The INGENIOUS trial: Impact of pharmacogenetic testing on adverse events in a pragmatic clinical trial.

Adverse drug events (ADEs) account for a significant mortality, morbidity, and cost burden. Pharmacogenetic testing has the potential to reduce ADEs and inefficacy. The objective of this INGENIOUS trial (NCT02297126) analysis was to determine whether conducting and reporting pharmacogenetic panel testing impacts ADE frequency. The trial was a pragmatic, randomized controlled clinical trial, adapted as a propensity matched analysis in individuals (N = 2612) receiving a new prescription for one or more of 26 pharmacogenetic-actionable drugs across a community safety-net and academic health system. The intervention was a pharmacogenetic testing panel for 26 drugs with dosage and selection recommendations returned to the health record. The primary outcome was occurrence of ADEs within 1 year, according to modified Common Terminology Criteria for Adverse Events (CTCAE). In the propensity-matched analysis, 16.1% of individuals experienced any ADE within 1-year. Serious ADEs (CTCAE level ≥ 3) occurred in 3.2% of individuals. When combining all 26 drugs, no significant difference was observed between the pharmacogenetic testing and control arms for any ADE (Odds ratio 0.96, 95% CI: 0.78-1.18), serious ADEs (OR: 0.91, 95% CI: 0.58-1.40), or mortality (OR: 0.60, 95% CI: 0.28-1.21). However, sub-group analyses revealed a reduction in serious ADEs and death in individuals who underwent pharmacogenotyping for aripiprazole and serotonin or serotonin-norepinephrine reuptake inhibitors (OR 0.34, 95% CI: 0.12-0.85). In conclusion, no change in overall ADEs was observed after pharmacogenetic testing. However, limitations incurred during INGENIOUS likely affected the results. Future studies may consider preemptive, rather than reactive, pharmacogenetic panel testing.

Establishing the value of genomics in medicine: the IGNITE Pragmatic Trials Network.

PURPOSE: A critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions. METHODS: The Implementing Genomics in Practice Pragmatic Trials Network (IGNITE PTN) was formed in 2018 to measure the clinical utility and cost-effectiveness of genomic medicine interventions, to assess approaches for real-world application of genomic medicine in diverse clinical settings, and to produce generalizable knowledge on clinical trials using genomic interventions. Five clinical sites and a coordinating center evaluated trial proposals and developed working groups to enable their implementation. RESULTS: Two pragmatic clinical trials (PCTs) have been initiated, one evaluating genetic risk APOL1 variants in African Americans in the management of their hypertension, and the other to evaluate the use of pharmacogenetic testing for medications to manage acute and chronic pain as well as depression. CONCLUSION: IGNITE PTN is a network that carries out PCTs in genomic medicine; it is focused on diversity and inclusion of underrepresented minority trial participants; it uses electronic health records and clinical decision support to deliver the interventions. IGNITE PTN will develop the evidence to support (or oppose) the adoption of genomic medicine interventions by patients, providers, and payers.

Qualitative study of system-level factors related to genomic implementation.

PURPOSE: Research on genomic medicine integration has focused on applications at the individual level, with less attention paid to implementation within clinical settings. Therefore, we conducted a qualitative study using the Consolidated Framework for Implementation Research (CFIR) to identify system-level factors that played a role in implementation of genomic medicine within Implementing GeNomics In PracTicE (IGNITE) Network projects. METHODS: Up to four study personnel, including principal investigators and study coordinators from each of six IGNITE projects, were interviewed using a semistructured interview guide that asked interviewees to describe study site(s), progress at each site, and factors facilitating or impeding project implementation. Interviews were coded following CFIR inner-setting constructs. RESULTS: Key barriers included (1) limitations in integrating genomic data and clinical decision support tools into electronic health records, (2) physician reluctance toward genomic research participation and clinical implementation due to a limited evidence base, (3) inadequate reimbursement for genomic medicine, (4) communication among and between investigators and clinicians, and (5) lack of clinical and leadership engagement. CONCLUSION: Implementation of genomic medicine is hindered by several system-level barriers to both research and practice. Addressing these barriers may serve as important facilitators for studying and implementing genomics in practice.

Automated pancreatic cyst screening using natural language processing: a new tool in the early detection of pancreatic cancer.

INTRODUCTION: As many as 3% of computed tomography (CT) scans detect pancreatic cysts. Because pancreatic cysts are incidental, ubiquitous and poorly understood, follow-up is often not performed. Pancreatic cysts may have a significant malignant potential and their identification represents a 'window of opportunity' for the early detection of pancreatic cancer. The purpose of this study was to implement an automated Natural Language Processing (NLP)-based pancreatic cyst identification system. METHOD: A multidisciplinary team was assembled. NLP-based identification algorithms were developed based on key words commonly used by physicians to describe pancreatic cysts and programmed for automated search of electronic medical records. A pilot study was conducted prospectively in a single institution. RESULTS: From March to September 2013, 566,233 reports belonging to 50,669 patients were analysed. The mean number of patients reported with a pancreatic cyst was 88/month (range 78-98). The mean sensitivity and specificity were 99.9% and 98.8%, respectively. CONCLUSION: NLP is an effective tool to automatically identify patients with pancreatic cysts based on electronic medical records (EMR). This highly accurate system can help capture patients 'at-risk' of pancreatic cancer in a registry.

A regional informatics platform for coordinated antibiotic-resistant infection tracking, alerting, and prevention.

BACKGROUND: We developed and assessed the impact of a patient registry and electronic admission notification system relating to regional antimicrobial resistance (AMR) on regional AMR infection rates over time. We conducted an observational cohort study of all patients identified as infected or colonized with methicillin-resistant Staphylococcus aureus (MRSA) and/or vancomycin-resistant enterococci (VRE) on at least 1 occasion by any of 5 healthcare systems between 2003 and 2010. The 5 healthcare systems included 17 hospitals and associated clinics in the Indianapolis, Indiana, region. METHODS: We developed and standardized a registry of MRSA and VRE patients and created Web forms that infection preventionists (IPs) used to maintain the lists. We sent e-mail alerts to IPs whenever a patient previously infected or colonized with MRSA or VRE registered for admission to a study hospital from June 2007 through June 2010. RESULTS: Over a 3-year period, we delivered 12 748 e-mail alerts on 6270 unique patients to 24 IPs covering 17 hospitals. One in 5 (22%-23%) of all admission alerts was based on data from a healthcare system that was different from the admitting hospital; a few hospitals accounted for most of this crossover among facilities and systems. CONCLUSIONS: Regional patient registries identify an important patient cohort with relevant prior antibiotic-resistant infection data from different healthcare institutions. Regional registries can identify trends and interinstitutional movement not otherwise apparent from single institution data. Importantly, electronic alerts can notify of the need to isolate early and to institute other measures to prevent transmission.

Feature engineering from medical notes: A case study of dementia detection.

Background and objectives: Medical notes are narratives that describe the health of the patient in free text format. These notes can be more informative than structured data such as the history of medications or disease conditions. They are routinely collected and can be used to evaluate the patient's risk for developing chronic diseases such as dementia. This study investigates different methodologies for transforming routine care notes into dementia risk classifiers and evaluates the generalizability of these classifiers to new patients and new health care institutions. Methods: The notes collected over the relevant history of the patient are lengthy. In this study, TF-ICF is used to select keywords with the highest discriminative ability between at risk dementia patients and healthy controls. The medical notes are then summarized in the form of occurrences of the selected keywords. Two different encodings of the summary are compared. The first encoding consists of the average of the vector embedding of each keyword occurrence as produced by the BERT or Clinical BERT pre-trained language models. The second encoding aggregates the keywords according to UMLS concepts and uses each concept as an exposure variable. For both encodings, misspellings of the selected keywords are also considered in an effort to improve the predictive performance of the classifiers. A neural network is developed over the first encoding and a gradient boosted trees model is applied to the second encoding. Patients from a single health care institution are used to develop all the classifiers which are then evaluated on held-out patients from the same health care institution as well as test patients from two other health care institutions. Results: The results indicate that it is possible to identify patients at risk for dementia one year ahead of the onset of the disease using medical notes with an AUC of 75% when a gradient boosted trees model is used in conjunction with exposure variables derived from UMLS concepts. However, this performance is not maintained with an embedded feature space and when the classifier is applied to patients from other health care institutions. Moreover, an analysis of the top predictors of the gradient boosted trees model indicates that different features inform the classification depending on whether or not spelling variants of the keywords are included. Conclusion: The present study demonstrates that medical notes can enable risk prediction models for complex chronic diseases such as dementia. However, additional research efforts are needed to improve the generalizability of these models. These efforts should take into consideration the length and localization of the medical notes; the availability of sufficient training data for each disease condition; and the variabilities resulting from different feature engineering techniques.

Design and rationale of GUARDD-US: A pragmatic, randomized trial of genetic testing for APOL1 and pharmacogenomic predictors of antihypertensive efficacy in patients with hypertension.

RATIONALE AND OBJECTIVE: APOL1 risk alleles are associated with increased cardiovascular and chronic kidney disease (CKD) risk. It is unknown whether knowledge of APOL1 risk status motivates patients and providers to attain recommended blood pressure (BP) targets to reduce cardiovascular disease. STUDY DESIGN: Multicenter, pragmatic, randomized controlled clinical trial. SETTING AND PARTICIPANTS: 6650 individuals with African ancestry and hypertension from 13 health systems. INTERVENTION: APOL1 genotyping with clinical decision support (CDS) results are returned to participants and providers immediately (intervention) or at 6 months (control). A subset of participants are re-randomized to pharmacogenomic testing for relevant antihypertensive medications (pharmacogenomic sub-study). CDS alerts encourage appropriate CKD screening and antihypertensive agent use. OUTCOMES: Blood pressure and surveys are assessed at baseline, 3 and 6 months. The primary outcome is change in systolic BP from enrollment to 3 months in individuals with two APOL1 risk alleles. Secondary outcomes include new diagnoses of CKD, systolic blood pressure at 6 months, diastolic BP, and survey results. The pharmacogenomic sub-study will evaluate the relationship of pharmacogenomic genotype and change in systolic BP between baseline and 3 months. RESULTS: To date, the trial has enrolled 3423 participants. CONCLUSIONS: The effect of patient and provider knowledge of APOL1 genotype on systolic blood pressure has not been well-studied. GUARDD-US addresses whether blood pressure improves when patients and providers have this information. GUARDD-US provides a CDS framework for primary care and specialty clinics to incorporate APOL1 genetic risk and pharmacogenomic prescribing in the electronic health record. TRIAL REGISTRATION: ClinicalTrials.govNCT04191824.

Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks.

Golden opportunities for clinical decision support in an era of team-based healthcare.

Computerized clinical decision support (CDS) will be essential to ensuring the safety and efficiency of new care delivery models, such as the patient-centered medical home. CDS will help empower non-physician team members, coordinate overall team efforts, and facilitate physician oversight. In this article, we discuss common clinical scenarios that could benefit from CDS optimized for team-based healthcare, including (1) low-acuity episodic illness, (2) diagnostic workup of new onset symptoms, (3) chronic care, (4) preventive care, and (5) care coordination. CDS that maximally supports teams may be one of biomedical informatics' best opportunities to decrease health care costs, improve quality, and increase clinical capacity.

An Automated Line-of-Therapy Algorithm for Adults With Metastatic Non-Small Cell Lung Cancer: Validation Study Using Blinded Manual Chart Review.

BACKGROUND: Extraction of line-of-therapy (LOT) information from electronic health record and claims data is essential for determining longitudinal changes in systemic anticancer therapy in real-world clinical settings. OBJECTIVE: The aim of this retrospective cohort analysis is to validate and refine our previously described open-source LOT algorithm by comparing the output of the algorithm with results obtained through blinded manual chart review. METHODS: We used structured electronic health record data and clinical documents to identify 500 adult patients treated for metastatic non-small cell lung cancer with systemic anticancer therapy from 2011 to mid-2018; we assigned patients to training (n=350) and test (n=150) cohorts, randomly divided proportional to the overall ratio of simple:complex cases (n=254:246). Simple cases were patients who received one LOT and no maintenance therapy; complex cases were patients who received more than one LOT and/or maintenance therapy. Algorithmic changes were performed using the training cohort data, after which the refined algorithm was evaluated against the test cohort. RESULTS: For simple cases, 16 instances of discordance between the LOT algorithm and chart review prerefinement were reduced to 8 instances postrefinement; in the test cohort, there was no discordance between algorithm and chart review. For complex cases, algorithm refinement reduced the discordance from 68 to 62 instances, with 37 instances in the test cohort. The percentage agreement between LOT algorithm output and chart review for patients who received one LOT was 89% prerefinement, 93% postrefinement, and 93% for the test cohort, whereas the likelihood of precise matching between algorithm output and chart review decreased with an increasing number of unique regimens. Several areas of discordance that arose from differing definitions of LOTs and maintenance therapy could not be objectively resolved because of a lack of precise definitions in the medical literature. CONCLUSIONS: Our findings identify common sources of discordance between the LOT algorithm and clinician documentation, providing the possibility of targeted algorithm refinement.

Identifying and Characterizing a Chronic Cough Cohort Through Electronic Health Records.

BACKGROUND: Chronic cough (CC) of 8 weeks or more affects about 10% of adults and may lead to expensive treatments and reduced quality of life. Incomplete diagnostic coding complicates identifying CC in electronic health records (EHRs). Natural language processing (NLP) of EHR text could improve detection. RESEARCH QUESTION: Can NLP be used to identify cough in EHRs, and to characterize adults and encounters with CC? STUDY DESIGN AND METHODS: A Midwestern EHR system identified patients aged 18 to 85 years during 2005 to 2015. NLP was used to evaluate text notes, except prescriptions and instructions, for mentions of cough. Two physicians and a biostatistician reviewed 12 sets of 50 encounters each, with iterative refinements, until the positive predictive value for cough encounters exceeded 90%. NLP, International Classification of Diseases, 10th revision, or medication was used to identify cough. Three encounters spanning 56 to 120 days defined CC. Descriptive statistics summarized patients and encounters, including referrals. RESULTS: Optimizing NLP required identifying and eliminating cough denials, instructions, and historical references. Of 235,457 cough encounters, 23% had a relevant diagnostic code or medication. Applying chronicity to cough encounters identified 23,371 patients (61% women) with CC. NLP alone identified 74% of these patients; diagnoses or medications alone identified 15%. The positive predictive value of NLP in the reviewed sample was 97%. Referrals for cough occurred for 3.0% of patients; pulmonary medicine was most common initially (64% of referrals). LIMITATIONS: Some patients with diagnosis codes for cough, encounters at intervals greater than 4 months, or multiple acute cough episodes may have been misclassified. INTERPRETATION: NLP successfully identified a large cohort with CC. Most patients were identified through NLP alone, rather than diagnoses or medications. NLP improved detection of patients nearly sevenfold, addressing the gap in ability to identify and characterize CC disease burden. Nearly all cases appeared to be managed in primary care. Identifying these patients is important for characterizing treatment and unmet needs.

Multi-Institutional Implementation of Clinical Decision Support for APOL1, NAT2, and YEATS4 Genotyping in Antihypertensive Management.

(1) Background: Clinical decision support (CDS) is a vitally important adjunct to the implementation of pharmacogenomic-guided prescribing in clinical practice. A novel CDS was sought for the APOL1, NAT2, and YEATS4 genes to guide optimal selection of antihypertensive medications among the African American population cared for at multiple participating institutions in a clinical trial. (2) Methods: The CDS committee, made up of clinical content and CDS experts, developed a framework and contributed to the creation of the CDS using the following guiding principles: 1. medical algorithm consensus; 2. actionability; 3. context-sensitive triggers; 4. workflow integration; 5. feasibility; 6. interpretability; 7. portability; and 8. discrete reporting of lab results. (3) Results: Utilizing the principle of discrete patient laboratory and vital information, a novel CDS for APOL1, NAT2, and YEATS4 was created for use in a multi-institutional trial based on a medical algorithm consensus. The alerts are actionable and easily interpretable, clearly displaying the purpose and recommendations with pertinent laboratory results, vitals and links to ordersets with suggested antihypertensive dosages. Alerts were either triggered immediately once a provider starts to order relevant antihypertensive agents or strategically placed in workflow-appropriate general CDS sections in the electronic health record (EHR). Detailed implementation instructions were shared across institutions to achieve maximum portability. (4) Conclusions: Using sound principles, the created genetic algorithms were applied across multiple institutions. The framework outlined in this study should apply to other disease-gene and pharmacogenomic projects employing CDS.

Computerized decision support for medication dosing in renal insufficiency: a randomized, controlled trial.

STUDY OBJECTIVE: Emergency physicians prescribe several discharge medications that require dosage adjustment for patients with renal disease. The hypothesis for this research was that decision support in a computerized physician order entry system would reduce the rate of excessive medication dosing for patients with renal impairment. METHODS: This was a randomized, controlled trial in an academic emergency department (ED), in which computerized physician order entry was used to write all prescriptions for patients being discharged from the ED. The sample included 42 physicians who were randomized to the intervention (21 physicians) or control (21 physicians) group. The intervention was decision support that provided dosing recommendations for targeted medications for patients aged 18 years and older when the patient's estimated creatinine clearance level was below the threshold for dosage adjustment. The primary outcome was the proportion of targeted medications that were excessively dosed. RESULTS: For 2,783 (46%) of the 6,015 patient visits, the decision support had sufficient information to estimate the patient's creatinine clearance level. The average age of these patients was 46 years, 1,768 (64%) were women, and 1,523 (55%) were black. Decision support was provided 73 times to physicians in the intervention group, who excessively dosed 31 (43%) prescriptions. In comparison, control physicians excessively dosed a significantly larger proportion of medications: 34 of 46, 74% (effect size=31%; 95% confidence interval 14% to 49%; P=.001). CONCLUSION: Emergency physicians often prescribed excessive doses of medications that require dosage adjustment for renal impairment. Computerized physician order entry with decision support significantly reduced excessive dosing of targeted medications.

Transforming primary medical research knowledge into clinical decision.

While the utility of computerized clinical decision support (CCDS) for multiple select clinical domains has been clearly demonstrated, much less is known about the full breadth of domains to which CCDS approaches could be productively applied. To explore the applicability of CCDS to general medical knowledge, we sampled a total of 500 primary research articles from 4 high-impact medical journals. Employing rule-based templates, we created high-level CCDS rules for 72% (361/500) of primary medical research articles. We subsequently identified data sources needed to implement those rules. Ourfindings suggest that CCDS approaches, perhaps in the form of non-interruptive infobuttons, could be much more broadly applied. In addition, our analytic methods appear to provide a means of prioritizing and quantitating the relative utility of available data sources for purposes of CCDS.

Survival, Chemotherapy Treatments, and Health Care Utilization Among Patients with Advanced Small Cell Lung Cancer: An Observational Study.

INTRODUCTION: Most cases of small cell lung cancer (SCLC) are diagnosed at an advanced stage. The objective of this study was to investigate patient characteristics, survival, chemotherapy treatments, and health care use after a diagnosis of advanced SCLC in subjects enrolled in a health system network. METHODS: This was a retrospective cohort study of patients aged ≥ 18 years who either were diagnosed with stage III/IV SCLC or who progressed to advanced SCLC during the study period (2005-2015). Patients identified from the Indiana State Cancer Registry and the Indiana Network for Patient Care were followed from their advanced diagnosis index date until the earliest date of the last visit, death, or the end of the study period. Patient characteristics, survival, chemotherapy regimens, associated health care visits, and durations of treatment were reported. Time-to-event analyses were performed using the Kaplan-Meier method. RESULTS: A total of 498 patients with advanced SCLC were identified, of whom 429 were newly diagnosed with advanced disease and 69 progressed to advanced disease during the study period. Median survival from the index diagnosis date was 13.2 months. First-line (1L) chemotherapy was received by 464 (93.2%) patients, most commonly carboplatin/etoposide, received by 213 (45.9%) patients, followed by cisplatin/etoposide (20.7%). Ninety-five (20.5%) patients progressed to second-line (2L) chemotherapy, where topotecan monotherapy (20.0%) was the most common regimen, followed by carboplatin/etoposide (14.7%). Median survival was 10.1 months from 1L initiation and 7.7 months from 2L initiation. CONCLUSION: Patients in a regional health system network diagnosed with advanced SCLC were treated with chemotherapy regimens similar to those in earlier reports based on SEER-Medicare data. Survival of patients with advanced SCLC was poor, illustrating the lack of progress over several decades in the treatment of this lethal disease and highlighting the need for improved treatments.

Passive Digital Signature for Early Identification of Alzheimer's Disease and Related Dementia.

OBJECTIVES: Developing scalable strategies for the early identification of Alzheimer's disease and related dementia (ADRD) is important. We aimed to develop a passive digital signature for early identification of ADRD using electronic medical record (EMR) data. DESIGN: A case-control study. SETTING: The Indiana Network for Patient Care (INPC), a regional health information exchange in Indiana. PARTICIPANTS: Patients identified with ADRD and matched controls. MEASUREMENTS: We used data from the INPC that includes structured and unstructured (visit notes, progress notes, medication notes) EMR data. Cases and controls were matched on age, race, and sex. The derivation sample consisted of 10 504 cases and 39 510 controls; the validation sample included 4500 cases and 16 952 controls. We constructed models to identify early 1- to 10-year, 3- to 10-year, and 5- to 10-year ADRD signatures. The analyses included 14 diagnostic risk variables and 10 drug classes in addition to new variables produced from unstructured data (eg, disorientation, confusion, wandering, apraxia, etc). The area under the receiver operating characteristics (AUROC) curve was used to determine the best models. RESULTS: The AUROC curves for the validation samples for the 1- to 10-year, 3- to 10-year, and 5- to 10-year models that used only structured data were .689, .649, and .633, respectively. For the same samples and years, models that used both structured and unstructured data produced AUROC curves of .798, .748, and .704, respectively. Using a cutoff to maximize sensitivity and specificity, the 1- to 10-year, 3- to 10-year, and 5- to 10-year models had sensitivity that ranged from 51% to 62% and specificity that ranged from 80% to 89%. CONCLUSION: EMR-based data provide a targeted and scalable process for early identification of risk of ADRD as an alternative to traditional population screening. J Am Geriatr Soc 68:511-518, 2020.

A web-based generalist-specialist system to improve scheduling of outpatient specialty consultations in an academic center.

BACKGROUND: Failed referrals for specialty care are common and often represent medical errors. Technological structures and processes account for many failures. Scheduling appointments for subspecialty evaluation is a first step in outpatient referral and consultation. OBJECTIVE: We determined whether moving from paper-based referrals to a Web-based system with automated tracking features was associated with greater scheduling of appointments among referred patients. DESIGN: Staggered implementation of a quality-improvement project, with comparison of intervention and control groups. PARTICIPANTS: Patients 21 or more years of age referred from any of 11 primary-care clinics to any of 25 specialty clinics. INTERVENTIONS: Faxed referrals were replaced by a Web-based application shared by generalists and specialists, with enhanced communications and automated notification to the specialty office. MEASUREMENTS: We compared scheduling before and after implementation and time from referral to appointment. A logistic regression analysis adjusted for demographics. MAIN RESULTS: Among 40,487 referrals, 54% led to scheduled specialty visits before intervention, compared to 83% with intervention. The median time to appointment was 168 days without intervention and 78 days with intervention. Scheduling increased more when duplicate referrals were not generated (54% for single orders, 24% for multiple orders). After adjustment, referrals with the intervention were more than twice as likely to have scheduled visits. CONCLUSIONS: With a new Web-based referrals system, referrals were more than twice as likely to lead to a scheduled visit. This system improves access to specialty medical services.

Drug-gene and drug-drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial.

Background: Tramadol and codeine are metabolized by CYP2D6 and are subject to drug-gene and drug-drug interactions. Methods: This interim analysis examined prescribing behavior and efficacy in 102 individuals prescribed tramadol or codeine while receiving pharmaco-genotyping as part of the INGENIOUS trial (NCT02297126). Results: Within 60 days of receiving tramadol or codeine, clinicians more frequently prescribed an alternative opioid in ultrarapid and poor metabolizers (odds ratio: 19.0; 95% CI: 2.8-160.4) as compared with normal or indeterminate metabolizers (p = 0.01). After adjusting the CYP2D6 activity score for drug-drug interactions, uncontrolled pain was reported more frequently in individuals with reduced CYP2D6 activity (odds ratio: 0.50; 95% CI: 0.25-0.94). Conclusion: Phenoconversion for drug-drug and drug-gene interactions is an important consideration in pharmacogenomic implementation; drug-drug interactions may obscure the potential benefits of genotyping.

An effective computerized reminder for contact isolation of patients colonized or infected with resistant organisms.

PURPOSE: To improve contact isolation rates among patients admitted to the hospital with a known history of infection with Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococci (VRE). METHODS: A before and after interventional study implementing computerized reminders for contact isolation between February 25, 2005 and February 28, 2006. We measured rates of appropriate contact isolation, and time to isolation for the 4 month pre-intervention period, and the 12 month intervention period. We conducted a survey of ordering physicians at the midpoint of the intervention period. RESULTS: Implementing a computerized reminder increased the rate of patients appropriately isolated from 33% to fully 89% (P<0.0001). The median time to writing contact isolation orders decreased from 16.6 to 0.0 h (P<0.0001). Physicians accepted the order 80% of the time on the first or second presentation. Ninety-five percent of physicians felt the reminder had no impact on workflow, or saved them time. CONCLUSION: A human reviewed computerized reminder can achieve high rates of compliance with infection control recommendations for contact isolation, and dramatically reduce the time to orders being written upon admission.

The IGNITE network: a model for genomic medicine implementation and research.

BACKGROUND: Patients, clinicians, researchers and payers are seeking to understand the value of using genomic information (as reflected by genotyping, sequencing, family history or other data) to inform clinical decision-making. However, challenges exist to widespread clinical implementation of genomic medicine, a prerequisite for developing evidence of its real-world utility. METHODS: To address these challenges, the National Institutes of Health-funded IGNITE (Implementing GeNomics In pracTicE; www.ignite-genomics.org ) Network, comprised of six projects and a coordinating center, was established in 2013 to support the development, investigation and dissemination of genomic medicine practice models that seamlessly integrate genomic data into the electronic health record and that deploy tools for point of care decision making. IGNITE site projects are aligned in their purpose of testing these models, but individual projects vary in scope and design, including exploring genetic markers for disease risk prediction and prevention, developing tools for using family history data, incorporating pharmacogenomic data into clinical care, refining disease diagnosis using sequence-based mutation discovery, and creating novel educational approaches. RESULTS: This paper describes the IGNITE Network and member projects, including network structure, collaborative initiatives, clinical decision support strategies, methods for return of genomic test results, and educational initiatives for patients and providers. Clinical and outcomes data from individual sites and network-wide projects are anticipated to begin being published over the next few years. CONCLUSIONS: The IGNITE Network is an innovative series of projects and pilot demonstrations aiming to enhance translation of validated actionable genomic information into clinical settings and develop and use measures of outcome in response to genome-based clinical interventions using a pragmatic framework to provide early data and proofs of concept on the utility of these interventions. Through these efforts and collaboration with other stakeholders, IGNITE is poised to have a significant impact on the acceleration of genomic information into medical practice.