Regulation of metE+ mRNA expression by FnrS small RNA in Salmonella enterica serovar Typhimurium.

Methionine is critical for variety of metabolic processes in biological organisms, acting as a precursor or intermediate for many final products. The last step for the synthesis of methionine is the methylation of homocysteine, which is catalyzed by MetE. Here, we use Salmonella enterica serovar Typhimurium LT2 to study the regulation of the metE+ gene by an anaerobically induced small non-coding RNA-FnrS, the expression of which is strictly dependent on the anaerobic regulator-FNR. The MetE-HA protein was expressed at an increased level in the fnrS- and hfq- deficient strains under anaerobic conditions. The Hfq protein is predicted to stabilize the binding between small RNA(s) and their target mRNA(s). A transcriptional (op) and translational (pr) metE::lacZ fusion gene were separately constructed, with the metE+-promoter fused to a lacZ reporter gene. In an anaerobic environment, the metE::lacZ (pr) fusion gene and reverse transcription-PCR identified that FnrS and/or FNR negatively regulate metE+ mRNA levels in the rich media. Analysis of FnrS revealed a sequence complementary to the 5' mRNA translational initiation region (TIR) of the metE+ gene. Mutation(s) predicted to disrupt base pairing between FnrS and metE+ TIR were constructed in fnrS, and most of those resulted in the loss of repressive activity. When compensatory mutation(s) were made in metE+ 5' TIR to restore base pairing with FnrS, the repressive regulation was completely restored. Therefore, in this study, we identified that in anaerobic phase, there is a repression of metE+ gene expression by FnrS and that base-paring, between both expressive transcripts, plays an important role for this negative regulation.

The asthma mobile health study, smartphone data collected using ResearchKit.

Widespread adoption of smart mobile platforms coupled with a growing ecosystem of sensors including passive location tracking and the ability to leverage external data sources create an opportunity to generate an unprecedented depth of data on individuals. Mobile health technologies could be utilized for chronic disease management as well as research to advance our understanding of common diseases, such as asthma. We conducted a prospective observational asthma study to assess the feasibility of this type of approach, clinical characteristics of cohorts recruited via a mobile platform, the validity of data collected, user retention patterns, and user data sharing preferences. We describe data and descriptive statistics from the Asthma Mobile Health Study, whereby participants engaged with an iPhone application built using Apple's ResearchKit framework. Data from 6346 U.S. participants, who agreed to share their data broadly, have been made available for further research. These resources have the potential to enable the research community to work collaboratively towards improving our understanding of asthma as well as mobile health research best practices.

From smartphone to EHR: a case report on integrating patient-generated health data.

Patient-generated health data (PGHD), collected from mobile apps and devices, represents an opportunity for remote patient monitoring and timely interventions to prevent acute exacerbations of chronic illness-if data are seen and shared by care teams. This case report describes the technical aspects of integrating data from a popular smartphone platform to a commonly used EHR vendor and explores the challenges and potential of this approach for disease management. Consented subjects using the Asthma Health app (built on Apple's ResearchKit platform) were able to share data on inhaler usage and peak expiratory flow rate (PEFR) with a local pulmonologist who ordered this data on Epic's EHR. For users who had installed and activated Epic's patient portal (MyChart) on their iPhone and enabled sharing of health data between apps via HealthKit, the pulmonologist could review PGHD and, if necessary, make recommendations. Four patients agreed to share data with their pulmonologist, though only two patients submitted more than one data point across the 4.5-month trial period. One of these patients submitted 101 PEFR readings across 65 days; another submitted 24 PEFR and inhaler usage readings across 66 days. PEFR for both patients fell within predefined physiologic parameters, except once where a low threshold notification was sent to the pulmonologist, who responded with a telephone discussion and new e-prescription to address symptoms. This research describes the technical considerations and implementation challenges of using commonly available frameworks for sharing PGHD, for the purpose of remote monitoring to support timely care interventions.

The Asthma Mobile Health Study, a large-scale clinical observational study using ResearchKit.

The feasibility of using mobile health applications to conduct observational clinical studies requires rigorous validation. Here, we report initial findings from the Asthma Mobile Health Study, a research study, including recruitment, consent, and enrollment, conducted entirely remotely by smartphone. We achieved secure bidirectional data flow between investigators and 7,593 participants from across the United States, including many with severe asthma. Our platform enabled prospective collection of longitudinal, multidimensional data (e.g., surveys, devices, geolocation, and air quality) in a subset of users over the 6-month study period. Consistent trending and correlation of interrelated variables support the quality of data obtained via this method. We detected increased reporting of asthma symptoms in regions affected by heat, pollen, and wildfires. Potential challenges with this technology include selection bias, low retention rates, reporting bias, and data security. These issues require attention to realize the full potential of mobile platforms in research and patient care.

METHODS FOR CLUSTERING TIME SERIES DATA ACQUIRED FROM MOBILE HEALTH APPS.

In our recent Asthma Mobile Health Study (AMHS), thousands of asthma patients across the country contributed medical data through the iPhone Asthma Health App on a daily basis for an extended period of time. The collected data included daily self-reported asthma symptoms, symptom triggers, and real time geographic location information. The AMHS is just one of many studies occurring in the context of now many thousands of mobile health apps aimed at improving wellness and better managing chronic disease conditions, leveraging the passive and active collection of data from mobile, handheld smart devices. The ability to identify patient groups or patterns of symptoms that might predict adverse outcomes such as asthma exacerbations or hospitalizations from these types of large, prospectively collected data sets, would be of significant general interest. However, conventional clustering methods cannot be applied to these types of longitudinally collected data, especially survey data actively collected from app users, given heterogeneous patterns of missing values due to: 1) varying survey response rates among different users, 2) varying survey response rates over time of each user, and 3) non-overlapping periods of enrollment among different users. To handle such complicated missing data structure, we proposed a probability imputation model to infer missing data. We also employed a consensus clustering strategy in tandem with the multiple imputation procedure. Through simulation studies under a range of scenarios reflecting real data conditions, we identified favorable performance of the proposed method over other strategies that impute the missing value through low-rank matrix completion. When applying the proposed new method to study asthma triggers and symptoms collected as part of the AMHS, we identified several patient groups with distinct phenotype patterns. Further validation of the methods described in this paper might be used to identify clinically important patterns in large data sets with complicated missing data structure, improving the ability to use such data sets to identify at-risk populations for potential intervention.

The Use of Smartphones for Health Research.

Because of their growing popularity and functionality, smartphones are increasingly valuable potential tools for health and medical research. Using ResearchKit, Apple's open-source platform to build applications ("apps") for smartphone research, collaborators have developed apps for researching asthma, breast cancer, cardiovascular disease, type 2 diabetes, and Parkinson disease. These research apps enhance widespread participation by removing geographical barriers to participation, provide novel ways to motivate healthy behaviors, facilitate high-frequency assessments, and enable more objective data collection. Although the studies have great potential, they also have notable limitations. These include selection bias, identity uncertainty, design limitations, retention, and privacy. As smartphone technology becomes increasingly available, researchers must recognize these factors to ensure that medical research is conducted appropriately. Despite these limitations, the future of smartphones in health research is bright. Their convenience grants unprecedented geographic freedom to researchers and participants alike and transforms the way clinical research can be conducted.

Stroke education in an emergency department waiting room: a comparison of methods.

BACKGROUND: Since the emergency department (ED) waiting room hosts a large, captive audience of patients and visitors, it may be an ideal location for conducting focused stroke education. The aim of this study was to assess the effectiveness of various stroke education methods. METHODS: Patients and visitors of an urban ED waiting room were randomized into one of the following groups: video, brochure, one-to-one teaching, combination of these three methods, or control group. We administered a 13-question multiple-choice test to assess stroke knowledge prior to, immediately after, and at 1 month post-education to patients and visitors in the ED waiting room. RESULTS: Of 4 groups receiving education, all significantly improved their test scores immediately post intervention (test scores 9.4±2.5-10.3±2.0, P<0.01). At 1 month, the combination group retained the most knowledge (9.4±2.4) exceeding pre-intervention and control scores (both 6.7±2.6, P<0.01). CONCLUSION: Among the various stroke education methods delivered in the ED waiting room, the combination method resulted in the highest knowledge retention at 1-month post intervention.

Medical utilization of kiosks in the delivery of patient education: a systematic review.

BACKGROUND: The utilization of kiosks has previously been shown to be effective for collecting information, delivering educational modules, and providing access to health information. We discuss a review of current literature for the utilization of kiosks for the delivery of patient education. METHODS: The criteria for inclusion in this literature review were: (1) study discusses the utilization of kiosks for patient health education; (2) study discusses the use of touch screens for patient health information; (3) published in English. Our review includes searches via MEDLINE databases and Google Scholar for the years 1996-2014. RESULTS: Overall, 167 articles were screened for final eligibility, and after discarding duplicates and non-eligible studies with abstract. Full-text review of 28 articles was included in the final analysis. CONCLUSION: The review of available literature demonstrates the effectiveness of touch screen kiosks to educate patients and to improve healthcare, both at a performance and cost advantage over other modes of patient education.

Supplemental oxygen delivery to suspected stroke patients in pre hospital and emergency department settings.

BACKGROUND: Recent data suggests that high-flow oxygen started promptly after stroke symptom onset salvages ischemic brain tissue. We investigated the consistency of oxygen delivery to suspected stroke patients in the pre-hospital (PH) and Emergency Department (ED) settings, and associated adverse events (AEs). METHODS: We retrospectively reviewed pre-hospital call reports of suspected stroke patients transported by our institution's paramedics. We extracted data on oxygen delivery in the PH and ED settings, demographics, Glasgow Coma Scale score (GCS), final diagnosis, and selected AEs (mortality, seizures, worsening neurological status, new infarction, and post-ischemic hemorrhage). Patients were grouped according to ED oxygen delivery: none, low-flow (2-4 L/min), and high-flow (10-15 L/min). RESULTS: Oxygen delivery was documented in 84% of 366 stroke transports, with 98% receiving 10-15 L/min. Our hospital received 164 patients. Oxygen delivery in the ED was documented in 150 patients, with 38% receiving none, 47% low-flow, and 15% high-flow oxygen. There were no instances of oxygen refusal, premature termination, or technical difficulties. Advanced age and low GCS predicted the use of higher flow rates. High-flow oxygen was more frequently administered to patients with symptom onset < 3 hours, and those with intracerebral hemorrhage (ICH), hypoxic-ischemic encephalopathy (HIE) or seizures (p < 0.001). More patients receiving high-flow oxygen were documented to have an AE (p = 0.02), however the low- and no-oxygen groups more frequently had multiple AEs (p = 0.01). The occurrence of AEs was predicted by the diagnosis of ICH/HIE/seizures (p = 0.013) and acute ischemic stroke (AIS)/transient ischemic attack (TIA) (p = 0.009), but not by the amount of oxygen. CONCLUSIONS: Suspected stroke patients routinely receive 10-15 L/min oxygen in the ambulance however in the ED there is wide variability due to factors such as clinical severity. Oxygen delivery appears safe in the PH and ED settings.

NIH Roundtable on Opportunities to Advance Research on Neurologic and Psychiatric Emergencies.

STUDY OBJECTIVE: The Institute of Medicine Committee on the Future of Emergency Care in the United States Health System (2003) identified a need to enhance the research base for emergency care. As a result, a National Institutes of Health (NIH) Task Force on Research in Emergency Medicine was formed to enhance NIH support for emergency care research. Members of the NIH Task Force and academic leaders in emergency care participated in 3 Roundtable discussions to prioritize current opportunities for enhancing and conducting emergency care research. We identify key research questions essential to advancing the science of emergency care and discuss the barriers and strategies to advance research by exploring the collaboration between NIH and the emergency care community. METHODS: Experts from emergency medicine, neurology, psychiatry, and public health assembled to review critical areas in need of investigation, current gaps in knowledge, barriers, and opportunities. Neurologic emergencies included cerebral resuscitation, pain, stroke, syncope, traumatic brain injury, and pregnancy. Mental health topics included suicide, agitation and delirium, substances, posttraumatic stress, violence, and bereavement. RESULTS: Presentations and group discussion firmly established the need for translational research to bring basic science concepts into the clinical arena. A coordinated continuum of the health care system that ensures rapid identification and stabilization and extends through discharge is necessary to maximize overall patient outcomes. There is a paucity of well-designed, focused research on diagnostic testing, clinical decisionmaking, and treatments in the emergency setting. Barriers include the limited number of experienced researchers in emergency medicine, limited dedicated research funding, and difficulties of conducting research in chaotic emergency environments stressed by crowding and limited resources. Several themes emerged during the course of the roundtable discussion, including the need for development of (1) a research infrastructure for the rapid identification, consent, and tracking of research subjects that incorporates innovative informatics technologies, essential for future research; (2) diagnostic strategies and tools necessary to understand key populations and the process of medical decisionmaking, including the investigation of the pathobiology of symptoms and symptom-oriented therapies; (3) collaborative research networks to provide unique opportunities to form partnerships, leverage patient cohorts and clinical and financial resources, and share data; (4) formal research training programs integral for creating new knowledge and advancing the science and practice of emergency medicine; and (5) recognition that emergency care is part of an integrated system from emergency medical services dispatch to discharge. The NIH Roundtable "Opportunities to Advance Research on Neurological and Psychiatric Emergencies" created a framework to guide future emergency medicine-based research initiatives. CONCLUSION: Emergency departments provide the portal of access to the health care system for most patients with acute neurologic and psychiatric illness. Emergency physicians and colleagues are primed to investigate neurologic and psychiatric emergencies that will directly improve the delivery of care and patient outcomes.

Effectiveness of stroke education in the emergency department waiting room.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of stroke education provided to patients and their significant others in the emergency department (ED) waiting area. Our focus was on the 4 main aspects of stroke: signs and symptoms, risk factors, behavior modification, and the urgency to seek medical attention. We hypothesized that showing educational videos, providing one-on-one counseling, and distributing literature would result in greater stroke knowledge and positive behavioral modification. METHODS: In this pilot, randomized controlled trial, our research team enrolled patients and visitors in the fast-track waiting area of the ED. After obtaining informed written consent, participants were randomly assigned to the control group or to the intervention group. The intervention group received an educational video program, one-on-one counseling, and stroke education materials, and completed a 13-question test after receiving the education. The control group completed the same test without receiving any education. Both groups completed the same test again at 1 and 3 months to assess stroke knowledge retention. RESULTS: There were a total of 329 participants: 151 in the control group and 178 in the intervention group. Gender, age, and educational level of participants did not differ between groups. At all time points of the study, participants receiving stroke education demonstrated better test scores than those in the control group. However, knowledge retention in the intervention group gradually declined during the follow-up. Individuals enrolled in the intervention group appeared to be more motivated to reduce their smoking habits, compared with control subjects; however, the number of cigarettes they smoked per day did not dramatically decrease in comparison with their own baseline. Receiving the education session did not result in positive diet or physical activity changes. CONCLUSIONS: ED stroke education, which includes video program, one-on-one counseling, and written educational materials, is able to significantly increase stroke knowledge. Modification and reinforcement of education is needed to achieve better knowledge retention and favorable lifestyle modifications.

Emergency physician and stroke specialist beliefs and expectations regarding telestroke.

BACKGROUND AND PURPOSE: Telestroke has been effective in the management of acute ischemic stroke. This study characterizes and compares stroke specialist (SS) and emergency physician (EP) perceptions of telestroke and identifies barriers preventing increased implementation. METHODS: A survey was developed and distributed nationwide to 382 SSs through an online survey system and in paper form to 226 EPs attending the 2008 American College of Emergency Physicians national conference. RESULTS: Stroke specialists perceived themselves to be more knowledgeable about telemedicine and telestroke (P<0.001 and P=0.010, respectively). A large majority of physicians in both specialties either strongly agreed or agreed that telestroke will reduce geographical differences in stroke management and that it is superior to telephone consultation. EPs perceived patient preference (P<0.001), recombinant tissue plasminogen activator side effects (P<0.001), level of technology (P=0.005), and recombinant tissue plasminogen activator not the standard of care (P<0.001) to be more significant obstacles to increased implementation of telestroke than SSs. However, SSs found increased personal work to be a greater barrier than EPs (P<0.001). CONCLUSIONS: SSs and EPs report positive beliefs regarding telestroke; however, perceived obstacles exist to implementation. Differences between barriers perceived by EPs and SSs need to be addressed to enhance acute ischemic stroke treatment.

Interpreter services in emergency medicine.

Emergency physicians are routinely confronted with problems associated with language barriers. It is important for emergency health care providers and the health system to strive for cultural competency when communicating with members of an increasingly diverse society. Possible solutions that can be implemented include appropriate staffing, use of new technology, and efforts to develop new kinds of ties to the community served. Linguistically specific solutions include professional interpretation, telephone interpretation, the use of multilingual staff members, the use of ad hoc interpreters, and, more recently, the use of mobile computer technology at the bedside. Each of these methods carries a specific set of advantages and disadvantages. Although professionally trained medical interpreters offer improved communication, improved patient satisfaction, and overall cost savings, they are often underutilized due to their perceived inefficiency and the inconclusive results of their effect on patient care outcomes. Ultimately, the best solution for each emergency department will vary depending on the population served and available resources. Access to the multiple interpretation options outlined above and solid support and commitment from hospital institutions are necessary to provide proper and culturally competent care for patients. Appropriate communications inclusive of interpreter services are essential for culturally and linguistically competent provider/health systems and overall improved patient care and satisfaction.

Transient ischemic attack overview: defining the challenges for improving outcomes.

Transient ischemic attacks are reversible neurologic events that herald potentially catastrophic strokes. Well designed studies have documented that approximately 10% of patients who have a transient ischemic attack will have a stroke within the succeeding 90 days; half of these strokes occur within 48 hours of the transient ischemic attack. Improved outcomes from transient ischemic attacks require a heightened awareness of the clinical features of transient ischemic attacks on the part of both patients and physicians. The significant potential for stroke in the immediate days after the transient ischemic attack imposes an urgency in the diagnostic evaluation of these patients. A review of the literature suggests that there is a need for pathways to promote facilitated evaluations of transient ischemic attack patients in order to identify underlying correctable pathologies, and to direct medical and surgical management strategies.

Effect of an educational video on emergency department patient stroke knowledge.

The purpose of this study was to explore whether passive watching of a stroke videotape in the Emergency Department waiting room could be an effective method for patient education. The setting was an urban, inner city teaching hospital. After providing informed consent, subjects were randomized into two arms: those watching a 12-min educational video on stroke developed by the American Stroke Association (video group) and those not undergoing an intervention (control group). Both groups were administered a 13-question quiz covering different stroke-related issues, but only the video group received this same test again after the completion of the educational program. Those enrolled were contacted after 1 month to determine knowledge retention via the same test. Immediately after watching the educational program, participants demonstrated improved knowledge of stroke-related questions, with an increase of test scores from 6.7 +/- 2.5 to 9.5 +/- 2.6 (p < 0.01). Even at the 1-month follow-up, the video group had significantly higher test scores than the control group. A stroke educational videotape improves the knowledge of this dangerous disease and may be a valuable and relatively low-cost tool for focused patient education in the Emergency Department waiting room.

Disaster management following the Chi-Chi earthquake in Taiwan.

The earthquake that occurred in Taiwan on 21 September 1999 killed >2,000 people and severely injured many survivors. Despite the large scale and sizeable impact of the event, a complete overview of its consequences and the causes of the inadequate rescue and treatment efforts is limited in the literature. This review examines the way different groups coped with the tragedy and points out the major mistakes made during the process. The effectiveness of Taiwan's emergency preparedness and disaster response system after the earthquake was analyzed. Problems encountered included: (1) an ineffective command center; (2) poor communication; (3) lack of cooperation between the civil government and the military; (4) delayed prehospital care; (5) overloading of hospitals beyond capacity; (6) inadequate staffing; and (7) mismanaged public health measures. The Taiwan Chi-Chi Earthquake experience demonstrates that precise disaster planning, the establishment of one designated central command, improved cooperation between central and local authorities, modern rescue equipment used by trained disaster specialists, rapid prehospital care, and medical personnel availability, as well earthquake-resistant buildings and infrastructure, are all necessary in order to improve disaster responses.

Tissue plasminogen activator for acute ischemic stroke: a New York city emergency medicine perspective.

Nationally, only 2-3% of patients with acute ischemic stroke (AIS) currently receive tissue plasminogen activator (TPA). To better understand the reasons, we investigated the practice patterns, level of familiarity and acceptance of TPA for AIS among emergency physicians in New York City (NYC). Fifty-seven 911-receiving hospital emergency department directors were surveyed regarding TPA use. Of those responding, 37% had never used TPA to treat AIS. Lack of neurological support was reported by 33%. Departments with formal protocols were more likely to use TPA for AIS. In conclusion, there is considerable variation in the practice, knowledge, and attitudes regarding the use of TPA for AIS in NYC emergency departments. Improved educational efforts and institutional support may be necessary to ensure the appropriate use of TPA by emergency physicians.