Is doctor referral to a low energy total diet replacement programme costeffective for the routine treatment of obesity?

ABTRACT Objective To estimate the cost-effectiveness of a commercially provided low energy total diet replacement (TDR) programme versus nurse-led behavioural support. Methods We used a multi-state lifetable model and the weight reduction observed in a randomised controlled trial to evaluate the quality-adjusted life-years (QALYs) and direct healthcare costs (in UK 2017 prices) over a lifetime with TDR versus nurse-led support in adults who were obese, assuming that: i) weight returns to baseline over 5 years, and ii) a 1 kg weight loss is maintained after 5 years following TDR. Results The per-person costs of the TDR and nurse-led programmes were £796 and £34, respectively. The incremental cost-effectiveness ratio (ICER) of TDR was £12,955 (95% confidence interval: £8,082 to £17,827) assuming all weight lost is regained and £3,203 (£2,580 to £3,825) assuming that a 1 kg weight loss is maintained after 5 years. TDR was estimated to be more cost-effective (i.e. lower ICERs) in older adults and those with higher body mass index, with little difference by gender. Conclusions At current retail prices and with plausible long-term weight regain trajectories, TDR is projected to be cost-effective in obese adults and could be considered as an option to treat obesity in routine healthcare setting

What works to support carers of older people and older carers? an international evidence map of interventions and outcomes

\ua9 The Author(s) 2024.Background: Unpaid carers of older people, and older unpaid carers, experience a range of adverse outcomes. Supporting carers should therefore be a public health priority. Our understanding of what works to support carers could be enhanced if future evaluations prioritise under-researched interventions and outcomes. To support this, we aimed to: map evidence about interventions to support carers, and the outcomes evaluated; and identify key gaps in current evidence. Methods: Evidence gap map review methods were used. Searches were carried out in three bibliographic databases for quantitative evaluations of carer interventions published in OECD high-income countries between 2013 and 2023. Interventions were eligible if they supported older carers (50 + years) of any aged recipient, or any aged carers of older people (50 + years). Findings: 205 studies reported across 208 publications were included in the evidence map. The majority evaluated the impact of therapeutic and educational interventions on carer burden and carers’ mental health. Some studies reported evidence about physical exercise interventions and befriending and peer support for carers, but these considered a limited range of outcomes. Few studies evaluated interventions that focused on delivering financial information and advice, pain management, and physical skills training for carers. Evaluations rarely considered the impact of interventions on carers’ physical health, quality of life, and social and financial wellbeing. Very few studies considered whether interventions delivered equitable outcomes. Conclusion: Evidence on what works best to support carers is extensive but limited in scope. A disproportionate focus on mental health and burden outcomes neglects other important areas where carers may need support. Given the impact of caring on carers’ physical health, financial and social wellbeing, future research could evaluate interventions that aim to support these outcomes. Appraisal of whether interventions deliver equitable outcomes across diverse carer populations is critical

In severe alcoholic hepatitis, serum keratin-18 fragments are diagnostic, prognostic, and theragnostic biomarkers.

INTRODUCTION: Up to 40% of patients with severe alcoholic hepatitis (AH) die within 6 months of presentation, making prompt diagnosis and appropriate treatment essential. We determined the associations between serum keratin-18 (K18) and histological features, prognosis, and differential response to prednisolone in patients with severe AH. METHODS: Total (K18-M65) and caspase-cleaved K18 (K18-M30) were quantified in pretreatment sera from 824 patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial (87 with suitable histological samples) and disease controls. RESULTS: K18 fragments were markedly elevated in severe AH and strongly predicted steatohepatitis (alcoholic steatohepatitis) on biopsy (area under receiver operating characteristics: 0.787 and 0.807). Application of published thresholds to predict alcoholic steatohepatitis would have rendered biopsy unnecessary in 84% of all AH cases. K18-M30 and M65 were associated with 90-day mortality, independent of age and Model for End-stage Liver Disease score in untreated patients. The association for K18-M65 was independent of both age and Model for End-stage Liver Disease in prednisolone-treated patients. Modelling of the effect of prednisolone on 90-day mortality as a function of pretreatment serum K18 levels indicated benefit in those with high serum levels of K18-M30. At low pretreatment serum K18 levels, prednisolone was potentially harmful. A threshold of K18-M30 5 kIU/L predicted therapeutic benefit from prednisolone above this level (odds ratio: 0.433, 95% confidence interval: 0.19-0.95, P = 0.0398), but not below (odds ratio: 1.271, 95% confidence interval: 0.88-1.84, P = 0.199). Restricting prednisolone usage to the former group would have reduced exposure by 87%. DISCUSSION: In a large cohort of patients with severe AH, serum K18 strongly correlated with histological severity, independently associated with 90-day mortality, and predicted response to prednisolone therapy. Quantification of serum K18 levels could assist in clinical decision-making

High resolution Thomson Parabola Spectrometer for full spectral capture of multi-species ion beams

We report on the experimental characterisation of laser-driven ion beams using a Thomson Parabola Spectrometer (TPS) equipped with trapezoidally-shaped electric plates, proposed by Gwynne et al. in Rev. Sci. Instrum. 85, 033304 (2014). While a pair of extended (30 cm long) electric plates was able to produce a significant increase in the separation between neighbouring ion species at high energies, deploying a trapezoidal design circumvented the spectral clipping at the low energy end of the ion spectra. The shape of the electric plate was chosen carefully considering, for the given spectrometer configuration, the range of detectable ion energies and species. Analytical tracing of the ion parabolas matches closely with the experimental data, which suggests a minimal effect of fringe fields on the escaping ions close to the wedged edge of the electrode. The analytical formulae were derived considering the relativistic correction required for the high energy ions to be characterised using such spectrometer

Enterprise Education Competitions: A Theoretically Flawed Intervention?

The demand for including enterprise in the education system, at all levels and for all pupils is now a global phenomenon. Within this context, the use of competitions and competitive learning activities is presented as a popular and effective vehicle for learning. The purpose of this chapter is to illustrate how a realist method of enquiry – which utilises theory as the unit of analysis – can shed new light on the assumed and unintended outcomes of enterprise education competitions. The case developed here is that there are inherent flaws in assuming that competitions will ‘work’ in the ways set out in policy and guidance. Some of the most prevalent stated outcomes – that competitions will motivate and reward young people, that they will enable the development of entrepreneurial skills, and that learners will be inspired by their peers – are challenged by theory from psychology and education. The issue at stake is that the expansion of enterprise education policy into primary and secondary education increases the likelihood that more learners will be sheep dipped in competitions, and competitive activities, without a clear recognition of the potential unintended effects. In this chapter, we employ a realist-informed approach to critically evaluate the theoretical basis that underpins the use of competitions and competitive learning activities in school-based enterprise education. We believe that our findings and subsequent recommendations will provide those who promote and practice the use of competitions with a richer, more sophisticated picture of the potential flaws within such activities.Peer reviewedFinal Published versio

The implications of defining obesity as a disease: a report from the Association for the Study of Obesity 2021 annual conference

Unlike various countries and organisations, including the World Health Organisation and the European Parliament, the United Kingdom does not formally recognise obesity as a disease. This report presents the discussion on the potential impact of defining obesity as a disease on the patient, the healthcare system, the economy, and the wider society. A group of speakers from a wide range of disciplines came together to debate the topic bringing their knowledge and expertise from backgrounds in medicine, psychology, economics, and politics as well as the experience of people living with obesity. The aim of their debate was not to decide whether obesity should be classified as a disease but rather to explore what the implications of doing so would be, what the gaps in the available data are, as well as to provide up-to-date information on the topic from experts in the field. There were four topics where speakers presented their viewpoints, each one including a question-and-answer section for debate. The first one focused on the impact that the recognition of obesity could have on people living with obesity regarding the change in their behaviour, either positive and empowering or more stigmatising. During the second one, the impact of defining obesity as a disease on the National Health Service and the wider economy was discussed. The primary outcome was the need for more robust data as the one available does not represent the actual cost of obesity. The third topic was related to the policy implications regarding treatment provision, focusing on the public's power to influence policy. Finally, the last issue discussed, included the implications of public health actions, highlighting the importance of the government's actions and private stakeholders. The speakers agreed that no matter where they stand on this debate, the goal is common: to provide a healthcare system that supports and protects the patients, strategies that protect the economy and broader society, and policies that reduce stigma and promote health equity. Many questions are left to be answered regarding how these goals can be achieved. However, this discussion has set a good foundation providing evidence that can be used by the public, clinicians, and policymakers to make that happen

Prediction of peptide and protein propensity for amyloid formation

Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation

A novel 'practical body image' therapy for adolescent inpatients with anorexia nervosa: a randomised controlled trial.

PURPOSE: To determine the potential effectiveness of a novel 10-week manualised Practical Body Image therapy (PBI) with mirror exposure (ME), when used as an adjuvant to an intensive treatment package (TAU) in adolescent inpatients with Anorexia Nervosa (AN). To evaluate the effectiveness of ME in an adolescent population. METHODS: Using a randomised control design, 40 girls aged 11-17 years with AN were assigned to PBI with TAU (n = 20) and TAU alone (n = 20). Both groups completed self-report measures of body image at week 1 and week 10 of the study to measure the potential effectiveness of PBI. The PBI group completed measures at week 7 to evaluate the ME component. RESULTS: 31 participants completed the study; 16 TAU, 15 PBI. PBI participants had greater improvement in all outcomes than TAU participants. Medium effect sizes were seen for self-reported weight concern, body image avoidance in terms of clothing and body image anxiety. ME produced effect sizes in self-reported body image avoidance in terms of clothing and grooming that were greater than 0.40, n = 14. CONCLUSION: The findings demonstrate that PBI supports an intensive inpatient treatment package and addresses elements of negative body image. PBI was beneficial for addressing body image dissatisfaction with improvements in weight concerns, body image avoidance and physical appearance trait anxiety following the ME component. The magnitude of the effect sizes is comparable to previous studies. Positive qualitative feedback indicated the intervention was acceptable to users. PBI is a promising new adjuvant treatment for AN. EMB RATING: Level I: randomized controlled trial

Positive reinforcement targeting abstinence in substance misuse (PRAISe): Study protocol for a Cluster RCT & process evaluation of contingency management

There are approximately 256,000 heroin and other opiate users in England of whom 155,000 are in treatment for heroin (or opiate) addiction. The majority of people in treatment receive opiate substitution treatment (OST) (methadone and buprenorphine). However, OST suffers from high attrition and persistent heroin use even whilst in treatment. Contingency management (CM) is a psychological intervention based on the principles of operant conditioning. It is delivered as an adjunct to existing evidence based treatments to amplify patient benefit and involves the systematic application of positive reinforcement (financial or material incentives) to promote behaviours consistent with treatment goals. With an international evidence base for CM, NICE recommended that CM be implemented in UK drug treatment settings alongside OST to target attendance and the reduction of illicit drug use. While there was a growing evidence base for CM, there had been no examination of its delivery in UK NHS addiction services. The PRAISe trial evaluates the feasibility, acceptability, clinical and cost effectiveness of CM in UK addiction services. It is a cluster randomised controlled effectiveness trial of CM (praise and financial incentives) targeted at either abstinence from opiates or attendance at treatment sessions versus no CM among individuals receiving OST. The trial includes an economic evaluation which explores the relative costs and cost effectiveness of the two CM intervention strategies compared to TAU and an embedded process evaluation to identify contextual factors and causal mechanisms associated with variations in outcome. This study will inform UK drug treatment policy and practice. Trial registration ISRCTN 01591254

Induced pseudoscalar coupling of the proton weak interaction

The induced pseudoscalar coupling $g_p$ is the least well known of the weak coupling constants of the proton's charged--current interaction. Its size is dictated by chiral symmetry arguments, and its measurement represents an important test of quantum chromodynamics at low energies. During the past decade a large body of new data relevant to the coupling $g_p$ has been accumulated. This data includes measurements of radiative and non radiative muon capture on targets ranging from hydrogen and few--nucleon systems to complex nuclei. Herein the authors review the theoretical underpinnings of $g_p$, the experimental studies of $g_p$, and the procedures and uncertainties in extracting the coupling from data. Current puzzles are highlighted and future opportunities are discussed.Comment: 58 pages, Latex, Revtex4, prepared for Reviews of Modern Physic