Patients' and Members of the Public's Wishes Regarding Transparency in the Context of Secondary Use of Health Data: Scoping Review.

BACKGROUND: Secondary use of health data has reached unequaled potential to improve health systems governance, knowledge, and clinical care. Transparency regarding this secondary use is frequently cited as necessary to address deficits in trust and conditional support and to increase patient awareness. OBJECTIVE: We aimed to review the current published literature to identify different stakeholders' perspectives and recommendations on what information patients and members of the public want to learn about the secondary use of health data for research purposes and how and in which situations. METHODS: Using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines, we conducted a scoping review using Medline, CINAHL, PsycINFO, Scopus, Cochrane Library, and PubMed databases to locate a broad range of studies published in English or French until November 2022. We included articles reporting a stakeholder's perspective or recommendations of what information patients and members of the public want to learn about the secondary use of health data for research purposes and how or in which situations. Data were collected and analyzed with an iterative thematic approach using NVivo. RESULTS: Overall, 178 articles were included in this scoping review. The type of information can be divided into generic and specific content. Generic content includes information on governance and regulatory frameworks, technical aspects, and scientific aims. Specific content includes updates on the use of one's data, return of results from individual tests, information on global results, information on data sharing, and how to access one's data. Recommendations on how to communicate the information focused on frequency, use of various supports, formats, and wording. Methods for communication generally favored broad approaches such as nationwide publicity campaigns, mainstream and social media for generic content, and mixed approaches for specific content including websites, patient portals, and face-to-face encounters. Content should be tailored to the individual as much as possible with regard to length, avoidance of technical terms, cultural competence, and level of detail. Finally, the review outlined 4 major situations where communication was deemed necessary: before a new use of data, when new test results became available, when global research results were released, and in the advent of a breach in confidentiality. CONCLUSIONS: This review highlights how different types of information and approaches to communication efforts may serve as the basis for achieving greater transparency. Governing bodies could use the results: to elaborate or evaluate strategies to educate on the potential benefits; to provide some knowledge and control over data use as a form of reciprocity; and as a condition to engage citizens and build and maintain trust. Future work is needed to assess which strategies achieve the greatest outreach while striking a balance between meeting information needs and use of resources.

Safety and Efficacy of Paclitaxel-Eluting Balloon Angioplasty for Dysfunctional Hemodialysis Access: A randomized trial Comparing with Angioplasty Alone.

PURPOSE: To assess whether angioplasty of hemodialysis access (HA) stenosis with a drug-coated balloon (DCB) would prevent restenosis in comparison with plain-balloon percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: This prospective randomized clinical trial enrolled 120 patients with dysfunctional arteriovenous fistulae (n = 109) and grafts (n = 11), due to a ≥50% stenosis between March 2014 and April 2018. All patients underwent high-pressure balloon angioplasty and were then randomized to either DCB (n = 60) or PTA (n = 60). Patients were followed-up for 1 year, and angiography was performed 6 months after angioplasty. The primary endpoint was the late lumen loss (LLL) at 6 months. Secondary endpoints included other angiographic parameters at 6 months and HA failures, adverse event, and mortality at 12 months. Continuous variables were compared with a Student t-test, and Kaplan-Meier curves were used for freedom from HA failure and for mortality. RESULTS: LLL in the DCB and in the PTA group were 0.64 mm ± 1.20 and 1.13 mm ± 1.51, respectively (P = .082, adjusted P = .0498). DCB was associated with lower percentage stenosis (54.2% ± 19.3 vs 61.7% ± 18.2; P = .047) and binary restenosis ≥50% (56.5% vs 81.1%; P = .009) than PTA. The number of HA failures after 12 months was lower for DCB than for PTA (45% vs 66.7%; P = .017). Mortality at 12 months was 10% and 8.3% in the DCB and PTA groups, respectively (P = .75). CONCLUSIONS: Despite LLL improvement that failed to reach statistical significance, this study demonstrated decreased incidence and severity of restenosis with DCB compared with PTA to treat dysfunctional HA.

Meta-consent for the secondary use of health data within a learning health system: a qualitative study of the public's perspective.

BACKGROUND: The advent of learning healthcare systems (LHSs) raises an important implementation challenge concerning how to request and manage consent to support secondary use of data in learning cycles, particularly research activities. Current consent models in Quebec were not established with the context of LHSs in mind and do not support the agility and transparency required to obtain consent from all involved, especially the citizens. Therefore, a new approach to consent is needed. Previous work identified the meta-consent model as a promising alternative to fulfill the requirements of LHSs, particularly large-scale deployments. We elicited the public's attitude toward the meta-consent model to evaluate if the model could be understood by the citizens and would be deemed acceptable to prepare for its possible implementation in Quebec. METHODS: Eight focus groups, with a total of 63 members of the general public from various backgrounds were conducted in Quebec, Canada, in 2019. Explicit attention was given to literacy levels, language spoken at home and rural vs urban settings. We assessed attitudes, concerns and facilitators regarding key components of the meta-consent model: predefined categories to personalized consent requests, a dynamic web-based infrastructure to record meta-consent, and default settings. To analyse the discussions, a thematic content analysis was performed using a qualitative software. RESULTS: Our findings showed that participants were supportive of this new approach of consent as it promotes transparency and offers autonomy for the management of their health data. Key facilitators were identified to be considered in the implementation of a meta-consent model in the Quebec LHSs: information and transparency, awareness campaigns, development of educational tools, collaboration of front-line healthcare professionals, default settings deemed acceptable by the society as well as close partnerships with recognized and trusted institutions. CONCLUSIONS: This qualitative study reveals the openness of a sample of the Quebec population regarding the meta-consent model for secondary use of health data for research. This first exploratory study conducted with the public is an important step in guiding decision-makers in the next phases of implementing the various strategies to support access and use of health data in Quebec.

A pharmacist-physician intervention model using a computerized alert system to reduce high-risk medication use in primary care.

PURPOSE: Potentially inappropriate medications (PIMs) have been associated with a greater risk of adverse drug events and hospitalizations. To reduce PIMs use, a family health team (FHT) implemented a knowledge translation (KT) strategy that included a pharmacist-physician intervention model based on alerts from a computerized alert system (CAS). METHODS: Our pragmatic, single-site, pilot study was conducted in an FHT clinic in Quebec, Canada. We included community-dwelling older adults (≥ 65 years), with at least 1 alert for selected PIMs and a medical appointment during the study period. PIMs were selected from the Beers and STOPP criteria. The primary outcome was PIMs cessation, decreased dose, or replacement. The secondary outcome was the clinical relevance of the alerts as assessed by the pharmacists. RESULTS: During the 134 days of the study, the CAS screened 369 individuals leading to the identification of 65 (18%) patients with at least 1 new alert. For those 65 patients, the mean age was 77 years, men accounted for 29% of the group and 55% were prescribed 10 or more drugs. One or more clinically relevant alerts were generated for 27 of 65 included patients for an overall clinical relevance of the alerts of 42%. Of the 27 patients with at least 1 relevant alert, 17 (63%) had at least 1 medication change as suggested by the pharmacist. CONCLUSION: An interdisciplinary pharmacist-physician intervention model, based on alerts generated by a CAS, reduced the use of PIMs in community-dwelling older adults followed by an FHT.

A Simplified Approach to Extravascular Lung Water Assessment Using Point-of-Care Ultrasound in Patients with End-Stage Chronic Renal Failure Undergoing Hemodialysis.

BACKGROUND: Fluid overload leading to pulmonary congestion is an important issue in patients undergoing hemodialysis. This study aimed to determine if a simplified method of extravascular lung water assessment using ultrasound provided clinically relevant information. METHODS: This prospective study recruited 47 patients from a single hemodialysis center. Pulmonary ultrasound was performed before and after 2 hemodialysis sessions in 28 regions on the thorax. The B-line score was defined as the percentage regions where B-lines were present. RESULTS: When B-lines were detected before hemodialysis, a significant relationship was found between fluid removal and the change in B-line score. Patients with a B-line score of ≥21.4% (4th quartile) after the second hemodialysis session were more likely to be hospitalized for pulmonary edema or acute coronary syndrome. CONCLUSIONS: A simplified pulmonary assessment using ultrasound provides relevant information about pulmonary congestion in hemodialysis patients and identifies patients at risk of hospitalization for heart-related problems.

Reduction in targeted potentially inappropriate medication use in elderly inpatients: a pragmatic randomized controlled trial.

PURPOSE: The use of potentially inappropriate medications (PIMs) in hospitalized older adults is a complex problem, but the use of computerized alert systems (CAS) has shown some potential. The study's objective is to assess the change in PIM use with a CAS-based pharmacist-physician intervention model compared to usual clinical care. METHODS: Pragmatic single-site randomized controlled trial was conducted at a university teaching hospital. Hospitalizations identified with selected Beers or STOPP criteria were randomized to usual clinical care or to the CAS-based pharmacist-physician intervention. The primary outcome was PIM drug cessation or dosage decrease. Clinical relevance of the CAS alerts was assessed. RESULTS: Analyses included 231 patients who had 128 and 126 hospitalizations in the control and intervention groups, respectively. Patients had a mean age of 81, and 60% were female. In the intervention compared to the control group, drug cessation or dosage decrease were more frequent at 48 h post-alert (45.8 vs 15.9%; absolute difference 30.0%; 95%CI 13.8 to 46.1%) and at discharge from the hospital (48.1 vs 27.3%; absolute difference 20.8%; 95%CI 4.6 to 37.0%). In a post hoc analysis of all alerts, regardless of their clinical relevance, the absolute difference in drug cessation or dosage decrease between the intervention and control groups was 16.2% (95%CI 2.9 to 29.6%) at 48 h and 8.0% (95%CI -4.0 to 20.0%) at discharge from the hospital. CONCLUSIONS: In hospitalized older adults, a CAS-based pharmacist-physician intervention, compared to usual clinical care, resulted in significant higher number of drug cessation and dosage reductions for targeted PIMs.

Sex-specific differences in hemodialysis prevalence and practices and the male-to-female mortality rate: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: A comprehensive analysis of sex-specific differences in the characteristics, treatment, and outcomes of individuals with end-stage renal disease undergoing dialysis might reveal treatment inequalities and targets to improve sex-specific patient care. Here we describe hemodialysis prevalence and patient characteristics by sex, compare the adult male-to-female mortality rate with data from the general population, and evaluate sex interactions with mortality. METHODS AND FINDINGS: We assessed the Human Mortality Database and 206,374 patients receiving hemodialysis from 12 countries (Australia, Belgium, Canada, France, Germany, Italy, Japan, New Zealand, Spain, Sweden, the UK, and the US) participating in the international, prospective Dialysis Outcomes and Practice Patterns Study (DOPPS) between June 1996 and March 2012. Among 35,964 sampled DOPPS patients with full data collection, we studied patient characteristics (descriptively) and mortality (via Cox regression) by sex. In all age groups, more men than women were on hemodialysis (59% versus 41% overall), with large differences observed between countries. The average estimated glomerular filtration rate at hemodialysis initiation was higher in men than women. The male-to-female mortality rate ratio in the general population varied from 1.5 to 2.6 for age groups <75 y, but in hemodialysis patients was close to one. Compared to women, men were younger (mean = 61.9 ± standard deviation 14.6 versus 63.1 ± 14.5 y), were less frequently obese, were more frequently married and recipients of a kidney transplant, more frequently had coronary artery disease, and were less frequently depressed. Interaction analyses showed that the mortality risk associated with several comorbidities and hemodialysis catheter use was lower for men (hazard ratio [HR] = 1.11) than women (HR = 1.33, interaction p<0.001). This study is limited by its inability to establish causality for the observed sex-specific differences and does not provide information about patients not treated with dialysis or dying prior to a planned start of dialysis. CONCLUSIONS: Women's survival advantage was markedly diminished in hemodialysis patients. The finding that fewer women than men were being treated with dialysis for end-stage renal disease merits detailed further study, as the large discrepancies in sex-specific hemodialysis prevalence by country and age group are likely explained by factors beyond biology. Modifiable variables, such as catheter use, showing significant sex interactions suggest interventional targeting. Please see later in the article for the Editors' Summary.

Building ontology-based temporal databases for data reuse: An applied example on hospital organizational structures.

Keeping track of data semantics and data changes in the databases is essential to support retrospective studies and the reproducibility of longitudinal clinical analysis by preventing false conclusions from being drawn from outdated data. A knowledge model combined with a temporal model plays an essential role in organizing the data and improving query expressiveness across time and multiple institutions. This paper presents a modelling framework for temporal relational databases using an ontology to derive a shareable and interoperable data model. The framework is based on: OntoRela an ontology-driven database modelling approach and Unified Historicization Framework a temporal database modelling approach. The method was applied to hospital organizational structures to show the impact of tracking organizational changes on data quality assessment, healthcare activities and data access rights. The paper demonstrated the usefulness of an ontology to provide a formal, interoperable, and reusable definition of entities and their relationships, as well as the adequacy of the temporal database to store, trace, and query data over time.

Distributed Statistical Analyses: A Scoping Review and Examples of Operational Frameworks Adapted to Health Analytics.

BACKGROUND: Data from multiple organizations are crucial for advancing learning health systems. However, ethical, legal, and social concerns may restrict the use of standard statistical methods that rely on pooling data. Although distributed algorithms offer alternatives, they may not always be suitable for health frameworks. OBJECTIVE: This paper aims to support researchers and data custodians in three ways: (1) providing a concise overview of the literature on statistical inference methods for horizontally partitioned data; (2) describing the methods applicable to generalized linear models (GLM) and assessing their underlying distributional assumptions; (3) adapting existing methods to make them fully usable in health settings. METHODS: A scoping review methodology was employed for the literature mapping, from which methods presenting a methodological framework for GLM analyses with horizontally partitioned data were identified and assessed from the perspective of applicability in health settings. Statistical theory was used to adapt methods and to derive the properties of the resulting estimators. RESULTS: From the review, 41 articles were selected, and six approaches were extracted for conducting standard GLM-based statistical analysis. However, these approaches assumed evenly and identically distributed data across nodes. Consequently, statistical procedures were derived to accommodate uneven node sample sizes and heterogeneous data distributions across nodes. Workflows and detailed algorithms were developed to highlight information-sharing requirements and operational complexity. CONCLUSIONS: This paper contributes to the field of health analytics by providing an overview of the methods that can be used with horizontally partitioned data, by adapting these methods to the context of heterogeneous health data and by clarifying the workflows and quantities exchanged by the methods discussed. Further analysis of the confidentiality preserved by these methods is needed to fully understand the risk associated with the sharing of summary statistics.

Effect of on-demand vs continuous prescription of proton pump inhibitors on symptom burden and quality of life: results of a real-world randomized controlled trial in primary care patients with gastroesophageal reflux disease.

OBJECTIVES: This study aimed to assess the impact of on-demand versus continuous prescribing of proton pump inhibitors (PPIs) on symptom burden and health-related quality of life in patients with gastroesophageal reflux disease (GERD) presenting to primary care. METHODS: Thirty-six primary care centres across Europe enrolled adult GERD patients from electronic health records. Participants were randomised to on-demand or continuous PPI prescriptions and were followed for 8 weeks. PPI intake, symptom burden, and quality of life were compared between the two groups using mixed-effect regression analyses. Spearman's correlation was used to assess the association between changes in PPI dose and patient-reported outcomes. RESULTS: A total of 488 patients (median age 51 years, 58% women) completed the initial visit, with 360 attending the follow-up visit. There was no significant difference in PPI use between the continuous and on-demand prescription groups (b=.57, 95%CI:0.40-1.53), although PPI use increased in both groups (b = 1.33, 95%CI:0.65 - 2.01). Advice on prescribing strategy did not significantly affect patient-reported outcomes. Both symptom burden (Reflux Disease Questionnaire, b=-0.61, 95%CI:-0.73 - -0.49) and quality of life (12-item Short Form Survey physical score b = 3.31, 95%CI:2.17 - 4.45) improved from baseline to follow-up in both groups. Increased PPI intake correlated with reduced reflux symptoms (n = 347, ρ=-0.12, p = 0.02) and improved quality of life (n = 217, ρ = 0.16, p = 0.02). CONCLUSION: In real-world settings, both continuous and on-demand PPI prescriptions resulted in similar increases in PPI consumption with no difference in treatment effects. Achieving an adequate PPI dose to alleviate reflux symptom burden improves quality of life in GERD patients. EudraCT number 2014-001314-25.

Continuous and on-demand prescription increase in proton pump inhibitor consumption equally in real-world settings and did not result in different outcomes.Reaching a sufficient dose of proton pump inhibitor to reduce reflux symptom burden improves quality of life in patients with gastroesophageal reflux disease.

Vascular access care and treatment practices associated with outcomes of arteriovenous fistula: international comparisons from the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Vascular access (VA) guidelines recommend the native arteriovenous fistula (AVF) as VA of first choice for chronic hemodialysis patients. AVF management is important in hemodialysis patient care. AVF survival is associated with various physical factors, but the effects of dialysis treatment factors upon AVF survival are still not clear. METHODS: Study patients were treated at 498 dialysis facilities participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) 2 or 3 (2002-2007). Analyses included 1,183 incident hemodialysis patients (on dialysis ≤7 days and using an AVF at study entry) and 949 prevalent patients (on dialysis >7 days at DOPPS entry and using a new AVF created during study observation). AVF survival was modeled from the study entry date for incident patients and date of first AVF use for prevalent patients. Predictors of primary and final AVF survival were compared across Japan, North America and Europe/Australia/New Zealand (EUR/ANZ) with adjustments for patient characteristics. RESULTS: No meaningful relationship was seen between AVF survival and various physician and staff practices. However, patients with prior catheter use displayed higher rates of primary and final AVF failure. Final AVF failure rates were higher in facilities with higher median blood flow rates (BFR). They were also greater in North America and EUR/ANZ than in Japan, but this difference was substantially attenuated after accounting for regional differences in facility median BFR. CONCLUSION: AVF longevity differed according to the DOPPS region, and was related to prior patient catheter use and facility BFR practice. Further longitudinal studies may help demonstrate meaningful associations between VA-handling skill and patency.

NRF2 Deficiency Attenuates Diabetic Kidney Disease in Db/Db Mice via Down-Regulation of Angiotensinogen, SGLT2, CD36, and FABP4 Expression and Lipid Accumulation in Renal Proximal Tubular Cells.

The role(s) of nuclear factor erythroid 2-related factor 2 (NRF2) in diabetic kidney disease (DKD) is/are controversial. We hypothesized that Nrf2 deficiency in type 2 diabetes (T2D) db/db mice (db/dbNrf2 knockout (KO)) attenuates DKD progression through the down-regulation of angiotensinogen (AGT), sodium-glucose cotransporter-2 (SGLT2), scavenger receptor CD36, and fatty -acid-binding protein 4 (FABP4), and lipid accumulation in renal proximal tubular cells (RPTCs). Db/dbNrf2 KO mice were studied at 16 weeks of age. Human RPTCs (HK2) with NRF2 KO via CRISPR-Cas9 genome editing and kidneys from patients with or without T2D were examined. Compared with db/db mice, db/dbNrf2 KO mice had lower systolic blood pressure, fasting blood glucose, kidney hypertrophy, glomerular filtration rate, urinary albumin/creatinine ratio, tubular lipid droplet accumulation, and decreased expression of AGT, SGLT2, CD36, and FABP4 in RPTCs. Male and female mice had similar results. NRF2 KO attenuated the stimulatory effect of the Nrf2 activator, oltipraz, on AGT, SGLT2, and CD36 expression and high-glucose/free fatty acid (FFA)-stimulated lipid accumulation in HK2. Kidneys from T2D patients exhibited markedly higher levels of CD36 and FABP4 in RPTCs than kidneys from non-diabetic patients. These data suggest that NRF2 exacerbates DKD through the stimulation of AGT, SGLT2, CD36, and FABP4 expression and lipid accumulation in RPTCs of T2D.

Using an Ontology to Derive a Sharable and Interoperable Relational Data Model for Heterogeneous Healthcare Data and Various Applications.

BACKGROUND: A large volume of heavily fragmented data is generated daily in different healthcare contexts and is stored using various structures with different semantics. This fragmentation and heterogeneity make secondary use of data a challenge. Data integration approaches that derive a common data model from sources or requirements have some advantages. However, these approaches are often built for a specific application where the research questions are known. Thus, the semantic and structural reconciliation is often not reusable nor reproducible. A recent integration approach using knowledge models has been developed with ontologies that provide a strong semantic foundation. Nonetheless, deriving a data model that captures the richness of the ontology to store data with their full semantic remains a challenging task. OBJECTIVES: This article addresses the following question: How to design a sharable and interoperable data model for storing heterogeneous healthcare data and their semantic to support various applications? METHOD: This article describes a method using an ontological knowledge model to automatically generate a data model for a domain of interest. The model can then be implemented in a relational database which efficiently enables the collection, storage, and retrieval of data while keeping semantic ontological annotations so that the same data can be extracted for various applications for further processing. RESULTS: This article (1) presents a comparison of existing methods for generating a relational data model from an ontology using 23 criteria, (2) describes standard conversion rules, and (3) presents O n t o R e l a , a prototype developed to demonstrate the conversion rules. CONCLUSION: This work is a first step toward automating and refining the generation of sharable and interoperable relational data models using ontologies with a freely available tool. The remaining challenges to cover all the ontology richness in the relational model are pointed out.

Reactive oxygen species promote caspase-12 expression and tubular apoptosis in diabetic nephropathy.

Apoptosis of tubular epithelial cells contributes to the tubular atrophy that accompanies diabetic nephropathy. Reactive oxygen species (ROS) promote tubular apoptosis, but the mechanisms by which this occurs are incompletely understood. Here, we sought proapoptotic genes that ROS differentially upregulate in renal proximal tubular cells of diabetic (db/db) mice. We performed microarray analysis using total RNA from freshly isolated renal proximal tubules of nondiabetic, diabetic, and diabetic transgenic mice overexpressing catalase in the proximal tubule (thereby attenuating ROS). We observed greater expression of caspase-12 in the proximal tubules of the diabetic mice compared with the nondiabetic and diabetic transgenic mice. Quantitative PCR and immunohistochemistry confirmed the enhanced expression of caspase-12, as well as members of the endoplasmic reticulum stress-induced apoptotic pathway. Ex vivo, albumin induced caspase-12 activity and expression (protein and mRNA) and mRNA expression of the CCAT/enhancer-binding protein homologous protein in freshly isolated wild-type proximal tubules but not in catalase-overexpressing proximal tubules. In vitro, albumin stimulated activity of both caspase-12 and caspase-3 as well as expression of caspase-12 and CCAT/enhancer-binding protein homologous protein in a human proximal tubule cell line (HK-2). The free radical scavenger tiron inhibited these effects. Furthermore, knockdown of caspase-12 with small interfering RNA reduced albumin-induced apoptosis in HK-2 cells. Taken together, these studies demonstrate that albuminuria may induce tubular apoptosis through generation of ROS and the subsequent expression and activation of endoplasmic reticulum stress genes in the diabetic kidney.

Expected clinical utility of automatable prediction models for improving palliative and end-of-life care outcomes: Toward routine decision analysis before implementation.

OBJECTIVE: The study sought to evaluate the expected clinical utility of automatable prediction models for increasing goals-of-care discussions (GOCDs) among hospitalized patients at the end of life (EOL). MATERIALS AND METHODS: We built a decision model from the perspective of clinicians who aim to increase GOCDs at the EOL using an automated alert system. The alternative strategies were 4 prediction models-3 random forest models and the Modified Hospital One-year Mortality Risk model-to generate alerts for patients at a high risk of 1-year mortality. They were trained on admissions from 2011 to 2016 (70 788 patients) and tested with admissions from 2017-2018 (16 490 patients). GOCDs occurring in usual care were measured with code status orders. We calculated the expected risk difference (beneficial outcomes with alerts minus beneficial outcomes without alerts among those at the EOL), the number needed to benefit (number of alerts needed to increase benefit over usual care by 1 outcome), and the net benefit (benefit minus cost) of each strategy. RESULTS: Models had a C-statistic between 0.79 and 0.86. A code status order occurred during 2599 of 3773 (69%) hospitalizations at the EOL. At a risk threshold corresponding to an alert prevalence of 10%, the expected risk difference ranged from 5.4% to 10.7% and the number needed to benefit ranged from 5.4 to 10.9 alerts. Using revealed preferences, only 2 models improved net benefit over usual care. A random forest model with diagnostic predictors had the highest expected value, including in sensitivity analyses. DISCUSSION: Prediction models with acceptable predictive validity differed meaningfully in their ability to improve over usual decision making. CONCLUSIONS: An evaluation of clinical utility, such as by using decision curve analysis, is recommended after validating a prediction model because metrics of model predictiveness, such as the C-statistic, are not informative of clinical value.

The Prescription of Drug Ontology 2.0 (PDRO): More Than the Sum of Its Parts.

While drugs and related products have profoundly changed the lives of people around the world, ongoing challenges remain, including inappropriate use of a drug product. Inappropriate uses can be explained in part by ambiguous or incomplete information, for example, missing reasons for treatments, ambiguous information on how to take a medication, or lack of information on medication-related events outside the health care system. In order to fully assess the situation, data from multiple systems (electronic medical records, pharmacy and radiology information systems, laboratory management systems, etc.) from multiple organizations (outpatient clinics, hospitals, long-term care facilities, laboratories, pharmacies, registries, governments) on a large geographical scale is needed. Formal knowledge models like ontologies can help address such an information integration challenge. Existing approaches like the Observational Medical Outcomes Partnership are discussed and contrasted with the use of ontologies and systems using them for data integration. The PRescription Drug Ontology 2.0 (PDRO 2.0) is then presented and entities that are paramount in addressing this problematic are described. Finally, the benefits of using PDRO are discussed through a series of exemplar situation.

Citizens, Research Ethics Committee Members and Researchers' Attitude Toward Information and Consent for the Secondary Use of Health Data: Implications for Research Within Learning Health Systems.

A survey was conducted to assess citizens, research ethics committee members, and researchers' attitude toward information and consent for the secondary use of health data for research within learning health systems (LHSs). Results show that the reuse of health data for research to advance knowledge and improve care is valued by all parties; consent regarding health data reuse for research has fundamental importance particularly to citizens; and all respondents deemed important the existence of a secure website to support the information and consent processes. This survey was part of a larger project that aims at exploring public perspectives on alternate approaches to the current consent models for health data reuse to take into consideration the unique features of LHSs. The revised model will need to ensure that citizens are given the opportunity to be better informed about upcoming research and have their say, when possible, in the use of their data.

Overexpression of Nrf2 in Renal Proximal Tubular Cells Stimulates Sodium-Glucose Cotransporter 2 Expression and Exacerbates Dysglycemia and Kidney Injury in Diabetic Mice.

We investigated the impact of nuclear factor erythroid 2-related factor 2 (Nrf2) overexpression in renal proximal tubular cells (RPTCs) on blood glucose, kidney injury, and sodium-glucose cotransporter 2 (Sglt2) expression in diabetic Akita Nrf2 -/-/Nrf2RPTC transgenic (Tg) mice. Immortalized human RPTCs (HK2) stably transfected with plasmid containing the SGLT2 promoter and human kidneys from patients with diabetes were also studied. Nrf2 overexpression was associated with increased blood glucose, glomerular filtration rate, urinary albumin-to-creatinine ratio, tubulointerstitial fibrosis, and Sglt2 expression in Akita Nrf2 -/-/Nrf2RPTC Tg mice compared with their Akita Nrf2 -/- littermates. In vitro, oltipraz or transfection of NRF2 cDNA stimulated SGLT2 expression and SGLT2 promoter activity in HK2, and these effects were inhibited by trigonelline or NRF2 siRNA. The deletion of the NRF2-responsive element (NRF2-RE) in the SGLT2 promoter abolished the stimulatory effect of oltipraz on SGLT2 promoter activity. NRF2 binding to the NRF2-RE of the SGLT2 promoter was confirmed by gel mobility shift assay and chromatin immunoprecipitation assays. Kidneys from patients with diabetes exhibited higher levels of NRF2 and SGLT2 in the RPTCs than kidneys from patients without diabetes. These results suggest a link by which NRF2 mediates hyperglycemia stimulation of SGLT2 expression and exacerbates blood glucose and kidney injury in diabetes.

Informed consent within a learning health system: A scoping review.

INTRODUCTION: A major consideration for the implementation of a learning health system (LHS) is consent from participants to the use of their data for research purposes. The main objective of this paper was to identify in the literature which types of consent have been proposed for participation in research observational activities in a LHS. We were particularly interested in understanding which approaches were seen as most feasible and acceptable and in which context, in order to inform the development of a Quebec-based LHS. METHODS: Using a scoping review methodology, we searched scientific and legal databases as well as the gray literature using specific terms. Full-text articles were reviewed independently by two authors on the basis of the following concepts: (a) LHS and (b) approach to consent. The selected papers were imported in NVivo software for analysis in the light of a conceptual framework that distinguishes various, largely independent dimensions of consent. RESULTS: A total of 93 publications were analysed for this review. Several studies reach opposing conclusions concerning the best approach to consent within a LHS. However, in the light of the conceptual framework we developed, we found that many of these results are distorted by the conflation between various characteristics of consent. Thus, when these characteristics are distinguished, the results mainly suggest the prime importance of the communication process, by contrast to the scope of consent or the kind of action required by participants (opt-in/opt-out). We identified two models of consent that were especially relevant for our purpose: metaconsent and dynamic consent. CONCLUSIONS: Our review shows the importance of distinguishing carefully the various features of the consent process. It also suggests that the metaconsent model is a valuable model within a LHS, as it addresses many of the issues raised with regards to feasibility and acceptability. We propose to complement this model by adding the modalities of the information process to the dimensions relevant in the metaconsent process.