all players, the majority of consecutive high-intensity actions in competition were performed after recovery durations ≥61s, recovery activity separating these efforts was generally active in nature with the major part of this spent walking, and players performed 1.1±1.1 repeated high-intensity bouts (a minimum of 3 consecutive high-intensity with a mean recovery time ≤20s separating efforts) per game. Players reporting lowest performance decrements in the repeated-sprint ability test performed more high-intensity actions interspersed by short recovery times (≤20s, p<0.01 and ≤30s, p<0.05) compared to those with higher decrements. Across positional roles, central-midfielders performed a greater number of high-intensity actions separated by short recovery times (≤20s) and spent a larger proportion of time running at higher intensities during recovery periods while fullbacks performed the most repeated high-intensity bouts (statistical differences across positional roles from p<0.05 to p<0.001). These findings have implications for repeated high-intensity testing and physical conditioning regimens

Negative impact of the first COVID-19 lockdown upon health-related behaviours and psychological wellbeing in people living with severe and complex obesity in the UK

BACKGROUND: Coronavirus disease 2019 (COVID-19) has led to unprecedented changes in the way we live, particularly for people at higher risk of severe illness from COVID-19. People with pre-existing health conditions have been markedly impacted and, in some instances, left unsupported due to reduced provision of routine healthcare services. People living with obesity (PLWO) are identified as at higher risk of severe illness from COVID-19 infection. Currently, there is a paucity of evidence about the impact of the first COVID-19 lockdown on PLWO, including those accessing weight management and bariatric surgery services (WMS). METHODS: 543 adults (16–80 years) with obesity (BMI ≥ 30 kg/m2) were recruited between 14th May and 9th July 2020 through social media advertisements, professional and patient obesity organisations and WMS. Participants completed an online survey regarding the impact of the first COVID-19 lockdown upon, mental health, well-being, health-related behaviours, risk mitigating behaviours, access to WMS and weight stigma. FINDINGS: During the first COVID-19 lockdown, the majority of PLWO reported deterioration of their mental health and health-related behaviours such as diet, physical activity (PA) and sleep. With 55% reporting an unhealthier diet, 61% reduced PA and 80% worsening of their sleep. Higher depression and lower wellbeing scores were found to associate with the greatest adverse impact upon health-related behaviours. PLWO who were attending WMS prior to the first lockdown reported a greater deterioration of their diet, with nearly 50% reporting worsening of their diet and PA worsening compared to PLWO who were not attending WMS. Most participants took two or more risk mitigating actions (73%). PLWO attending WMS reported reduced access (44%) with insufficient information (49%) from their clinical service providers. The majority of participants reported no change in perceived weight stigma. INTERPRETATION: This study shows the detrimental impact of the first COVID-19 lockdown on PLWO in relation to health-related behaviours, mental health and access to WMS. Our findings show that PLWO with poor mental health and those attending WMS were most adversely impacted and highlights the need for greater mental health support and continued provision of support from WMS for PLWO during future lockdowns. FUNDING: This research was funded through National Institute for Health Research University College London Hospitals Biomedical Research Centre funding

Predictors and moderators of response to internet-delivered Interpersonal Psychotherapy and Cognitive Behavior Therapy for depression

Background: By identifying which predictors and moderators lead to beneficial outcomes, accurate selection of the best initial treatment will have significant benefits for depressed individuals. Method: An automated, fully self guided randomized controlled internet-delivered noninferiority trial was conducted comparing two new interventions (Interpersonal Psychotherapy [IPT; n=620] and Cognitive Behavioral Therapy [CBT; n=610]) to an active control intervention (MoodGYM; n=613) over a period of 4 weeks to spontaneous visitors of an internet-delivered therapy vvebsite (e couch). A range of putative predictors and moderators (socio-demographic characteristics [age, gender, marital status, education level], clinical characteristics [depression/anxiety symptoms, disability, quality of life, medication use], skills [mastery and dysfunctional attitudes] and treatment preference) were assessed using internet-delivered self-report measures at baseline and immediately following treatment and at six months follow-up. Analyses were conducted using Mixed Model Repeated Measures (MMRM). Results: Female gender, lower mastery and lower dysfunctional attitudes predicted better outcome at post-test and/or follow-up regardless of intervention. No overall differential effects for condition On depression as a function of outcome were found. However, based on time-specific estimates, a significant interaction effect of age was found. For younger people, intemet-delivered IPT may be the preferred treatment choice, whereas older participants derive more benefits from internet-delivered CBT programs. Limitations: Although the sample of participants was large, power to detect moderator effects was still lacking. Conclusions: Different e-mental health programs may be more beneficial for specific age groups. The Findings raise important possibilities for increasing depression treatment effectiveness and improving clinical practice guidelines for depression treatment of different age groups. (C) 2013 Elsevier B.V. All rights reserved

Distorted chemosensory perception and female sex associate with persistent smell and/or taste loss in people with SARS-CoV-2 antibodies: a community based cohort study investigating clinical course and resolution of acute smell and/or taste loss in people with and without SARS-CoV-2 antibodies in London, UK

BACKGROUND: Loss of smell and/or taste are cardinal symptoms of COVID-19. 'Long-COVID', persistence of symptoms, affects around one fifth of people. However, data regarding the clinical resolution of loss of smell and/or taste are lacking. In this study we assess smell and taste loss resolution at 4-6 week follow-up, aim to identify risk factors for persistent smell loss and describe smell loss as a feature of long-COVID in a community cohort in London with known SARS-CoV-2 IgG/IgM antibody status. We also compare subjective and objective smell assessments in a subset of participants. METHODS: Four hundred sixty-seven participants with acute loss of smell and/or taste who had undergone SARS-CoV-2 IgG/IgM antibody testing 4-6 weeks earlier completed a follow-up questionnaire about resolution of their symptoms. A subsample of 50 participants completed an objective olfactory test and results were compared to subjective smell evaluations. RESULTS: People with SARS-CoV-2 antibodies with an acute loss of sense of smell and taste were significantly less likely to recover their sense of smell/taste than people who were seronegative (smell recovery: 57.7% vs. 72.1%, p = 0.027. taste recovery 66.2% vs. 80.3%, p = 0.017). In SARS-CoV-2 positive participants, a higher percentage of male participants reported full resolution of smell loss (72.8% vs. 51.4%; p  40 years) than those who reported full resolution. Participants who experienced parosmia reported lower smell recovery rates and participants with distorted taste perception lower taste recovery rates. Parosmia had a significant association to unresolved smell loss (OR 2.47, 95%CI 1.54-4.00, p  40 years) and people with a distorted perception of their sense of smell/taste are likely to benefit from prioritised early therapeutic interventions. TRIALS REGISTRATION: ClinicalTrials.gov NCT04377815 Date of registration: 23/04/2020

Reported appetite, taste and smell changes following Roux-en-Y gastric bypass and sleeve gastrectomy: Effect of gender, type 2 diabetes and relationship to post-operative weight loss.

Reduced energy intake drives weight loss following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) procedures. Post-operative changes in subjective appetite, taste, and smell and food preferences are reported and suggested to contribute to reduced energy intake. We aimed to investigate the prevalence of these changes following RYGB and SG and to evaluate their relationship with weight loss. 98 patients post-RYGB and 155 post-SG from a single bariatric centre were recruited to a cross-sectional study. Participants completed a questionnaire, previously utilised in post-operative bariatric patients, to assess the prevalence of post-operative food aversions and subjective changes in appetite, taste and smell. Anthropometric data were collected and percentage weight loss (%WL) was calculated. The relationship between food aversions, changes in appetite, taste and smell and %WL was assessed. The influence of time post-surgery, gender and type 2 diabetes (T2D) were evaluated. Following RYGB and SG the majority of patients reported food aversions (RYGB = 62%, SG = 59%), appetite changes (RYGB = 91%, SG = 91%) and taste changes (RYGB = 64%, SG = 59%). Smell changes were more common post-RYGB than post-SG (RYGB = 41%, SG = 28%, p = 0.039). No temporal effect was observed post-RYGB. In contrast, the prevalence of appetite changes decreased significantly with time following SG. Post-operative appetite changes associated with and predicted higher %WL post-SG but not post-RYGB. Taste changes associated with and predicted higher %WL following RYGB but not post-SG. There was no gender effect post-RYGB. Post-SG taste changes were less common in males (female = 65%, males = 40%, p = 0.008). T2D status in females did not influence post-operative subjective changes. However, in males with T2D, taste changes were less common post-SG than post-RYGB together with lower %WL (RYGB = 27.5 ± 2.7, SG = 14.6 ± 2.1, p = 0.003). Further research is warranted to define the biology underlying these differences and to individualise treatments

A case of severe anorexia, excessive weight loss and high peptide YY levels after sleeve gastrectomy

Sleeve gastrectomy (SG) is the second most commonly performed bariatric procedure worldwide. Altered circulating gut hormones have been suggested to contribute post-operatively to appetite suppression, decreased caloric intake and weight reduction. In the present study, we report a 22-year-old woman who underwent laparoscopic SG for obesity (BMI 46 kg/m2). Post-operatively, she reported marked appetite reduction, which resulted in excessive weight loss (1-year post-SG: BMI 22 kg/m2, weight loss 52%, >99th centile of 1-year percentage of weight loss from 453 SG patients). Gastrointestinal (GI) imaging, GI physiology/motility studies and endoscopy revealed no anatomical cause for her symptoms, and psychological assessments excluded an eating disorder. Despite nutritional supplements and anti-emetics, her weight loss continued (BMI 19 kg/m2), and she required nasogastric feeding. A random gut hormone assessment revealed high plasma peptide YY (PYY) levels. She underwent a 3 h meal study following an overnight fast to assess her subjective appetite and circulating gut hormone levels. Her fasted nausea scores were high, with low hunger, and these worsened with nutrient ingestion. Compared to ten other post-SG female patients, her fasted circulating PYY and nutrient-stimulated PYY and active glucagon-like peptide 1 (GLP1) levels were markedly elevated. Octreotide treatment was associated with suppressed circulating PYY and GLP1 levels, increased appetite, increased caloric intake and weight gain (BMI 22 kg/m2 after 6 months). The present case highlights the value of measuring gut hormones in patients following bariatric surgery who present with anorexia and excessive weight loss and suggests that octreotide treatment can produce symptomatic relief and weight regain in this setting

Issues in the determination of “responders” and “non‐responders” in physiological research

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 or intervention that cannot be attributed to random within-subjects 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/interventions for research purposes. We focus on the classical parallel-group randomised controlled trial (RCT) design 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-subjects 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

Metabolic state alters economic decision making under risk in humans

Background: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity