Participants' perspectives of being recruited into a randomised trial of a weight loss intervention before colorectal cancer surgery: a qualitative interview study.

BACKGROUND: The period between cancer diagnosis and surgery presents an opportunity for trials to assess the feasibility of behaviour change interventions. However, this can be a worrying time for patients and may hinder recruitment. We describe the perspectives of patients with excess weight awaiting colorectal cancer surgery about their recruitment into a randomised trial of a prehabilitation weight loss intervention. METHODS: We interviewed the first 26 participants from the 8 recruitment sites across England in the 'CARE' feasibility trial. Participants were randomised into either usual care (n = 13) or a low-energy nutritionally-replete total diet replacement programme with weekly remote behavioural support by a dietitian (n = 13). The semi-structured interviews occurred shortly after recruitment and the questions focused on participants' recollections of being recruited into the trial. We analysed data rapidly and then used a mind-mapping technique to develop descriptive themes. Themes were agreed by all co-authors, including a person with lived-experience of colorectal surgery. RESULTS: Participants had a mean body mass index (± SD) of 38 kg/m2 (± 6), age of 50 years (± 12), and 42% were female. People who participated in the trial were motivated by the offer of structured weight loss support that could potentially help them improve their surgical outcomes. However, participants also had concerns around the potential unpalatability of the intervention diet and side effects. Positive attitudes of clinicians towards the trial facilitated recruitment but participants were disappointed when they were randomised to usual care due to clinical teams' overemphasis on the benefits of losing weight. CONCLUSIONS: Patients were motivated to take part by the prospect of improved surgical outcomes. However, the strong preference to be allocated to the intervention suggests that balanced communication of equipoise is crucial to minimise disappointment from randomisation to usual care and differential dropout from the trial. CLINICAL TRIAL REGISTRATION: ISRCTN39207707, Registration date 13/03/2023.

Effect of planned pauses versus continuous energy restriction on weight loss and attrition: a systematic review.

OBJECTIVE: The objective of this study was to investigate whether pausing a weight loss program for a defined period of time could enhance weight loss and reduce attrition. METHODS: Five databases and two trial registries were searched from inception to July 2023. Randomized-controlled trials of adults with overweight and/or obesity were included if they compared planned-pause interventions with continuous energy restriction (CER), usual care, or a minimal intervention. To be included, the weight loss intervention must have incorporated a pause of at least 1 week. Pooled mean differences for weight change and risk ratios for attrition were calculated using random-effects meta-analyses. RESULTS: Nine intervention arms (N = 796 participants, 77% female) were included. Pooled results did not detect a significant difference in weight change between planned pauses and CER interventions at the end of the active intervention at a median 26 weeks (planned pauses vs. CER mean: -7.09 vs. -7.0 kg; mean difference: -0.09 kg; 95% CI: -1.10 to 0.93) or at final follow-up at a median 52 weeks (planned pauses vs. CER mean: -6.91 vs. -6.19 kg; mean difference: -0.72 kg; 95% CI: -2.92 to 1.48). There was no difference in attrition between planned pauses and CER interventions at the end of the active intervention (risk ratio: 1.20, 95% CI: 0.82 to 1.75) or at final follow-up (risk ratio: 1.04, 95% CI: 0.89 to 1.22). CONCLUSIONS: Planned pauses were consistently found to be no more or less effective than CER for weight loss or attrition.

Associations between types and sources of dietary carbohydrates and liver fat: a UK Biobank study.

BACKGROUND AND AIMS: Excess energy intake can lead to metabolic dysfunction-associated steatotic liver disease (MASLD), but the relationship between dietary carbohydrate intake and liver fat content remains unclear. This study aimed to examine the associations between types and sources of dietary carbohydrates and liver fat content. METHODS: UK Biobank participants with no pre-existing diabetes, liver disease or cardiovascular disease reported dietary intake of types and sources of carbohydrates (total carbohydrates, free sugars, non-free sugars, starch from whole grains, starch from refined grains, and fibre) on at least two 24-h dietary assessments. In cross-sectional analyses, (n = 22,973), odds ratios (OR) of high liver fat content (defined as a score of ≥ 36 in the hepatic steatosis index) by quintiles of carbohydrate intakes were estimated using multivariable logistic regression models. In prospective analyses, a second sample (n = 9268) had liver proton density fat fraction (PDFF) measured by magnetic resonance imaging (2014-2020). Multivariable linear regression models estimated geometric means of PDFF (%) by quintiles of carbohydrate intakes. Models were adjusted for demographic and lifestyle confounders, including total energy intake. RESULTS: In the cross-sectional analyses, 6894 cases of high liver fat content were identified. Inverse associations between intakes of fibre (OR of highest vs. lowest quintile 0.46 [95% CI: 0.41-0.52]), non-free sugars (0.63 [0.57-0.70]) and starch from whole grains (0.52 [0.47-0.57]) with liver fat were observed. There were positive associations between starch from refined grains and liver fat (1.33 [1.21-1.46]), but no association with free sugars (p=0.61). In prospective analyses, inverse associations with PDFF (%) were observed for intakes of fibre (- 0.48 geometric mean difference between highest and lowest quintile of intake [- 0.60 to - 0.35]), non-free sugars (- 0.37 [- 0.49 to - 0.25]) and starch from whole grains (- 0.31 [- 0.42 to - 0.19]). Free sugars, but not starch from refined grains, were positively associated with PDFF (0.17 [0.05 to 0.28]). CONCLUSION: This study suggests that different carbohydrate types and sources have varying associations with liver fat, which may be important for MASLD prevention. Non-free sugars, fibre, and starch from whole grains could be protective, while associations with free sugars and starch from refined grains are less clear.

CARE: Protocol of a randomised trial evaluating the feasibility of preoperative intentional weight loss to support postoperative recovery in patients with excess weight and colorectal cancer.

AIM: Excess weight increases the risk of morbidity following colorectal cancer surgery. Weight loss may improve morbidity, but it is uncertain whether patients can follow an intensive weight loss intervention while waiting for surgery and there are concerns about muscle mass loss. The aim of this trial is to assess the feasibility of intentional weight loss in this setting and determine progression to a definitive trial. METHODS: CARE is a prospectively registered, multicentre, feasibility, parallel, randomised controlled trial with embedded evaluation and optimisation of the recruitment process. Participants with excess weight awaiting curative colorectal resection for cancer are randomised 1:1 to care as usual or a low-energy nutritionally-replete total diet replacement programme with weekly remote behavioural support by a dietitian. Progression criteria will be based on the recruitment, engagement, adherence, and retention rates. Data will be collected on the 30-day postoperative morbidity, the typical primary outcome of prehabilitation trials. Secondary outcomes will include, among others, length of hospital stay, health-related quality of life, and body composition. Qualitative interviews will be used to understand patients' experiences of and attitudes towards trial participation and intervention engagement and adherence. CONCLUSION: CARE will evaluate the feasibility of intensive intentional weight loss as prehabilitation before colorectal cancer surgery. The results will determine the planning of a definitive trial.

The Association Between Goal Setting and Weight Loss: Prospective Analysis of a Community Weight Loss Program.

BACKGROUND: Goal setting aids health-related behavior changes; however, the influence of different types of goals on weight loss remains unclear. OBJECTIVE: We aimed to investigate the association of 3 aspects of goal setting with weight and program dropout over a 24-week period. METHODS: This study was a prospective longitudinal analysis of participants in a 12-week digital behavioral weight loss program. Weight and engagement data for eligible participants (N=36,794) were extracted from the database. Eligible participants were adults in the United Kingdom who had enrolled in the program, had a BMI ≥25 kg/m2, and a weight reading recorded at baseline. Three aspects of goal setting were self-reported at enrollment: weight loss motivation (appearance, health, fitness, or self-efficacy), overall goal preference (low, medium, or high), and percentage weight loss goal (<5%, 5%-10%, or >10%). Weight was measured at 4, 12, and 24 weeks. Mixed models for repeated measures were used to explore the association between goals and weight across the 24-week period. To measure sustained weight change, the primary outcome was weight at 24 weeks. We explored dropout rates over the 24-week period by goal and whether engagement mediated the association between goals and weight loss. RESULTS: Of the 36,794 participants (mean 46.7, SD 11.1 years; 33,902/36,794, 92.14% female) included in the cohort, 13.09% (n=4818) reported weight at 24 weeks. Most participants set goals of 5%-10% weight loss (23,629/36,794, 64.22%), but setting goals for >10% was associated with greater weight loss (mean difference 5.21 kg, 95% CI 5.01-5.41; P<.001). There was no difference between goals of 5%-10% and <5% (mean difference 0.59 kg, 95% CI 0.00-1.18; P=.05). Appearance was the most prevalent motivational factor (14,736/36,794, 40.05%), but health and fitness were associated with greater weight losses (mean difference health vs appearance 1.40 kg, 95% CI 1.15-1.65; P<.001 and mean difference fitness vs appearance 0.38 kg, 95% CI 0.05-0.70; P=.03). Goal preference had no association with weight. Engagement was an independent predictor of weight loss but not a mediator of the effect of goal setting. At 24 weeks, those who set goals of >10% were less likely to drop out compared with 5%-10% goals (odds ratio [OR] 0.40, 95% CI 0.38-0.42; P<.001); those who liked to set overall high goals were more likely to drop out compared with medium goals (OR 1.20, 95% CI 1.11-1.29; P<.001); and those motivated by fitness or health were less likely to drop out compared with appearance (OR 0.92, 95% CI 0.85-0.995; P=.04 and OR 0.84, 95% CI 0.78-0.89; P<.001, respectively). CONCLUSIONS: Setting higher weight loss goals and being motivated by health or fitness were associated with greater weight loss and lower likelihood of dropout. Randomized trials for setting these types of goals are required to confirm causality.

A low-energy total diet replacement program demonstrates a favorable safety profile and improves liver disease severity in nonalcoholic steatohepatitis.

OBJECTIVE: Low-energy diets are used to treat obesity and diabetes, but there are fears that they may worsen liver disease in patients with nonalcoholic steatohepatitis (NASH) and significant-to-advanced fibrosis. METHODS: In this 24-week single-arm trial, 16 adults with NASH, fibrosis, and obesity received one-to-one remote dietetic support to follow a low-energy (880 kcal/d) total diet replacement program for 12 weeks and stepped food reintroduction for another 12 weeks. Liver disease severity was blindly evaluated (magnetic resonance imaging proton density fat fraction [MRI-PDFF], iron-corrected T1 [cT1], liver stiffness on magnetic resonance elastography [MRE], and liver stiffness on vibration-controlled transient elastography [VCTE]). Safety signals included liver biochemical markers and adverse events. RESULTS: A total of 14 participants (87.5%) completed the intervention. Weight loss was 15% (95% CI: 11.2%-18.6%) at 24 weeks. Compared with baseline, MRI-PDFF reduced by 13.1% (95% CI: 8.9%-16.7%), cT1 by 159 milliseconds (95% CI: 108-216.5), MRE liver stiffness by 0.4 kPa (95% CI: 0.1-0.8), and VCTE liver stiffness by 3.9 kPa (95% CI: 2.6-7.2) at 24 weeks. The proportions with clinically relevant reductions in MRI-PDFF (≥30%), cT1 (≥88 milliseconds), MRE liver stiffness (≥19%), and VCTE liver stiffness (≥19%) were 93%, 77%, 57%, and 93%, respectively. Liver biochemical markers improved. There were no serious intervention-related adverse events. CONCLUSIONS: The intervention demonstrates high adherence, favorable safety profile, and promising efficacy as a treatment for NASH.

Association between the month of starting a weight management program and weight change in people at high risk of type 2 diabetes: A prospective cohort study.

OBJECTIVE: Weight loss is one of the most common New Year's resolutions, but it is unclear whether attempting to lose weight in January is more successful than attempting it at other times of the year. METHODS: In this prospective cohort study from the English National Health Service (NHS) Diabetes Prevention Program, adults with nondiabetic hyperglycemia were enrolled in a structured behavioral weight management program. Repeated measures models assessed the mean difference between baseline and follow-up weight adjusting for monthly variation in weight among those with ≥1 weight measurement. RESULTS: Among 85,514 participants with a mean baseline BMI of 30.3 kg/m2 (range: 13.4 to 84.2), mean weight change at the end of the program after an average 7.9 (SD: 4.5) sessions over 6.4 (SD: 5.6) months was -2.00 kg (95% CI: -2.02 to -1.97 kg) or -2.33% (95% CI: -2.35% to -2.32%). Compared with participants starting in January, participants starting in other months lost less weight, ranging between 0.28 kg (95% CI: 0.10 to 0.45 kg) less weight in those starting in March and 0.71 kg (95% CI: 0.55 to 0.87 kg) less weight in those starting in November. April and May were the only exceptions, in which the estimates followed the same direction but were not statistically significant. Higher session attendance mediated the effects, with participants starting in January attending, on average, 0.2 to 0.7 more sessions than those starting in other months. CONCLUSIONS: People starting a weight management program in January lost 12% to 30% more weight than people starting it at other times of the year.

A paradigm shift in cystic fibrosis nutritional care: Clinicians' views on the management of patients with overweight and obesity.

BACKGROUND: Overweight and obesity among people with cystic fibrosis (pwCF) has become more prevalent since the widespread adoption of CF transmembrane conductance regulator (CFTR) modulator therapies and presents a new challenge for nutritional care. We aimed to explore how clinicians working in CF care approach the management of adults with overweight and obesity. METHODS: We conducted semi-structured interviews with n = 20 clinicians (n = 6 physiotherapists, n = 6 doctors and n = 8 dietitians) working in 15 adult CF centres in the United Kingdom. The interviews explored their perspectives and current practices caring for people with CF and overweight/obesity. Data were analysed using reflexive thematic analysis. RESULTS: Four main themes were identified: 1) challenges of raising the topic of overweight and obesity in the CF clinic (e.g., clinician-patient rapport and concerns around weight stigma); 2) the changing landscape of assessment due to CF-specific causes of weight gain: (e.g., impact of CFTR modulators and CF legacy diet) 3) presence of clinical equipoise for weight management due to the lack of CF-specific evidence on the consequences of obesity and intentional weight loss (e.g., unclear consequences on respiratory outcomes and risk of weight related co-morbidities) and 4) opportunities for a safe, effective, and acceptable weight management treatment for people with CF (e.g., working collaboratively with current multidisciplinary CF care). CONCLUSIONS: Approaching weight management in the CF setting is complex. Trials are needed to assess the equipoise of weight management interventions in this group and CF-specific issues should be considered when developing such interventions.

Changes in virus-transmission habits during the COVID-19 pandemic: a cross-national, repeated measures study.

OBJECTIVE: The COVID-19 pandemic saw promotion of novel virus transmission-reduction behaviours, and discouragement of familiar transmission-conducive behaviours. Understanding changes in the automatic nature of such behaviours is important, because habitual behaviours may be more easily reactivated in future outbreaks and disrupting old habits may discontinue unwanted behaviours. DESIGN: A repeated-measures, multi-national design tracked virus-transmission habits and behaviour fortnightly over six months (Apr-Sept 2020) among 517 participants (age M = 42 ± 16y, 79% female). MAIN OUTCOME MEASURES: Within-participant habit trajectories across all timepoints, and engagement in transmission-reduction behaviours (handwashing when entering home; handwashing with soap for 20 seconds; physical distancing) and transmission-conducive behaviours (coughing/sneezing into hands; making physical contact) summed over the final two timepoints. RESULTS: Three habit trajectory types were observed. Habits that remained strong ('stable strong habit') and habits that strengthened ('habit formation') were most common for transmission-reduction behaviours. Erosion of initially strong habits ('habit degradation') was most common for transmission-conducive behaviours. Regression analyses showed 'habit formation' and 'stable strong habit' trajectories were associated with greater behavioural engagement at later timepoints. CONCLUSION: Participants typically maintained or formed transmission-reduction habits, which encouraged later performance, and degraded transmission-conducive habits, which decreased performance. Findings suggest COVID-19-preventive habits may be recoverable in future virus outbreaks.

Association of changes in histologic severity of nonalcoholic steatohepatitis and changes in patient-reported quality of life.

Nonalcoholic steatohepatitis (NASH) is a prevalent chronic disease that is associated with a spectrum of liver fibrosis and can lead to cirrhosis. Patients with NASH report lower health-related quality of life (HRQoL) than the general population. It remains uncertain how changes in histologic severity are associated with changes in HRQoL. This is a secondary analysis of the Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment (FLINT) and Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis (PIVENS) randomized controlled trials in patients with biopsy-proven NASH. HRQoL was assessed using short form-36 at baseline and at follow-up biopsy (at 72 and 96 weeks, respectively). Adjusted linear regression models were used to examine the association between changes in liver fibrosis (primary analysis), nonalcoholic fatty liver disease (NAFLD) activity score (secondary analysis), and changes in HRQoL scores. Compared with stable fibrosis, improvement of fibrosis by at least one stage was significantly associated with improvements only in the physical function component by 1.8 points (95% confidence interval, 0.1, 3.5). Worsening of fibrosis by at least one stage was not associated with statistically significant changes in any HRQoL domain compared with stable fibrosis. Associations between HRQoL and NAFLD disease activity score in the secondary analysis were of similar magnitude. Weight loss was associated with small improvements in physical function, general health, and energy levels. Conclusion: Improvements in fibrosis stage were associated with improvements in the physical component of HRQoL, but the clinical impact was modest. As improving fibrosis may not meaningfully improve well-being, treatment for NASH will be cost effective only if it prevents long-term hepatic and cardiovascular disease.

Strategies to reduce the energy content of foods pre-ordered for lunch in the workplace: a randomised controlled trial in an experimental online canteen.

BACKGROUND: Prompting employees to swap their usual lunches for lower-energy alternatives may help align energy intake with public health recommendations. We tested the effect of offering lower-energy swaps with and without physical activity calorie equivalent (PACE) information on the energy of lunches pre-ordered in an online hypothetical workplace canteen. METHODS: UK employed adults (n = 2,150) were invited to hypothetically pre-order their lunch from the canteen through a custom-made online platform. They were randomised 1:1:1 to: (i) control: no swaps offered; (ii) lower-energy swaps offered; or (iii) lower-energy swaps offered with PACE information. The primary outcome was the total energy ordered using analysis of covariance and controlling for the energy content of the initial items ordered. Secondary outcomes were swap acceptance rate and intervention acceptability. RESULTS: Participants were 54% female, had a mean age of 36.8 (SD = 11.6) and a BMI of 26.3 (SD = 5.6). Compared with an average 819 kcal energy ordered in the control, both the swaps and swaps + PACE interventions significantly reduced average energy ordered by 47 kcal (95% CI: -82 to -13, p = 0.003) and 66 kcal (95% CI: -100 to -31, p < 0.001), respectively. Compared with offering swaps only, the swaps + PACE intervention led to significantly higher swap acceptance (OR: 1.63, 95% CI: 1.27 to 2.09, p < 0.001) but did not significantly reduce energy ordered (-19 kcal, 95% CI: -53 to 16, p = 0.591). About 65% and 16% of intervention participants found the swap interventions acceptable and unacceptable, respectively, with the swaps + PACE intervention being considered more acceptable than swaps only (OR: 1.32, 95%CI: 1.09 to 1.60, p < 0.004). CONCLUSION: Offering lower-energy swaps with or without PACE information reduced the energy of pre-ordered lunches experimentally. Both interventions hold promise for reducing the energy of purchased foods and drinks. Trial Registration As Predicted reference number: 56358, 22/01/21, https://aspredicted.org/pw2qr.pdf.

The association of weight loss with changes in the gut microbiota diversity, composition, and intestinal permeability: a systematic review and meta-analysis.

The gut microbiome may be a mediator between obesity and health outcomes. However, it is unclear how intentional weight loss changes the gut microbiota and intestinal permeability. We aimed to systematically review and quantify this association. We searched Medline, Embase, CINAHL, Cochrane databases, and trial registries until June 2020 (PROSPERO: CRD42020205292). We included trials of weight loss interventions (energy-restricted diets, pharmacotherapy, bariatric surgery) reporting on the microbiome. Two reviewers independently completed screening, extraction, and risk assessment with the ROBINS-I tool. Pooled standardized mean differences (SMDs) were obtained from random-effects meta-analyses. Forty-seven trials with 1,916 participants (81% female) and a median follow-up of 6 months (range: 2-24) were included. Based on imprecise evidence but with fairly consistent direction of effect, weight loss was associated with a statistically significant increase in α-diversity [SMD: 0.4 (95% CI: 0.2, 0.6], p < .0001, I2 = 70%, n = 30 studies) and a statistically significant reduction in intestinal permeability [SMD: -0.7 (95% CI: -0.9, -0.4), p < .0001, I2 = 83%, n = 17 studies]. Each kg of weight loss was associated with a 0.012 (95% CI: 0.0003, 0.024, p = .045) increase in α-diversity and a -0.017 (95% CI: -0.034, -0.001, p = .038) reduction in intestinal permeability. There was clear evidence of increases in the relative abundance of Akkermansia, but no clear evidence of changes in individual phyla, species, or fecal short-chain fatty acids. Restricting the analyses to the studies with lower risk of bias did not materially alter the estimates. Increasing weight loss is positively associated with increases in gut microbiota α-diversity and reductions in intestinal permeability.

Association of Weight Changes With Changes in Histological Features and Blood Markers in Nonalcoholic Steatohepatitis.

BACKGROUND AND AIMS: Weight loss is recommended for patients with non-alcoholic steatohepatitis (NASH) but the impact of weight change on disease activity remains unclear. We examined the association between weight change (gain/loss) and changes in biochemical and histological features of NASH. METHODS: This was an analysis of the PIVENS and FLINT trials in adults with NASH who had liver biopsies at baseline and at either 1.5 years or 2 years. Multivariable regression models examined how weight change was associated with changes in (a) blood liver markers, (b) NASH resolution with no fibrosis worsening, (c) fibrosis improving with no NASH worsening, and (d) individual histological features. RESULTS: The BMI of the 421 participants was 34.3 kg/m2 (SD:6.5) and their mean weight change was +0.5 kg (SD:6.5). Weight change was independently and positively associated with changes in liver enzymes and the Fibrosis-4 score (all P < .001). Each kg of weight loss was associated with 7% (95% CI, 3%-10%; P < .001) increase in odds of achieving NASH resolution with no fibrosis worsening and with 5% (95% CI, 1%-8%; P = .01) increase in odds of achieving fibrosis improvement with no NASH worsening. Weight gain was associated with worsening of disease activity. For every kg of weight lost, the odds of fibrosis improving were 5% (95% CI, 2%-8%; P = .001). There was no evidence that the association between weight change and outcome depended upon pharmacological treatment, trial, body mass index, and baseline fibrosis. CONCLUSIONS: Weight change was independently and monotonically associated with changes in biochemical and histological features of NASH. Guidelines for NASH management should incorporate recommendations for both avoidance of weight gain and support to lose weight.

Identifying and measuring the behavioural, dietary, and physical activity components of weight management consultations delivered by general practice nurses in routine care.

BACKGROUND: Many people with obesity receive weight loss consultations by general practice nurses (GPNs) in routine primary care. This exploratory study aimed to characterise the components of these consultations, including behaviour change techniques (BCTs), and dietary and physical activity recommendations. METHODS: We analysed audio recordings of weight management consultations conducted by 8 GPNs as part of the 'usual care' group in a randomised controlled trial (ISRCTN75092026). Consultations were coded against three taxonomies to classify BCTs, dietary recommendations, and physical activity recommendations. Associations between coded content and weight loss were assessed. Differences in the content of consultations where weight loss was < 5% or ≥ 5% from baseline weight at 6 months were explored. RESULTS: One hundred and fifty audio recordings were available from 53 out of 140 (38%) participants in the usual care group. Participants had on average 3 (SD = 1) recorded consultations over 3 months, lasting 14 (SD = 7) minutes each. Weight change at 3, 6, and 12 months was -3.6% (SD = 4.3), -5.5% (SD = 6.0) and -4.2% (SD = 6.5) for participants with audio recordings. GPNs used 3.9 (SD = 1.6) of 93 BCTs, 3.3 (SD = 2.7) of 30 dietary recommendations and 1.4 (SD = 1.2) of 10 physical activity recommendations per consultation. The most commonly employed BCTs were feedback on outcome of behaviour (80.0%), problem solving (38.0%), and social reward (34.3%). The most common dietary recommendations were about portion size (31.3%), nutrients (28.0%), and balanced diet (19.7%). The main physical activity recommendation was about walking (30.3%). There was no association between weight loss and the number of dietary recommendations, physical activity recommendations, or BCTs used per consultation, or per participant. Social reward was the only technique used significantly more in consultations of participants that lost ≥ 5% of their baseline weight at 6 months. CONCLUSIONS: The study provides a new method that could be used to describe the content of weight management consultations. Specific dietary or physical activity recommendations and BCTs were used infrequently and inconsistently in this group of GPNs. Although replication is required in larger samples, this may point to a weakness in current practice.

What proportion of people have a follow-up biopsy in randomized trials of treatments for non-alcoholic steatohepatitis?: A systematic review and meta-analysis.

BACKGROUND AND AIM: Trials of treatments for non-alcoholic steatohepatitis require endpoint assessment with liver biopsies. Previous large-scale trials have calculated their sample size expecting high retention but on average did not achieve this. We aimed to quantify the proportion of participants with a valid follow-up biopsy. METHODS: We conducted a systematic review of MEDLINE and Embase until May 2020 and included randomized clinical trials of any intervention in non-alcoholic steatohepatitis with at least 1-year follow-up. We were guided by Cochrane methods to run a meta-analysis with generalized linear mixed models with random effects. RESULTS: Forty-one trials (n = 6,695) were included. The proportion of participants with a valid follow-up biopsy was 82% (95%CI: 78%-86%, I2 = 92%). There was no evidence of a difference by location, trial length, or by allocated treatment group. Reasons for missing follow-up biopsies were, in ranked order, related to participants (95 per 1,000 participants (95%CI: 69-129, I2 = 92%), medical factors, protocol, trial conduct, and other/unclear. Biopsy-related serious adverse events occurred in 16 per 1,000 participants (95% CI: 8-33, I2 = 54%). No biopsy-related deaths were reported. CONCLUSIONS: The proportion of participants with a valid follow-up biopsy in therapeutic trials in non-alcoholic steatohepatitis is on average 82%, with around 1 in 10 participants declining a follow-up biopsy. These findings can inform adequately-powered trials.

The effect of the magnitude of weight loss on non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND: Trials show that weight loss interventions improve biomarkers of non-alcoholic fatty liver disease (NAFLD), but it is unclear if a dose-response relationship exists. OBJECTIVE: We aimed to quantify the dose-response relationship between the magnitude of weight loss and improvements in NAFLD. METHODS: Nine databases and trial registries were searched until October 2020. Single-arm, non-randomized comparative, or randomized trials of weight loss interventions (behavioral weight loss programs [BWLPs], pharmacotherapy, or bariatric surgery) in people with NAFLD were eligible for inclusion if they reported an association between changes in weight and changes in blood, radiological, or histological biomarkers of liver disease. The review followed Cochrane methods and the risk of bias was assessed using the Newcastle-Ottawa scale. Pooled unstandardized b coefficients were calculated using random-effect meta-analyses. RESULTS: Forty-three studies (BWMPs: 26, pharmacotherapy: 9, surgery: 8) with 2809 participants were included. The median follow-up was 6 (interquartile range: 6) months. The direction of effect was generally consistent but the estimates imprecise. Every 1 kg of weight lost was associated with a 0.83-unit (95% CI: 0.53 to 1.14, p < 0.0001, I2 = 92%, n = 18) reduction in alanine aminotransferase (U/L), a 0.56-unit (95% CI: 0.32 to 0.79, p < 0.0001, I2 = 68%, n = 11) reduction in aspartate transaminase (U/L), and a 0.77 percentage point (95% CI: 0.51 to 1.03, p < 0.0001, I2 = 72%, n = 11) reduction in steatosis assessed by radiology or histology. There was evidence of a dose-response relationship with liver inflammation, ballooning, and resolution of NAFLD or NASH, but limited evidence of a dose-response relationship with fibrosis or NAFLD activity score. On average, the risk of bias for selection and outcome was medium and low, respectively. CONCLUSION: Clinically significant improvements in NAFLD are achieved even with modest weight loss, but greater weight loss is associated with greater improvements. Embedding support for formal weight loss programs as part of the care pathway for the treatment of NAFLD could reduce the burden of disease. PROSPERO: CRD42018093676.

Experience of Using an Online Pre-Ordering System for A Workplace Canteen That Offers Lower-Energy Swaps: A Think-Aloud Study.

Online systems that allow employees to pre-order their lunch may help reduce energy intake. We investigated the acceptability of a pre-ordering website for a workplace canteen that prompts customers to swap to lower-energy swaps and the factors influencing swap acceptance. Employees (n = 30) placed a hypothetical lunch order through a pre-ordering website designed for their canteen while thinking aloud. Semi-structured interview questions supported data collection. Data were analysed using thematic analysis. Acceptability was generally high, but potentially context dependent. Practical considerations, such as reminders to pre-order, user-friendliness, provision of images of menu items and energy information while browsing, an ability to reserve pre-ordered meals, and a swift collection service facilitated acceptability. The restrictive timeframe within which orders could be placed, a lack of opportunity to see foods before ordering, and prompts to swap being perceived as threatening autonomy were barriers to acceptability. Swap acceptance was facilitated by the provision of physical activity calorie equivalents (PACE) information, and swap similarity in terms of taste, texture, and expected satiety as well as the perception that alternatives provided meaningful energy savings. Online canteen pre-ordering systems that prompt lower-energy swaps may be an acceptable approach to help reduce energy intake in the workplace.

Obesity, self-reported symptom severity, and quality of life in people with atrial fibrillation: A community-based cross-sectional survey.

BACKGROUND AND AIMS: Intentional weight loss may reduce symptom severity of atrial fibrillation (AF) in relatively young AF patients with overweight. We examined whether symptom severity and quality of life (QoL) are associated with weight status in the general population with AF. METHODS AND RESULTS: Patients with electrocardiogram-confirmed AF completed validated questionnaires: the EuroQol 5 Dimensions QoL questionnaire and the Toronto Atrial Fibrillation Severity Scale (AFSS). The AFSS assessed the AF burden scoring on AF-related symptoms and the total AF burden measured as a combination of duration, frequency, and severity of an irregular heartbeat. Generalized liner models examined the association of body mass index (BMI) with AF severity and QoL adjusting for confounders. Between 2018 and 2019, 882 of 1901 (46%) mailed questionnaires were returned completed. Participants had a mean (SD) age of 74 (10) years old and a BMI of 27.4 (5.6) kg/m2. Sixteen percent reported having never experienced an irregular heartbeat. A 5 kg/m2 higher BMI was associated with a 0.65 (95%CI: 0.25 to 1.06) higher symptom score, where 3 points represent a clinically relevant change in state. A 5 kg/m2 higher BMI was associated with a -1.61 (95%CI: -2.72 to -0.50) lower QoL score. The coefficient of the total AF burden for a 5 kg/m2 higher BMI was 0.17 (95% CI: -0.01 to 0.68). CONCLUSION: BMI was positively associated with symptoms and negatively associated with one of the two measures of QoL, but not with the total AF burden. However, the strength of association was small and not clinically meaningful.

Fatigue, quality of life and physical fitness following an exercise intervention in multiple myeloma survivors (MASCOT): an exploratory randomised Phase 2 trial utilising a modified Zelen design.

BACKGROUND: Exercise may improve fatigue in multiple myeloma survivors, but trial evidence is limited, and exercise may be perceived as risky in this older patient group with osteolytic bone destruction. METHODS: In this Phase 2 Zelen trial, multiple myeloma survivors who had completed treatment at least 6 weeks ago, or were on maintenance only, were enrolled in a cohort study and randomly assigned to usual care or a 6-month exercise programme of tailored aerobic and resistance training. Outcome assessors and usual care participants were masked. The primary outcome was the FACIT-F fatigue score with higher scores denoting less fatigue. RESULTS: During 2014-2016, 131 participants were randomised 3:1 to intervention (n = 89) or usual care (n = 42) to allow for patients declining allocation to the exercise arm. There was no difference between groups in fatigue at 3 months (between-group mean difference: 1.6 [95% CI: -1.1-4.3]) or 6 months (0.3 [95% CI: -2.6-3.1]). Muscle strength improved at 3 months (8.4 kg [95% CI: 0.5-16.3]) and 6 months (10.8 kg [95% CI: 1.2-20.5]). Using per-protocol analysis, cardiovascular fitness improved at 3 months (+1.2 ml/kg/min [95% CI: 0.3-3.7]). In participants with clinical fatigue (n = 17), there was a trend towards less fatigue with exercise over 6 months (6.3 [95% CI: -0.6-13.3]). There were no serious adverse events. CONCLUSIONS: Exercise appeared safe and improved muscle strength and cardiovascular fitness, but benefits in fatigue appeared limited to participants with clinical fatigue at baseline. Future studies should focus on patients with clinical fatigue. CLINICAL TRIAL REGISTRATION: The study was registered with ISRCTN (38480455) and is completed.

The adapted Zelen was a feasible design to trial exercise in myeloma survivors.

OBJECTIVES: We used a method rarely seen in cancer behavioral trials to explore methods of overcoming difficulties often seen in randomized controlled trials. We report our experiences of the adapted Zelen design, so that other researchers can consider this approach for behavioral trials. STUDY DESIGN AND SETTING: The adapted Zelen design was used to explore the effects of exercise on multiple myeloma patients fatigue, quality of life, and physical outcomes. All participants consented to an observational cohort study of lifestyle factors but were unaware of subsequent randomization to remain in cohort only group or be offered an exercise intervention requiring second consent. RESULTS: There was lower than expected uptake to the exercise offered group (57%), so the length of recruitment increased from 24 to 29 months to ensure power was reached. At enrollment, patients were unaware of the potential increased commitment, and as a result, 62% of participants allocated to the intervention declined because of the extra time/travel commitment required. This emulates clinical settings and suggests improvements in intervention delivery are required. Our findings suggest that the adapted Zelen design may be useful in limiting dropout of controls due to dissatisfaction from group allocation, or contamination of control arm. CONCLUSION: Future use of this design warrants careful consideration of the study resources and recruitment time frames required but holds potential value in reducing contamination, control group dissatisfaction, and resulting dropout. Adapted Zelen design reduces selection bias and therefore gives clinicians a better understanding of acceptability in clinical settings. Future studies should evaluate control group experiences of the design and formally record contamination throughout the study to confirm its acceptability.