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Background The Medical Certificate of Stillbirth (MCS) records data about a baby's death after 24 weeks of gestation but before birth. Major errors that could alter interpretation of the MCS were widespread in two UK-based regional studies. Methods A multicentre evaluation was conducted, examining MCS issued 1 January 2018 to 31 December 2018 in 76 UK obstetric units. A systematic case-note review of stillbirths was conducted by Obstetric and Gynaecology trainees, generating individual 'ideal MCSs' and comparing these to the actual MCS issued. Anonymized central data analysis described rates and types of error, agreement and factors associated with major errors. Results There were 1120 MCSs suitable for assessment, with 126 additional submitted data sets unsuitable for accuracy analysis (total 1246 cases). Gestational age demonstrated 'substantial' agreement [K = 0.73 (95% CI 0.70–0.76)]. Primary cause of death (COD) showed 'fair' agreement [K = 0.26 (95% CI 0.24–0.29)]. Major errors [696/1120; 62.1% (95% CI 59.3–64.9%)] included certificates issued for fetal demise at <24 weeks' gestation [23/696; 3.3% (95% CI 2.2–4.9%)] or neonatal death [2/696; 0.3% (95% CI 0.1–1.1%)] or incorrect primary COD [667/696; 95.8% (95% CI 94.1–97.1%)]. Of 540/1246 [43.3% (95% CI 40.6–46.1%)] 'unexplained' stillbirths, only 119/540 [22.0% (95% CI 18.8–25.7%)] remained unexplained; the majority were redesignated as either fetal growth restriction [FGR: 195/540; 36.1% (95% CI 32.2–40.3%)] or placental insufficiency [184/540; 34.1% (95% CI 30.2–38.2)]. Overall, FGR [306/1246; 24.6% (95% CI 22.3–27.0%)] was the leading primary COD after review, yet only 53/306 [17.3% (95% CI 13.5–22.1%)] FGR cases were originally attributed correctly. Conclusion This study demonstrates widespread major errors in MCS completion across the UK. MCS should only be completed following structured case-note review, with particular attention on the fetal growth trajectory. [ABSTRACT FROM AUTHOR]

Motivation Polygenic risk scores (PRSs) predict individuals' genetic risk of developing complex diseases. They summarize the effect of many variants discovered in genome-wide association studies (GWASs). However, to date, large GWASs exist primarily for the European population and the quality of PRS prediction declines when applied to other ethnicities. Genetic profiling of individuals in the discovery set (on which the GWAS was performed) and target set (on which the PRS is applied) is typically done by SNP arrays that genotype a fraction of common SNPs. Therefore, a key step in GWAS analysis and PRS calculation is imputing untyped SNPs using a panel of fully sequenced individuals. The imputation results depend on the ethnic composition of the imputation panel. Imputing genotypes with a panel of individuals of the same ethnicity as the genotyped individuals typically improves imputation accuracy. However, there has been no systematic investigation into the influence of the ethnic composition of imputation panels on the accuracy of PRS predictions when applied to ethnic groups that differ from the population used in the GWAS. Results We estimated the effect of imputation of the target set on prediction accuracy of PRS when the discovery and the target sets come from different ethnic groups. We analyzed binary phenotypes on ethnically distinct sets from the UK Biobank and other resources. We generated ethnically homogenous panels, imputed the target sets, and generated PRSs. Then, we assessed the prediction accuracy obtained from each imputation panel. Our analysis indicates that using an imputation panel matched to the ethnicity of the target population yields only a marginal improvement and only under specific conditions. Availability and implementation The source code used for executing the analyses is this paper is available at https://github.com/Shamir-Lab/PRS-imputation-panels. [ABSTRACT FROM AUTHOR]

Background Older people are often explicitly or implicitly excluded from research, in particular clinical trials. This means that study findings may not be applicable to them, or that older people may not be offered treatments due to an absence of evidence. Aims The aim of this work was to develop recommendations to guide all research relevant to older people. Methods A diverse stakeholder group identified barriers and solutions to including older people in research. In parallel, a rapid literature review of published papers was undertaken to identify existing papers on the inclusion of older people in research. The findings were synthesised and mapped onto a socio-ecological model. From the synthesis we identified themes that were developed into initial recommendations that were iteratively refined with the stakeholder group. Results A range of individual, interpersonal, organisational, community and policy factors impact on the inclusion of older people in research. A total of 14 recommendations were developed such as removing upper age limits and comorbidity exclusions, involving older people, advocates and health and social care professionals with expertise in ageing in designing the research, and considering flexible or alternative approaches to data collection to maximise opportunities for participation. We also developed four questions that may guide those developing, reviewing and funding research that is inclusive of older people. Conclusion Our recommendations provide up to date, practical advice on ways to improve the inclusion of older people in health and care research. [ABSTRACT FROM AUTHOR]

Background Alcohol increases cancer risk, but less is known about public awareness of this link. This scoping review summarizes recent findings on the public awareness of alcohol as a cancer risk factor in European Union and UK. Methods Four databases (Web of Science, MEDLINE, PsycInfo, CINAHL) were searched for papers containing data on awareness of alcohol as cancer risk factor in EU or UK published between January 2017 and December 2022, and complemented with grey literature searches. Results In total, 45 studies were included covering 18 EU countries (Austria, Belgium, Cyprus, Czechia, Denmark, Finland, France, Germany, Hungary, Ireland, Italy, Netherlands, Poland, Romania, Slovakia, Slovenia, Spain, Sweden) and UK, presenting data collected between 2009 and 2022. Studies covered general population (17 studied a nationally representative sample), women, health professionals, patients and young people. Awareness of alcohol causing cancer in general was higher and studied more often than awareness of alcohol's impact on specific cancers. Among the EU general population, awareness of the link between alcohol and breast cancer ranged between 10% and 20%, head and neck cancer 15–25%, colorectal and oesophagus cancer 15–45% and liver cancer 40%. Awareness was higher among young people and specialized health professions and lower among women (the latter specifically for the breast cancer). Conclusions While awareness rates varied depending on the exact question wording, many studies showed low awareness of the alcohol-cancer link, especially for specific types such as breast and colon cancer. Public should be better informed about alcohol consumption-related cancer risk. [ABSTRACT FROM AUTHOR]

Over the past few decades, a small but growing group of people have worked remotely from their homes. With the arrival of the coronavirus pandemic, millions of people found themselves joining this group overnight. In this position paper, we examine the kinds of work that 'went remote' in response to the pandemic, and consider the ways in which this transition was influenced by (and in turn came to influence) contemporary trends in digital workplace measurement and evaluation. We see that employers appeared reluctant to let certain classes of employee work remotely. When the pandemic forced staff home, employers compensated by turning to digital surveillance tools, even though, as we argue, these tools seem unable to overcome the significant conceptual barriers to understanding how people are working. We also observed that, in the United Kingdom context, the pandemic didn't mean remote work for a significant proportion of the population. We assert that, to maximize its impact, 'future of work' research in human-centred computing must be more inclusive and representative of work, rather than focusing on the experiences of knowledge workers and those involved in new forms of work. [ABSTRACT FROM AUTHOR]

As people age they are at increased risk of cardiovascular disease, the leading cause of mortality and morbidity worldwide. Understanding cardiovascular ageing is essential to preserving healthy ageing and preventing serious health outcomes. This collection of papers published in Age and Ageing since 2011 cover key themes in cardiovascular ageing, with a separate collection on stroke and atrial fibrillation planned. Treating high blood pressure remains important as people age and reduces strokes and heart attacks. That said, a more personalised approach to blood pressure may be even more important as people age to lower blood pressure to tight targets where appropriate but avoid overtreatment in vulnerable groups. As people age, more people experience blood pressure drops on standing (orthostatic hypotension), particularly as they become frail. This can predispose them to falls. The papers in this collection provide an insight into blood pressure and orthostatic hypotension. They highlight areas for further research to understand blood pressure changes and management in the ageing population. Inpatient clinical care of older people with heart attacks differs from younger people in UK national audit data. People aged over 80 had improved outcomes in survival after heart attack over time, but had lower rates of specialist input from cardiology compared with younger people. This may partly reflect different clinical presentations, with heart attacks occurring in the context of other health conditions, frailty and multimorbidity. The care and outcomes of acute and chronic cardiovascular disease are impacted by the frailty and health status of an individual at baseline. The research included in this collection reinforces the wide variations in the ageing population and the necessity to focus on the individual needs and priorities, and provide a person-centred multidisciplinary approach to care. [ABSTRACT FROM AUTHOR]

Background COVID-19 brought additional challenges to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) decision-making, which was already a contentious issue. In the UK, reports of poor DNACPR decision-making and communication emerged in 2020, including from the regulator, the Care Quality Commission. This paper explores the experiences of people who discussed DNACPR with a healthcare professional on behalf of a relative during the coronavirus pandemic, with the aim of identifying areas of good practice and what needs to be improved. Methods a total of 39 people participated in semi-structured interviews via video conferencing software or telephone. Data were evaluated using Framework Analysis. Findings results are presented around three main themes: understanding, communication and impact. Participants' understanding about DNACPR was important, as those with better understanding tended to reflect more positively on their discussions with clinicians. The role of relatives in the decision-making process was a frequent source of misunderstanding. Healthcare professionals' communication skills were important. Where discussions went well, relatives were given clear explanations and the opportunity to ask questions. However many relatives felt that conversations were rushed. DNACPR discussions can have a lasting impact—relatives reported them to be significant moments in care journeys. Many relatives perceived that they were asked to decide whether their relative should receive CPR and described enduring emotional consequences, including guilt. Conclusion the pandemic has illuminated deficiencies in current practice around DNACPR discussion, which can have difficult to anticipate and lasting negative consequences for relatives. This research raises questions about the current approach to DNACPR decision-making. [ABSTRACT FROM AUTHOR]

Background vaccination uptake in the UK and increased care home testing are likely affecting care home visitation. With scant scientific evidence to date, the aim of this longitudinal qualitative study was to explore the impact of both (vaccination and testing) on the conduct and experiences of care home visits. Methods family carers of care home residents with dementia and care home staff from across the UK took part in baseline (October/November 2020) and follow-up interviews (March 2021). Public advisers were involved in all elements of the research. Data were analysed using thematic analysis. Results across 62 baseline and follow-up interviews with family carers (n  = 26; 11) and care home staff (n  = 16; 9), five core themes were developed: delayed and inconsistent offers of face-to-face visits; procedures and facilitation of visits; variable uptake of the COVID-19 vaccine; misinformation, education and free choice; frustration and anger among family carers. The variable uptake in staff, compared to family carers, was a key factor seemingly influencing visitation, with a lack of clear guidance leading care homes to implement infection control measures and visitation rights differently. Conclusions we make five recommendations in this paper to enable improved care home visitation in the ongoing, and in future, pandemics. Visits need to be enabled and any changes to visiting rights must be used as a last resort, reviewed regularly in consultation with residents and carers and restored as soon as possible as a top priority, whilst more education needs to be provided surrounding vaccination for care home staff. [ABSTRACT FROM AUTHOR]

In recent years, there has been a risen interest in heat recovery systems for building applications due to concerns about the energy crisis and global climate change. In this paper, the intention to understand the performance of a window thermoelectric heat pump/heat recovery system (Ecopump) for heating has been developed. An overview to the prototype design, heat transfer model, experimental parameters and environmental feasibility is discussed. The variation of MATLAB modelling results followed the same regularity as the experimental results. The MATLAB model along with Revit has been used to simulate the Ecopump's performance when installed in a sustainable house in the UK. From the calculation, Ecopump can provide 670 kWh heating energy and reduce 90.6 kg CO2 emissions per year. The proposed Ecopump system combined with window frame could be a promising technology to enhance space heating for domestic buildings while reducing energy consumption during daily ventilation. Further in situ experiments should be conducted to explore its comprehensive performance in the future. [ABSTRACT FROM AUTHOR]

With the development of genome-wide association studies, how to gain information from a large scale of data has become an issue of common concern, since traditional methods are not fully developed to solve problems such as identifying loci-to-loci interactions (also known as epistasis). Previous epistatic studies mainly focused on local information with a single outcome (phenotype), while in this paper, we developed a two-stage global search algorithm, Greedy Equivalence Search with Local Modification (GESLM), to implement a global search of directed acyclic graph in order to identify genome-wide epistatic interactions with multiple outcome variables (phenotypes) in a case–control design. GESLM integrates the advantages of score-based methods and constraint-based methods to learn the phenotype-related Bayesian network and is powerful and robust to find the interaction structures that display both genetic associations with phenotypes and gene interactions. We compared GESLM with some common phenotype-related loci detecting methods in simulation studies. The results showed that our method improved the accuracy and efficiency compared with others, especially in an unbalanced case–control study. Besides, its application on the UK Biobank dataset suggested that our algorithm has great performance when handling genome-wide association data with more than one phenotype. [ABSTRACT FROM AUTHOR]

Objective Real-world secukinumab gastrointestinal-related adverse events (GIRAE) data during treatment for AS and PsA are lacking. We aimed to obtain this through baseline evaluation of pre-existing IBD rates and predictors of GIRAE. Methods Patient electronic and paper records commencing secukinumab from 10 UK hospitals between 2016 and 2019 were reviewed. GIRAE after initiation were defined as: definite [objective evidence of IBD (biopsy proven), clear temporal association, resolution of symptoms on drug withdrawal, no alternative explanation felt more likely], probable (as per definite, but without biopsy confirmation) or possible (gastrointestinal symptoms not fulfilling definite or probable criteria). Results Data for all 306 patients started on secukinumab were analysed: 124 (40.5%) AS and 182 (59.5%) PsA. Twenty-four of 306 (7.8%) experienced GIRAE after starting secukinumab. Amongst patients who developed GIRAE, four (1.3%) had definite, seven (2.3%) probable and 13 (4.2%) possible IBD. All definite cases were patients with AS and stopped secukinumab; two had pre-existing IBD and two (0.7%) were de novo cases of which one required surgical intervention. Seven patients (2.3%) had pre-existing diagnoses of IBD prior to initiation, of which five patients experienced GIRAE. Conclusion Absolute rates of new IBD in patients starting secukinumab are low. The majority of patients developing new GIRAE did not develop objective evidence of IBD or stop therapy. For patients with pre-existing IBD and AS the risk of GIRAE is much higher, and prescribing alternatives should be considered. [ABSTRACT FROM AUTHOR]

Orthopaedic surgeons have a responsibility to minimise risks of ionising radiation to patients, themselves and staff. This study aims to establish the understanding of radiation practice, legislation and risk by orthopaedic surgeons. A nationwide online survey of UK-based orthopaedic surgeons was conducted. Participants answered 18 multiple-choice questions assessing level of radiation safety training, basic principles/knowledge of ionising radiation, relevant legislation and operating practice. A total of 406 surgeons completed the survey. 92% reported using intraoperative ionising radiation at least once per week. 38% received no formal training on radiation safety. Knowledge of basic principles of radiation and legislation was limited. There was variable knowledge when labelling an image intensifier machine and choosing its safest orientation. Poor uptake of radiation protection equipment was noted. Only 19% agreed they had adequate training in ionising radiation safety and 27% reported receiving adequate training in equipment emitting ionising radiation in the operating theatre. Many orthopaedic surgeons in the UK do not believe they are adequately trained in radiation safety. There is a deficiency amongst practicing surgeons in basic knowledge, relevant legislation and practicalities of the use of ionising radiation in the operating room. This could potentially put patients and health-care professionals at additional risk. We recommend that a standardised national training programme on the basic principles and safety of ionising radiation is implemented for all practicing orthopaedic surgeons. This paper is the first UK national survey amongst orthopaedic surgeons and is one of the largest reported internationally. [ABSTRACT FROM AUTHOR]

Introduction process evaluations (PE) are increasingly used in parallel with randomised controlled trials (RCT) to inform the implementation of complex health interventions. This paper explores the learning accrued from conducting a PE within the Falls in Care Homes Study (FinCH), a large UK RCT. Methods in the FinCH study, six purposively sampled care homes provided data for the PE, which followed a realist approach. In this study researchers kept written diaries of their experiences in completing the interviews, focus groups and observations. We have reflected on these and present the main themes for discussion. Findings care home staff were enthusiastic to participate in the PE but researchers found it difficult to collect data due to staff not having time to take part, environmental factors such as no space for focus groups and low levels of research understanding. Researchers found that the expectations of the PE protocol were often unrealistic due to these limitations. Flexible and pragmatic approaches such as interviews in place of focus groups enabled data collection but required a reduced sample size and length of data collection to be accepted by researchers. Conclusion to enable care home staff to participate in successful PEs, researchers should build flexibility into research schedules, spend time building trust, collaborate with all levels of care home staff prior to data collection, increase research capacity in care home staff and co-design research projects. [ABSTRACT FROM AUTHOR]

Background dementia policy suggests diagnosing dementia early can reduce the risk of potentially harmful hospital admissions or emergency department (ED) attendances; however, there is little evidence to support this. A diagnosis of mild cognitive impairment (MCI) before dementia is a helpful proxy to explore early diagnosis. This study investigated the association between an early diagnosis of dementia and subsequent hospitalisations and ED attendances. Method a retrospective cohort study of electronic health care records from 15,836 patients from a large secondary care database in South London, UK. Participants were divided into two groups: those with a diagnosis of MCI before dementia, an early diagnosis, and those without. Cox regression models were used to compare the risk of hospitalisation and ED attendance after dementia diagnosis and negative binomial regression models were used to compare the average length of stay and average number of ED attendances. Results participants with an early diagnosis were more likely to attend ED after their diagnosis of dementia (HR = 1.09, CI = 1.00–1.18); however, there was no difference in the number of ED attendances (IRR = 1.04, CI = 0.95–1.13). There was no difference in the risk of hospitalisation (HR = 0.99, CI = 0.91–1.08) or length of stay between the groups (IRR = 0.97, CI = 0.85–1.12). Conclusion the findings of this study do not support the assumption that an early diagnosis reduces the risk of hospitalisation or ED attendance. The patterns of health service use in this paper could reflect help-seeking behaviour before diagnosis or levels of co-morbidity. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES We sought to provide further evidence on the safety and efficacy of aortic valve neocuspidization (AVNeo) using autologous pericardium in adult patients with aortic valve disease by reporting clinical and echocardiographic results from the first UK experience and performing a meta-analytic comparison with other biological valve substitutes. METHODS We reported clinical and echocardiographic outcomes of 55 patients (mean age 58 ± 15 years) undergoing AVNeo with autologous pericardium in 2 UK centres from 2018 to 2020. These results were included in a meta-analytic comparison between series on AVNeo (7 studies, 1205 patients, mean weighted follow-up 3.6 years) versus Trifecta (10 studies, 8705 patients, 3.8 years), Magna Ease (3 studies, 3137 patients, 4.1 years), Freedom Solo (4 studies, 1869 patients, 4.4 years), Freestyle (4 studies, 4307 patients, 7 years), Mitroflow (4 studies, 4760 patients, 4.1 years) and autograft aortic valve (7 papers, 3839 patients, 9.1 years). RESULTS In the present series no patients required intraoperative conversion. After mean follow-up of 12.5 ± 0.9 months, 3 patients presented with endocarditis and 1 required reintervention. The remaining patients had absent or mild aortic valve insufficiency with very low peak and mean transvalvular gradients (16 ± 3.7 and 9 ± 2.2 mmHg, respectively). Meta-analytic estimates showed non-significant difference between AVNeo and all but Magna Ease valves with regards to structural valve degeneration, reintervention and endocarditis. When compared Magna Ease valve, AVNeo and other valve substitutes showed an excess of valve-related events. CONCLUSIONS AVNeo is safe, associated with excellent haemodynamic profile. Its midterm risk of valve-related events is comparable to most biological valve substitutes. Magna Ease is potentially the best biological choice as far as risk of reintervention is concerned. [ABSTRACT FROM AUTHOR]

Telecare technologies support people to live in the community safely. In the UK, the existing analogue telephone services for telecare will be switched off by 2025, as the telecommunications infrastructure is upgraded to digital connectivity. Internationally, analogue telephone services are also being decommissioned. The shift from analogue to digital presents a rare and major opportunity for new digital solutions that address current issues with adoption and use of telecare. This paper describes a user-centred study to design innovative digital telecare concepts. The main contributions are as follows: findings from user engagement activities, which identified issues that may be more important and less important to users; the synthesis of ideas generated through the design process, which identified four themes for future work in the field–community-based support, telecare you do not wear or notice, expand the use of telecare and introduce telecare earlier; and seven concept designs that illustrate how the themes could be approached. [ABSTRACT FROM AUTHOR]

Objective The aim of this paper is to present a UK-based consensus of principles and recommendations to guide rheumatology US training and practice. Method A Delphi process was conducted involving 19 US experts representing each of the 14 regions of the UK. A working group of experienced British Society for Rheumatology Ultrasound Special Interest Group (BSRUSSIG) members made seven proposals that were presented to the whole group for further discussion. This resulted in minor modifications and seven preliminary recommendations. Members were then asked to anonymously agree or disagree with each recommendation using an electronic ballot. A threshold of 75% was used to determine consensus agreement. Results were collated by an independent chairperson and presented to the BSRUSSIG in a face to face meeting where agreement for each recommendation was ratified and an action plan agreed for dissemination of the results and future development work. Results Using a validated process, experts in rheumatology US have worked through an iterative process and have unanimously agreed seven recommendations for rheumatology training and practice. These cover a hierarchy of practice indications, education and training, including the need for practitioners to demonstrate lifelong learning, as well as a commitment to support mentors and trainers through the BSRUSSIG. Conclusion These are the first specific education and practice recommendations for rheumatology US in the UK and have been developed and endorsed by the BSRUSSIG. We intend that these proposals will help to support and validate rheumatology US practice and inform the development of future rheumatology training curricula and education programmes. [ABSTRACT FROM AUTHOR]

Background: In the first wave of COVID-19, the UK Government relied heavily on digital channels to provide information to the public. This disproportionately excluded older people - one of the groups with least access to (or experience of) using the internet. Approximately 11.5 million people in the UK lack digital skills and 4.8 million people never go online, with around half (51%) of these being aged over 65. The Greater Manchester (GM) response was to work collaboratively with a number of key Ageing groups to develop Keeping Well at Home, a booklet providing evidence based health and wellbeing information and advice for older people during COVID-19 restrictions. Methods: An evaluation of the booklet was undertaken during summer 2020 by the Healthy Ageing team at the Applied Research Collaboration GM. As national restrictions on movement remained in place at the time, a postal questionnaire was distributed to a sample of older adults in GM. Results: Nearly 500 questionnaires were returned. The response was overwhelmingly positive; 92% found the information helpful; 90% agreed the booklet would help older people stay healthy during lockdown; 74% had used the home exercises section; 78% found the tips for keeping their mind well helpful. Around 50% of respondents did not have internet access. Paper based resources was the preferred choice for 92% of respondents with only 6% opting for digital versions. Conclusions: The evidence from the evaluation challenges the growing trend towards communicating just through digital channels, and emphasises the need for tailored paper-based materials for older adults. The Keeping Well at Home booklet also shows the value of working with older adults to ensure the content and design are inviting to readers. Information, support and services must be made available in an offline equivalent and proactively disseminated to reach those who otherwise would not have access to it. Key messages: Print-based communications are preferred over digital for some groups; ensuring inclusivity is critical as the ‘digital by default’ approach excludes large numbers of our population. Including target group representatives as co-editors to advise on content and stylistic design is key to ensure content is relevant and useful. [ABSTRACT FROM AUTHOR]

Background Intake of macronutrients and its components are associated with mortality and morbidity. Isocaloric substitution analysis is a tool to examine how changing the source of energy intake (e.g. from saturated to monounsaturated fat) is associated with health. However, conventional methods assume linearity, which may be untrue in many cases. This paper presents a nonlinear alternative, using UK Biobank data as an example data set. Methods Nonlinear isocaloric substitution analysis was conducted using penalised cubic splines in Cox proportional hazard models. In the UK Biobank, 195,658 participants completed at least one dietary questionnaire and were included in the analyses. Diet was assessed using the Oxford WebQ, a web-based 24-hour recall questionnaire. Prospective all-cause mortality was derived from on linked death records. Results More than half of the associations between macronutrient intake and all-cause mortality were nonlinear. Nonlinear isocaloric substitution analysis provides effect sizes conditional on the current intake, while conventional analysis provides an average over the whole range of intake. For example, conventional isocaloric substitution estimated no effect of replacing sugar with starch. However, the nonlinear method revealed that replacing sugar with starch was associated with a higher risk when the current starch intake was greater than 30% of total energy, and with a lower risk when current intake was less than 25%. Conclusions Nonlinear isocaloric substitution provides an alternative to conventional isocaloric substitution analysis when the underlying association is nonlinear. Key messages Nonlinear associations are common in nutritional epidemiology. In such cases, nonlinear isocaloric substitution analyses should be used. [ABSTRACT FROM AUTHOR]