Studying de-implementation in health: an analysis of funded research grants

Background

Studying de-implementation—defined herein as reducing or stopping the use of a health service or practice provided to patients by healthcare practitioners and systems—has gained traction in recent years. De-implementing ineffective, unproven, harmful, overused, inappropriate, and/or low-value health services and practices is important for mitigating patient harm, improving processes of care, and reducing healthcare costs. A better understanding of the state-of-the-science is needed to guide future objectives and funding initiatives. To this end, we characterized de-implementation research grants funded by the United States (US) National Institutes of Health (NIH) and the Agency for Healthcare Research and Quality (AHRQ).

Methods

We used systematic methods to search, identify, and describe de-implementation research grants funded across all 27 NIH Institutes and Centers (ICs) and AHRQ from fiscal year 2000 through 2017. Eleven key terms and three funding opportunity announcements were used to search for research grants in the NIH Query, View and Report (QVR) system. Two coders identified eligible grants based on inclusion/exclusion criteria. A codebook was developed, pilot tested, and revised before coding the full grant applications of the final sample.

Results

A total of 1277 grants were identified through the QVR system; 542 remained after removing duplicates. After the multistep eligibility assessment and review process, 20 grant applications were coded. Many grants were funded by NIH (n?=?15), with fewer funded by AHRQ, and a majority were funded between fiscal years 2015 and 2016 (n?=?11). Grant proposals focused on de-implementing a range of health services and practices (e.g., medications, therapies, screening tests) across various health areas (e.g., cancer, cardiovascular disease) and delivery settings (e.g., hospitals, nursing homes, schools). Grants proposed to use a variety of study designs and research methods (e.g., experimental, observational, mixed methods) to accomplish study aims.

Conclusions

Based on the systematic portfolio analysis of NIH- and AHRQ-funded research grants over the past 17 years, relatively few have focused on studying the de-implementation of ineffective, unproven, harmful, overused, inappropriate, and/or low-value health services and practices provided to patients by healthcare practitioners and systems. Strategies for raising the profile and growing the field of research on de-implementation are discussed.

     

The role of interdisciplinary research team in the impact of health apps in health and computer science publications: a systematic review

Background

Several studies have estimated the potential economic and social impact of the mHealth development. Considering the latest study by Institute for Healthcare Informatics, more than 165.000 apps of health and medicine are offered including all the stores from different platforms. Thus, the global mHealth market was an estimated $10.5 billion in 2014 and is expected to grow 33.5 percent annually between 2015 and 2020s. In fact, apps of Health have become the third-fastest growing category, only after games and utilities.

Methods

This study aims to identify, study and evaluate the role of interdisciplinary research teams in the development of articles and applications in the field of mHealth. It also aims to evaluate the impact that the development of mHealth has had on the health and computer science field, through the study of publications in specific databases for each area which have been published until nowadays.

Results

Interdisciplinary nature is strongly connected to the scientific quality of the journal in which the work is published. This way, there are significant differences in those works that are made up by an interdisciplinary research team because of they achieve to publish in journals with higher quartiles. There are already studies that warn of methodological deficits in some studies in mHealth, low accuracy and no reproducibility. Studies of low precision and poor reproducibility, coupled with the low evidence, provide low degrees of recommendation of the interventions targeted and therefore low applicability.

Conclusions

From the evidence of this study, working in interdisciplinary groups from different areas greatly enhances the quality of research work as well as the quality of the publications derived from its results.

     

NMR-based metabolic characterization of chicken tissues and biofluids: a model for avian research

Introduction

Poultry is one of the most consumed meat in the world and its related industry is always looking for ways to improve animal welfare and productivity. It is therefore essential to understand the metabolic response of the chicken to new feed formulas, various supplements, infections and treatments.

Objectives

As a basis for future research investigating the impact of diet and infections on chicken’s metabolism, we established a high-resolution proton nuclear magnetic resonance (NMR)-based metabolic atlas of the healthy chicken (Gallus gallus).

Methods

Metabolic extractions were performed prior to ¹H-NMR and 2D NMR spectra acquisition on twelve biological matrices: liver, kidney, spleen, plasma, egg yolk and white, colon, caecum, faecal water, ileum, pectoral muscle and brain of 6 chickens. Metabolic profiles were then exhaustively characterized.

Results

Nearly 80 metabolites were identified. A cross-comparison of these matrices was performed to determine metabolic variations between and within each section and highlighted that only eight core metabolites were systematically found in every matrice.

Conclusion

This work constitutes a database for future NMR-based metabolomic investigations in relation to avian production and health.

     

The effect of family policies and public health initiatives on breastfeeding initiation among 18 high-income countries: a qualitative comparative analysis research design

Background

The objective of this study is to examine the effects of macro-level factors – welfare state policies and public health initiatives – on breastfeeding initiation among eighteen high-income countries.

Methods

This study utilizes fuzzy-set Qualitative Comparative Analysis methods to examine the combinations of conditions leading to both high and low national breastfeeding initiation rates among eighteen high-income countries.

Results

The most common pathway leading to high breastfeeding initiation is the combination of conditions including a high percentage of women in parliament, a low national cesarean section rate, and either low family spending, high rates of maternity leave, or high rates of women working part-time. The most common pathway leading to low breastfeeding initiation includes the necessary condition of low national adherence to the Baby-Friendly Hospital Initiative.

Conclusion

This research suggests that there is a connection between broad level welfare state polices, public health initiatives, and breastfeeding initiation. Compliance with the WHO/UNICEF initiatives depends on welfare regime policies and overall support for women in both productive and reproductive labor.

     

Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome

Context

Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance.

Objective

To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls.

Design

Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs.

Setting

Referral practice and research center.

Participants

60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test.

Main outcome measures

Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof.

Results

CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests.

Conclusion

A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition.

     

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.

     

Effectiveness of online learning on health researcher capacity to appropriately integrate sex,gender, or both in grant proposals

Background

To describe the effectiveness of online learning to augment academic capacity to consider sex and gender in the conduct of basic science, clinical research, and population health studies.

Method

The analysis compares pre- and post-test scores from 1441 individuals who completed the Canadian Institutes of Health Research Institute of Gender and Health’s interactive e-learning modules between February 2016 and May 2017. The tests measured knowledge, self-efficacy, and self-reported intent to change behavior for three competencies: (1) the ability to appropriately define and distinguish between sex-related versus gender-related variables, (2) the application of methods for integrating sex and gender, and (3) the critical appraisal of sex and gender integration in the design, methods, and analysis plan of research proposals and publications.

Results

Of the 543 individuals who completed the basic science module, 62% demonstrated improved knowledge, and 86% increased self-efficacy across all competencies. Gains in knowledge and self-efficacy also occurred among 84% and 77% of completers of the human data collection module (n?=?463) and among 73% and 82% of those who completed the secondary data analysis module (n?=?435). In aggregate, 95% of participants reported an intent to change their behavior with respect to sex and gender in health research.

Conclusions

Interactive online learning combined with feedback and self-assessment results in improved knowledge and self-efficacy for integrating sex and gender in health research.

     

Children as ethnobotanists: methods and local impact of a participatory research project with children on wild plant gathering in the Grosses Walsertal Biosphere Reserve,Austria

Background

Ethically sound research in applied ethnobiology should benefit local communities by giving them full access to research processes and results. Participatory research may ensure such access, but there has been little discussion on methodological details of participatory approaches in ethnobiological research. This paper presents and discusses the research processes and methods developed in the course of a three-year research project on wild plant gathering, the involvement of children as co-researchers and the project’s indications for local impact.

Method

Research was conducted in the Grosses Walsertal Biosphere Reserve, Austria, between 2008 and 2010 in four research phases. In phase 1, 36 freelist interviews with local people and participant observation was conducted. In phase 2 school workshops were held in 14 primary school classes and their 189 children interviewed 506 family members with structured questionnaires. In phase 3, 27 children and two researchers co-produced participatory videos. In phase 4 indications for the impact of the project were investigated with questionnaires from ten children and with participant observation.

Results

Children participated in various ways in the research process and the scientific output and local impact of the project was linked to the phases, degrees and methods of children’s involvement. Children were increasingly involved in the project, from non-participation to decision-making. Scientific output was generated from participatory and non-participatory activities whereas local impact - on personal, familial, communal and institutional levels - was mainly generated through the participatory involvement of children as interviewers and as co-producers of videos. Creating scientific outputs from participatory video is little developed in ethnobiology, whereas bearing potential.

Conclusions

As ethnobotanists and ethnobiologists, if we are truly concerned about the impact and benefits of our research processes and results to local communities, the details of the research processes need to be deliberately planned and evaluated and then reported and discussed in academic publications.

     

Factor XIII Val34Leu polymorphism and risk of recurrent pregnancy loss in Iranian population: a case control study

BACKGROUND

Recurrent pregnancy loss (RPL) is a heterogeneous condition and thrombophilias have been considered as a probable cause.

OBJECTIVE

The aim of this study was to investigate the prevalence of the coagulation factor XIII Val34Leu polymorphism among women with unexplained RPL.

METHODS

A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Val34Leu polymorphism among the cases and controls was investigated using PCR-RFLP method.

RESULTS

Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls (P<0.05): 33.5% vs. 15%, and 9.2% vs. 2%, respectively.

CONCLUSION

These results indicate a significant association between FXIII Val34Leu polymorphism and unexplained RPL in the Iranian patient.

     

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.

     

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 metabolomics guided exploration of marine natural product chemical space

Introduction

Natural products from culture collections have enormous impact in advancing discovery programs for metabolites of biotechnological importance. These discovery efforts rely on the metabolomic characterization of strain collections.

Objective

Many emerging approaches compare metabolomic profiles of such collections, but few enable the analysis and prioritization of thousands of samples from diverse organisms while delivering chemistry specific read outs.

Method

In this work we utilize untargeted LC–MS/MS based metabolomics together with molecular networking to inventory the chemistries associated with 1000 marine microorganisms.

Result

This approach annotated 76 molecular families (a spectral match rate of 28 %), including clinically and biotechnologically important molecules such as valinomycin, actinomycin D, and desferrioxamine E. Targeting a molecular family produced primarily by one microorganism led to the isolation and structure elucidation of two new molecules designated maridric acids A and B.

Conclusion

Molecular networking guided exploration of large culture collections allows for rapid dereplication of know molecules and can highlight producers of uniques metabolites. These methods, together with large culture collections and growing databases, allow for data driven strain prioritization with a focus on novel chemistries.

     

Corneal Collagen Cross-Linking for the Management of Mycotic Keratitis

Purpose

To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.

Design

Retrospective case series in a tertiary university hospital.

Participants

CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.

Methods

The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.

Main Outcome Measures

Grade of the corneal infection.

Results

Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).

Conclusions

The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.

     

Three-dimensional co-culture microfluidic model and its application for research on cancer stem-like cells inducing migration of endothelial cells

Objectives

To build a three-dimensional co-culture model in a microfluidic device for cancer research and evaluate its feasibility by investigating cancer stem-like cells (SCs) induced migration of human umbilical vein endothelial cells (ECs).

Results

The microfluidic device provided two-dimensional and three-dimensional (2D/3D) culture and co-culture environments without affecting cell viability. The device also provided an effective concentration for the chemiotaxis of cells, and to support real-time monitoring of cell behavior. In this model, SCs significantly increased the migration area of ECs with a hepatocarcinoma cell line (MHCC97H; MCs). The presence of ECs also induced both MCs and SCs invasion into Matrigel. The migration area of MCs and SCs significantly increased when co-cultured with ECs.

Conclusions

This 3D co-culture microfluidic model is a suitable model in cancer research. Compared with MCs, SCs had greater potential in inducing EC migration and interacting with ECs.

     

LacaScore: a novel plasma sample quality control tool based on ascorbic acid and lactic acid levels

Introduction

Metabolome analysis is complicated by the continuous dynamic changes of metabolites in vivo and ex vivo. One of the main challenges in metabolomics is the robustness and reproducibility of results, partially driven by pre-analytical variations.

Objectives

The objective of this study was to analyse the impact of pre-centrifugation time and temperature, and to determine a quality control marker in plasma samples.

Methods

Plasma metabolites were measured by gas chromatography-mass spectrometry (GC–MS) and analysed with the MetaboliteDetector software. The metabolites, which were the most labile to pre-analytical variations, were further measured by enzymatic assays. A score was calculated for their use as quality control markers.

Results

The pre-centrifugation temperature was shown to be critical in the stability of plasma samples and had a significant impact on metabolite concentration profiles. In contrast, pre-centrifugation delay had only a minor impact. Based on the results of this study, whole blood should be kept on wet ice and centrifuged within maximum 3 h as a prerequisite for preparing EDTA plasma samples fit for the purpose of metabolome analysis.

Conclusions

We have established a novel blood sample quality control marker, the LacaScore, based on the ascorbic acid to lactic acid ratio in plasma, which can be used as an indicator of the blood pre-centrifugation conditions, and hence the suitability of the sample for metabolome analyses. This method can be applied in research institutes and biobanks, enabling assessment of the quality of their plasma sample collections.

     

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.

     

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.

     

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.