Implementation science in resource-poor countries and communities

Background

Implementation science in resource-poor countries and communities is arguably more important than implementation science in resource-rich settings, because resource poverty requires novel solutions to ensure that research results are translated into routine practice and benefit the largest possible number of people.

Methods

We reviewed the role of resources in the extant implementation science frameworks and literature. We analyzed opportunities for implementation science in resource-poor countries and communities, as well as threats to the realization of these opportunities.

Results

Many of the frameworks that provide theoretical guidance for implementation science view resources as contextual factors that are important to (i) predict the feasibility of implementation of research results in routine practice, (ii) explain implementation success and failure, (iii) adapt novel evidence-based practices to local constraints, and (iv) design the implementation process to account for local constraints. Implementation science for resource-poor settings shifts this view from “resources as context” to “resources as primary research object.” We find a growing body of implementation research aiming to discover and test novel approaches to generate resources for the delivery of evidence-based practice in routine care, including approaches to create higher-skilled health workers—through tele-education and telemedicine, freeing up higher-skilled health workers—through task-shifting and new technologies and models of care, and increasing laboratory capacity through new technologies and the availability of medicines through supply chain innovations. In contrast, only few studies have investigated approaches to change the behavior and utilization of healthcare resources in resource-poor settings. We identify three specific opportunities for implementation science in resource-poor settings. First, intervention and methods innovations thrive under constraints. Second, reverse innovation transferring novel approaches from resource-poor to research-rich settings will gain in importance. Third, policy makers in resource-poor countries tend to be open for close collaboration with scientists in implementation research projects aimed at informing national and local policy.

Conclusions

Implementation science in resource-poor countries and communities offers important opportunities for future discoveries and reverse innovation. To harness this potential, funders need to strongly support research projects in resource-poor settings, as well as the training of the next generation of implementation scientists working on new ways to create healthcare resources where they lack most and to ensure that those resources are utilized to deliver care that is based on the latest research results.

     

Crop metabolomics: from diagnostics to assisted breeding

Background

Until recently, plant metabolomics have provided a deep understanding on the metabolic regulation in individual plants as experimental units. The application of these techniques to agricultural systems subjected to more complex interactions is a step towards the implementation of translational metabolomics in crop breeding.

Aim of Review

We present here a review paper discussing advances in the knowledge reached in the last years derived from the application of metabolomic techniques that evolved from biomarker discovery to improve crop yield and quality.

Key Scientific Concepts of Review

Translational metabolomics applied to crop breeding programs.

     

Using a multi-state Learning Community as an implementation strategy for immediate postpartum long-acting reversible contraception

Background

Implementation strategies are imperative for the successful adoption and sustainability of complex evidence-based public health practices. Creating a learning collaborative is one strategy that was part of a recently published compilation of implementation strategy terms and definitions. In partnership with the Centers for Disease Control and Prevention and other partner agencies, the Association of State and Territorial Health Officials recently convened a multi-state Learning Community to support cross-state collaboration and provide technical assistance for improving state capacity to increase access to long-acting reversible contraception (LARC) in the immediate postpartum period, an evidence-based practice with the potential for reducing unintended pregnancy and improving maternal and child health outcomes. During 2015–2016, the Learning Community included multi-disciplinary, multi-agency teams of state health officials, payers, clinicians, and health department staff from 13 states. This qualitative study was conducted to better understand the successes, challenges, and strategies that the 13 US states in the Learning Community used for increasing access to immediate postpartum LARC.

Methods

We conducted telephone interviews with each team in the Learning Community. Interviews were semi-structured and organized by the eight domains of the Learning Community. We coded transcribed interviews for facilitators, barriers, and implementation strategies, using a recent compilation of expert-defined implementation strategies as a foundation for coding the latter.

Results

Data analysis showed three ways that the activities of the Learning Community helped in policy implementation work: structure and accountability, validity, and preparing for potential challenges and opportunities. Further, the qualitative data demonstrated that the Learning Community integrated six other implementation strategies from the literature: organize clinician implementation team meetings, conduct educational meetings, facilitation, promote network weaving, provide ongoing consultation, and distribute educational materials.

Conclusions

Convening a multi-state learning collaborative is a promising approach for facilitating the implementation of new reimbursement policies for evidence-based practices complicated by systems challenges. By integrating several implementation strategies, the Learning Community serves as a meta-strategy for supporting implementation.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Biotherapeutic protein formulation variables influence protein integrity and can promote post-translational modifications as shown using chicken egg white lysozyme as a model system

Objectives

The effect of different formulations variables on protein integrity were investigated using lysozyme as a model protein for the development of biotherapeutic protein formulations for use in the clinic.

Results

Buffer composition/concentration was the key variable of formulation reagents investigated in determining lysozyme stability and authenticity independent of protein concentration whilst the storage temperature and time, not surprisingly, were also key variables. Tryptic peptide mapping of the protein showed that the modifications occurred when formulated under specific conditions but not others. A model peptide system was developed that reflected the same behavior under formulation conditions as intact lysozyme.

Conclusions

Peptide models may mirror the stability of proteins, or regions of proteins, in the same formulations and be used to help develop a rapid screen of formulations for stabilisation of biotherapeutic proteins.

     

Untargeted metabolomics suffers from incomplete raw data processing

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.

     

A complex endeavour: an ethnographic study of the implementation of the Sepsis Six clinical care bundle

Background

Implementation of the ‘Sepsis Six’ clinical care bundle within an hour of recognition of sepsis is recommended as an approach to reduce mortality in patients with sepsis, but achieving reliable delivery of the bundle has proved challenging. There remains little understanding of the barriers to reliable implementation of bundle components. We examined frontline clinical practice in implementing the Sepsis Six.

Methods

We conducted an ethnographic study in six hospitals participating in the Scottish Patient Safety Programme Sepsis collaborative. We conducted around 300 h of non-participant observation in emergency departments, acute medical receiving units and medical and surgical wards. We interviewed a purposive sample of 43 members of hospital staff. Data were analysed using a constant comparative approach.

Results

Implementation strategies to promote reliable use of the Sepsis Six primarily focused on education, engaging and motivating staff, and providing prompts for behaviour, along with efforts to ensure that equipment required was readily available. Although these strategies were successful in raising staff awareness of sepsis and engagement with implementation, our study identified that completing the bundle within an hour was not straightforward. Our emergent theory suggested that rather than being an apparently simple sequence of six steps, the Sepsis Six actually involved a complex trajectory comprising multiple interdependent tasks that required prioritisation and scheduling, and which was prone to problems of coordination and operational failures. Interventions that involved allocating specific roles and responsibilities for completing the Sepsis Six in ways that reduced the need for coordination and task switching, and the use of process mapping to identify system failures along the trajectory, could help mitigate against some of these problems.

Conclusions

Implementation efforts that focus on individual behaviour change to improve uptake of the Sepsis Six should be supplemented by an understanding of the bundle as a complex trajectory of work in which improving reliability requires attention to coordination of workflow, as well as addressing the mundane problems of interruptions and operational failures that obstruct task completion.

     

NMRProcFlow: a graphical and interactive tool dedicated to 1D spectra processing for NMR-based metabolomics

Introduction

Concerning NMR-based metabolomics, 1D spectra processing often requires an expert eye for disentangling the intertwined peaks.

Objectives

The objective of NMRProcFlow is to assist the expert in this task in the best way without requirement of programming skills.

Methods

NMRProcFlow was developed to be a graphical and interactive 1D NMR (¹H & ¹³C) spectra processing tool.

Results

NMRProcFlow (http://nmrprocflow.org), dedicated to metabolic fingerprinting and targeted metabolomics, covers all spectra processing steps including baseline correction, chemical shift calibration and alignment.

Conclusion

Biologists and NMR spectroscopists can easily interact and develop synergies by visualizing the NMR spectra along with their corresponding experimental-factor levels, thus setting a bridge between experimental design and subsequent statistical analyses.

     

Factors affecting implementation of perinatal mental health screening in women of refugee background

Background

For women of refugee background, the increased risk of mental illness associated with pregnancy is compounded by pre- and post-settlement stressors. In Australia, antenatal screening for depression and anxiety symptoms using the Edinburgh Postnatal Depression Scale is recommended for all women. Despite this, screening is not routinely implemented and little is known about barriers and enablers to implementation for women of refugee background.

Methods

Semi-structured interviews were conducted with a range of health professionals (n?=?28: midwives, obstetricians, perinatal mental health and refugee health experts, interpreters) and women of refugee background (n?=?9). Themes generated from thematic analysis were examined in relation to the Theoretical Domains Framework and Cultural Competence Conceptual Framework, followed by identification of effective behaviour change techniques to address the barriers and enablers identified by participants. These techniques formed the basis of recommendations to inform sustainable implementation of screening and referral.

Results

Almost all participants perceived perinatal mental health screening to be necessary and most recognised the importance of post-traumatic stress disorder (PTSD) screening. Barriers and enablers were identified and related to eight domains: knowledge, skills, professional roles, beliefs about capabilities and consequences, environmental context, social influences and behavioural regulation.

Conclusions

This research clarifies how mental health screening may be integrated into routine antenatal care for women of refugee background, in order to improve provision of recommended care. These theory-informed recommendations include an inter-disciplinary approach, coordinating care within and across services, addition of PTSD screening, and effective communication with women.

     

Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.

Objective

Investigate the maternal hair metabolome for predictive biomarkers of ICP.

Methods

The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.

Results

Of 105 metabolites detected in hair, none were significantly associated with ICP.

Conclusion

Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.

     

Iridoid and phenylethanoid/phenylpropanoid metabolite profiles of <Emphasis Type="Italic">Scrophularia</Emphasis> and <Emphasis Type="Italic">Verbascum</Emphasis> species used medicinally in North America

Introduction

Botanicals containing iridoid and phenylethanoid/phenylpropanoid glycosides are used worldwide for the treatment of inflammatory musculoskeletal conditions that are primary causes of human years lived with disability, such as arthritis and lower back pain.

Objectives

We report the analysis of candidate anti-inflammatory metabolites of several endemic Scrophularia species and Verbascum thapsus used medicinally by peoples of North America.

Methods

Leaves, stems, and roots were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and partial least squares-discriminant analysis (PLS-DA) was performed in MetaboAnalyst 3.0 after processing the datasets in Progenesis QI.

Results

Comparison of the datasets revealed significant and differential accumulation of iridoid and phenylethanoid/phenylpropanoid glycosides in the tissues of the endemic Scrophularia species and Verbascum thapsus.

Conclusions

Our investigation identified several species of pharmacological interest as good sources for harpagoside and other important anti-inflammatory metabolites.

     

Production,purification, characterization,immobilization, and application of Serrapeptase: a review

Background

Serrapeptase is a proteolytic enzyme with many favorable biological properties like anti-inflammatory, analgesic, anti-bacterial, fibrinolytic properties and hence, is widely used in clinical practice for the treatment of many diseases. Although Serrapeptase is widely used, there are very few published papers and the information available about the enzyme is very meagre. Hence this review article compiles all the information about this important enzyme Serrapeptase.

Methods

A literature search against various databases and search engines like PubMed, SpringerLink, Scopus etc. was performed.

Results

We gathered and highlight all the published information regarding the molecular aspects, properties, sources, production, purification, detection, optimizing yield, immobilization, clinical studies, pharmacology, interaction studies, formulation, dosage and safety of the enzyme Serrapeptase.

Conclusion

Serrapeptase is used in many clinical studies against various diseases for its anti-inflammatory, fibrinolytic and analgesic effects. There is insufficient data regarding the safety of the enzyme as a health supplement. Data about the antiatherosclerotic activity, safety, tolerability, efficacy and mechanism of action of the Serrapeptase are still required.

     

Implementation fidelity trajectories of a health promotion program in multidisciplinary settings: managing tensions in rehabilitation care

Background

Although the importance of evaluating implementation fidelity is acknowledged, little is known about heterogeneity in fidelity over time. This study aims to generate insight into the heterogeneity in implementation fidelity trajectories of a health promotion program in multidisciplinary settings and the relationship with changes in patients’ health behavior.

Methods

This study used longitudinal data from the nationwide implementation of an evidence-informed physical activity promotion program in Dutch rehabilitation care. Fidelity scores were calculated based on annual surveys filled in by involved professionals (n?=?±?70). Higher fidelity scores indicate a more complete implementation of the program’s core components. A hierarchical cluster analysis was conducted on the implementation fidelity scores of 17 organizations at three different time points. Quantitative and qualitative data were used to explore organizational and professional differences between identified trajectories. Regression analyses were conducted to determine differences in patient outcomes.

Results

Three trajectories were identified as the following: ‘stable high fidelity’ (n?=?9), ‘moderate and improving fidelity’ (n?=?6), and ‘unstable fidelity’ (n?=?2). The stable high fidelity organizations were generally smaller, started earlier, and implemented the program in a more structured way compared to moderate and improving fidelity organizations. At the implementation period’s start and end, support from physicians and physiotherapists, professionals’ appreciation, and program compatibility were rated more positively by professionals working in stable high fidelity organizations as compared to the moderate and improving fidelity organizations (p?<?.05). Qualitative data showed that the stable high fidelity organizations had often an explicit vision and strategy about the implementation of the program. Intriguingly, the trajectories were not associated with patients’ self-reported physical activity outcomes (adjusted model β?=???651.6, t(613)?=???1032, p?=?.303).

Conclusions

Differences in organizational-level implementation fidelity trajectories did not result in outcome differences at patient-level. This suggests that an effective implementation fidelity trajectory is contingent on the local organization’s conditions. More specifically, achieving stable high implementation fidelity required the management of tensions: realizing a localized change vision, while safeguarding the program’s standardized core components and engaging the scarce physicians throughout the process. When scaling up evidence-informed health promotion programs, we propose to tailor the management of implementation tensions to local organizations’ starting position, size, and circumstances.

Trial registration

The Netherlands National Trial Register NTR3961. Registered 18 April 2013.

     

Quantitative analysis of tetrahydrofolate metabolites from <Emphasis Type="Italic">clostridium autoethanogenum</Emphasis>

Introduction

Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.

Objective

To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.

Methods

Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.

Results

Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.

Conclusion

Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.

     

The EcoSpold 2 format—why a new format?

Purpose

This paper introduces the new EcoSpold data format for life cycle inventory (LCI).

Methods

A short historical retrospect on data formats in the life cycle assessment (LCA) field is given. The guiding principles for the revision and implementation are explained. Some technical basics of the data format are described, and changes to the previous data format are explained.

Results

The EcoSpold 2 data format caters for new requirements that have arisen in the LCA field in recent years.

Conclusions

The new data format is the basis for the Ecoinvent v3 database, but since it is an open data format, it is expected to be adopted by other LCI databases. Several new concepts used in the new EcoSpold 2 data format open the way for new possibilities for the LCA practitioners and to expand the application of the datasets in other fields beyond LCA (e.g., Material Flow Analysis, Energy Balancing).

     

A methodology for elucidating regulatory mechanisms leading to changes in lipid profiles

Introduction

It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.

Objectives

This work simplifies this process.

Methods

A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.

Results

The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.

Conclusion

This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.

     

KniMet: a pipeline for the processing of chromatography–mass spectrometry metabolomics data

Introduction

Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.

Objectives

Merge in the same platform the steps required for metabolomics data processing.

Methods

KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.

Results

The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.

Conclusion

KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.

     

<Emphasis Type="Italic">massPix</Emphasis>: an R package for annotation and interpretation of mass spectrometry imaging data for lipidomics

Introduction

Mass spectrometry imaging (MSI) experiments result in complex multi-dimensional datasets, which require specialist data analysis tools.

Objectives

We have developed massPix—an R package for analysing and interpreting data from MSI of lipids in tissue.

Methods

massPix produces single ion images, performs multivariate statistics and provides putative lipid annotations based on accurate mass matching against generated lipid libraries.

Results

Classification of tissue regions with high spectral similarly can be carried out by principal components analysis (PCA) or k-means clustering.

Conclusion

massPix is an open-source tool for the analysis and statistical interpretation of MSI data, and is particularly useful for lipidomics applications.