Cost Effectiveness of the Baveno VI Criteria Compared With Endoscopy for High-Risk Varices in Patients With Child-Pugh A Cirrhosis.

BACKGROUND & AIMS: Although upper gastrointestinal endoscopy (EGD) remains the gold standard for detecting varices in cirrhosis, the Baveno VI criteria proposed a combination of transient elastography and platelet count that could rule out high-risk varices, therefore sparing the need for an endoscopy, with significant potential cost savings. We performed a cost-effectiveness analysis of the Baveno VI criteria compared with EGD in the diagnosis of high-risk varices in cirrhosis. METHODS: We built an analytical decision model to estimate the cost and benefits of using the Baveno VI criteria compared with EGD in patients with Child-Pugh A cirrhosis. The analysis was performed from the UK National Health Service perspective, over 1, 5, and 20 years. A Markov model was populated with data from published evidence. Outcomes were measured in terms of quality-adjusted life years (QALYs) and avoided deaths. The analyses were repeated for Canada and Spain, using relevant cost inputs. RESULTS: The Baveno VI criteria were cost effective compared with endoscopy in all analyses. For 1000 patients, they produced 0.16 additional QALYs at an incremental cost of £326 ($443.41) over 5 years, resulting in an incremental cost of £2081 ($2830) per additional QALY gained. The incremental net monetary benefit of Baveno VI compared with EGD was £2808 ($3819) over 5 years per patient. Baveno VI criteria also were cost effective in Canada and Spain. Deterministic and probabilistic sensitivity analysis supported these findings. CONCLUSIONS: The findings demonstrate that the Baveno VI criteria are cost effective, suggesting that they should be considered for widespread implementation on the basis of safety, appropriateness, and economic grounds.

Cytoreductive surgery plus hyperthermic intraoperative peritoneal chemotherapy for people with peritoneal metastases from colorectal, ovarian or gastric origin: A systematic review of randomized controlled trials.

BACKGROUND: There is uncertainty in the relative benefits and harms of hyperthermic intraoperative peritoneal chemotherapy (HIPEC) when added to cytoreductive surgery (CRS) +/- systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric, or ovarian cancers. METHODS: We searched randomized controlled trials (RCTs) in the medical literature until April 14, 2022 and applied methods used for high-quality systematic reviews. FINDINGS: We included a total of eight RCTs (seven RCTs included in quantitative analysis as one RCT did not provide data in an analyzable format). All comparisons other than ovarian cancer contained only one trial. For gastric cancer, there is high uncertainty about the effect of CRS + HIPEC + systemic chemotherapy. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, CRS + HIPEC + systemic chemotherapy probably decreases all-cause mortality compared to CRS + systemic chemotherapy. For colorectal cancer, CRS + HIPEC + systemic chemotherapy probably results in little to no difference in all-cause mortality and may increase the serious adverse events proportions compared to CRS +/- systemic chemotherapy, but probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone. INTERPRETATION: The role of CRS + HIPEC in gastric peritoneal metastases is uncertain. CRS + HIPEC should be standard of care in women with stage III or greater epithelial ovarian cancer undergoing interval CRS. CRS + systemic chemotherapy should be standard of care for people with colorectal peritoneal metastases, with HIPEC given only as part of a RCT focusing on subgroups and regimes. PROSPERO REGISTRATION: CRD42019130504.

Evaluating the Acceptability of the Drink Less App and the National Health Service Alcohol Advice Web Page: Qualitative Interview Process Evaluation.

BACKGROUND: The extent to which interventions are perceived as acceptable to users impacts engagement and efficacy. OBJECTIVE: In this study, we evaluated the acceptability of (1) the smartphone app Drink Less (intervention) and (2) the National Health Service (NHS) alcohol advice web page (usual digital care and comparator) among adult drinkers in the United Kingdom participating in a randomized controlled trial evaluating the effectiveness of the Drink Less app. METHODS: A subsample of 26 increasing- and higher-risk drinkers (Alcohol Use Disorders Identification Test score≥8) assigned to the intervention group (Drink Less; n=14, 54%; female: n=10, 71%; age: 22-72 years; White: n=9, 64%) or usual digital care group (NHS alcohol advice web page; n=12, 46%; female: n=5, 42%; age: 23-68 years: White: n=9, 75%) took part in semistructured interviews. The interview questions were mapped on to the 7 facets of acceptability according to the Theoretical Framework of Acceptability: affective attitude, burden, perceived effectiveness, ethicality, intervention coherence, opportunity costs, and self-efficacy. Alongside these constructs, we also included a question on perceived personal relevance, which previous research has linked to acceptability and engagement. Framework and thematic analysis of data was undertaken. RESULTS: The Drink Less app was perceived as being ethical, easy, user-friendly, and effective for the period the app was used. Participants reported particularly liking the tracking and feedback sections of the app, which they reported increased personal relevance and which resulted in positive affect when achieving their goals. They reported no opportunity cost. Factors such as negative affect when not meeting goals and boredom led to disengagement in the longer term for some participants. The NHS alcohol advice web page was rated as being easy and user-friendly with no opportunity costs. However, the information presented was not perceived as being personally relevant or effective in changing drinking behavior. Most participants reported neutral or negative affect, most participants thought the alcohol advice web page was accessible, and some participants reported ethical concerns around the availability of suggested resources. Some participants reported that it had acted as a starting point or a signpost to other resources. Participants in both groups discussed motivation to change and contextual factors such as COVID-19 lockdowns, which influenced their perceived self-efficacy regardless of their assigned intervention. CONCLUSIONS: Drink Less appears to be an acceptable digital intervention among the recruited sample. The NHS alcohol advice web page was generally considered unacceptable as a stand-alone intervention among the recruited sample, although it may signpost and help people access other resources and interventions.

REFINE-Lung implements a novel multi-arm randomised trial design to address possible immunotherapy overtreatment.

Increasing evidence suggests that some immunotherapy dosing regimens for patients with advanced cancer could result in overtreatment. Given the high costs of these agents, and important implications for quality of life and toxicity, new approaches are needed to identify and reduce unnecessary treatment. Conventional two-arm non-inferiority designs are inefficient in this context because they require large numbers of patients to explore a single alternative to the standard of care. Here, we discuss the potential problem of overtreatment with anti-PD-1 directed agents in general and introduce REFINE-Lung (NCT05085028), a UK multicentre phase 3 study of reduced frequency pembrolizumab in advanced non-small-cell lung cancer. REFINE-Lung uses a novel multi-arm multi-stage response over continuous interventions (MAMS-ROCI) design to determine the optimal dose frequency of pembrolizumab. Along with a similarly designed basket study of patients with renal cancer and melanoma, REFINE-Lung and the MAMS-ROCI design could contribute to practice-changing advances in patient care and form a template for future immunotherapy optimisation studies across cancer types and indications. This new trial design is applicable to many new or existing agents for which optimisation of dose, frequency, or duration of therapy is desirable.

Health technology assessment of paediatric medicines: European landscape, challenges and opportunities inside the conect4children project.

The medicine development process is complex and requires time and effort to ensure safety, efficacy and quality. In paediatrics, this process is even more challenging, as it involves a subgroup of the population that already faces a considerable gap in the clinical evaluation of medicines and devices compared to the adult population. Moreover, access to therapies is heavily influenced by national health technology assessment (HTA) recommendations, which often form the basis for pricing and reimbursement decisions that affect the availability of effective treatments within the national health systems. Yet performing an HTA to assess the relative effectiveness and cost-effectiveness of a new children's treatment has several non-trivial implications, creating a critical issue for the paediatric population. In addition, the advent of innovative health technologies for children emphasises the need to empower the role of HTAs in paediatrics. This article aims at describing the most relevant elements of the drug development process in the paediatric field by focusing on the HTA. Particular attention will be paid to the factors that influence market access for new paediatric medicines and patients' access to treatment. The article will also highlight some central methodological challenges in conducting HTA in the paediatric field. Finally, the article will provide insight into how initiatives, such as conect4children, may subsequently reinforce HTA awareness in the paediatric community and strengthen collaborations through network mechanisms.

Community Occupational Therapy for people with dementia and family carers (COTiD-UK) versus treatment as usual (Valuing Active Life in Dementia [VALID]) study: A single-blind, randomised controlled trial.

BACKGROUND: We aimed to estimate the clinical effectiveness of Community Occupational Therapy for people with dementia and family carers-UK version (Community Occupational Therapy in Dementia-UK version [COTiD-UK]) relative to treatment as usual (TAU). We hypothesised that COTiD-UK would improve the ability of people with dementia to perform activities of daily living (ADL), and family carers' sense of competence, compared with TAU. METHODS AND FINDINGS: The study design was a multicentre, 2-arm, parallel-group, assessor-masked, individually randomised controlled trial (RCT) with internal pilot. It was conducted in 15 sites across England from September 2014 to January 2018. People with a diagnosis of mild to moderate dementia living in their own home were recruited in pairs with a family carer who provided domestic or personal support for at least 4 hours per week. Pairs were randomised to either receive COTiD-UK, which comprised 10 hours of occupational therapy delivered over 10 weeks in the person with dementia's home or TAU, which comprised the usual local service provision that may or may not include standard occupational therapy. The primary outcome was the Bristol Activities of Daily Living Scale (BADLS) score at 26 weeks. Secondary outcomes for the person with dementia included the following: the BADLS scores at 52 and 78 weeks, cognition, quality of life, and mood; and for the family carer: sense of competence and mood; plus the number of social contacts and leisure activities for both partners. Participants were analysed by treatment allocated. A total of 468 pairs were recruited: people with dementia ranged from 55 to 97 years with a mean age of 78.6 and family carers ranged from 29 to 94 with a mean of 69.1 years. Of the people with dementia, 74.8% were married and 19.2% lived alone. Of the family carers, 72.6% were spouses, and 22.2% were adult children. On randomisation, 249 pairs were assigned to COTiD-UK (62% people with dementia and 23% carers were male) and 219 to TAU (52% people with dementia and 32% carers were male). At the 26 weeks follow-up, data were available for 364 pairs (77.8%). The BADLS score at 26 weeks did not differ significantly between groups (adjusted mean difference estimate 0.35, 95% CI -0.81 to 1.51; p = 0.55). Secondary outcomes did not differ between the groups. In total, 91% of the activity-based goals set by the pairs taking part in the COTiD-UK intervention were fully or partially achieved by the final COTiD-UK session. Study limitations include the following: Intervention fidelity was moderate but varied across and within sites, and the reliance on primarily proxy data focused on measuring the level of functional or cognitive impairment which may not truly reflect the actual performance and views of the person living with dementia. CONCLUSIONS: Providing community occupational therapy as delivered in this study did not improve ADL performance, cognition, quality of life, or mood in people with dementia nor sense of competence or mood in family carers. Future research should consider measuring person-centred outcomes that are more meaningful and closely aligned to participants' priorities, such as goal achievement or the quantity and quality of activity engagement and participation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10748953.

The economic costs of child maltreatment in UK.

Child maltreatment is a major public health problem with significant consequences for individual victims and for society. In this paper, we quantify for the first time the economic costs of fatal and nonfatal child maltreatment in the UK in relation to several short-, medium-, and long-term outcomes ranging from physical and mental health problems to labor market outcomes and welfare use. We combine novel regression analysis of rich data from the National Child Development Study and the English Longitudinal Study of Aging with secondary evidence to produce an incidence-based estimate of the lifetime costs of child maltreatment from a societal perspective. The discounted average lifetime incidence cost of nonfatal child maltreatment by a primary caregiver is estimated at £89,390 (95% uncertainty interval £44,896 to £145,508); the largest contributors to this are costs from social care, short-term health, and long-term labor market outcomes. The discounted lifetime cost per death from child maltreatment is estimated at £940,758, comprising health care and lost productivity costs. Our estimates provide the first comprehensive benchmark to quantify the costs of child maltreatment in the UK and the benefits of interventions aimed at reducing or preventing it.

Centralising acute stroke care within clinical practice in the Netherlands: lower bounds of the causal impact.

BACKGROUND: Authors in previous studies demonstrated that centralising acute stroke care is associated with an increased chance of timely Intra-Venous Thrombolysis (IVT) and lower costs compared to care at community hospitals. In this study we estimated the lower bound of the causal impact of centralising IVT on health and cost outcomes within clinical practice in the Northern Netherlands. METHODS: We used observational data from 267 and 780 patients in a centralised and decentralised system, respectively. The original dataset was linked to the hospital information systems. Literature on healthcare costs and Quality of Life (QoL) values up to 3 months post-stroke was searched to complete the input. We used Synthetic Control Methods (SCM) to counter selection bias. Differences in SCM outcomes included 95% Confidence Intervals (CI). To deal with unobserved heterogeneity we focused on recently developed methods to obtain the lower bounds of the causal impact. RESULTS: Using SCM to assess centralising acute stroke 3 months post-stroke revealed healthcare savings of $US 1735 (CI, 505 to 2966) while gaining 0.03 (CI, - 0.01 to 0.73) QoL per patient. The corresponding lower bounds of the causal impact are $US 1581 and 0.01. The dominant effect remained stable in the deterministic sensitivity analyses with $US 1360 (CI, 476 to 2244) as the most conservative estimate. CONCLUSIONS: In this study we showed that a centralised system for acute stroke care appeared both cost-saving and yielded better health outcomes. The results are highly relevant for policy makers, as this is the first study to address the issues of selection and unobserved heterogeneity in the evaluation of centralising acute stroke care, hence presenting causal estimates for budget decisions.

Cost-comparison analysis of FIB-4, ELF and fibroscan in community pathways for non-alcoholic fatty liver disease.

BACKGROUND: The identification of patients with advanced liver fibrosis secondary to non-alcoholic fatty liver disease (NAFLD) remains challenging. Using non-invasive liver fibrosis tests (NILT) in primary care may permit earlier detection of patients with clinically significant disease for specialist review, and reduce unnecessary referral of patients with mild disease. We constructed an analytical model to assess the clinical and cost differentials of such strategies. METHODS: A probabilistic decisional model simulated a cohort of 1000 NAFLD patients over 1 year from a healthcare payer perspective. Simulations compared standard care (SC) (scenario 1) to: Scenario 2: FIB-4 for all patients followed by Enhanced Liver Fibrosis (ELF) test for patients with indeterminate FIB-4 results; Scenario 3: FIB-4 followed by fibroscan for indeterminate FIB-4; Scenario 4: ELF alone; and Scenario 5: fibroscan alone. Model estimates were derived from the published literature. The primary outcome was cost per case of advanced fibrosis detected. RESULTS: Introduction of NILT increased detection of advanced fibrosis over 1 year by 114, 118, 129 and 137% compared to SC in scenarios 2, 3, 4 and 5 respectively with reduction in unnecessary referrals by 85, 78, 71 and 42% respectively. The cost per case of advanced fibrosis (METAVIR ≥F3) detected was £25,543, £8932, £9083, £9487 and £10,351 in scenarios 1, 2, 3, 4 and 5 respectively. Total budget spend was reduced by 25.2, 22.7, 15.1 and 4.0% in Scenarios 2, 3, 4 and 5 compared to £670 K at baseline. CONCLUSION: Our analyses suggest that the use of NILT in primary care can increases early detection of advanced liver fibrosis and reduce unnecessary referral of patients with mild disease and is cost efficient. Adopting a two-tier approach improves resource utilization.

Obstetric brachial plexus injuries (OBPIs): health-related quality of life in affected adults and parents.

BACKGROUND: Obstetric brachial plexus injuries (OBPIs) are rare but can have significant implications for those affected, their caregivers and the health system. Symptoms can range from restricted movement to complete paralysis of the arm. We investigated health-related quality of life in adults with OBPIs and parents of children with permanent OBPIs, compared these with population norms, and investigated whether certain socio-demographic or clinical factors were associated with the quality of life in these cohorts. METHODS: A cross-sectional study examined 50 affected adults and 78 parents. Participants completed EQ-5D-5 L and characteristics questionnaires. EQ-5D-5 L responses were mapped onto an EQ-5D-3 L value set to generate utility scores. Mean utility scores were compared with English population norms. Univariable and multivariable linear regression models were conducted to assess for associations between participant characteristics and the utility scores. RESULTS: The overall mean utility scores for affected adults and parents were 0.56 (SD 0.28) and 0.80 (SD 0.19) respectively. Affected adults (95% CI (- 0.38, - 0.22), p < 0.001) and parents of children with permanent OBPIs (95% CI (- 0.10, - 0.02), p = 0.007) had lower mean utility scores, and therefore quality of life, compared to English population norms. For affected adults, previous OBPI surgery (95% CI (0.01, 0.25), p = 0.040), employment in non-manual work (95% CI (0.06, 0.30), p = 0.005) and having a partner (95% CI (0.04, 0.25), p = 0.009) appeared to be positively associated with the utility score. Affected adults receiving disability benefits related to OBPIs appeared to have worse utility scores than those not receiving any disability benefits (95% CI (- 0.31, - 0.06), p = 0.005). For parents, employment was associated with better utility scores (95% CI (0.02, 0.20), p = 0.024) but the presence of one or more medical condition appeared to be associated with worse utility scores (95% CI (- 0.16, - 0.04), p = 0.001). CONCLUSIONS: Adults with OBPIs and parents of children with permanent OBPIs reported worse utility scores, and therefore quality of life, compared to the English general population. We also identified certain characteristics as possible factors to consider when dealing with utility scores in these cohorts. The utility scores in this study can be used in future economic evaluations related to OBPIs.

Impact and experiences of delayed discharge: A mixed-studies systematic review.

BACKGROUND: The impact of delayed discharge on patients, health-care staff and hospital costs has been incompletely characterized. AIM: To systematically review experiences of delay from the perspectives of patients, health professionals and hospitals, and its impact on patients' outcomes and costs. METHODS: Four of the main biomedical databases were searched for the period 2000-2016 (February). Quantitative, qualitative and health economic studies conducted in OECD countries were included. RESULTS: Thirty-seven papers reporting data on 35 studies were identified: 10 quantitative, 8 qualitative and 19 exploring costs. Seven of ten quantitative studies were at moderate/low methodological quality; 6 qualitative studies were deemed reliable; and the 19 studies on costs were of moderate quality. Delayed discharge was associated with mortality, infections, depression, reductions in patients' mobility and their daily activities. The qualitative studies highlighted the pressure to reduce discharge delays on staff stress and interprofessional relationships, with implications for patient care and well-being. Extra bed-days could account for up to 30.7% of total costs and cause cancellations of elective operations, treatment delay and repercussions for subsequent services, especially for elderly patients. CONCLUSIONS: The poor quality of the majority of the research means that implications for practice should be cautiously made. However, the results suggest that the adverse effects of delayed discharge are both direct (through increased opportunities for patients to acquire avoidable ill health) and indirect, secondary to the pressures placed on staff. These findings provide impetus to take a more holistic perspective to addressing delayed discharge.

Mixed methods evaluation of the Getting it Right First Time programme - improvements to NHS orthopaedic care in England: study protocol.

BACKGROUND: Orthopaedic procedures, such as total hip replacement and total knee replacement, are among the commonest surgical procedures in England. The Getting it Right First Time project (GIRFT) aims to deliver improvements in quality and reductions in the cost of NHS orthopaedic care across the country. We will examine whether the planned changes have delivered improvements in the quality of care and patient outcomes. We will also study the processes involved in developing and implementing changes to care, and professional and organisational factors influencing these processes. In doing so, we will identify lessons to guide future improvement work in other services. METHODS/DESIGN: We will evaluate the implementation of the GIRFT programme, and its impact on outcomes and cost, using a mixed methods design. Qualitative methods will be used to understand the programme theory underlying the approach and study the effect of the intervention on practice, using a case study approach. This will include an analysis of the central GIRFT programme and local provider responses. Data will be collected via semi-structured interviews, non-participant observation, and documentary analysis. Quantitative methods will be used to examine 'what works and at what cost?' We will also conduct focus groups with patients and members of the public to explore their perceptions of the GIRFT programme. The research will draw on theories of adoption, diffusion, and sustainability of innovation; its characteristics; and contextual factors at provider-level that influence implementation. DISCUSSION: We will identify generalisable lessons to inform the organisation and delivery of future improvement programmes, to optimise their implementation and impact, both within the UK and internationally. Potential challenges involved in conducting the evaluation include the phased implementation of the intervention in different provider organisations; the inclusion of both retrospective and prospective components; and the effects of ongoing organisational turbulence in the English NHS. However, these issues reflect the realities of service change and its evaluation.

The cost of local, multi-professional obstetric emergencies training.

INTRODUCTION: We aim to outline the annual cost of setting up and running a standard, local, multi-professional obstetric emergencies training course, PROMPT (PRactical Obstetric Multi-Professional Training), at Southmead Hospital, Bristol, UK - a unit caring for approximately 6500 births per year. MATERIAL AND METHODS: A retrospective, micro-costing analysis was performed. Start-up costs included purchasing training mannequins and teaching props, printing of training materials and assembly of emergency boxes (real and training). The variable costs included administration time, room hire, additional printing and the cost of releasing all maternity staff in the unit, either as attendees or trainers. Potential, extra start-up costs for maternity units without established training were also included. RESULTS: The start-up costs were €5574 and the variable costs for 1 year were €143 232. The total cost of establishing and running training at Southmead for 1 year was €148 806. Releasing staff as attendees or trainers accounted for 89% of the total first year costs, and 92% of the variable costs. The cost of running training in a maternity unit with around 6500 births per year was approximately €23 000 per 1000 births for the first year and around €22 000 per 1000 births in subsequent years. CONCLUSIONS: The cost of local, multi-professional obstetric emergencies training is not cheap, with staff costs potentially representing over 90% of the total expenditure. It is therefore vital that organizations consider the clinical effectiveness of local training packages before implementing them, to ensure the optimal allocation of finite healthcare budgets.

Cost-Utility Analysis of Mechanical Thrombectomy Using Stent Retrievers in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Recently, 5 randomized controlled trials demonstrated the benefit of endovascular therapy compared with intravenous tissue-type plasminogen activator in acute stroke. Economic evidence evaluating stent retrievers is limited. We compared the cost-effectiveness of intravenous tissue-type plasminogen activator alone versus mechanical thrombectomy and intravenous tissue-type plasminogen activator as a bridging therapy in eligible patients in the UK National Health Service. METHODS: A model-based cost-utility analysis was performed using a lifetime horizon. A Markov model was constructed and populated with probabilities, outcomes, and cost data from published sources, including 1-way and probabilistic sensitivity analysis. RESULTS: Mechanical thrombectomy was more expensive than intravenous tissue-type plasminogen activator, but it improved quality-adjusted life expectancy. The incremental cost per (quality-adjusted life year) gained of mechanical thrombectomy over a 20 year period was $11 651 (£7061). The probabilistic sensitivity analysis demonstrated that thrombectomy had a 100% probability of being cost-effective at the minimum willingness to pay for a quality-adjusted life year commonly used in United Kingdom. CONCLUSIONS: Although the upfront costs of thrombectomy are high, the potential quality-adjusted life year gains mean this intervention is cost-effective. This is an important factor for consideration in deciding whether to commission this intervention.

Patient and public involvement: how much do we spend and what are the benefits?

BACKGROUND AND OBJECTIVES: Patient and public involvement (PPI) is seen as a way of helping to shape health policy and ensure a patient-focused health-care system. While evidence indicates that PPI can improve health-care decision making, it also consumes monetary and non-monetary resources. Given the financial climate, it is important to start thinking about the costs and benefits of PPI and how to evaluate it in economic terms. DESIGN: We conducted a literature review to assess the potential benefits and costs of involvement and the challenges in carrying out an economic evaluation of PPI. RESULTS: The benefits of PPI include effects on the design of new projects or services, on NHS governance, on research design and implementation and on citizenship and equity. Economic evaluation of PPI activities is limited. The lack of an appropriate analytical framework, data recording and understanding of the potential costs and benefits of PPI, especially from participants' perspectives, represent serious constraints on the full evaluation of PPI. CONCLUSIONS: By recognizing the value of PPI, health-care providers and commissioners can embed it more effectively within their organizations. Better knowledge of costs may prompt organizations to effectively plan, execute, evaluate and target resources. This should increase the likelihood of more meaningful activity, avoid tokenism and enhance organizational efficiency and reputation.

REMOTE-ILD study: Description of the protocol for a multicentre, 12-month randomised controlled trial to assess the clinical and cost-effectiveness of remote monitoring of spirometry and pulse oximetry in patients with interstitial lung disease.

INTRODUCTION: Remote monitoring of home physiological measurements has been proposed as a solution to support patients with chronic diseases as well as facilitating virtual consultations and pandemic preparedness for the future. Daily home spirometry and pulse oximetry have been demonstrated to be safe and acceptable to patients with interstitial lung disease (ILD) but there is currently limited evidence to support its integration into clinical practice. AIM: Our aim is to understand the clinical utility of frequent remote physiological measurements in ILD and the impact of integrating these into clinical practice from a patient, clinical and health economic perspective. METHODS AND ANALYSIS: 132 patients with fibrotic ILD will be recruited and randomised to receive either usual care with remote digital monitoring of home spirometry and pulse oximetry or usual care alone for 12 months. All participants will complete health-related quality of life and experience questionnaires.The primary outcome compares the availability of spirometry measurements within the 2 weeks preceding planned clinic appointments. Secondary outcomes will explore other aspects of clinical and cost-effectiveness of the remote monitoring programme. ETHICS AND DISSEMINATION: The study has been approved by the Camden and Kings Cross Research Ethics Committee (22/LO/0309). All participants will provide informed consent.This study is registered with www. CLINICALTRIALS: gov (NCT05662124).The results of the study will be submitted for presentation at regional and national conferences and submitted for peer-reviewed publication. Reports will be prepared for study participants with the support from our public involvement representatives through the charity Action for Pulmonary Fibrosis.

Cost-Effectiveness of Whole-Genome vs Whole-Exome Sequencing Among Children With Suspected Genetic Disorders.

Importance: The diagnosis of rare diseases and other genetic conditions can be daunting due to vague or poorly defined clinical features that are not recognized even by experienced clinicians. Next-generation sequencing technologies, such as whole-genome sequencing (WGS) and whole-exome sequencing (WES), have greatly enhanced the diagnosis of genetic diseases by expanding the ability to sequence a large part of the genome, rendering a cost-effectiveness comparison between them necessary. Objective: To assess the cost-effectiveness of WGS compared with WES and conventional testing in children with suspected genetic disorders. Design, Setting, and Participants: In this economic evaluation, a bayesian Markov model was implemented from January 1 to June 30, 2023. The model was developed using data from a cohort of 870 pediatric patients with suspected genetic disorders who were enrolled and underwent testing in the Ospedale Pediatrico Bambino Gesù, Rome, Italy, from January 1, 2015, to December 31, 2022. The robustness of the model was assessed through probabilistic sensitivity analysis and value of information analysis. Main Outcomes and Measures: Overall costs, number of definitive diagnoses, and incremental cost-effectiveness ratios per diagnosis were measured. The cost-effectiveness analyses involved 4 comparisons: first-tier WGS with standard of care; first-tier WGS with first-tier WES; first-tier WGS with second-tier WES; and first-tier WGS with second-tier WGS. Results: The ages of the 870 participants ranged from 0 to 18 years (539 [62%] girls). The results of the analysis suggested that adopting WGS as a first-tier strategy would be cost-effective compared with all other explored options. For all threshold levels above €29 800 (US $32 408) per diagnosis that were tested up to €50 000 (US $54 375) per diagnosis, first-line WGS vs second-line WES strategy (ie, 54.6%) had the highest probability of being cost-effective, followed by first-line vs second-line WGS (ie, 54.3%), first-line WGS vs the standard of care alternative (ie, 53.2%), and first-line WGS vs first-line WES (ie, 51.1%). Based on sensitivity analyses, these estimates remained robust to assumptions and parameter uncertainty. Conclusions and Relevance: The findings of this economic evaluation encourage the development of policy changes at various levels (ie, macro, meso, and micro) of international health systems to ensure an efficient adoption of WGS in clinical practice and its equitable access.

Do engagement and behavioural mechanisms underpin the effectiveness of the Drink Less app?

This is a process evaluation of a large UK-based randomised controlled trial (RCT) (n = 5602) evaluating the effectiveness of recommending an alcohol reduction app, Drink Less, compared with usual digital care in reducing alcohol consumption in increasing and higher risk drinkers. The aim was to understand whether participants' engagement ('self-reported adherence') and behavioural characteristics were mechanisms of action underpinning the effectiveness of Drink Less. Self-reported adherence with both digital tools was over 70% (Drink Less: 78.0%, 95% CI = 77.6-78.4; usual digital care: 71.5%, 95% CI = 71.0-71.9). Self-reported adherence to the intervention (average causal mediation effect [ACME] = -0.250, 95% CI = -0.42, -0.11) and self-monitoring behaviour (ACME = -0.235, 95% CI = -0.44, -0.03) both partially mediated the effect of the intervention (versus comparator) on alcohol reduction. Following the recommendation (self-reported adherence) and the tracking (self-monitoring behaviour) feature of the Drink Less app appear to be important mechanisms of action for alcohol reduction among increasing and higher risk drinkers.

Effectiveness of a smartphone app (Drink Less) versus usual digital care for reducing alcohol consumption among increasing-and-higher-risk adult drinkers in the UK: a two-arm, parallel-group, double-blind, randomised controlled trial.

Background: Digital interventions, including apps and websites, can be effective for reducing alcohol consumption. However, many are not evidence- or theory-informed and have not been evaluated. We tested the effectiveness of the Drink Less app for reducing alcohol consumption compared with usual digital care in the UK. Methods: In this two-arm, parallel group, double-blind, randomised controlled trial, we enrolled increasing-and-higher-risk drinkers (AUDIT ≥ 8) in the UK, who were motivated to reduce their alcohol consumption and willing to use a digital intervention to do so, via online methods. Participants were randomly assigned (1:1), using an online algorithm, to receive a web link to download the Drink Less app (intervention) or to the NHS alcohol advice webpage (usual digital care). Researchers were masked to group allocation. Participants were followed up at one, three and six months. The primary outcome was self-reported weekly alcohol consumption at six months, adjusting for baseline consumption. The full analytic sample was used in most analyses, though missing data was treated in different ways. The primary, pre-registered intention-to-treat analysis assumed baseline-carried-forwards. Secondary pre-registered analyses also focused on the full analytic sample and used alternatives including multiple imputation and last observation carried forwards. This trial is registered with the ISRCTN registry, ISRCTN64052601. Findings: Between 07/13/2020 and 03/29/2022, 5602 people were randomly assigned to the Drink Less app (n = 2788) or comparator (n = 2814) groups. Six-month follow-up rates were 79% and 80%, respectively. The primary pre-registered conservative intention-to-treat approach assuming non-responders were drinking at baseline levels of consumption, found a non-significant greater reduction of 0.98 units in weekly alcohol consumption in the intervention group at 6-month follow-up (95% CI -2.67 to 0.70). The data were insensitive to detect the hypothesised effect (Bayes factor = 1.17). Data were not missing completely at random, with 6-month follow-up rates differing in terms of education, occupation, and income. We therefore conducted the pre-registered sensitivity analysis using multiple imputation, showing that the Drink Less app resulted in a 2.00-unit greater weekly reduction at 6-month follow-up compared with the NHS alcohol advice webpage (95% CI -3.76 to -0.24). Fewer than 0.1% of participants in both arms who responded to one, three or six-month follow-up reported adverse events linked to participation in the trial. Interpretation: The Drink Less app may be effective in reducing the alcohol consumption in increasing-and-higher-risk drinkers motivated to reduce their consumption. Funding: NIHR Public Health Research Programme.