From Data to Wisdom: Biomedical Knowledge Graphs for Real-World Data Insights.

Graph data models are an emerging approach to structure clinical and biomedical information. These models offer intriguing opportunities for novel approaches in healthcare, such as disease phenotyping, risk prediction, and personalized precision care. The combination of data and information in a graph model to create knowledge graphs has rapidly expanded in biomedical research, but the integration of real-world data from the electronic health record has been limited. To broadly apply knowledge graphs to EHR and other real-world data, a deeper understanding of how to represent these data in a standardized graph model is needed. We provide an overview of the state-of-the-art research for clinical and biomedical data integration and summarize the potential to accelerate healthcare and precision medicine research through insight generation from integrated knowledge graphs.

Characteristics of Chiropractic Patients in the Veterans Health Administration During the COVID-19 Pandemic: A Cross-Sectional Analysis.

OBJECTIVE: The purpose of this study was to determine whether patient characteristics were associated with face-to-face (F2F) and telehealth visits for those receiving chiropractic care for musculoskeletal conditions in the US Veterans Health Administration (VHA) during the COVID-19 pandemic. METHODS: A retrospective cross-sectional analysis of all patients (veterans, dependents, and spouses) who received chiropractic care nationwide at the VHA from March 1, 2020, to February 28, 2021, was performed. Patients were allocated into 1 of the following 3 groups: only telehealth visits, only F2F visits, and combined F2F and telehealth visits. Patient characteristics included age, sex, race, ethnicity, marital status, and Charlson Comorbidity Index. Multinomial logistic regression estimated associations of these variables with visit type. RESULTS: The total number of unique patients seen by chiropractors between March 2020 and February 2021 was 62 658. Key findings were that patients of non-White race and Hispanic or Latino ethnicity were more likely to attend telehealth-only visits (Black [odds ratio 1.20, 95% confidence interval {1.10-1.31}], other races [1.36 {1.16-1.59}], and Hispanic or Latino [1.35 {1.20-1.52}]) and combination telehealth and F2F care (Black [1.32 {1.25-1.40}], other races [1.37 {1.23-1.52}], and Hispanic or Latino [1.63 {1.51-1.76}]). Patients younger than 40 years of age were more likely to choose telehealth visits ([1.13 {1.02-1.26}], 66-75 years [1.17 {1.01-1.35}], and >75 years [1.26 {1.06-1.51}] vs those 40-55 years of age). Sex, visit frequency, and Charlson Comorbidity Index showed significant relationships as well, while marital status did not. CONCLUSION: During the COVID-19 pandemic, VHA patients with musculoskeletal complaints using chiropractic telehealth were more ethnically and racially diverse than those using F2F care alone.

LinkedImm: a linked data graph database for integrating immunological data.

BACKGROUND: Many systems biology studies leverage the integration of multiple data types (across different data sources) to offer a more comprehensive view of the biological system being studied. While SQL (Structured Query Language) databases are popular in the biomedical domain, NoSQL database technologies have been used as a more relationship-based, flexible and scalable method of data integration. RESULTS: We have created a graph database integrating data from multiple sources. In addition to using a graph-based query language (Cypher) for data retrieval, we have developed a web-based dashboard that allows users to easily browse and plot data without the need to learn Cypher. We have also implemented a visual graph query interface for users to browse graph data. Finally, we have built a prototype to allow the user to query the graph database in natural language. CONCLUSION: We have demonstrated the feasibility and flexibility of using a graph database for storing and querying immunological data with complex biological relationships. Querying a graph database through such relationships has the potential to discover novel relationships among heterogeneous biological data and metadata.

Knowledge, socio-cognitive perceptions and the practice of hand hygiene and social distancing during the COVID-19 pandemic: a cross-sectional study of UK university students.

BACKGROUND: During the first wave of the COVID-19 pandemic, social distancing and hand hygiene have been the primary means of reducing transmission in the absence of effective treatments or vaccines, but understanding of their determinants is limited. This study aimed to investigate knowledge and socio-cognitive perceptions, and their associations with such protective behaviours, in UK university students. METHODS: A cross-sectional online survey of 293 students was undertaken on 13 May 2020. Survey questions addressed demographics, knowledge of the disease and effectiveness of the protective measures, risk perception, socio-cognitive perceptions (e.g. attitude, social support, and self-efficacy), habit, time factors and trust, as well as the hand hygiene and social distancing behaviours. Multiple linear regression was used to identify the strongest associations of potential determinants with behaviour. RESULTS: Participants reported high levels of social distancing with 88.9% answering "Mostly" or "Always" for every activity, but only 42.0% reporting the same for all hand hygiene activities. Knowledge of the effectiveness of each activity in preventing transmission was high, with 90.7% and 93.5% respectively identifying at least 7 of 8 hand hygiene or 9 of 10 social distancing activities correctly. Habit (ß = 0.39, p = 0.001) and time factors (ß = 0.28, p = 0.001) were the greatest contributors to unique variance in hand hygiene behaviour, followed by ethnicity (ß = - 0.13, p = 0.014) and risk perception (ß = 0.13, p = 0.016). For social distancing behaviour, the determinants were self-efficacy (ß = 0.25, p < 0.001), perceived advantages (ß = 0.15, p = 0.022), trust in policy (ß = 0.14, p = 0.026) and gender (ß = - 0.14, p = 0.016). Regression models explained 40% hand hygiene and 25% social distancing variance. CONCLUSIONS: This study indicated that communications about effectiveness of hand hygiene and social distancing behaviours had been effective in terms of knowledge acquisition. However, in the light of likely second waves of COVID-19, attention to maintaining social distancing behaviour and improving hand hygiene behaviour may need to address more difficult areas of changing habits, overcoming time factors and building trust, as well as interventions to increase self-efficacy and address risk perception concerns.

Knowledge and perceptions of Alzheimer's disease in three ethnic groups of younger adults in the United Kingdom.

BACKGROUND: Alzheimer's disease (AD) is a global public health problem with an ageing population. Knowledge is essential to promote early awareness, diagnosis and treatment of AD symptoms. AD knowledge is influenced by many cultural factors including cultural beliefs, attitudes and language barriers. This study aims: (1) to define AD knowledge level and perceptions amongst adults between 18 and 49 years of age in the UK; (2) to compare knowledge and perceptions of AD among three main ethnic groups (Asian, Blacks, and Whites); and (3) to assess potential associations of age, gender, education level, affinity with older people (65 or over), family history and caregiving history with AD knowledge. METHODS: Data was collected from 186 participants as a convenience sample of younger adults of three different ethnicities (16.1% Asian, 16.7% Black, 67.2% White), living in the UK, recruited via an online research platform. The majority of the participants were in the 18-34 years age group (87.6%). Demographic characteristics of participants and AD knowledge correlation were assessed by the 30-item Alzheimer's Disease Knowledge Scale (ADKS), comprising 7 content domains. ANOVA/ANCOVA were used to assess differences in AD knowledge by ethnicity, gender, education level, age and affinity with dementia and Alzheimer's patients. RESULTS: For AD general knowledge across all respondents only 45.0% answers were correct. No significant differences were found for the total ADKS score between ethnicities in this younger age group, who did not differ in education level. However, there were significant knowledge differences for the ADKS symptom domain score even after controlling for other demographics variables such as gender, education level (p = 0.005). White respondents were more likely to know about AD symptoms than their Black counterparts (p = 0.026). CONCLUSION: The study's findings suggest that the AD knowledge level is not adequate for all ethnic groups. Meanwhile, significant differences were observed in symptoms, between ethnic groups, and therefore, differ in their needs regards health communication. The study contributes to an understanding of ethnicity differences in AD knowledge amongst adults from 18 to 49 years of age in the UK and may also provide input into an intervention plan for different ethnicities' information needs.

Spoken Animated Self-Management Video Messages Aimed at Improving Physical Activity in People With Type 2 Diabetes: Development and Interview Study.

BACKGROUND: Web-based tailored interventions are a promising approach to help people with type 2 diabetes successfully adopt regular physical activity. Spoken animation seems to be effective regardless of the characteristics of the user and may be a relevant strategy to communicate complex health information. OBJECTIVE: The objectives of our study were to evaluate (1) pretesting communication elements and user appreciation, and (2) the applied behavior change techniques of the previously designed spoken animated video messages in a tailored self-management program for people with type 2 diabetes. METHODS: We conducted semistructured interviews with patients with type 2 diabetes recruited from general practices located in different socioeconomic status urban neighborhoods. Based on the pretesting key communication elements of Salazar's model, we asked participants about the spoken animated video messages' attractiveness, comprehensibility, acceptance, believability, involvement, and relevance and to what extent the video messages motivated them to become more physically active. We also assessed participants' intention to use the spoken animated video messages and to recommend them to others. To evaluate participants' appreciation of the different applied behavior change techniques, we conducted a post hoc analysis of the qualitative data using the MAXQDA program. Transcripts were coded by 2 coders using iterative qualitative content analysis methods to uncover key health communication issues. RESULTS: Of 23 patients who expressed an interest in participating, 17 met the inclusion criteria and 15 took part in the interviews. The positive appreciation of the comprehensibility, believability, and personalization was supported by participants' statements on behavior change techniques and other communication elements. Reinforcement of and feedback on participants' answers were positively evaluated as was the simplicity and concreteness of the spoken animated video messages. Most participants indicated reasons for not feeling motivated to increase their physical activity level, including being already sufficiently physically active and the presence of other impeding health factors. CONCLUSIONS: Spoken animated video messages should be simple, short, concrete, and without the use of medical terminology. Providing positive reinforcement, feedback on participants' answers, examples that match user characteristics, and the possibility to identify with the animation figures will enhance involvement in the health message. To connect more with patients' needs and thereby increase the perceived relevance of and motivation to use an animated video program, we suggest offering the program soon after diabetes mellitus is diagnosed. We recommend piloting behavior change techniques to identify potential resistance.

Genome-wide association study of cognitive performance in U.S. veterans with schizophrenia or bipolar disorder.

Cognitive impairment is a frequent and serious problem in patients with various forms of severe mental illnesses (SMI), including schizophrenia (SZ) and bipolar disorder (BP). Recent research suggests genetic links to several cognitive phenotypes in both SMI and in the general population. Our goal in this study was to identify potential genomic signatures of cognitive functioning in veterans with severe mental illness and compare them to previous findings for cognition across different populations. Veterans Affairs (VA) Cooperative Studies Program (CSP) Study #572 evaluated cognitive and functional capacity measures among SZ and BP patients. In conjunction with the VA Million Veteran Program, 3,959 European American (1,095 SZ, 2,864 BP) and 2,601 African American (1,095 SZ, 2,864 BP) patients were genotyped using a custom Affymetrix Axiom Biobank array. We performed a genome-wide association study of global cognitive functioning, constructed polygenic scores for SZ and cognition in the general population, and examined genetic correlations with 2,626 UK Biobank traits. Although no single locus attained genome-wide significance, observed allelic effects were strongly consistent with previous studies. We observed robust associations between global cognitive functioning and polygenic scores for cognitive performance, intelligence, and SZ risk. We also identified significant genetic correlations with several cognition-related traits in UK Biobank. In a diverse cohort of U.S. veterans with SZ or BP, we demonstrate broad overlap of common genetic effects on cognition in the general population, and find that greater polygenic loading for SZ risk is associated with poorer cognitive performance.

Reporting and connecting cell type names and gating definitions through ontologies.

BACKGROUND: Human immunology studies often rely on the isolation and quantification of cell populations from an input sample based on flow cytometry and related techniques. Such techniques classify cells into populations based on the detection of a pattern of markers. The description of the cell populations targeted in such experiments typically have two complementary components: the description of the cell type targeted (e.g. 'T cells'), and the description of the marker pattern utilized (e.g. CD14-, CD3+). RESULTS: We here describe our attempts to use ontologies to cross-compare cell types and marker patterns (also referred to as gating definitions). We used a large set of such gating definitions and corresponding cell types submitted by different investigators into ImmPort, a central database for immunology studies, to examine the ability to parse gating definitions using terms from the Protein Ontology (PRO) and cell type descriptions, using the Cell Ontology (CL). We then used logical axioms from CL to detect discrepancies between the two. CONCLUSIONS: We suggest adoption of our proposed format for describing gating and cell type definitions to make comparisons easier. We also suggest a number of new terms to describe gating definitions in flow cytometry that are not based on molecular markers captured in PRO, but on forward- and side-scatter of light during data acquisition, which is more appropriate to capture in the Ontology for Biomedical Investigations (OBI). Finally, our approach results in suggestions on what logical axioms and new cell types could be considered for addition to the Cell Ontology.

The Share Project: Building Capacity of Justice-Involved Individuals, Policymakers, and Researchers to Collectively Transform Health Care Delivery.

The Share Project (TSP), a US health justice initiative, convened key stakeholders to advance the use of inclusive research methods and data sharing to engage groups that are typically marginalized from research. TSP trained justice-involved patients, community health workers, policymakers, and researchers in participatory research and the use of a data-sharing platform developed with justice-involved patients. The platform allowed users to analyze health and criminal justice data to develop new research that is patient driven and responsive to the needs of providers.

Measuring coordination of epilepsy care: A mixed methods evaluation of social network analysis versus relational coordination.

OBJECTIVES: Coordination of multidisciplinary care is critical to address the complex needs of people with neurological disorders; however, quality improvement and research tools to measure coordination of neurological care are not well-developed. This study explored and compared the value of social network analysis (SNA) and relational coordination (RC) in measuring coordination of care in a neurology setting. The Department of Veterans Affairs Healthcare System (VA) established an Epilepsy Centers of Excellence (ECOE) hub and spoke model of care, which provides a setting to measure coordination of care across networks of providers. METHODS: In a parallel mixed methods approach, we compared coordination of care of VA providers who formally engage the ECOE system to VA providers outside the ECOE system using SNA and RC. Coordination of care scores were compiled from provider teams across 66 VA facilities, and key informant interviews of 80 epilepsy care team members were conducted concurrently to describe the quality of epilepsy care coordinating in the VA healthcare system. RESULTS: On average, members of healthcare teams affiliated with the ECOE program rated quality of communication and respect higher than non-ECOE physicians. Connectivity between neurologist and primary care providers as well as between neurologists and mental health providers were higher within ECOE hub facilities compared to spoke referring facilities. Key informant interviews reported the important role of formal and informal programming, social support and social capital, and social influence on epilepsy care networks. CONCLUSION: For quality improvement and research purposes, SNA and RC can be used to measure coordination of neurological care; RC provides a detailed assessment of the quality of communication within and across healthcare teams but is difficult to administer and analyze; SNA provides large scale coordination of care maps and metrics to compare across large healthcare systems. The two measures provide complimentary coordination of care data at a local as well as population level. Interviews describe the mechanisms of developing and sustaining health professional networks that are not captured in either SNA or RC measures.

CEDAR OnDemand: a browser extension to generate ontology-based scientific metadata.

BACKGROUND: Public biomedical data repositories often provide web-based interfaces to collect experimental metadata. However, these interfaces typically reflect the ad hoc metadata specification practices of the associated repositories, leading to a lack of standardization in the collected metadata. This lack of standardization limits the ability of the source datasets to be broadly discovered, reused, and integrated with other datasets. To increase reuse, discoverability, and reproducibility of the described experiments, datasets should be appropriately annotated by using agreed-upon terms, ideally from ontologies or other controlled term sources. RESULTS: This work presents "CEDAR OnDemand", a browser extension powered by the NCBO (National Center for Biomedical Ontology) BioPortal that enables users to seamlessly enter ontology-based metadata through existing web forms native to individual repositories. CEDAR OnDemand analyzes the web page contents to identify the text input fields and associate them with relevant ontologies which are recommended automatically based upon input fields' labels (using the NCBO ontology recommender) and a pre-defined list of ontologies. These field-specific ontologies are used for controlling metadata entry. CEDAR OnDemand works for any web form designed in the HTML format. We demonstrate how CEDAR OnDemand works through the NCBI (National Center for Biotechnology Information) BioSample web-based metadata entry. CONCLUSION: CEDAR OnDemand helps lower the barrier of incorporating ontologies into standardized metadata entry for public data repositories. CEDAR OnDemand is available freely on the Google Chrome store https://chrome.google.com/webstore/search/CEDAROnDemand.

Impact of genotyping errors on statistical power of association tests in genomic analyses: A case study.

A key step in genomic studies is to assess high throughput measurements across millions of markers for each participant's DNA, either using microarrays or sequencing techniques. Accurate genotype calling is essential for downstream statistical analysis of genotype-phenotype associations, and next generation sequencing (NGS) has recently become a more common approach in genomic studies. How the accuracy of variant calling in NGS-based studies affects downstream association analysis has not, however, been studied using empirical data in which both microarrays and NGS were available. In this article, we investigate the impact of variant calling errors on the statistical power to identify associations between single nucleotides and disease, and on associations between multiple rare variants and disease. Both differential and nondifferential genotyping errors are considered. Our results show that the power of burden tests for rare variants is strongly influenced by the specificity in variant calling, but is rather robust with regard to sensitivity. By using the variant calling accuracies estimated from a substudy of a Cooperative Studies Program project conducted by the Department of Veterans Affairs, we show that the power of association tests is mostly retained with commonly adopted variant calling pipelines. An R package, GWAS.PC, is provided to accommodate power analysis that takes account of genotyping errors (http://zhaocenter.org/software/).

Understanding perceived availability and importance of tobacco control interventions to inform European adoption of a UK economic model: a cross-sectional study.

BACKGROUND: The evidence on the extent to which stakeholders in different European countries agree with availability and importance of tobacco-control interventions is limited. This study assessed and compared stakeholders' views from five European countries and compared the perceived ranking of interventions with evidence-based ranking using cost-effectiveness data. METHODS: An interview survey (face-to-face, by phone or Skype) was conducted between April and July 2014 with five categories of stakeholders - decision makers, service purchasers, service providers, evidence generators and health promotion advocates - from Germany, Hungary, the Netherlands, Spain, and the United Kingdom. A list of potential stakeholders drawn from the research team's contacts and snowballing served as the sampling frame. An email invitation was sent to all stakeholders in this list and recruitment was based on positive replies. Respondents were asked to rate availability and importance of 30 tobacco control interventions. Kappa coefficients assessed agreement of stakeholders' views. A mean importance score for each intervention was used to rank the interventions. This ranking was compared with the ranking based on cost-effectiveness data from a published review. RESULTS: Ninety-three stakeholders (55.7% response rate) completed the survey: 18.3% were from Germany, 17.2% from Hungary, 30.1% from the Netherlands, 19.4% from Spain, and 15.1% from the UK. Of those, 31.2% were decision makers, 26.9% evidence generators, 19.4% service providers, 15.1% health-promotion advocates, and 7.5% purchasers of services/pharmaceutical products. Smoking restrictions in public areas were rated as the most important intervention (mean score = 1.89). The agreement on availability of interventions between the stakeholders was very low (kappa = 0.098; 95% CI = [0.085, 0.111] but the agreement on the importance of the interventions was fair (kappa = 0.239; 95% CI = [0.208, 0.253]). A correlation was found between availability and importance rankings for stage-based interventions. The importance ranking was not statistically concordant with the ranking based on published cost-effectiveness data (Kendall rank correlation coefficient = 0.40; p-value = 0.11; 95% CI = [- 0.09, 0.89]). CONCLUSIONS: The intrinsic differences in stakeholder views must be addressed while transferring economic evidence Europe-wide. Strong engagement with stakeholders, focussing on better communication, has a potential to mitigate this challenge.

OPTIMIZING USABILITY OF AN ECONOMIC DECISION SUPPORT TOOL: PROTOTYPE OF THE EQUIPT TOOL.

OBJECTIVES: Economic decision-support tools can provide valuable information for tobacco control stakeholders, but their usability may impact the adoption of such tools. This study aims to illustrate a mixed-method usability evaluation of an economic decision-support tool for tobacco control, using the EQUIPT ROI tool prototype as a case study. METHODS: A cross-sectional mixed methods design was used, including a heuristic evaluation, a thinking aloud approach, and a questionnaire testing and exploring the usability of the Return of Investment tool. RESULTS: A total of sixty-six users evaluated the tool (thinking aloud) and completed the questionnaire. For the heuristic evaluation, four experts evaluated the interface. In total twenty-one percent of the respondents perceived good usability. A total of 118 usability problems were identified, from which twenty-six problems were categorized as most severe, indicating high priority to fix them before implementation. CONCLUSIONS: Combining user-based and expert-based evaluation methods is recommended as these were shown to identify unique usability problems. The evaluation provides input to optimize usability of a decision-support tool, and may serve as a vantage point for other developers to conduct usability evaluations to refine similar tools before wide-scale implementation. Such studies could reduce implementation gaps by optimizing usability, enhancing in turn the research impact of such interventions.

Care coordination in epilepsy: Measuring neurologists' connectivity using social network analysis.

OBJECTIVE: The study sought to quantify coordination of epilepsy care, over time, between neurologists and other health care providers using social network analysis (SNA). METHODS: The Veterans Health Administration (VA) instituted an Epilepsy Center of Excellence (ECOE) model in 2008 to enhance care coordination between neurologists and other health care providers. Provider networks in the 16 VA ECOE facilities (hub sites) were compared to a subset of 33 VA facilities formally affiliated (consortium sites) and 14 unaffiliated VA facilities. The number of connections between neurologists and each provider (node degree) was measured by shared epilepsy patients and tallied to generate estimates at the facility level separately within and across facilities. Mixed models were used to compare change of facility-level node degree over time across the three facility types, adjusted for number of providers per facility. RESULTS: Over the time period 2000-2013, epilepsy care coordination both within and across facilities significantly increased. These increases were seen in all three types of facilities namely hub, consortium, and unaffiliated site, relatively equally. The increase in connectivity was more dramatic with providers across facilities compared to providers within the same facilities. CONCLUSION: Establishment of the ECOE hub and spoke model contributed to an increase in epilepsy care coordination both within and across facilities from 2000 to 2013, but there was substantial variation across different facilities. SNA is a tool that may help measure coordination of specialty care.

The impact of non-response bias due to sampling in public health studies: A comparison of voluntary versus mandatory recruitment in a Dutch national survey on adolescent health.

BACKGROUND: In public health monitoring of young people it is critical to understand the effects of selective non-response, in particular when a controversial topic is involved like substance abuse or sexual behaviour. Research that is dependent upon voluntary subject participation is particularly vulnerable to sampling bias. As respondents whose participation is hardest to elicit on a voluntary basis are also more likely to report risk behaviour, this potentially leads to underestimation of risk factor prevalence. Inviting adolescents to participate in a home-sent postal survey is a typical voluntary recruitment strategy with high non-response, as opposed to mandatory participation during school time. This study examines the extent to which prevalence estimates of adolescent health-related characteristics are biased due to different sampling methods, and whether this also biases within-subject analyses. METHODS: Cross-sectional datasets collected in 2011 in Twente and IJsselland, two similar and adjacent regions in the Netherlands, were used. In total, 9360 youngsters in a mandatory sample (Twente) and 1952 youngsters in a voluntary sample (IJsselland) participated in the study. To test whether the samples differed on health-related variables, we conducted both univariate and multivariable logistic regression analyses controlling for any demographic difference between the samples. Additional multivariable logistic regressions were conducted to examine moderating effects of sampling method on associations between health-related variables. RESULTS: As expected, females, older individuals, as well as individuals with higher education levels, were over-represented in the voluntary sample, compared to the mandatory sample. Respondents in the voluntary sample tended to smoke less, consume less alcohol (ever, lifetime, and past four weeks), have better mental health, have better subjective health status, have more positive school experiences and have less sexual intercourse than respondents in the mandatory sample. No moderating effects were found for sampling method on associations between variables. CONCLUSIONS: This is one of first studies to provide strong evidence that voluntary recruitment may lead to a strong non-response bias in health-related prevalence estimates in adolescents, as compared to mandatory recruitment. The resulting underestimation in prevalence of health behaviours and well-being measures appeared large, up to a four-fold lower proportion for self-reported alcohol consumption. Correlations between variables, though, appeared to be insensitive to sampling bias.

Exploring consensus on how to measure smoking cessation. A Delphi study.

BACKGROUND: Different criteria regarding outcome measures in smoking research are used, which can lead to confusion about study results. Consensus in outcome criteria may enhance the comparability of future studies. This study aims (1) to provide an overview of tobacco researchers' considered preferences regarding outcome criteria in randomized controlled smoking cessation trials, and (2) to identify the extent to which researchers can reach consensus on the importance of these outcome criteria. METHODS: A three-round online Delphi study was conducted among smoking cessation experts. In the first round, the most important smoking cessation outcome measures were collected by means of open-ended questions, which were categorized around self-reported and biochemical validation measures. Experts (n = 17) were asked to name the outcome measures (as well as their assessment method and ideal follow-up period) that they thought were important when assessing smoking-related outcomes. In the second (n = 48) and third rounds (n = 37), a list of outcome measures-identified in the first round-was presented to experts. Asking them to rate the importance of each measure on a seven-point scale. RESULTS: Experts reached consensus on several items. For self-reports, experts agreed that prolonged abstinence (6 or/and 12 months), point prevalence abstinence (7 days), continuous abstinence (6 months), and the number of cigarettes smoked (7 days) are important outcome measures. Experts reached consensus that biochemical validation methods should not always be used. The preferred biochemical validation methods were carbon monoxide (expired air) and cotinine (saliva). Preferred follow-ups included 6 and/or 12 months, with or without intermediate measurements. CONCLUSIONS: Findings suggest only partial compliance with the Russell standard and that more outcome measures may be important (including seven-day point-prevalence abstinence, number of cigarettes smoked, and cotinine when using biochemical validation). This study showed where there is and is not consensus, reflecting the need to develop a more comprehensive standard. For these purposes we provided suggestions for the Russell 2.0 standard.

MOST IMPORTANT BARRIERS AND FACILITATORS REGARDING THE USE OF HEALTH TECHNOLOGY ASSESSMENT.

OBJECTIVES: Several studies have reported multiple barriers to and facilitators for the uptake of health technology assessment (HTA) information by policy makers. This study elicited, using best-worst scaling (BWS), the most important barriers and facilitators and their relative weight in the use of HTA by policy makers. METHODS: Two BWS object case surveys (one for barriers, one for facilitators) were conducted among sixteen policy makers and thirty-three HTA experts in the Netherlands. A list of twenty-two barriers and nineteen facilitators was included. In each choice task, participants were asked to choose the most important and the least important barrier/facilitator from a set of five. We used Hierarchical Bayes modeling to generate the mean relative importance score (RIS) for each factor and a subgroup analysis was conducted to assess differences between policy makers and HTA experts. RESULTS: The five most important barriers (RIS > 6.00) were "no explicit framework for decision-making process," "insufficient support by stakeholders," "lack of support," "limited generalizability," and "absence of appropriate incentives." The six most important facilitators were: "availability of explicit framework for decision making," "sufficient support by stakeholders," "appropriate incentives," "sufficient quality," "sufficient awareness," and "sufficient support within the organization." Overall, perceptions did not differ markedly between policy makers and HTA experts. CONCLUSIONS: Our study suggests that barriers and facilitators related to "policy characteristics" and "organization and resources" were particularly important. It is important to stimulate a pulse at the national level to create an explicit framework for including HTA in the decision-making context.

A Review of the Theoretical Basis, Effects, and Cost Effectiveness of Online Smoking Cessation Interventions in the Netherlands: A Mixed-Methods Approach.

BACKGROUND: Tobacco smoking is a worldwide public health problem. In 2015, 26.3% of the Dutch population aged 18 years and older smoked, 74.4% of them daily. More and more people have access to the Internet worldwide; approximately 94% of the Dutch population have online access. Internet-based smoking cessation interventions (online cessation interventions) provide an opportunity to tackle the scourge of tobacco. OBJECTIVE: The goal of this paper was to provide an overview of online cessation interventions in the Netherlands, while exploring their effectivity, cost effectiveness, and theoretical basis. METHODS: A mixed-methods approach was used to identify Dutch online cessation interventions, using (1) a scientific literature search, (2) a grey literature search, and (3) expert input. For the scientific literature, the Cochrane review was used and updated by two independent researchers (n=651 identified studies), screening titles, abstracts, and then full-text studies between 2013 and 2016 (CENTRAL, MEDLINE, and EMBASE). For the grey literature, the researchers conducted a Google search (n=100 websites), screening for titles and first pages. Including expert input, this resulted in six interventions identified in the scientific literature and 39 interventions via the grey literature. Extracted data included effectiveness, cost effectiveness, theoretical factors, and behavior change techniques used. RESULTS: Overall, many interventions (45 identified) were offered. Of the 45 that we identified, only six that were included in trials provided data on effectiveness. Four of these were shown to be effective and cost effective. In the scientific literature, 83% (5/6) of these interventions included changing attitudes, providing social support, increasing self-efficacy, motivating smokers to make concrete action plans to prepare their attempts to quit and to cope with challenges, supporting identity change and advising on changing routines, coping, and medication use. In all, 50% (3/6) of the interventions included a reward for abstinence. Interventions identified in the grey literature were less consistent, with inclusion of each theoretical factor ranging from 31% to 67% and of each behavior change technique ranging from 28% to 54%. CONCLUSIONS: Although the Internet may provide the opportunity to offer various smoking cessation programs, the user is left bewildered as far as efficacy is concerned, as most of these data are not available nor offered to the smokers. Clear regulations about the effectiveness of these interventions need to be devised to avoid disappointment and failed quitting attempts. Thus, there is a need for policy regulations to regulate the proliferation of these interventions and to foster their quality in the Netherlands.

Communicating diagnostic certainty of psychogenic nonepileptic seizures - a national study of provider documentation.

Management of psychogenic nonepileptic seizures (PNES) requires collaboration among and between health care professionals. Although criteria are established for diagnosis of PNES, miscommunication between neurologists, primary care providers, and mental health professionals may occur if the clinical impression is not clearly articulated. We extracted progress notes from the Department of Veterans Affairs (VA) electronic health record (EHR) nationally to study veterans who were evaluated for PNES. Of the 750 patients being worked up for PNES, the majority of patients did not meet criteria for PNES (64.6%). Of those who were thought to suffer from PNES, 147 (19.6%) met International League Against Epilepsy (ILAE) criteria for documented PNES, 14 (1.9%) for clinically established PNES, and 104 (13.9%) for probable or possible PNES. Neurologists tended to use ambiguous language, such as "thought to be" or "suggestive of" to describe their impressions of patients overall, even those with definitive PNES. Ambiguous language may lead to miscommunication across providers and inappropriate health care.