Applied Research Programme Research Articles

The implementation checklist: A pragmatic instrument for accelerating research-to-implementation cycles.

Learning health systems require rapid-cycle research and nimble implementation processes to maximize innovation across disparate specialties and operations. Existing detailed research-to-implementation frameworks require extensive time commitments and can be overwhelming for physician-researchers with clinical and operational responsibilities, inhibiting their widespread adoption. The creation of a short, pragmatic checklist to inform implementation processes may substantially improve uptake and implementation efficiency across a variety of health systems. We conducted a systematic review of existing implementation frameworks to identify core concepts. Utilizing comprehensive stakeholder engagement with 25 operational leaders, embedded physician-researchers, and delivery scientists, concepts were iteratively integrated to create and implement a final concise instrument. A systematic review identified 894 publications describing implementation frameworks, which included 15 systematic reviews. Among these, domains were extracted from three commonly utilized instruments: the Quality Implementation Framework (QIF), the Consolidated Framework for Implementation Research (CFIR), and the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Iterative testing and stakeholder engagement revision of a four-page draft implementation document with five domains resulted in a concise, one-page implementation planning instrument to be used at project outset and periodically throughout project implementation planning. The instrument addresses end-user feasibility concerns while retaining the main goals of more complex tools. This instrument was then systematically integrated into projects within the Kaiser Permanente Northern California Delivery Science and Applied Research program to address stakeholder engagement, efficiency, project planning, and operational implementation of study results. A streamlined one-page implementation planning instrument, incorporating core concepts of existing frameworks, provides a pragmatic, robust framework for evidence-based healthcare innovation cycles that is being broadly implemented within a learning health system. These streamlined processes could inform other settings needing a best practice rapid-cycle research-to-implementation tool for large numbers of diverse projects.

What motivates us to be intellectually humble?: A necessary bridge to applied work

ABSTRACT In our reaction to Ballantyne (current issue), we consider a question we view as important when considering applied work on intellectual humility: What motivates us to be intellectually humble, and how does our cultural context influence our motivations? In particular, we reflect on the potential benefits and costs of intellectual humility. Compared with other virtues that have developed thriving applied research programs (e.g., forgiveness, gratitude), there has been less developed theory and empirical work explaining why individuals and groups would want to become more intellectually humble in the first place. In closing, we consider some strategies that might help individuals and groups identify why they would want to grow in intellectual humility, which could lay an important foundation for future applied work (e.g., developing effective interventions to promote intellectual humility) in this field.

Improved cryopreservation media formulation reduces costs of maintenance while preserving function of genetically modified insect cells.

Insect cell lines are an invaluable resource that facilitate various fundamental and applied research programs. Genetically engineered insect cell lines, in particular, serve as a platform through which the function of heterologously expressed proteins can be studied. However, a barrier to more widespread utilization and distribution of insect cell lines, genetically modified or not, is the technical and operational challenge associated with traditional cryopreservation methods, including their dependence on the use of liquid nitrogen facilities, animal or human serum products, and relatively high concentrations of permeating cryoprotectants (e.g., DMSO). Recent innovations in cryopreservation technologies have produced reagents with improved abilities to effectively preserve mammalian cell lines for long periods in regular laboratory deep freezers without using serum products, but their effectiveness in preserving genetically engineered insect cell lines has not yet been evaluated. In this study, we engineered Sf9 cells to express a dopamine receptor and used them as a model for evaluating the efficacy of a novel cryopreservation medium product, C80EZ®-INSECT, in not only preserving cell viability and proliferation efficiency but also maintaining the insect cell line's "functionality" after storage at -80°C. We found that the engineered Sf9 cells frozen using C80EZ®-INSECT with 5% DMSO alone and stored at -80°C for 6 mo displayed higher viability and growth rates than cells frozen using traditional fetal bovine serum (FBS)-based cryopreservation media with 10% DMSO that were stored at -80°C or in liquid nitrogen for the same period of time. We also found that after 6 mo of storage at -80°C or in liquid nitrogen the cells retained a responsiveness to dopamine comparable to that of the initial cell line, regardless of the cryopreservation reagent used. These results suggest that, due to the unique characteristics of C80EZ®-INSECT in preventing ice recrystallization and reducing ice crystal size and cellular apoptosis during cryostorage procedures, it is an effective cryopreservation reagent for genetically engineered Sf9 cells, and it practically eliminates the need for liquid nitrogen-based storage facilities and FBS-based cryopreservation formulations, as well as reduces the use of permeating cryoprotectants.

Digital interventions for hypertension and asthma to support patient self-management in primary care: the DIPSS research programme including two RCTs

Digital interventions for hypertension and asthma to support patient self-management in primary care: the DIPSS research programme including two RCTs

Ultrasound Simulation for Training Trainees when the Luxury Becomes Essential: Opinion and Evidence Obtained during the Latvian Research Council Project Implementation.

Simulation as a proxy tool for conditional clinical training became a powerful technique for introducing trainees to the ultrasound imaging world, allowing them to become a trained sonographer taking into consideration different rates of progress in completing a specific task against the time and ensuring the long-lasting maintenance of the obtained practical skills. Adding a costly, but effective high-fidelity simulator to the residency program justified the expense, demonstrating efficiency of training for improving the clinical performance and confidence of trainees. A pilot study in Riga Maternity Hospital within the framework of the study "Role of metabolome, biomarkers and ultrasound parameters in successful labor induction" (Fundamental and Applied Research Programme lzp-2021/1-0300) was performed between March 1st 2022 and 31st April 2022. A virtual-reality simulator (ScanTrainer, MedaphorTM, Cardiff, UK) was used with the teaching module for assessment of the uterine cervix. Five trainees in obstetrics and two young specialists included in the study. None of them had Fetal Medicine Foundation certificate of competence in the assessment of the uterine cervical lenght before. The time used on the simulator, the number of simulations and a mean confidence in cervical length assessment before and after simulation were recorded. The study on assesment of uterine cervical lenght demonstrated statistically significant increase in confidence (p=0.008) and statistically significant decrease in time needed to complete correctly the same tasks for the trainees (p=0.008) that shows a positive learning curve over the time of training on ScanTrainer, Medaphor. The simple task allows to become a certified specialist in uterine cervical assessment in the short period of time. That support the productiveness of the simulation-based education. The training program should be updated taking into consideration simulation curriculum.

The BioExperience Research and Entrepreneurship Challenge: An iGEM-inspired applied research program for BIOSTEM talent and skills development

Post-secondary education is falling behind in delivering the talent and skills development needed to support the growth of biology-based economies and the demands of professional and research-based graduate degree programs. Here, we describe an applied research program, the BioExperience Research and Entrepreneurship Challenge, launched in May 2020 to mitigate the impact of the COVID-19 pandemic on undergraduate experiential learning programs at the University of Ottawa, Ontario, Canada. The program provided undergraduates with meaningful talent and skills development opportunities by implementing a student-centred, project-based learning approach inspired by the International Genetically Engineered Machine (iGEM) competition. We present evidence from participant exit surveys suggesting that the program delivers a high-quality learning environment and improves learning outcomes compared to traditional work-integrated learning. Notably, 84% of respondents reported an excellent or exceptional learning experience and significant or profound improvements in skills, such as leadership (72% of respondents), problem-solving (42% of respondents) and research preparedness (52%) that are difficult to develop in conventional academic programs. Remarkably, 60% of respondents report that the job-readiness training provided by the program is better or much better than traditional work-integrated learning. Our study demonstrates that a cost-effective and scalable alternative to the iGEM competition can improve talent and skills development in BIOSTEM fields.

Infection after total joint replacement of the hip and knee: research programme including the INFORM RCT

Infection after total joint replacement of the hip and knee: research programme including the INFORM RCT

Development and evaluation of a collaborative care intervention for male prison leavers with mental health problems: the Engager research programme

Background Many male prison leavers have significant mental health problems. Prison leavers often have a history of trauma, ongoing substance misuse and housing insecurity. Only a minority of prison leavers receive mental health care on release from prison. Objectives The aim of the Engager research programme was to develop and evaluate a theory- and evidence-informed complex intervention designed to support individuals with common mental health problems (e.g. anxiety, depression) and other complex needs, including mental health comorbidity, before and after release from prison. Methods In phase 1, the intervention was developed through a set of realist-informed substudies, including a realist review of psychosocial care for individuals with complex needs, case studies within services demonstrating promising intervention features, focus groups with individuals from under-represented groups, a rapid realist review of the intervention implementation literature and a formative process evaluation of the prototype intervention. In a parallel randomised trial, methodological development included selecting outcome measures through reviewing literature, piloting measures and a consensus process, developing ways to quantify intervention receipt, piloting trial procedures and modelling economic outcomes. In phase 2, we conducted an individually randomised superiority trial of the Engager intervention, cost-effectiveness and cost–consequence analyses and an in-depth mixed-methods process evaluation. Patient and public involvement influenced the programme throughout, primarily through a Peer Researcher Group. Results In phase 1, the Engager intervention included multiple components. A practitioner offered participants practical support, emotional help (including mentalisation-based approaches) and liaison with other services in prison on the day of the participant’s release and for 3–5 months post release. An intervention delivery platform (i.e. training, manual, supervision) supported implementation. Outcome measures were selected through testing and stakeholder consensus to represent a broad range of domains, with a general mental health outcome as the primary measure for the trial. Procedures for recruitment and follow-up were tested and included flexible approaches to engagement and retention. In phase 2, the trial was conducted in three prison settings, with 280 participants randomised in a 1 : 1 ratio to receive either Engager plus usual care (n = 140) or usual care only (n = 140). We achieved a follow-up rate of 65% at 6 months post release from prison. We found no difference between the two groups for the Clinical Outcomes in Routine Evaluation – Outcome Measure at 6 months. No differences in secondary measures and sensitivity analyses were found beyond those expected by chance. The cost-effectiveness analysis showed that Engager cost significantly more at £2133 (95% of iterations between £997 and £3374) with no difference in quality-adjusted life-years (–0.017, 95% of iterations between –0.042 and 0.007). The mixed-methods process evaluation demonstrated implementation barriers. These barriers included problems with retention of the intervention team, and the adverse health and criminal justice system context. Seventy-seven per cent (108/140) of individuals had at least one community contact. Significant proportions of participants engaging received day release work and practical support. In contrast, there was evidence that the psychological components, mentalisation and developing a shared understanding were used less consistently. When engagement was positive, these components were associated with positive achievement of goals for individuals. We were also able to identify how to improve the intervention programme theory, including how to support individuals who were unrealistic in their perception of their ability to cope with challenges post release. Strengths and limitations Our development work provides a worked example of the development of a complex intervention, particularly given little prior evidence or theory specific to male offenders to build on. Our trial methodological development enabled the completion of, to the best of our knowledge, the first fully powered trial of a mental health intervention for prison leavers with common mental health problems. There were potential weaknesses in the trial methodology in terms of follow-up rates and outcome measures, with the latter potentially being insufficiently sensitive to important but highly individual changes in participants who responded to the intervention. Conclusions Delivering a randomised controlled trial for prison leavers with acceptable levels of follow-up is possible, despite adverse conditions. Full intervention implementation was challenging, but this is to be expected. Some individuals did respond well to the intervention when both practical and psychological support were flexibly deployed as intended, with evidence that most components were experienced as helpful for some individuals. It is recommended that several key components be developed further and tested, along with improved training and supervision, to support delivery of the Engager intervention within existing teams working with prison leavers. Trial registration This trial is registered as ISRCTN11707331. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 10, No. 8. See the NIHR Journals Library website for further project information.

Developing decision support tools incorporating personalised predictions of likely visual benefit versus harm for cataract surgery: research programme

Developing decision support tools incorporating personalised predictions of likely visual benefit versus harm for cataract surgery: research programme

Electronic prescribing systems in hospitals to improve medication safety: a multimethods research programme

Electronic prescribing systems in hospitals to improve medication safety: a multimethods research programme

Longitudinal phenotyping of maternal antenatal depression in obese pregnant women supports multiple-hit hypothesis for fetal brain development, a secondary analysis of the UPBEAT study.

SummaryBackgroundMaternal antenatal depression is associated with offspring psychological disorders, but obesity is also widely implicated in maternal depression and neurodevelopment. In pregnant women with obesity we explored interrelationships between antenatal depressive symptom trajectories and multiple exposures implicated in fetal neurodevelopment which could explain these associations, as a prelude to exploring associations with infant mental health.MethodsThe UK Pregnancies Better Eating and Activity Trial (UPBEAT) recruited multi-ethnic pregnant women with obesity (BMI >= 30kg/m2) between March 2009 and June 2014 from 8 UK sites and 1369 were included to model longitudinal antenatal depressive symptoms from Edinburgh Postnatal Depression Scale (EPDS) scores using Latent Class Growth Analysis. Classes were compared on maternal baseline demography, biomarkers of metabolism, inflammation and placental function, infection, diet and by pregnancy and birth outcomes. Odds ratios, mean differences and 95% Confidence Intervals were calculated using robust auxiliary modelling techniques.FindingsThe chosen model produced four classes: “Not Depressed” (n=575 [42%], “reference”), “Mild” (n=523 [37·5%]), “Moderate” (n=219 [16%]) and “Severe” (n=62 [4·5%]) symptom trajectories. Socio-economic deprivation and ethnic diversity were greater in Severe and Moderate classes. Dietary glycaemic load and saturated fat intake were higher in Severe and Moderate classes (at 17 and 27 weeks). Higher Interleukin-6, glycoprotein acetyls (17 weeks), glucose (34 weeks) and lower placental growth factor (PlGF, 17 and 27 weeks) was found in the Severe class. PlGF was lower in the Moderate class (27 weeks). Infection was least likely in the Not Depressed class across gestation. Risks of preterm birth were associated with Severe depressive symptoms (aOR 3·05[1·11 to 8·36]).InterpretationComprehensive phenotyping exposes important fetal exposures implicated in adverse neurodevelopment, differing by depression class. This study expands substantially on causal models of suboptimal fetal neurodevelopment and offers potential new targets for intervention in obese pregnant women.FundingJNS was funded by a PhD studentship from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas’ NHS Foundation Trust and King's College London. UPBEAT was supported by the European Union's 7th Framework Programme (FP7/2007-2013), project EarlyNutrition; grant agreement no. 289346 and the National Institute for Health Research (NIHR) (UK) Programme Grants for Applied Research Programme (RP-0407-10452), Medical Research Council UK Project Grant (MR/L002477/1). Support was also provided by the Chief Scientist Office Scotland, Guy's and St Thomas’ Charity and Tommy's Charity (Registered charity no. 1060508). LP and SLW are funded by Tommy's Charity.

Perinatal mental health services in pregnancy and the year after birth: the ESMI research programme including RCT

Perinatal mental health services in pregnancy and the year after birth: the ESMI research programme including RCT

Improving outcomes for women aged 70 years or above with early breast cancer: research programme including a cluster RCT

Improving outcomes for women aged 70 years or above with early breast cancer: research programme including a cluster RCT

Improving emergency treatment for patients with acute stroke: the PEARS research programme, including the PASTA cluster RCT

Improving emergency treatment for patients with acute stroke: the PEARS research programme, including the PASTA cluster RCT

FEM Strength Analysis of Circumferential Compensation with Integrated Lips in Gear Pumps

Currently, gear pumps are developed with a aim to increase their efficiency, reduce internal leaks, and increase their working pressures. This development direction requires new solutions which would compensate backlash while ensuring an optimal size of the gaps for the entire range of working pressures. One of the solutions intended to meet this demand is to design circumferential compensation with the so-called integrated lips. The presented backlash compensation method is the result of research performed as part of a project named Designing High-Pressure Gear Pumps. The project was granted funding under path A of the Applied Research Program, contract No. PBS3/A6/22/2015. The research works were performed in the Laboratory of Hydraulic Drives and Vibroacoustics of Machines at Wrocław University of Science and Technology, and in cooperation with Hydrotor SA.

Identifying and managing psoriasis-associated comorbidities: the IMPACT research programme

BackgroundPsoriasis is a common, lifelong inflammatory skin disease, the severity of which can range from limited disease involving a small body surface area to extensive skin involvement. It is associated with high levels of physical and psychosocial disability and a range of comorbidities, including cardiovascular disease, and it is currently incurable.ObjectivesTo (1) confirm which patients with psoriasis are at highest risk of developing additional long-term conditions and identify service use and costs to patient, (2) apply knowledge about risk of comorbid disease to the development of targeted screening services to reduce risk of further disease, (3) learn how patients with psoriasis cope with their condition and about their views of service provision, (4) identify the barriers to provision of best care for patients with psoriasis and (5) develop patient self-management resources and staff training packages to improve the lives of people with psoriasis.DesignMixed methods including two systematic reviews, one population cohort study, one primary care screening study, one discrete choice study, four qualitative studies and three mixed-methodology studies.SettingPrimary care, secondary care and online surveys.ParticipantsPeople with psoriasis and health-care professionals who manage patients with psoriasis.ResultsPrevalence rates for psoriasis vary by geographical location. Incidence in the UK was estimated to be between 1.30% and 2.60%. Knowledge about the cost-effectiveness of therapies is limited because high-quality clinical comparisons of interventions have not been done or involve short-term follow-up. After adjusting for known cardiovascular risk factors, psoriasis (including severe forms) was not found to be an independent risk factor for major cardiovascular events; however, co-occurrence of inflammatory arthritis was a risk factor. Traditional risk factors were high in patients with psoriasis. Large numbers of patients with suboptimal management of known risk factors were found by screening patients in primary care. Risk information was seldom discussed with patients as part of screening consultations, meaning that a traditional screening approach may not be effective in reducing comorbidities associated with psoriasis. Gaps in training of health-care practitioners to manage psoriasis effectively were identified, including knowledge about risk factors for comorbidities and methods of facilitating behavioural change. Theory-based, high-design-quality patient materials broadened patient understanding of psoriasis and self-management. A 1-day training course based on motivational interviewing principles was effective in increasing practitioner knowledge and changing consultation styles. The primary economic analysis indicated a high level of uncertainty. Sensitivity analysis indicated some situations when the interventions may be cost-effective. The interventions need to be assessed for long-term (cost-)effectiveness.LimitationsThe duration of patient follow-up in the study of cardiovascular disease was relatively short; as a result, future studies with longer follow-up are recommended.ConclusionsRecognition of the nature of the psoriasis and its impact, knowledge of best practice and guideline use are all limited in those most likely to provide care for the majority of patients. Patients and practitioners are likely to benefit from the provision of appropriate support and/or training that broadens understanding of psoriasis as a complex condition and incorporates support for appropriate health behaviour change. Both interventions were feasible and acceptable to patients and practitioners. Cost-effectiveness remains to be explored.Future workPatient support materials have been created for patients and NHS providers. A 1-day training programme with training materials for dermatologists, specialist nurses and primary care practitioners has been designed. Spin-off research projects include a national study of responses to psoriasis therapy and a global study of the prevalence and incidence of psoriasis. A new clinical service is being developed locally based on the key findings of the Identification and Management of Psoriasis Associated ComorbidiTy (IMPACT) programme.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 10, No. 3. See the NIHR Journals Library website for further project information.

Enhanced feedback interventions to promote evidence-based blood transfusion guidance and reduce unnecessary use of blood components: the AFFINITIE research programme including two cluster factorial RCTs

Enhanced feedback interventions to promote evidence-based blood transfusion guidance and reduce unnecessary use of blood components: the AFFINITIE research programme including two cluster factorial RCTs

Electronic self-reporting of adverse events for patients undergoing cancer treatment: the eRAPID research programme including two RCTs

Electronic self-reporting of adverse events for patients undergoing cancer treatment: the eRAPID research programme including two RCTs

LATENT MIGRANTOPHOBIA IN REGIONAL DIMENSION: ON THE MATERIALS OF MARI EL AND MORDOVIA

The article analyzes the features of public perception of foreign labor migration in modern Russia, identified in the course of a sociological survey conducted by the authors of the article in the Republic of Mari El and the Republic of Mordovia. As a phenomenon of a global order, migration processes have their own specifics in different regions of the world. Thus, the migration situation in the countries of Western Europe, characterized by the so-called “crisis of multiculturalism”, has become widely known. The situation is fundamentally different in Russia, where the main source of labor migration is the states that were previously part of the USSR as union republics. In the presence of manifestations of migrant-phobia (latent or open) in most Russian regions, the migration situation for our country still does not have such a critical and acute character. To a large extent, its features can be traced to the example of individual subjects of the Russian Federation. In September - October 2020, the authors of this article conducted a survey of the population in the Republic of Mari El and the Republic of Mordovia. This survey was conducted within the framework of the Program of Fundamental and Applied Research on the topic “Ethnocultural Diversity of Russian Society and Strengthening the All-Russian Identity” (2020-2022). The survey showed that a significant part of the respondents view migrants as a threat to the economic security of the regions under consideration. The most effective management measures to prevent ethnopolitical and interethnic conflicts associated with migration are support for ethnic and cultural associations, interdepartmental and inter-level coordination in the implementation of state national policy, including the prevention of extremism and early warning of conflicts, as well as constant monitoring of the ethnopolitical sphere and interethnic relationships.

An Introduction to Machine Learning Approaches for Biomedical Research.

Machine learning (ML) approaches are a collection of algorithms that attempt to extract patterns from data and to associate such patterns with discrete classes of samples in the data—e.g., given a series of features describing persons, a ML model predicts whether a person is diseased or healthy, or given features of animals, it predicts weather an animal is treated or control, or whether molecules have the potential to interact or not, etc. ML approaches can also find such patterns in an agnostic manner, i.e., without having information about the classes. Respectively, those methods are referred to as supervised and unsupervised ML. A third type of ML is reinforcement learning, which attempts to find a sequence of actions that contribute to achieving a specific goal. All of these methods are becoming increasingly popular in biomedical research in quite diverse areas including drug design, stratification of patients, medical images analysis, molecular interactions, prediction of therapy outcomes and many more. We describe several supervised and unsupervised ML techniques, and illustrate a series of prototypical examples using state-of-the-art computational approaches. Given the complexity of reinforcement learning, it is not discussed in detail here, instead, interested readers are referred to excellent reviews on that topic. We focus on concepts rather than procedures, as our goal is to attract the attention of researchers in biomedicine toward the plethora of powerful ML methods and their potential to leverage basic and applied research programs.