Effectiveness of Interventions for Changing More Than One Behavior at a Time to Manage Chronic Conditions: A Systematic Review and Meta-analysis.

BACKGROUND: Health behaviors play a significant role in chronic disease management. Rather than being independent of one another, health behaviors often co-occur, suggesting that targeting more than one health behavior in an intervention has the potential to be more effective in promoting better health outcomes. PURPOSE: We aimed to conduct a systematic review and meta-analysis of randomized trials of interventions that target more than one behavior to examine the effectiveness of multiple health behavior change interventions in patients with chronic conditions. METHODS: Five electronic databases (Web of Science, PubMed, CINAHL, EMBASE, and Cochrane) were systematically searched in November 2023, and studies included in previous reviews were also consulted. We included randomized trials of interventions aiming to change more than one health behavior in individuals with chronic conditions. Two independent reviewers screened and extracted data, and used Cochrane's Risk of Bias 2 tool. Meta-analyses were conducted to estimate the effects of interventions on change in health behaviors. Results were presented as Cohen's d for continuous data, and risk ratio for dichotomous data. RESULTS: Sixty-one studies were included spanning a range of chronic diseases: cardiovascular (k = 25), type 2 diabetes (k = 15), hypertension (k = 10), cancer (k = 7), one or more chronic conditions (k = 3), and multiple conditions (k = 1). Most interventions aimed to change more than one behavior simultaneously (rather than in sequence) and most targeted three particular behaviors at once: "physical activity, diet and smoking" (k = 20). Meta-analysis of 43 eligible studies showed for continuous data (k = 29) a small to substantial positive effect on behavior change for all health behaviors (d = 0.081-2.003) except for smoking (d = -0.019). For dichotomous data (k = 23) all analyses showed positive effects of targeting more than one behavior on all behaviors (RR = 1.026-2.247). CONCLUSIONS: Targeting more than one behavior at a time is effective in chronic disease management and more research should be directed into developing the science of multiple behavior change.

Many recommendations suggest engaging in more than one health behavior to manage a chronic disease; however, most research trying to understand or support health behavior tends to focus on only one behavior. We wanted to clarify if interventions aiming to support people in changing more than one health behavior are effective and promote better health outcomes. We aimed to conduct a systematic review to summarize the effects of studies reporting randomized trials of interventions that target more than one behavior in people with a chronic condition. We found and analyzed 61 studies published up to November 2023 covering people with a variety of chronic diseases: cardiovascular conditions, type 2 diabetes, hypertension, cancer, and, in some studies, people with multiple conditions. Most interventions tried to change three particular behaviors at once (physical activity, diet, and smoking) and, overall, interventions that tried to change more than one behavior had positive effects on diet, physical activity, medication adherence, and alcohol consumption, but not smoking cessation. Findings highlight the benefits of targeting more than one behavior in health behavior change interventions. Future research could seek to identify if findings are similar across settings and populations and how they can inform routine healthcare and self-management interventions.

Ultrasonography to Access Diaphragm Dysfunction and Predict the Success of Mechanical Ventilation Weaning in Critical Care: A Narrative Review.

INTRODUCTION: Weaning failure is common in mechanically ventilated patients, and whether ultrasound (US) can predict weaning outcome remains controversial. This review aims to evaluate the diaphragmatic function measured by US as a predictor of weaning outcome. METHODS: PubMed was searched to identify original articles about the use of diaphragmatic US in ICU patients. A total of 61 citations were retrieved initially; available data of 26 studies were included in this review. RESULTS: To assess diaphragmatic dysfunction in adults, six studies evaluated excursion, five evaluated thickening fraction, and both in nine. Despite heterogeneity in the diagnostic accuracy of diaphragm US among the studies, the sonographic indices showed good diagnostic performance for predicting weaning outcome. CONCLUSIONS: Diaphragmatic US can be a useful and accurate tool to detect diaphragmatic dysfunction in critically ill patients and predict weaning outcome.

MyBack - effectiveness and implementation of a behavior change informed exercise programme to prevent low back pain recurrences: a hybrid effectiveness-implementation randomized controlled study protocol.

BACKGROUND: Low back pain (LBP) is a common health condition and the leading cause of years lived with disability worldwide. Most LBP episodes have a favourable prognosis, but recurrences within a year are common. Despite the individual and societal impact related to LBP recurrences, there is limited evidence on effective strategies for secondary prevention of LBP and successful implementation of intervention programmes in a real-world context. The aim of this study is to analyse the effectiveness of a tailored exercise and behavioural change programme (MyBack programme) in the secondary prevention of LBP; and evaluate acceptability, feasibility and determinants of implementation by the different stakeholders, as well as the implementation strategy of the MyBack programme in real context. METHODS: This protocol describes a hybrid type I, randomized controlled trial to evaluate the effectiveness and implementation of MyBack programme in the context of primary health care. The Behaviour Change Wheel framework and FITT-VP principles will inform the development of the behaviour change and exercise component of MyBack programme, respectively. Patients who have recently recovered from an episode of non-specific LBP will be randomly assigned to MyBack and usual care group or usual care group. The primary outcome will be the risk of LBP recurrence. The secondary outcomes will include disability, pain intensity, musculoskeletal health, and health-related quality of life. Participants will be followed monthly for 1 year. Costs data related to health care use and the MyBack programme will be also collected. Implementation outcomes will be assessed in parallel with the effectiveness study using qualitative methods (focus groups with participants and health providers) and quantitative data (study enrolment and participation data; participants adherence). DISCUSSION: To our knowledge, this is the first study assessing the effectiveness and implementation of a tailored exercise and behaviour change programme for prevention of LBP recurrences. Despite challenges related to hybrid design, it is expected that data on the effectiveness, cost-effectiveness, and implementation of the MyBack programme may contribute to improve health care in patients at risk of LBP recurrences, contributing to direct and indirect costs reduction for patients and the health system. TRIAL REGISTRATION NUMBER: NCT05841732.

Clustering of Health Behaviors in Canadians: A Multiple Behavior Analysis of Data from the Canadian Longitudinal Study on Aging.

BACKGROUND: Health behaviors such as physical inactivity, unhealthy eating, smoking tobacco, and alcohol use are each leading risk factors for non-communicable chronic disease. Better understanding which behaviors tend to co-occur (i.e., cluster together) and co-vary (i.e., are correlated) may provide novel opportunities to develop more comprehensive interventions to promote multiple health behavior change. However, whether co-occurrence or co-variation-based approaches are better suited for this task remains relatively unknown. PURPOSE: To compare the utility of co-occurrence vs. co-variation-based approaches for understanding the interconnectedness between multiple health-impacting behaviors. METHODS: Using baseline and follow-up data (N = 40,268) from the Canadian Longitudinal Study of Aging, we examined the co-occurrence and co-variation of health behaviors. We used cluster analysis to group individuals based on their behavioral tendencies across multiple behaviors and to examine how these clusters are associated with demographic characteristics and health indicators. We compared outputs from cluster analysis to behavioral correlations and compared regression analyses of clusters and individual behaviors predicting future health outcomes. RESULTS: Seven clusters were identified, with clusters differentiated by six of the seven health behaviors included in the analysis. Sociodemographic characteristics varied across several clusters. Correlations between behaviors were generally small. In regression analyses individual behaviors accounted for more variance in health outcomes than clusters. CONCLUSIONS: Co-occurrence-based approaches may be more suitable for identifying sub-groups for intervention targeting while co-variation approaches are more suitable for building an understanding of the relationships between health behaviors.

Health behaviors such as physical inactivity, unhealthy eating, smoking tobacco, and alcohol use are each leading risk factors for non-communicable chronic disease. A better understanding of which behavioral combinations people engage in, and which behaviors are associated with each other, may provide new insights to support the development of interventions to promote multiple health behavior change. Using data with two time points (N = 40,268) from the Canadian Longitudinal Study of Aging, we grouped people into clusters based on their health behaviors and examined how these clusters are associated with demographic characteristics and health indicators. Seven clusters were identified with sociodemographic patterns evident across several clusters. Correlations between behaviors were generally small. We compared whether individual health behaviors, or groupings of people based on their health behaviors, were better predictors of future health outcomes. Individual behaviors were slightly better predictors of future health outcomes than clusters.

Content and quality of physical activity ontologies: a systematic review.

INTRODUCTION: Ontologies are a formal way to represent knowledge in a particular field and have the potential to transform the field of health promotion and digital interventions. However, few researchers in physical activity (PA) are familiar with ontologies, and the field can be difficult to navigate. This systematic review aims to (1) identify ontologies in the field of PA, (2) assess their content and (3) assess their quality. METHODS: Databases were searched for ontologies on PA. Ontologies were included if they described PA or sedentary behavior, and were available in English language. We coded whether ontologies covered the user profile, activity, or context domain. For the assessment of quality, we used 12 criteria informed by the Open Biological and Biomedical Ontology (OBO) Foundry principles of good ontology practice. RESULTS: Twenty-eight ontologies met the inclusion criteria. All ontologies covered PA, and 19 included information on the user profile. Context was covered by 17 ontologies (physical context, n = 12; temporal context, n = 14; social context: n = 5). Ontologies met an average of 4.3 out of 12 quality criteria. No ontology met all quality criteria. DISCUSSION: This review did not identify a single comprehensive ontology of PA that allowed reuse. Nonetheless, several ontologies may serve as a good starting point for the promotion of PA. We provide several recommendations about the identification, evaluation, and adaptation of ontologies for their further development and use.

Are motivational and self-regulation factors associated with 12 months' weight regain prevention in the NoHoW study? An analysis of European adults.

PURPOSE: Preventing weight regain can only be achieved by sustained changes in energy balance-related behaviors that are associated with weight, such as diet and physical activity. Changes in motivation and self-regulatory skills can support long-term behavioral changes in the context of weight loss maintenance. We propose that experiencing a supportive climate care is associated with enhanced satisfaction of basic psychological needs, intrinsic goals, and autonomous motivation. These factors are expected to be associate with the utilization of self-regulation skills, leading to more sustained behavior changes and ultimately preventing weight regain. This hypothesis was tested in this ancillary analysis of the NoHoW trial, where the study arms were pooled and followed for 12 months. METHODS: The NoHoW was a three-center, large-scale weight regain prevention full factorial trial. In this longitudinal study, data were collected in adults who lost > 5% weight in the past year (N = 870, complete data only, 68.7% female, 44.10 ± 11.86 years, 84.47 ± 17.03 kg) during their participation in a 12-month digital behavior change intervention. Weight and validated measures of motivational- and self-regulatory skills-related variables were collected at baseline, six- and 12 months. Change variables were used in Mplus' path analytical models informed by NoHoW's logic model. RESULTS: The bivariate correlations confirmed key mediators' potential effect on weight outcomes in the expected causal direction. The primary analysis showed that a quarter of the variance (r2 = 23.5%) of weight regain prevention was achieved via the mechanisms of action predicted in the logic model. Specifically, our results show that supportive climate care is associated with needs satisfaction and intrinsic goal content leading to better weight regain prevention via improvements in self-regulatory skills and exercise-controlled motivation. The secondary analysis showed that more mechanisms of action are significant in participants who regained or maintained their weight. CONCLUSIONS: These results contribute to a better understanding of the mechanisms of action leading to behavior change in weight regain prevention. The most successful participants used only a few intrinsic motivation-related mechanisms of action, suggesting that habits may have been learned. While developing a digital behavior change intervention, researchers and practitioners should consider creating supportive climate care to improve needs satisfaction and intrinsic goal contents. TRIAL REGISTRATION: ISRCTN, ISRCTN88405328 , registered 12/22/2016.

Linking lesions in sensorimotor cortex to contralateral hand function in multiple sclerosis: a 7†T MRI study.

Cortical lesions constitute a key manifestation of multiple sclerosis and contribute to clinical disability and cognitive impairment. Yet it is unknown whether local cortical lesions and cortical lesion subtypes contribute to domain-specific impairments attributable to the function of the lesioned cortex. In this cross-sectional study, we assessed how cortical lesions in the primary sensorimotor hand area relate to corticomotor physiology and sensorimotor function of the contralateral hand. Fifty relapse-free patients with relapsing-remitting or secondary-progressive multiple sclerosis and 28 healthy age- and sex-matched participants underwent whole-brain 7 T MRI to map cortical lesions. Brain scans were also used to estimate normalized brain volume, pericentral cortical thickness, white matter lesion fraction of the corticospinal tract, infratentorial lesion volume and the cross-sectional area of the upper cervical spinal cord. We tested sensorimotor hand function and calculated a motor and sensory composite score for each hand. In 37 patients and 20 healthy controls, we measured maximal motor-evoked potential amplitude, resting motor threshold and corticomotor conduction time with transcranial magnetic stimulation and the N20 latency from somatosensory-evoked potentials. Patients showed at least one cortical lesion in the primary sensorimotor hand area in 47 of 100 hemispheres. The presence of a lesion was associated with worse contralateral sensory (P = 0.014) and motor (P = 0.009) composite scores. Transcranial magnetic stimulation of a lesion-positive primary sensorimotor hand area revealed a decreased maximal motor-evoked potential amplitude (P < 0.001) and delayed corticomotor conduction (P = 0.002) relative to a lesion-negative primary sensorimotor hand area. Stepwise mixed linear regressions showed that the presence of a primary sensorimotor hand area lesion, higher white-matter lesion fraction of the corticospinal tract, reduced spinal cord cross-sectional area and higher infratentorial lesion volume were associated with reduced contralateral motor hand function. Cortical lesions in the primary sensorimotor hand area, spinal cord cross-sectional area and normalized brain volume were also associated with smaller maximal motor-evoked potential amplitude and longer corticomotor conduction times. The effect of cortical lesions on sensory function was no longer significant when controlling for MRI-based covariates. Lastly, we found that intracortical and subpial lesions had the largest effect on reduced motor hand function, intracortical lesions on reduced motor-evoked potential amplitude and leucocortical lesions on delayed corticomotor conduction. Together, this comprehensive multilevel assessment of sensorimotor brain damage shows that the presence of a cortical lesion in the primary sensorimotor hand area is associated with impaired corticomotor function of the hand, after accounting for damage at the subcortical level. The results also provide preliminary evidence that cortical lesion types may affect the various facets of corticomotor function differentially.

Tuberculosis incidence in foreign-born people residing in European countries in 2020.

BackgroundEuropean-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.AimWe aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.MethodsThe Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.ResultsData on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.ConclusionsCountry of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.

MicroRNAs Present in Malignant Pleural Fluid Increase the Migration of Normal Mesothelial Cells In Vitro and May Help Discriminate between Benign and Malignant Effusions.

The sensitivity of pleural fluid (PF) analyses for the diagnosis of malignant pleural effusions (MPEs) is low to moderate. Knowledge about the pathobiology and molecular characteristics of this condition is limited. In this study, the crosstalk between stromal cells and tumor cells was investigated in vitro in order to reveal factors that are present in PF which can mediate MPE formation and aid in discriminating between benign and malignant etiologies. Eighteen PF samples, in different proportions, were exposed in vitro to mesothelial MeT-5A cells to determine the biological effects on these cells. Treatment of normal mesothelial MeT-5A cells with malignant PF increased cell viability, proliferation, and migration, and activated different survival-related signaling pathways. We identified differentially expressed miRNAs in PF samples that could be responsible for these changes. Consistently, bioinformatics analysis revealed an enrichment of the discovered miRNAs in migration-related processes. Notably, the abundance of three miRNAs (miR-141-3p, miR-203a-3, and miR-200c-3p) correctly classified MPEs with false-negative cytological examination results, indicating the potential of these molecules for improving diagnosis. Malignant PF produces phenotypic and functional changes in normal mesothelial cells. These changes are partly mediated by certain miRNAs, which, in turn, could serve to differentiate malignant from benign effusions.

Platform for Orthogonal N-Cysteine-Specific Protein Modification Enabled by Cyclopropenone Reagents.

Protein conjugates are valuable tools for studying biological processes or producing therapeutics, such as antibody-drug conjugates. Despite the development of several protein conjugation strategies in recent years, the ability to modify one specific amino acid residue on a protein in the presence of other reactive side chains remains a challenge. We show that monosubstituted cyclopropenone (CPO) reagents react selectively with the 1,2-aminothiol groups of N-terminal cysteine residues to give a stable 1,4-thiazepan-5-one linkage under mild, biocompatible conditions. The CPO-based reagents, all accessible from a common activated ester CPO-pentafluorophenol (CPO-PFP), allow selective modification of N-terminal cysteine-containing peptides and proteins even in the presence of internal, solvent-exposed cysteine residues. This approach enabled the preparation of a dual protein conjugate of 2×cys-GFP, containing both internal and N-terminal cysteine residues, by first modifying the N-terminal residue with a CPO-based reagent followed by modification of the internal cysteine with a traditional cysteine-modifying reagent. CPO-based reagents enabled a copper-free click reaction between two proteins, producing a dimer of a de novo protein mimic of IL2 that binds to the ß-IL2 receptor with low nanomolar affinity. Importantly, the reagents are compatible with the common reducing agent dithiothreitol (DTT), a useful property for working with proteins prone to dimerization. Finally, quantum mechanical calculations uncover the origin of selectivity for CPO-based reagents for N-terminal cysteine residues. The ability to distinguish and specifically target N-terminal cysteine residues on proteins facilitates the construction of elaborate multilabeled bioconjugates with minimal protein engineering.

Locus Coeruleus Shows a Spatial Pattern of Structural Disintegration in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) causes a loss of neuromelanin-positive, noradrenergic neurons in the locus coeruleus (LC), which has been implicated in nonmotor dysfunction. OBJECTIVES: We used "neuromelanin sensitive" magnetic resonance imaging (MRI) to localize structural disintegration in the LC and its association with nonmotor dysfunction in PD. METHODS: A total of 42 patients with PD and 24 age-matched healthy volunteers underwent magnetization transfer weighted (MTw) MRI of the LC. The contrast-to-noise ratio of the MTw signal (CNRMTw ) was used as an index of structural LC integrity. We performed slicewise and voxelwise analyses to map spatial patterns of structural disintegration, complemented by principal component analysis (PCA). We also tested for correlations between regional CNRMTw and severity of nonmotor symptoms. RESULTS: Mean CNRMTw of the right LC was reduced in patients relative to controls. Voxelwise and slicewise analyses showed that the attenuation of CNRMTw was confined to the right mid-caudal LC and linked regional CNRMTw to nonmotor symptoms. CNRMTw attenuation in the left mid-caudal LC was associated with the orthostatic drop in systolic blood pressure, whereas CNRMTw attenuation in the caudal most portion of right LC correlated with apathy ratings. PCA identified a bilateral component that was more weakly expressed in patients. This component was characterized by a gradient in CNRMTw along the rostro-caudal and dorso-ventral axes of the nucleus. The individual expression score of this component reflected the overall severity of nonmotor symptoms. CONCLUSION: A spatially heterogeneous disintegration of LC in PD may determine the individual expression of specific nonmotor symptoms such as orthostatic dysregulation or apathy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Evaluation of the Immediate Effects of Web-Based Intervention Modules for Goals, Planning, and Coping Planning on Physical Activity: Secondary Analysis of a Randomized Controlled Trial on Weight Loss Maintenance.

BACKGROUND: The use of digital interventions can be accurately monitored via log files. However, monitoring engagement with intervention goals or enactment of the actual behaviors targeted by the intervention is more difficult and is usually evaluated based on pre-post measurements in a controlled trial. OBJECTIVE: The objective of this paper is to evaluate if engaging with 2 digital intervention modules focusing on (1) physical activity goals and action plans and (2) coping with barriers has immediate effects on the actual physical activity behavior. METHODS: The NoHoW Toolkit (TK), a digital intervention developed to support long-term weight loss maintenance, was evaluated in a 2 x 2 factorial randomized controlled trial. The TK contained various modules based on behavioral self-regulation and motivation theories, as well as contextual emotion regulation approaches, and involved continuous tracking of weight and physical activity through connected commercial devices (Fitbit Aria and Charge 2). Of the 4 trial arms, 2 had access to 2 modules directly targeting physical activity: a module for goal setting and action planning (Goal) and a module for identifying barriers and coping planning (Barriers). Module visits and completion were determined based on TK log files and time spent in the module web page. Seven physical activity metrics (steps; activity; energy expenditure; fairly active, very active and total active minutes; and distance) were compared before and after visiting and completing the modules to examine whether the modules had immediate or sustained effects on physical activity. Immediate effect was determined based on 7-day windows before and after the visit, and sustained effects were evaluated for 1 to 8 weeks after module completion. RESULTS: Out of the 811 participants, 498 (61.4%) visited the Goal module and 406 (50.1%) visited the Barriers module. The Barriers module had an immediate effect on very active and total active minutes (very active minutes: before median 24.2, IQR 10.4-43.0 vs after median 24.9, IQR 10.0-46.3; P=.047; total active minutes: before median 45.1, IQR 22.9-74.9 vs after median 46.9, IQR 22.4-78.4; P=.03). The differences were larger when only completed Barriers modules were considered. The Barriers module completion was also associated with sustained effects in fairly active and total active minutes for most of the 8 weeks following module completion and for 3 weeks in very active minutes. CONCLUSIONS: The Barriers module had small, significant, immediate, and sustained effects on active minutes measured by a wrist-worn activity tracker. Future interventions should pay attention to assessing barriers and planning coping mechanisms to overcome them. TRIAL REGISTRATION: ISRCTN Registry ISRCTN88405328; https://www.isrctn.com/ISRCTN88405328.

Users' Experiences With the NoHoW Web-Based Toolkit With Weight and Activity Tracking in Weight Loss Maintenance: Long-term Randomized Controlled Trial.

BACKGROUND: Digital behavior change interventions (DBCIs) offer a promising channel for providing health promotion services. However, user experience largely determines whether they are used, which is a precondition for effectiveness. OBJECTIVE: The primary aim of this study is to evaluate user experiences with the NoHoW Toolkit (TK)-a DBCI that targets weight loss maintenance-over a 12-month period by using a mixed methods approach and to identify the main strengths and weaknesses of the TK and the external factors affecting its adoption. The secondary aim is to objectively describe the measured use of the TK and its association with user experience. METHODS: An 18-month, 2×2 factorial randomized controlled trial was conducted. The trial included 3 intervention arms receiving an 18-week active intervention and a control arm. The user experience of the TK was assessed quantitatively through electronic questionnaires after 1, 3, 6, and 12 months of use. The questionnaires also included open-ended items that were thematically analyzed. Focus group interviews were conducted after 6 months of use and thematically analyzed to gain deeper insight into the user experience. Log files of the TK were used to evaluate the number of visits to the TK, the total duration of time spent in the TK, and information on intervention completion. RESULTS: The usability level of the TK was rated as satisfactory. User acceptance was rated as modest; this declined during the trial in all the arms, as did the objectively measured use of the TK. The most appreciated features were weekly emails, graphs, goal setting, and interactive exercises. The following 4 themes were identified in the qualitative data: engagement with features, decline in use, external factors affecting user experience, and suggestions for improvements. CONCLUSIONS: The long-term user experience of the TK highlighted the need to optimize the technical functioning, appearance, and content of the DBCI before and during the trial, similar to how a commercial app would be optimized. In a trial setting, the users should be made aware of how to use the intervention and what its requirements are, especially when there is more intensive intervention content. TRIAL REGISTRATION: ISRCTN Registry ISRCTN88405328; https://www.isrctn.com/ISRCTN88405328. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-029425.

Cysteine-Assisted Click-Chemistry for Proximity-Driven, Site-Specific Acetylation of Histones.

Post-translational modifications of histones are essential in the regulation of chromatin structure and function. Among these modifications, lysine acetylation is one of the most established. Earlier studies relied on the use of chromatin containing heterogeneous mixtures of histones acetylated at multiple sites. Differentiating the individual contribution of single acetylation events towards chromatin regulation is thus of great relevance. However, it is difficult to access homogeneous samples of histones, with a single acetylation, in sufficient quantities for such studies. By engineering histone H3 with a cysteine in proximity of the lysine of interest, we demonstrate that conjugation with maleimide-DBCO followed by a strain-promoted alkyne-azide cycloaddition reaction results in the acetylation of a single lysine in a controlled, site-specific manner. The chemical precision offered by our click-to-acetylate approach will facilitate access to and the study of acetylated histones.

A Theory- and Evidence-Based Digital Intervention Tool for Weight Loss Maintenance (NoHoW Toolkit): Systematic Development and Refinement Study.

BACKGROUND: Many weight loss programs show short-term effectiveness, but subsequent weight loss maintenance is difficult to achieve. Digital technologies offer a promising means of delivering behavior change approaches at low costs and on a wide scale. The Navigating to a Healthy Weight (NoHoW) project, which was funded by the European Union's Horizon 2020 research and innovation program, aimed to develop, test, and evaluate a digital toolkit designed to promote successful long-term weight management. The toolkit was tested in an 18-month, large-scale, international, 2×2 factorial (motivation and self-regulation vs emotion regulation) randomized controlled trial that was conducted on adults with overweight or obesity who lost ≥5% of their body weight in the preceding 12 months before enrollment into the intervention. OBJECTIVE: This paper aims to describe the development of the NoHoW Toolkit, focusing on the logic models, content, and specifications, as well as the results from user testing. METHODS: The toolkit was developed by using a systematic approach, which included the development of the theory-based logic models, the selection of behavior change techniques, the translation of these techniques into a web-based app (NoHoW Toolkit components), technical development, and the user evaluation and refinement of the toolkit. RESULTS: The toolkit included a set of web-based tools and inputs from digital tracking devices (smart scales and activity trackers) and modules that targeted weight, physical activity, and dietary behaviors. The final toolkit comprised 34 sessions that were distributed through 15 modules and provided active content over a 4-month period. The motivation and self-regulation arm consisted of 8 modules (17 sessions), the emotion regulation arm was presented with 7 modules (17 sessions), and the combined arm received the full toolkit (15 modules; 34 sessions). The sessions included a range of implementations, such as videos, testimonies, and questionnaires. Furthermore, the toolkit contained 5 specific data tiles for monitoring weight, steps, healthy eating, mood, and sleep. CONCLUSIONS: A systematic approach to the development of digital solutions based on theory, evidence, and user testing may significantly contribute to the advancement of the science of behavior change and improve current solutions for sustained weight management. Testing the toolkit by using a 2×2 design provided a unique opportunity to examine the effect of motivation and self-regulation and emotion regulation separately, as well as the effect of their interaction in weight loss maintenance.

A Digital Platform to Support Self-management of Multiple Chronic Conditions (ProACT): Findings in Relation to Engagement During a One-Year Proof-of-Concept Trial.

BACKGROUND: Populations globally are ageing, resulting in higher incidence rates of chronic diseases. Digital health platforms, designed to support those with chronic conditions to self-manage at home, offer a promising solution to help people monitor their conditions and lifestyle, maintain good health, and reduce unscheduled clinical visits. However, despite high prevalence rates of multimorbidity or multiple chronic conditions, most platforms tend to focus on a single disease. A further challenge is that despite the importance of users actively engaging with such systems, little research has explored engagement. OBJECTIVE: The objectives of this study are to design and develop a digital health platform, ProACT, for facilitating older adults self-managing multimorbidity, with support from their care network, and evaluate end user engagement and experiences with this platform through a 12-month trial. METHODS: The ProACT digital health platform is presented in this paper. The platform was evaluated in a year-long proof-of-concept action research trial with 120 older persons with multimorbidity in Ireland and Belgium. Alongside the technology, participants had access to a clinical triage service responding to symptom alerts and a technical helpdesk. Interactions with the platform during the trial were logged to determine engagement. Semistructured interviews were conducted with participants and analyzed using inductive thematic analysis, whereas usability and user burden were examined using validated questionnaires. RESULTS: This paper presents the ProACT platform and its components, along with findings on engagement with the platform and its usability. Of the 120 participants who participated, 24 (20%) withdrew before the end of the study, whereas 3 (2.5%) died. The remaining 93 participants actively used the platform until the end of the trial, on average, taking 2 or 3 health readings daily over the course of the trial in Ireland and Belgium, respectively. The participants reported ProACT to be usable and of low burden. Findings from interviews revealed that participants experienced multiple benefits as a result of using ProACT, including improved self-management, health, and well-being and support from the triage service. For those who withdrew, barriers to engagement were poor health and frustration when technology, in particular sensing devices, did not work as expected. CONCLUSIONS: This is the first study to present findings from a longitudinal study of older adults using digital health technology to self-manage multimorbidity. Our findings show that older adults sustained engagement with the technology and found it usable. Potential reasons for these results include a strong focus on user-centered design and engagement throughout the project lifecycle, resulting in a platform that meets user needs, as well as the integration of behavior change techniques and personal analytics into the platform. The provision of triage and technical support services alongside the platform during the trial were also important facilitators of engagement. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/22125.

Complete surgical revascularization: Different definitions, same impact?

BACKGROUND: There are several different definitions of complete revascularization on coronary surgery across the literature. Despite the importance of this definition, there is no agreement on which one has the most impact. The aim of this study was to evaluate which definition of complete surgical revascularization correlates with early and late outcomes. METHODS: All consecutive patients submitted to isolated CABG from 2012 to 2016 with previous myocardial scintigraphy were evaluated. EXCLUSION CRITERIA: emergent procedures and previous cardiac surgery procedures. The population of 162 patients, follow-up complete in 100% patients; median 5.5; IQR: 4.4-6.9 years. Each and all of the 162 patients were classified as complying or not with the four different definitions: numerical, functional, anatomical conditional, and anatomical unconditional. Perioperative outcome: MACCE; long-term outcomes: survival and repeat revascularization. Univariable and multivariable analyses were developed to detect predictors of outcomes. RESULTS: Complete functional revascularization was a predictor of increased survival (HR: 0.47; CI 95: 0.226-0.969; p = .041). No other definitions showed effect on follow-up mortality. Age and cardiac dysfunction increased long-term mortality. The definition of complete revascularization did not have an impact on MACCE or the need for revascularization CONCLUSIONS: A uniformly accepted definition of complete coronary revascularization is lacking. This study raises awareness about the importance of viability guidance for CABG.

Development of a European competency framework for health and other professionals to support behaviour change in persons self-managing chronic disease.

BACKGROUND: Healthcare and other professionals are expected to support behaviour change in people living with chronic disease. However, effective behaviour change interventions are largely absent in routine encounters. The Train4Health project, a European strategic partnership for higher education, sought to address this problem. The primary aim of this study, which is part of an early work package, was to develop an interprofessional competency framework for health and other professions to support behaviour change for the self-management of chronic disease at a European level. A secondary aim was to derive a set of behaviour change techniques (BCTs) from an established taxonomy to link with framework competencies. METHODS: The study comprised two interlinked parts. Part 1 involved a two-round e-Delphi study with an interprofessional panel of 48 experts across 12 European countries to develop the behaviour change competency framework. Preparatory work included drafting a list of competency statements based on seven existing frameworks. Part 2 involved an expert panel of six behavioural psychologists deriving a set of BCTs to link with framework competencies. Their feedback was based on preparatory work, which focused on seven high priority chronic diseases for self-management, identified through European projects on self-management and identifying five relevant target behaviours from key clinical guidelines. A literature search yielded 29 effective BCTs for the target behaviours in the selected chronic diseases. RESULTS: Twenty-seven competency statements, were presented in Round 1 to the Delphi panel. Consensus was achieved for all statements. Based on comments, two statements were removed, one was added, and 14 were modified. All 15 statements subjected to Round 2 were consensus-approved, yielding a total of 12 foundational competencies for behaviour change in self-management of chronic disease and 14 behaviour change competencies. Four behaviour change competencies related to BCTs. Behavioural psychologists' feedback led to a core set of 21 BCTs deemed applicable to the five target behaviours across the seven chronic diseases. CONCLUSIONS: A behaviour change competency framework comprising 26 statements for European health and other professionals to support self-management of chronic disease was developed, linked with a core set of 21 BCTs from an established taxonomy.

A scalable insect cell-based production process of the human recombinant BMX for in-vitro covalent ligand high-throughput screening.

Bone Marrow Tyrosine kinase in the chromosome X (BMX) is a TEC family kinase associated with numerous pathological pathways in cancer cells. Covalent inhibition of BMX activity holds promise as a therapeutic approach against cancer. To screen for potent and selective covalent BMX inhibitors, large quantities of highly pure BMX are normally required which is challenging with the currently available production and purification processes. Here, we developed a scalable production process for the human recombinant BMX (hrBMX) using the insect cell-baculovirus expression vector system. Comparable expression levels were obtained in small-scale shake flasks (13 mL) and in stirred-tank bioreactors (STB, 5 L). A two-step chromatographic-based process was implemented, reducing purification times by 75% when compared to traditional processes, while maintaining hrBMX stability. The final production yield was 24 mg of purified hrBMX per litter of cell culture, with a purity of > 99%. Product quality was assessed and confirmed through a series of biochemical and biophysical assays, including circular dichroism and dynamic light scattering. Overall, the platform herein developed was capable of generating 100 mg purified hrBMX from 5 L STB in just 34 days, thus having the potential to assist in-vitro covalent ligand high-throughput screening for BMX activity inhibition.

Development and cross-cultural validation of the Goal Content for Weight Maintenance Scale (GCWMS).

PURPOSE: Long-term weight management requires sustained engagement with energy-balance-related behaviours. According to self-determination theory, behaviour goals can support or undermine motivation depending on the quality of their content (i.e., extrinsic and intrinsic motivation). This study aimed to develop and validate the goal content for weight loss maintenance scale (GCWMS). METHODS: The GCWMS was administered to 1511 participants who had achieved clinically significant weight losses and were taking part in a large weight loss maintenance study: the NoHoW Trial (ISRCTN88405328). The scale derived from two well-established questionnaires regarding exercise goals. Construct validity was examined for 4 theory-driven domains: Health Management, Challenge, Image, and Social Recognition. Split-sample confirmatory factor analysis was conducted to test the factorial validity and multi-group measurement invariance (configural, metric, scalar, and residual invariance). The reliability estimates were also assessed, and discriminant validity was evaluated using 2 conceptually related questionnaires. RESULTS: The first analysis showed a poor fit of the original factorial structure. Subsequent investigation with a new specified model indicated close fit to the data after removal of 3 items χ2(58) = 599.982; p < .001; χ2/df = 10.345; CFI = 0.940; GFI = 0.941; SRMR = 0.063; RMSEA = 0.079 (LL = 0.073; UL = .084). Good internal consistency was achieved in all subscales (α > .775), convergent and divergent validity were verified through associations with other theoretical related constructs. Findings from multi-group invariance test demonstrated that the specified model of GCWMS achieved full measurement invariance for gender but did not support residual invariance across countries. CONCLUSION: Findings support the hypothesised four-dimension structure of the GCWMS, confirming reliability and multi-group invariance in factor structure. Analysis also supports valid group means comparisons on latent factors at gender and at cross-cultural level. Ways to improve the quality of the scale are discussed. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive.