Weight regain after behavioural weight management programmes and its impact on quality of life and cost effectiveness: Evidence synthesis and health economic analyses.

AIMS: We used data from a recent systematic review to investigate weight regain after behavioural weight management programmes (BWMPs, sometimes referred to as lifestyle modification programmes) and its impact on quality-of-life and cost-effectiveness. MATERIALS AND METHODS: Trial registries, databases and forward-citation searching (latest search December 2019) were used to identify randomized trials of BWMPs in adults with overweight/obesity reporting outcomes at ≥12 months, and after programme end. Two independent reviewers screened records. One reviewer extracted data and a second checked them. The differences between intervention and control groups were synthesized using mixed-effect, meta-regression and time-to-event models. We examined associations between weight difference and difference in quality-of-life. Cost-effectiveness was estimated from a health sector perspective. RESULTS: In total, 155 trials (n > 150 000) contributed to analyses. The longest follow-up was 23 years post-programme. At programme end, intervention groups achieved -2.8 kg (95%CI -3.2 to -2.4) greater weight loss than controls. Weight regain after programme end was 0.12-0.32 kg/year greater in intervention relative to control groups, with a between-group difference evident for at least 5 years. Quality-of-life increased in intervention groups relative to control at programme end and thereafter returned to control as the difference in weight between groups diminished. BWMPs with this initial weight loss and subsequent regain would be cost-effective if delivered for under £560 (£8.80-£3900) per person. CONCLUSIONS: Modest rates of weight regain, with persistent benefits for several years, should encourage health care practitioners and policymakers to offer obesity treatments that cost less than our suggested thresholds as a cost-effective intervention to improve long-term weight management. REGISTRATION: The review is registered on PROSPERO, CRD42018105744.

A case of severe refractory Darier's disease of the feet in which management with carbon dioxide (CO2) laser therapy demonstrated superior outcomes to surgical excision.

Darier's disease is a rare genodermatosis typically characterized by scaly or crusted papules. Usual management comprises topical and oral treatments, however medical therapy may be inadequate in cases of severe disease. For these patients, further treatment options may include the use of carbon dioxide (CO2) laser therapy or surgical excision with skin grafting. We describe a unique situation in which both CO2 laser therapy and surgical excision were trialed in comparable areas within a single patient. Superior outcomes over a 7-year follow up period have been seen with the use of CO2 laser therapy.

Long-Term Effect of Weight Regain Following Behavioral Weight Management Programs on Cardiometabolic Disease Incidence and Risk: Systematic Review and Meta-Analysis.

BACKGROUND: Behavioral weight management programs (BWMPs) enhance weight loss in the short term, but longer term cardiometabolic effects are uncertain as weight is commonly regained. We assessed the impact of weight regain after BWMPs on cardiovascular risk factors, diabetes, and cardiovascular disease. METHODS: Trial registries, 11 databases, and forward-citation searching (latest search, December 19) were used to identify articles published in English, from any geographical region. Randomized trials of BWMPs in adults with overweight/obesity reporting cardiometabolic outcomes at ≥12 months at and after program end were included. Differences between more intensive interventions and comparator groups were synthesized using mixed-effects, meta-regression, and time-to-event models to assess the impact of weight regain on cardiovascular disease incidence and risk. RESULTS: One hundred twenty-four trials reporting on ≥1 cardiometabolic outcomes with a median follow-up of 28 (range, 11-360) months after program end were included. Median baseline participant body mass index was 33 kg/m2; median age was 51 years. Eight and 15 study arms (7889 and 4202 participants, respectively) examined the incidence of cardiovascular disease and type 2 diabetes, respectively, with imprecise evidence of a lower incidence for at least 5 years. Weight regain in BWMPs relative to comparators reduced these differences. One and 5 years after program end, total cholesterol/HDL (high-density lipoprotein) ratio was 1.5 points lower at both times (82 studies; 19 003 participants), systolic blood pressure was 1.5 mm mercury and 0.4 mm lower (84 studies; 30 836 participants), and HbA1c (%) 0.38 lower at both times (94 studies; 28 083 participants). Of the included studies, 22% were judged at high risk of bias; removing these did not meaningfully change results. CONCLUSIONS: Despite weight regain, BWMPs reduce cardiometabolic risk factors with effects lasting at least 5 years after program end and dwindling with weight regain. Evidence that they reduce the incidence of cardiovascular disease or diabetes is less certain. Few studies followed participants for ≥5 years. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42018105744.

Association between characteristics of behavioural weight loss programmes and weight change after programme end: systematic review and meta-analysis.

OBJECTIVE: To determine if the characteristics of behavioural weight loss programmes influence the rate of change in weight after the end of the programme. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Trial registries, 11 electronic databases, and forward citation searching (from database inception; latest search December 2019). Randomised trials of behavioural weight loss programmes in adults with overweight or obesity, reporting outcomes at ≥12 months, including at the end of the programme and after the end of the programme. REVIEW METHODS: Studies were screened by two independent reviewers with discrepancies resolved by discussion. 5% of the studies identified in the searches met the inclusion criteria. One reviewer extracted the data and a second reviewer checked the data. Risk of bias was assessed with Cochrane's risk of bias tool (version 1). The rate of change in weight was calculated (kg/month; converted to kg/year for interpretability) after the end of the programme in the intervention versus control groups by a mixed model with a random intercept. Associations between the rate of change in weight and prespecified variables were tested. RESULTS: Data were analysed from 249 trials (n=59 081) with a mean length of follow-up of two years (longest 30 years). 56% of studies (n=140) had an unclear risk of bias, 21% (n=52) a low risk, and 23% (n=57) a high risk of bias. Regain in weight was faster in the intervention versus the no intervention control groups (0.12-0.32 kg/year) but the difference between groups was maintained for at least five years. Each kilogram of weight lost at the end of the programme was associated with faster regain in weight at a rate of 0.13-0.19 kg/year. Financial incentives for weight loss were associated with faster regain in weight at a rate of 1-1.5 kg/year. Compared with programmes with no meal replacements, interventions involving partial meal replacements were associated with faster regain in weight but not after adjustment for weight loss during the programme. Access to the programme outside of the study was associated with slower regain in weight. Programmes where the intensity of the interaction reduced gradually were also associated with slower regain in weight in the multivariable analysis, although the point estimate suggested that the association was small. Other characteristics did not explain the heterogeneity in regain in weight. CONCLUSION: Faster regain in weight after weight loss was associated with greater initial weight loss, but greater initial weight loss was still associated with reduced weight for at least five years after the end of the programme, after which data were limited. Continued availability of the programme to participants outside of the study predicted a slower regain in weight, and provision of financial incentives predicted faster regain in weight; no other clear associations were found. STUDY REGISTRATION: PROSPERO CRD42018105744.

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.

Association between antihypertensive treatment and adverse events: systematic review and meta-analysis.

OBJECTIVE: To examine the association between antihypertensive treatment and specific adverse events. DESIGN: Systematic review and meta-analysis. ELIGIBILITY CRITERIA: Randomised controlled trials of adults receiving antihypertensives compared with placebo or no treatment, more antihypertensive drugs compared with fewer antihypertensive drugs, or higher blood pressure targets compared with lower targets. To avoid small early phase trials, studies were required to have at least 650 patient years of follow-up. INFORMATION SOURCES: Searches were conducted in Embase, Medline, CENTRAL, and the Science Citation Index databases from inception until 14 April 2020. MAIN OUTCOME MEASURES: The primary outcome was falls during trial follow-up. Secondary outcomes were acute kidney injury, fractures, gout, hyperkalaemia, hypokalaemia, hypotension, and syncope. Additional outcomes related to death and major cardiovascular events were extracted. Risk of bias was assessed using the Cochrane risk of bias tool, and random effects meta-analysis was used to pool rate ratios, odds ratios, and hazard ratios across studies, allowing for between study heterogeneity (τ2). RESULTS: Of 15 023 articles screened for inclusion, 58 randomised controlled trials were identified, including 280 638 participants followed up for a median of 3 (interquartile range 2-4) years. Most of the trials (n=40, 69%) had a low risk of bias. Among seven trials reporting data for falls, no evidence was found of an association with antihypertensive treatment (summary risk ratio 1.05, 95% confidence interval 0.89 to 1.24, τ2=0.009). Antihypertensives were associated with an increased risk of acute kidney injury (1.18, 95% confidence interval 1.01 to 1.39, τ2=0.037, n=15), hyperkalaemia (1.89, 1.56 to 2.30, τ2=0.122, n=26), hypotension (1.97, 1.67 to 2.32, τ2=0.132, n=35), and syncope (1.28, 1.03 to 1.59, τ2=0.050, n=16). The heterogeneity between studies assessing acute kidney injury and hyperkalaemia events was reduced when focusing on drugs that affect the renin angiotensin-aldosterone system. Results were robust to sensitivity analyses focusing on adverse events leading to withdrawal from each trial. Antihypertensive treatment was associated with a reduced risk of all cause mortality, cardiovascular death, and stroke, but not of myocardial infarction. CONCLUSIONS: This meta-analysis found no evidence to suggest that antihypertensive treatment is associated with falls but found evidence of an association with mild (hyperkalaemia, hypotension) and severe adverse events (acute kidney injury, syncope). These data could be used to inform shared decision making between doctors and patients about initiation and continuation of antihypertensive treatment, especially in patients at high risk of harm because of previous adverse events or poor renal function. REGISTRATION: PROSPERO CRD42018116860.

Comment on: Jilkova, Z.M.; et al. "Predictive Factors for Response to PD-1/PD-L1 Checkpoint Inhibition in the Field of Hepatocellular Carcinoma: Current Status and Challenges" Cancers 2019, 11, 1554.

I read with interest the article 'Predictive Factors for Response to PD-1/PD-L1 Checkpoint Inhibition in the Field of Hepatocellular Carcinoma: Current Status and Challenges' [...].

Interventional bundle for venous thromboembolism prevention: ensuring quality and effectiveness.

Hospital-associated thromboses (HATs) are a potentially preventable cause of morbidity and mortality. Oxford University Hospitals NHS Foundation Trust was designated a Venous Thromboembolism (VTE) Exemplar Centre by NHS England in 2014. However, following delayed reporting of a potentially preventable HAT in 2015, a benchmarking exercise suggested HATs were being under-reported, and also that the established hospital-wide audits of VTE prevention had significant limitations. The aim of this interventional bundle was to ensure high-quality data for key VTE prevention measures across the hospital, to identify areas for improvement and demonstrate a reduction in the number of potentially preventable HATs over a 2-year period. The project team engaged with hospital leadership and collaborated with hospital-wide stakeholders. A multifaceted approach was taken and 'Plan Do Study Act' cycles were used to test interventions with continuous evaluation of impact. The percentage of inpatients receiving appropriate thromboprophylaxis progressively increased from 94% to 98%. The project did not achieve its secondary aim of a reduction in the number of potentially preventable HATs. Revision of the HAT reporting process resulted in better detection and an initial increase in reporting of potentially preventable HATs, although data suggest that the level of harm from errors is now reducing. The improvement in overall appropriate thromboprophylaxis is considered to be due to robust audits of appropriate thromboprophylaxis, upskilling of ward pharmacists, improved detection of potentially preventable HATs resulting in additional safety nets such as linking the 'outcome recommendation' of the electronic VTE risk assessment directly to electronic prescribing, and increased awareness and education. Combining low-cost actions in a coordinated interventional bundle has produced measurable improvements in our VTE management programme, enhancing patient safety. We believe the model to be sustainable and replicable in other general hospitals.