Impaired neuronal proteostasis is a salient feature of many neurodegenerative diseases, highlighting alterations in the function of the endoplasmic reticulum (ER). We previously reported that ...targeting the transcription factor XBP1, a key mediator of the ER stress response, delays disease progression and reduces protein aggregation in various models of neurodegeneration. To identify disease modifier genes that may explain the neuroprotective effects of XBP1 deficiency, we performed gene expression profiling of brain cortex and striatum of these animals and uncovered insulin-like growth factor 2 (
Igf2
) as the major upregulated gene. Here, we studied the impact of IGF2 signaling on protein aggregation in models of Huntington’s disease (HD) as proof of concept. Cell culture studies revealed that IGF2 treatment decreases the load of intracellular aggregates of mutant huntingtin and a polyglutamine peptide. These results were validated using induced pluripotent stem cells (iPSC)-derived medium spiny neurons from HD patients and spinocerebellar ataxia cases. The reduction in the levels of mutant huntingtin was associated with a decrease in the half-life of the intracellular protein. The decrease in the levels of abnormal protein aggregation triggered by IGF2 was independent of the activity of autophagy and the proteasome pathways, the two main routes for mutant huntingtin clearance. Conversely, IGF2 signaling enhanced the secretion of soluble mutant huntingtin species through exosomes and microvesicles involving changes in actin dynamics. Administration of IGF2 into the brain of HD mice using gene therapy led to a significant decrease in the levels of mutant huntingtin in three different animal models. Moreover, analysis of human postmortem brain tissue and blood samples from HD patients showed a reduction in IGF2 level. This study identifies IGF2 as a relevant factor deregulated in HD, operating as a disease modifier that buffers the accumulation of abnormal protein species.
Abstract Purpose Diabetes self-management is essential for diabetes control, yet little is known about patient preferences for sources of health information or about the extent to which information ...is sought directly or received passively through various media sources. The aim of this qualitative study was to identify how individuals with diabetes seek and use health care information. Methods Using a health information model to guide our research, we conducted 9 focus groups with 46 adults with a diagnosis of diabetes and then analyzed the transcripts and notes from these focus groups. Results Five themes emerged: (1) passive receipt of health information about diabetes is an important aspect of health information behavior; (2) patients weave their own information web depending on their disease trajectory; (3) patients' personal relationships help them understand and use this information; (4) a relationship with a health care professional is needed to cope with complicated and sometimes conflicting information; and (5) health literacy makes a difference in patients' ability to understand and use information. Conclusions Patients make decisions about diabetes self-management depending on their current needs, seeking and incorporating diverse information sources not traditionally viewed as providing health information. Based on our findings, we have developed a new health information model that reflects both the nonlinear nature of health information-seeking behavior and the interplay of both active information seeking and passive receipt of information.
Abstract Purpose Health care leaders encourage clinicians to offer portals that enable patients to access personal health records, but implementation has been a challenge. Although large integrated ...health systems have promoted use through costly advertising campaigns, other implementation methods are needed for small to medium-sized practices where most patients receive their care. Methods We conducted a mixed methods assessment of a proactive implementation strategy for a patient portal (an interactive preventive health record IPHR) offered by 8 primary care practices. The practices implemented a series of learning collaboratives with practice champions and redesigned workflow to integrate portal use into care. Practice implementation strategies, portal use, and factors influencing use were assessed prospectively. Results A proactive and customized implementation strategy designed by practices resulted in 25.6% of patients using the IPHR, with the rate increasing 1.0% per month over 31 months. Fully 23.5% of IPHR users signed up within 1 day of their office visit. Older patients and patients with comorbidities were more likely to use the IPHR, but blacks and Hispanics were less likely. Older age diminished as a factor after adjusting for comorbidities. Implementation by practice varied considerably (from 22.1% to 27.9%, P <.001) based on clinician characteristics and workflow innovations adopted by practices to enhance uptake. Conclusions By directly engaging patients to use a portal and supporting practices to integrate use into care, primary care practices can match or potentially surpass the usage rates achieved by large health systems.
Abstract Purpose Americans receive only one-half of recommended preventive services. Information technologies have been advocated to engage patients. We tested the effectiveness of an interactive ...preventive health record (IPHR) that links patients to their clinician's record, explains information in lay language, displays tailored recommendations and educational resources, and generates reminders. Methods This randomized controlled trial involved 8 primary care practices. Four thousand five hundred patients were randomly selected to receive a mailed invitation to use the IPHR or usual care. Outcomes were measured using patient surveys and electronic medical record data and included IPHR use and service delivery. Comparisons were made between invited and usual-care patients and between users and nonusers among those invited to use the IPHR. Results At 4 and 16 months, 229 (10.2%) and 378 (16.8%) of invited patients used the IPHR. The proportion of patients up-to-date with all services increased between baseline and 16 months by 3.8% among intervention patients (from 11.4% to 15.2%, P <.001) and by 1.5% among control patients (from 11.1% to 12.6%, P = .07), a difference of 2.3% ( P = .05). Greater increases were observed among patients who used the IPHR. At 16 months, 25.1% of users were up-to-date with all services, double the rate among nonusers. At 4 months, delivery of colorectal, breast, and cervical cancer screening increased by 19%, 15%, and 13%, respectively, among users. Conclusions Information systems that feature patient-centered functionality, such as the IPHR, have potential to increase preventive service delivery. Engaging more patients to use systems could have important public health benefits.
This study shows how a few nanometer-sized crystals markedly increase the viscosity of a magma leading to explosive eruptions.
Although gas exsolution is a major driving force behind explosive ...volcanic eruptions, viscosity is critical in controlling the escape of bubbles and switching between explosive and effusive behavior. Temperature and composition control melt viscosity, but crystallization above a critical volume (>30 volume %) can lock up the magma, triggering an explosion. Here, we present an alternative to this well-established paradigm by showing how an unexpectedly small volume of nano-sized crystals can cause a disproportionate increase in magma viscosity. Our in situ observations on a basaltic melt, rheological measurements in an analog system, and modeling demonstrate how just a few volume % of nanolites results in a marked increase in viscosity above the critical value needed for explosive fragmentation, even for a low-viscosity melt. Images of nanolites from low-viscosity explosive eruptions and an experimentally produced basaltic pumice show syn-eruptive growth, possibly nucleating a high bubble number density.
Effectively engaging patients in their care is essential to improve health outcomes, improve satisfaction with the care experience, reduce costs, and even benefit the clinician experience. This ...chapter will address the topic of patient engagement directly and review the relationships between health literacy and patient engagement. While there are many ways to define patient and family engagement, this chapter will consider engagement as "patients, families, their representatives, and health professionals working in active partnership at various levels across the health care system - direct care, organizational design and governance, and policy making - to improve health and health care 1." We will specifically focus on the patient engagement and health literacy needs for three scenarios (1) decision-making, (2) health behavior change, and (3) chronic disease management; we will include the theoretical underpinnings of engagement, the systems required to better support patient engagement, how social determinants of health influence patient engagement, and practical examples to demonstrate approaches to better engage patients in their health and wellbeing. We will close by describing the future of patient engagement, which extends beyond the traditional domains of decision-making and self-care to describe how patient engagement can influence the design of the healthcare delivery system; local, state, and national health policies; and future research relevant to the needs and experiences of patients.
Since the Institute of Medicine (IOM) reports on medical errors and quality, national attention has focused on improving patient safety through changes in "systems" of care. These reports resulted in ...a new paradigm that, rather than centering on individual errors, focuses on the "systems" necessary to facilitate and enhance quality and protect patients.
To assess the status of hospital patient safety systems since the release of the IOM reports and to identify changes over time in 2 states that collaborated on a patient safety project funded by the Agency for Healthcare Research and Quality.
Survey of all acute care hospitals in Missouri and Utah at 2 points in time, in 2002 and 2004, using a 91-item comprehensive questionnaire (n = 126 for survey 1 and n = 128 for survey 2). To assess changes over time, we also studied the cohort of 107 hospitals that responded to both surveys.
Responses to the 91-question survey as well as changes in responses to the survey questions over an 18-month period. Seven latent variables were constructed to represent the most important patient safety constructs studied: computerized physician order entry systems, computerized test results, and assessments of adverse events; specific patient safety policies; use of data in patient safety programs; drug storage, administration, and safety procedures; manner of handling adverse event/error reporting; prevention policies; and root cause analysis. For each hospital, the 7 latent variables were summed to give an overall measure of the patient safety status of the hospital.
Development and implementation of patient safety systems is at best modest. Self-reported regression in patient safety systems was also found. While 74% of hospitals reported full implementation of a written patient safety plan, nearly 9% reported no plan. The area of surgery appears to have the greatest level of patient safety systems. Other areas, such as medications, with a long history of efforts in patient safety and error prevention, showed improvements, but the percentage of hospitals with various safety systems was already high at baseline for many systems. Some findings are surprising, given the overall trends; for example, while a substantial percentage of hospitals have medication safety systems, only 34.1% corrected reported full implementation at survey 2 of computerized physician order entry systems for medications, despite the growth of computer technology in general and in hospital billing systems in particular.
The current status of hospital patient safety systems is not close to meeting IOM recommendations. Data are consistent with recent reports that patient safety system progress is slow and is a cause for great concern. Efforts for improvement must be accelerated.
Evidence-based preventive services offer profound health benefits, yet Americans receive only half of indicated care. A variety of government and specialty society policy initiatives are promoting ...the adoption of information technologies to engage patients in their care, such as personal health records, but current systems may not utilize the technology's full potential.
Using a previously described model to make information technology more patient-centered, we developed an interactive preventive health record (IPHR) designed to more deeply engage patients in preventive care and health promotion. We recruited 14 primary care practices to promote the IPHR to all adult patients and sought practice and patient input in designing the IPHR to ensure its usability, salience, and generalizability. The input involved patient usability tests, practice workflow observations, learning collaboratives, and patient feedback. Use of the IPHR was measured using practice appointment and IPHR databases.
The IPHR that emerged from this process generates tailored patient recommendations based on guidelines from the U.S. Preventive Services Task Force and other organizations. It extracts clinical data from the practices' electronic medical record and obtains health risk assessment information from patients. Clinical content is translated and explained in lay language. Recommendations review the benefits and uncertainties of services and possible actions for patients and clinicians. Embedded in recommendations are self management tools, risk calculators, decision aids, and community resources--selected to match patient's clinical circumstances. Within six months, practices had encouraged 14.4% of patients to use the IPHR (ranging from 1.5% to 28.3% across the 14 practices). Practices successfully incorporated the IPHR into workflow, using it to prepare patients for visits, augment health behavior counseling, explain test results, automatically issue patient reminders for overdue services, prompt clinicians about needed services, and formulate personalized prevention plans.
The IPHR demonstrates that a patient-centered personal health record that interfaces with the electronic medical record can give patients a high level of individualized guidance and be successfully adopted by busy primary care practices. Further study and refinement are necessary to make information systems even more patient-centered and to demonstrate their impact on care.
Clinicaltrials.gov identifier: NCT00589173.
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