Feasibility, safety, and patient acceptability of electronic inspiratory muscle training in patients who require prolonged mechanical ventilation in the intensive care unit: A dual-centre observational study.

BACKGROUND: Inspiratory muscle training (IMT) is an intervention that can be used to rehabilitate the respiratory muscle deconditioning experienced by patients with critical illness, requiring prolonged mechanical ventilation. Clinicians are currently using mechanical threshold IMT devices that have limited resistance ranges. OBJECTIVES: The objective of this study was to evaluate the safety, feasibility, and acceptability of using an electronic device to facilitate IMT with participants requiring prolonged mechanical ventilation. METHOD: A dual-centre observational cohort study, with convenience sampling, was conducted at two tertiary intensive care units. Daily training supervised by intensive care unit physiotherapists was completed with the electronic IMT device. A priori definitions for feasibility, safety, and acceptability were determined. Feasibility was defined as more than 80% of planned sessions completed. Safety was defined as no major adverse events and less than 3% minor adverse event rate, and acceptability was evaluated following the acceptability of intervention framework principles. RESULTS: Forty participants completed 197 electronic IMT treatment sessions. Electronic IMT was feasible, with 81% of planned sessions completed. There were 10% minor adverse events and no major adverse events. All the minor adverse events were transient without clinical consequences. All the participants who recalled completing electronic IMT sessions reported that the training was acceptable. Acceptability was demonstrated; over 85% of participants reported that electronic IMT was either helpful or beneficial and that electronic IMT assisted their recovery. CONCLUSION: Electronic IMT is feasible and acceptable to complete with critically ill participants who require prolonged mechanical ventilation. As all minor adverse events were transient without clinical consequences, electronic IMT can be considered a relatively safe intervention with patients who require prolonged mechanical ventilation.

A methodology for projecting the return on investment of training technologies.

Each year significant tax dollars are spent on the development of new technologies to increase efficiency and/or reduce costs of military training. However, there are currently no validated methods or measures to quantify the return on investment for adopting these new technologies for military training. Estimating the return on investment (ROI) for training technology adoption involves 1) developing a methodology or framework, 2) validating measures and methods, and 3) assessing predictive validity. The current paper describes a projective methodology using the Kirkpatrick framework to compare projected tangible and intangible benefits against tangible and intangible costs to estimate future ROI. The use-case involved an advanced technology demonstration in which sixty aircrew participated in a series of live, virtual, and constructive (LVC) exercises over a five-week period. Participants evaluated the technology's potential costs and benefits according to the Kirkpatrick framework of training program evaluation, and analyses resulted in a nominal projection of $488 million dollars saved, significant enhancements in large-force proficiency, and 1.4 lives saved over ten years at an implementation rate of 0.5% of budgeted flight hours. A discussion of theoretical implications, data-based limitations, and recommendations for future research are provided.

Trajectories of Child Cognitive and Socioemotional Development and Associations with Adolescent Health in the UK Millennium Cohort Study.

OBJECTIVE: To identify and describe distinct trajectories of cognitive and socioemotional development during childhood and to examine their relationships with adolescent health. STUDY DESIGN: We used group-based multitrajectory modeling applied to longitudinal data on 11 564 children up to age 14 years from the UK Millennium Cohort study to identify trajectories of cognitive and socioemotional development measured using validated instruments. We assessed associations between the derived trajectories and baseline socioeconomic, parental, and school factors using multinomial regression. Logistic regression was used to assess associations between trajectory groups and adolescent health at age 14 and 17 years. RESULTS: Four child development trajectories were identified: "no problems" (76.5%); "late socio-emotional problems" (10.1%); "early cognitive and socioemotional problems" (8.6%); and "persistent cognitive and socioemotional problems" (4.8%). Those in the problem trajectories were more socioeconomically disadvantaged. Compared with the "no problem" trajectory, the "late socioemotional problems" trajectory had increased odds of overweight and mental ill-health at age 14 years of 1.50 (95% CI 1.24-1.81) and 2.51 (2.03-3.10), respectively. For the "persistent problems" group, the OR for overweight was 1.41 (1.04-1.91), and for mental ill-health, 3.01 (2.10-3.30). For both groups, the associations persisted to age 17 years. CONCLUSIONS: In a representative UK cohort, groups of distinct trajectories of cognitive and socioemotional development were identified. Adverse development, if unresolved, can have a negative impact on weight and mental health in adolescence. Socioemotional development was the main driver of the impact on adolescent health and this requires emphasis in child health policy.

Guidance on the use of complex systems models for economic evaluations of public health interventions.

To help health economic modelers respond to demands for greater use of complex systems models in public health. To propose identifiable features of such models and support researchers to plan public health modeling projects using these models. A working group of experts in complex systems modeling and economic evaluation was brought together to develop and jointly write guidance for the use of complex systems models for health economic analysis. The content of workshops was informed by a scoping review. A public health complex systems model for economic evaluation is defined as a quantitative, dynamic, non-linear model that incorporates feedback and interactions among model elements, in order to capture emergent outcomes and estimate health, economic and potentially other consequences to inform public policies. The guidance covers: when complex systems modeling is needed; principles for designing a complex systems model; and how to choose an appropriate modeling technique. This paper provides a definition to identify and characterize complex systems models for economic evaluations and proposes guidance on key aspects of the process for health economics analysis. This document will support the development of complex systems models, with impact on public health systems policy and decision making.

"Stick or Twist?" Negotiating Price and Data in an Era of Conditional Approval.

BACKGROUND: Changes in the regulatory context enable faster approval of transformative medicines. They also lead to health technology assessment (HTA) agencies having to make decisions with less evidence. In response, HTA agencies have also initiated forms of conditional approval. When the evidence base for a new oncology treatment leaves substantial uncertainty, the new Cancer Drugs Fund allows the National Institute for Heath and Care Excellence to give the manufacturer two options: (1) offer a low price based on conservative assumptions and obtain immediate approval ("stick") or (2) wait until the evidence base has further matured before finalizing a potentially higher agreed price ("twist"). OBJECTIVES: The purpose of this article is to explain how, using the theoretical framework of the expected value of sample information, simulation methods can help inform a manufacturer's decisions when faced with the option to stick or twist. METHODS: We first summarize a general model to help frame the manufacturer's negotiating strategy. We then use a motivating case study, based on a hypothetical immunotherapy, to illustrate how manufacturers can use simulation methods to robustly characterize the uncertainty inherent to further data collection and incorporate this uncertainty within their decision making. RESULTS: Our approach allows us to estimate the commercial value of generating additional data (the difference between the estimated net present value of stick and twist). We test the sensitivity of the results to different assumptions via scenario analyses. CONCLUSIONS: This article shows that simulation methods can be used to help pharmaceutical managers make informed strategic decisions in contexts of uncertainty.

Value of Information Analytical Methods: Report 2 of the ISPOR Value of Information Analysis Emerging Good Practices Task Force.

The allocation of healthcare resources among competing priorities requires an assessment of the expected costs and health effects of investing resources in the activities and of the opportunity cost of the expenditure. To date, much effort has been devoted to assessing the expected costs and health effects, but there remains an important need to also reflect the consequences of uncertainty in resource allocation decisions and the value of further research to reduce uncertainty. Decision making with uncertainty may turn out to be suboptimal, resulting in health loss. Consequently, there may be value in reducing uncertainty, through the collection of new evidence, to better inform resource decisions. This value can be quantified using value of information (VOI) analysis. This report from the ISPOR VOI Task Force describes methods for computing 4 VOI measures: the expected value of perfect information, expected value of partial perfect information (EVPPI), expected value of sample information (EVSI), and expected net benefit of sampling (ENBS). Several methods exist for computing EVPPI and EVSI, and this report provides guidance on selecting the most appropriate method based on the features of the decision problem. The report provides a number of recommendations for good practice when planning, undertaking, or reviewing VOI analyses. The software needed to compute VOI is discussed, and areas for future research are highlighted.

Value of Information Analysis for Research Decisions-An Introduction: Report 1 of the ISPOR Value of Information Analysis Emerging Good Practices Task Force.

Healthcare resource allocation decisions made under conditions of uncertainty may turn out to be suboptimal. In a resource constrained system in which there is a fixed budget, these suboptimal decisions will result in health loss. Consequently, there may be value in reducing uncertainty, through the collection of new evidence, to make better resource allocation decisions. This value can be quantified using a value of information (VOI) analysis. This report, from the ISPOR VOI Task Force, introduces VOI analysis, defines key concepts and terminology, and outlines the role of VOI for supporting decision making, including the steps involved in undertaking and interpreting VOI analyses. The report is specifically aimed at those tasked with making decisions about the adoption of healthcare or the funding of healthcare research. The report provides a number of recommendations for good practice when planning, undertaking, or reviewing the results of VOI analyses.

Computing the Expected Value of Sample Information Efficiently: Practical Guidance and Recommendations for Four Model-Based Methods.

Value of information (VOI) analyses can help policy makers make informed decisions about whether to conduct and how to design future studies. Historically a computationally expensive method to compute the expected value of sample information (EVSI) restricted the use of VOI to simple decision models and study designs. Recently, 4 EVSI approximation methods have made such analyses more feasible and accessible. Members of the Collaborative Network for Value of Information (ConVOI) compared the inputs, the analyst's expertise and skills, and the software required for the 4 recently developed EVSI approximation methods. Our report provides practical guidance and recommendations to help inform the choice between the 4 efficient EVSI estimation methods. More specifically, this report provides: (1) a step-by-step guide to the methods' use, (2) the expertise and skills required to implement the methods, and (3) method recommendations based on the features of decision-analytic problems.

Learning across the UK: a review of public health systems and policy approaches to early child development since political devolution.

BACKGROUND: Giving children the best start in life is critical for their future health and wellbeing. Political devolution in the UK provides a natural experiment to explore how public health systems contribute to children's early developmental outcomes across four countries. METHOD: A systematic literature review and input from a stakeholder group was used to develop a public health systems framework. This framework then informed analysis of public health policy approaches to early child development. RESULTS: A total of 118 studies met the inclusion criteria. All national policies championed a 'prevention approach' to early child development. Political factors shaped divergence, with variation in national conceptualizations of child development ('preparing for life' versus 'preparing for school') and pre-school provision ('universal entitlement' or 'earned benefit'). Poverty and resourcing were identified as key system factors that influenced outcomes. Scotland and Wales have enacted distinctive legislation focusing on wider determinants. However, this is limited by the extent of devolved powers. CONCLUSION: The systems framework clarifies policy complexity relating to early child development. The divergence of child development policies in the four countries and, particularly, the explicit recognition in Scottish and Welsh policy of wider determinants, creates scope for this topic to be a tracer area to compare UK public health systems longer term.

A software architecture for mechanism-based social systems modelling in agent-based simulation models.

This paper introduces the MBSSM (Mechanism-Based Social Systems Modelling) software architecture that is designed for expressing mechanisms of social theories with individual behaviour components in a unified way and implementing these mechanisms in an agent-based simulation model. The MBSSM architecture is based on a middle-range theory approach most recently expounded by analytical sociology and is designed in the object-oriented programming paradigm with Unified Modelling Language diagrams. This paper presents two worked examples of using the architecture for modelling individual behaviour mechanisms that give rise to the dynamics of population-level alcohol use: a single-theory model of norm theory and a multi-theory model that combines norm theory with role theory. The MBSSM architecture provides a computational environment within which theories based on social mechanisms can be represented, compared, and integrated. The architecture plays a fundamental enabling role within a wider simulation model-based framework of abductive reasoning in which families of theories are tested for their ability to explain concrete social phenomena.

27 years of prenatal diagnosis for Huntington disease in the United Kingdom.

PURPOSE: There is little long-term, population-based data on uptake of prenatal diagnosis for Huntington disease (HD), a late-onset autosomal dominant neurodegenerative disorder, and the effect of the availability of preimplantation genetic diagnosis (PGD) on families' decisions about conventional prenatal diagnosis is not known. We report trends in prenatal diagnosis and preimplantation diagnosis for HD in the United Kingdom since services commenced. METHODS: Long-term UK-wide prospective case record-based service evaluation in 23 UK Regional Genetic Centres 1988-2015, and four UK PGD centers 2002-2015. RESULTS: From 1988 to 2015, 479 prenatal diagnoses were performed in the UK for HD. An exclusion approach was used in 150 (31%). The annual rate of HD prenatal diagnosis has remained around 18 (3.5/million) over 27 years, despite a steady increase in the use of PGD for HD since 2002. CONCLUSION: Although increasing number of couples are choosing either direct or exclusion PGD to prevent HD in their offspring, both direct and exclusion prenatal diagnosis remain important options in a health system where both PGD and prenatal diagnosis are state funded. At-risk couples should be informed of all options available to them, preferably prepregnancy.

Valuing breastfeeding: a qualitative study of women's experiences of a financial incentive scheme for breastfeeding.

BACKGROUND: A cluster randomised controlled trial of a financial incentive for breastfeeding conducted in areas with low breastfeeding rates in the UK reported a statistically significant increase in breastfeeding at 6-8 weeks. In this paper we report an analysis of interviews with women eligible for the scheme, exploring their experiences and perceptions of the scheme and its impact on breastfeeding to support the interpretation of the results of the trial. METHODS: Semi-structured interviews were carried out with 35 women eligible for the scheme during the feasibility and trial stages. All interviews were recorded and verbatim transcripts analysed using a Framework Analysis approach. RESULTS: Women reported that their decisions about infant feeding were influenced by the behaviours and beliefs of their family and friends, socio-cultural norms and by health and practical considerations. They were generally positive about the scheme, and felt valued for the effort involved in breastfeeding. The vouchers were frequently described as a reward, a bonus and something to look forward to, and helping women keep going with their breastfeeding. They were often perceived as compensation for the difficulties women encountered during breastfeeding. The scheme was not thought to make a difference to mothers who were strongly against breastfeeding. However, women did believe the scheme would help normalise breastfeeding, influence those who were undecided and help women to keep going with breastfeeding and reach key milestones e.g. 6 weeks or 3 months. CONCLUSIONS: The scheme was acceptable to women, who perceived it as rewarding and valuing them for breastfeeding. Women reported that the scheme could raise awareness of breastfeeding and encourage its normalisation. This provides a possible mechanism of action to explain the results of the trial. TRIAL REGISTRATION: The trial is registered with the ISRCTN registry, number 44898617 , https://www.isrctn.com.

Predictive testing of minors for Huntington's disease: The UK and Netherlands experiences.

A consistent feature of predictive testing guidelines for Huntington's disease (HD) is the recommendation not to undertake predictive tests on those < 18 years. Exceptions are made but the extent of, and reasons for, deviation from the guidelines are unknown. The UK Huntington's Prediction Consortium has collected data annually on predictive tests undertaken from the 23 UK genetic centers. DNA analysis for HD in the Netherlands is centralized in the Laboratory for Diagnostic Genome Analysis in Leiden. In the UK, 60 tests were performed on minors between 1994 and 2015 representing 0.63% of the total number of tests performed. In the Netherlands, 23 tests were performed on minors between 1997 and 2016. The majority of the tests were performed on those aged 16 and 17 years for both countries (23% and 57% for the UK, and 26% and 57% for the Netherlands). Data on the reasons for testing were identified for 36 UK and 22 Netherlands cases and included: close to the age of 18 years, pregnancy, currently in local authority care and likely to have less support available after 18 years, person never having the capacity to consent and other miscellaneous reasons. This study documents the extent of HD testing of minors in the UK and the Netherlands and suggests that, in general, the recommendation is being followed. We provide some empirical evidence as to reasons why clinicians have departed from the recommendation. We do not advise changing the recommendation but suggest that testing of minors continues to be monitored.

Improving ART programme retention and viral suppression are key to maximising impact of treatment as prevention - a modelling study.

BACKGROUND: UNAIDS calls for fewer than 500,000 new HIV infections/year by 2020, with treatment-as-prevention being a key part of their strategy for achieving the target. A better understanding of the contribution to transmission of people at different stages of the care pathway can help focus intervention services at populations where they may have the greatest effect. We investigate this using Uganda as a case study. METHODS: An individual-based HIV/ART model was fitted using history matching. 100 model fits were generated to account for uncertainties in sexual behaviour, HIV epidemiology, and ART coverage up to 2015 in Uganda. A number of different ART scale-up intervention scenarios were simulated between 2016 and 2030. The incidence and proportion of transmission over time from people with primary infection, post-primary ART-naïve infection, and people currently or previously on ART was calculated. RESULTS: In all scenarios, the proportion of transmission by ART-naïve people decreases, from 70% (61%-79%) in 2015 to between 23% (15%-40%) and 47% (35%-61%) in 2030. The proportion of transmission by people on ART increases from 7.8% (3.5%-13%) to between 14% (7.0%-24%) and 38% (21%-55%). The proportion of transmission by ART dropouts increases from 22% (15%-33%) to between 31% (23%-43%) and 56% (43%-70%). CONCLUSIONS: People who are currently or previously on ART are likely to play an increasingly large role in transmission as ART coverage increases in Uganda. Improving retention on ART, and ensuring that people on ART remain virally suppressed, will be key in reducing HIV incidence in Uganda.

Universal test, treat, and keep: improving ART retention is key in cost-effective HIV control in Uganda.

BACKGROUND: With ambitious new UNAIDS targets to end AIDS by 2030, and new WHO treatment guidelines, there is increased interest in the best way to scale-up ART coverage. We investigate the cost-effectiveness of various ART scale-up options in Uganda. METHODS: Individual-based HIV/ART model of Uganda, calibrated using history matching. 22 ART scale-up strategies were simulated from 2016 to 2030, comprising different combinations of six single interventions (1. increased HIV testing rates, 2. no CD4 threshold for ART initiation, 3. improved ART retention, 4. increased ART restart rates, 5. improved linkage to care, 6. improved pre-ART care). The incremental net monetary benefit (NMB) of each intervention was calculated, for a wide range of different willingness/ability to pay (WTP) per DALY averted (health-service perspective, 3% discount rate). RESULTS: For all WTP thresholds above $210, interventions including removing the CD4 threshold were likely to be most cost-effective. At a WTP of $715 (1 × per-capita-GDP) interventions to improve linkage to and retention/re-enrolment in HIV care were highly likely to be more cost-effective than interventions to increase rates of HIV testing. At higher WTP (> ~ $1690), the most cost-effective option was 'Universal Test, Treat, and Keep' (UTTK), which combines interventions 1-5 detailed above. CONCLUSIONS: Our results support new WHO guidelines to remove the CD4 threshold for ART initiation in Uganda. With additional resources, this could be supplemented with interventions aimed at improving linkage to and/or retention in HIV care. To achieve the greatest reductions in HIV incidence, a UTTK policy should be implemented.

Trends in alcohol-related admissions to hospital by age, sex and socioeconomic deprivation in England, 2002/03 to 2013/14.

BACKGROUND: Prevalence of alcohol-related harms in England are among the highest in Europe and represents an important policy issue. Understanding how alcohol-related trends vary by demographic factors is important for informing policy debates. The aim of our study was to examine trends in alcohol-related admissions to hospital in England, with a focus on variations by sex, age and socioeconomic deprivation. METHODS: We used data on hospital admissions for England for the financial years 2002/03 to 2013/14. Our four main outcome variables were acute and chronic conditions wholly and partially attributable to alcohol consumption. We also looked at four specific conditions wholly attributable to alcohol. Socioeconomic deprivation was measured using the English Indices of Deprivation of a patient's residence (categorised by quintile). We calculated crude rates, age-specific rates (visualised by Lexis plots) and directly standardised rates by deprivation category, separately for males and females. RESULTS: Total admissions for all alcohol-attributable admissions increased from 201,398 in 2002/03 to 303,716 in 2013/14. The relative increase of these admissions was larger than compared to non-alcohol attributable admissions. Acute admissions wholly attributable to alcohol had the largest relative increase of our outcome measures, and displayed a bimodal distribution with higher rates in adolescence/young adults and middle age. Chronic conditions wholly attributable to alcohol were concentrated in middle age (particularly males). While admission rates were generally higher for males, females had higher rates of hospitalisations due to 'Intentional self-poisoning due to alcohol'. We also found evidence of wide social inequalities by level of deprivation, which were wider for men than compared to women across all of our outcome measures other than 'Intentional self-poisoning due to alcohol'. CONCLUSIONS: Our study expands the evidence base to help understand population level trends in alcohol-related admissions by age, sex and socioeconomic deprivation. There have been increasing hospital admissions attributable to alcohol between 2002/03 and 2013/14, particularly concentrated in middle aged males and deprived areas. However, the increase in young females being admitted for 'Intentional self-poisoning due to alcohol' raises additional concerns.

Efficient Value of Information Calculation Using a Nonparametric Regression Approach: An Applied Perspective.

BACKGROUND: Value-of-information (VOI) analysis provides an analytical framework to assess whether obtaining additional evidence is worthwhile to reduce decision uncertainty. The reporting of VOI measures, particularly the expected value of perfect parameter information (EVPPI) and the expected value of sample information (EVSI), is limited because of the computational burden associated with typical two-level Monte-Carlo-based solution. Recently, a nonparametric regression approach was proposed that allows the estimation of multiparameter EVPPI and EVSI directly from a probabilistic sensitivity analysis sample. OBJECTIVES: To demonstrate the value of the nonparametric regression approach in calculating VOI measures in real-world cases and to compare its performance with the standard approach of the Monte-Carlo simulation. METHODS: We used the regression approach to calculate EVPPI and EVSI in two models, and compared the results with the estimates obtained via the standard Monte-Carlo simulation. RESULTS: The VOI values from the two approaches were very close; computation using the regression method, however, was faster. CONCLUSION: The nonparametric regression approach provides an efficient and easy-to-implement alternative for EVPPI and EVSI calculation in economic models.

Patterns of multimorbidity and their association with health outcomes within Yorkshire, England: baseline results from the Yorkshire Health Study.

BACKGROUND: Multimorbidity is increasingly being recognized as a serious public health concern. Research into its determinants, prevalence, and management is needed and as the risk of experiencing multiple chronic conditions increases over time, attention should be given to investigating the development of multimorbidity through prospective cohort design studies. Here we examine the baseline patterns of multimorbidity and their association with health outcomes for residents in Yorkshire, England using data from the Yorkshire Health Study. METHODS: Baseline data from the Yorkshire Health Study (YHS) was collected from 27,806 patients recruited between 2010 and 2012. A two-stage sampling strategy was implemented which first involved recruiting 43 general practice surgeries and then having them consent to mailing invitations to their patients to complete postal or online questionnaires. The questionnaire collected information on chronic health conditions, demographics, health-related behaviours, healthcare and medication usage, and a range of other health related variables. Descriptive statistics (chi-square and t tests) were used to examine associations between these variables and multimorbidity. RESULTS: In the YHS cohort, 10,332 participants (37.2 %) reported having at least two or more long-term health conditions (multimorbidity). Older age, BMI and deprivation were all positively associated with multimorbidity. Nearly half (45.7 %) of participants from the most deprived areas experienced multimorbidity. Based on the weighted sample, average health-related quality of life decreased with the number of health conditions reported; the mean EQ-5D score for participants with no conditions was 0.945 compared to 0.355 for participants with five or more. The mean number of medications used for those without multimorbidity was 1.81 (range 1-13, SD = 1.25) compared to 3.81 (range 1-14, SD = 2.44) for those with at least two long-term conditions and 7.47 (range 1-37, SD = 7.47) for those with 5+ conditions. CONCLUSION: Patterns of multimorbidity within the Yorkshire Health Study support research on multimorbidity within previous observational cross-sectional studies. The YHS provides both a facility for participant recruitment to intervention trials, and a large population-based longitudinal cohort for observational research. It is planned to continue to record chronic conditions and other health related behaviours in future waves which will be useful for examining determinants and trends in chronic disease and multimorbidity.

Encouraging breastfeeding: financial incentives.

The NOSH (Nourishing Start for Health) three-phase research study is testing whether offering financial incentives for breastfeeding improves six-eight-week breastfeeding rates in low-rate areas. This article describes phase one development work, which aimed to explore views about practical aspects of the design of the scheme. Interviews and focus groups were held with women (n = 38) and healthcare providers (n = 53). Overall both preferred shopping vouchers over cash payments, with a total amount of £200-250 being considered a reasonable amount. There was concern that seeking proof of breastfeeding might impact negatively on women and the relationship with their healthcare providers. The most acceptable method to all was that women sign a statement that their baby was receiving breast milk: this was co-signed by a healthcare professional to confirm that they had discussed breastfeeding. These findings have informed the design of the financial incentive scheme being tested in the feasibility phase of the NOSH study.