Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters.

R-loops are three-stranded nucleic acid structures found abundantly and yet often viewed as by-products of transcription. Studying cells from patients with a motor neuron disease (amyotrophic lateral sclerosis 4 [ALS4]) caused by a mutation in senataxin, we uncovered how R-loops promote transcription. In ALS4 patients, the senataxin mutation depletes R-loops with a consequent effect on gene expression. With fewer R-loops in ALS4 cells, the expression of BAMBI, a negative regulator of transforming growth factor ß (TGF-ß), is reduced; that then leads to the activation of the TGF-ß pathway. We uncovered that genome-wide R-loops influence promoter methylation of over 1,200 human genes. DNA methyl-transferase 1 favors binding to double-stranded DNA over R-loops. Thus, in forming R-loops, nascent RNA blocks DNA methylation and promotes further transcription. Hence, our results show that nucleic acid structures, in addition to sequences, influence the binding and activity of regulatory proteins.

Persistent GDNF Expression 45 Months after Putaminal Infusion of AAV2-GDNF in a Patient with Parkinson's Disease.

OBJECTIVE: Gene therapy by convection-enhanced delivery of type 2 adeno-associated virus-glial cell derived neurotrophic factor (AAV2-GDNF) to the bilateral putamina seeks to increase GDNF gene expression and treat Parkinson's disease (PD). METHODS: A 63-year-old man with advanced PD received AAV2-GDNF in a clinical trial. He died from pneumonia after anterior cervical discectomy and fusion 45 months later. An autopsy included brain examination for GDNF transgene expression. Putaminal catecholamine concentrations were compared to in vivo 18F-Fluorodopa (18F-FDOPA) positron emission tomography (PET) scanning results before and 18 months after AAV2-GDNF infusion. RESULTS: Parkinsonian progression stabilized clinically. Postmortem neuropathology confirmed PD. Bilateral putaminal regions previously infused with AAV2-GDNF expressed the GDNF gene. Total putaminal dopamine was 1% of control, confirming the striatal dopaminergic deficiency suggested by baseline 18F-DOPA-PET scanning. Putaminal regions responded as expected to AAV2-GDNF. CONCLUSION: After AAV2-GDNF infusion, infused putaminal regions showed increased GDNF gene expression, tyrosine hydroxylase immunoreactive sprouting, catechol levels, and 18F-FDOPA-PET signal, suggesting the regenerative potential of AAV2-GDNF in PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Impact of Mediterranean Dietary Education on Symptoms for Adults at Risk for Nonalcoholic Fatty Liver Disease.

This 2-month quasi-experimental study focused on the impact of education regarding the Mediterranean diet on symptoms for adults who are at risk for nonalcoholic fatty liver disease (NAFLD). The study was conducted on a sample of 28 adults who presented to Pinnacle clinical research for NAFLD screening via a fibroscan. These individuals who are at risk for NAFLD received a single 15-minute one-on-one in person education regarding the Mediterranean diet. The diet encourages fruits, vegetables, whole grains, legumes, nuts, seeds, fish, and olive oil. The results of the study showed that the Mediterranean diet education was associated with significant improvement of abdominal symptoms ( t = 3.34, p = .03), improvement of fatigue symptoms ( t = 5.88, p < .001), and decrease in hepatic steatosis ( t = 5.77, p < .001). Our study suggests that the education on the Mediterranean diet may be associated with improvement of self-reported abdominal symptoms, fatigue, and steatosis score.

Altered SYNJ2BP-mediated mitochondrial-ER contacts in motor neuron disease.

Synaptojanin 2 binding protein (SYNJ2BP) is an outer mitochondrial membrane protein with a cytosolic PDZ domain that functions as a cellular signaling hub. Few studies have evaluated its role in disease. Here we use induced pluripotent stem cell (iPSC)-derived motor neurons and post-mortem tissue from patients with two hereditary motor neuron diseases, spinal and bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis type 4 (ALS4), and show that SYNJ2BP expression is increased in diseased motor neurons. Similarly, we show that SYNJ2BP expression increases in iPSC-derived motor neurons undergoing stress. Using proteomic analysis, we found that elevated SYNJ2BP alters the cellular distribution of mitochondria and increases mitochondrial-ER membrane contact sites. Furthermore, decreasing SYNJ2BP levels improves mitochondrial oxidative function in the diseased motor neurons. Together, our observations offer new insight into the molecular pathology of motor neuron disease and the role of SYNJ2BP in mitochondrial dysfunction.

A Comparison of Voice Recognition Program and Traditional Keyboard Charting for Nurse Documentation.

The purposes of this study are threefold: (1) compare the document times between a voice recognition system and keyboard charting, (2) compare the number of errors between the two methods, and (3) identify factors influencing documentation time. Voice recognition systems are considered a potential solution to decrease documentation time. However, little is known to what extent voice recognition systems can save nurses' documentation time. A pilot, simulation study was conducted using a voice recognition system and keyboard charting with 15 acute care nurses. A crossover method with repeated measures was utilized. Each nurse was given two simple and two complex assessment scenarios, assigned in random order, to document using both methods. Paired t-tests and multivariate linear regression models were used for data analysis. The voice recognition method saved the nurses 2.3 minutes (simple scenario) and 6.1 minutes (complex scenario) on average and was statistically significant (P < .001). There were no significant differences in errors or factors identified influencing documentation times. Eighty percent reported a preference of using voice recognition systems, and 87% agreed this method helped speed up charting. This study can show how a voice recognition system can improve documentation times compared with keyboard charting while still having thorough documentation.

Conversations about wellness: A qualitative analysis of patient narratives post annual wellness visit.

Support for successful aging in place requires an understanding of the factors that impede or support health promotion behaviors. Nurse-led monthly follow-up calls between annual wellness visits (AWV) offer the opportunity to both provide support and collect data which can inform development of effective health promotion strategies. The aim of this research was to provide ongoing support for health promotion efforts and explore factors playing a role in meeting AWV recommendations. A total of 144 visit summaries for 47 Medicare beneficiaries (65+) who had completed an AWV within the last year were analyzed using a thematic approach. Themes were organized into 7 categories with findings indicating the complexity of factors which influence health promotion behaviors. The importance of ensuring personalization of health promotion recommendations using data collected during the AWV and provision of ongoing support between visits may enhance health outcomes.

Mass Casualty Mini Drills on Trauma Surgery Department Staff Knowledge: An Educational Improvement Study.

BACKGROUND: Over the last decade, the United States has witnessed an increase in mass casualty incidents (MCIs). The outcome of an MCI depends upon hospital preparedness, yet many hospitals are unfamiliar with their facility MCI procedure. Educational training drills may be one method to improve staff knowledge of policy and procedure. OBJECTIVE: This study aimed to improve knowledge gained through educational MCI mini drills of institutional mass casualty policy and procedure in surgery department staff at a level II trauma center. METHODS: A pre-/posttest design was utilized. The hospital implemented MCI mini training drills as a quality improvement project using Plan-Do-Study-Act iterative cycles with prospective data collection. Knowledge scores were measured using a 12-item surgery department MCI policy and procedure questionnaire that was developed by the author and leadership. RESULTS: A one-way analysis of covariance analysis in participants that mini drilled more than once indicated significant effect on mean cycle score differences among three cycles F(2,21) = 12.96, p = .00. Multiple comparison using Games-Howell indicated the mean score for Cycle 4 (M = 96.15, SD = 6.54) was significantly different from Cycle 3 (M = 59.71, SD = 25.15). Gender, shift, and credentials of participants influenced knowledge improvement. CONCLUSION: Implementation of hospital MCI mini drills improved staff knowledge of institutional mass casualty policy and procedure in the surgery department and may be applied to surgery departments with similar policy, procedure, and participant characteristics. Hospital mass casualty response education and preparation is essential to saving lives.

Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment.

BACKGROUND AND PURPOSE: In large artery occlusion stroke, both intravenous (IV) tPA (tissue-type plasminogen activator) and endovascular stroke treatment (EST) are standard-of-care. It is unknown how often tPA causes distal embolization, in which a procedurally accessible large artery occlusion is converted to a more distal and potentially inaccessible occlusion. METHODS: We analyzed data from a decentralized stroke telemedicine program in an integrated healthcare delivery system covering 21 hospitals, with 2 high-volume EST centers. We captured all cases sent for EST and examined the relationship between IV tPA administration and the rate of distal embolization, the rate of target recanalization (modified Treatment in Cerebral Infarction scale 2b/3), clinical improvement before EST, and short-term and long-term clinical outcomes. RESULTS: Distal embolization before EST was quite common (63/314 [20.1%]) and occurred more often after IV tPA before EST (57/229 [24.9%]) than among those not receiving IV tPA (6/85 [7.1%]; P<0.001). Distal embolization was associated with an inability to attempt EST: after distal embolization, 26/63 (41.3%) could not have attempted EST because of the new clot location, while in cases without distal embolization, only 8/249 (3.2%) were unable to have attempted EST (P<0.001). Among patients who received IV tPA, 13/242 (5.4%) had sufficient symptom improvement that a catheter angiogram was not performed; 6/342 (2.5%) had improvement to within 2 points of their baseline NIHSS. At catheter angiogram, 2/229 (0.9%) of patients who had received tPA had complete recanalization without distal embolization. Both IV tPA and EST recanalization were associated with improved long-term outcome. CONCLUSIONS: IV tPA administration before EST for large artery occlusion is associated with distal embolization, which in turn may reduce the chance that EST can be attempted and recanalization achieved. At the same time, some IV tPA-treated patients show symptomatic improvement and complete recanalization. Because IV tPA is associated with both distal embolization and improved long-term clinical outcome, there is a need for prospective clinical trials testing the net benefit or harm of IV tPA before EST.

Traumatic microbleeds suggest vascular injury and predict disability in traumatic brain injury.

Traumatic microbleeds are small foci of hypointensity seen on T2*-weighted MRI in patients following head trauma that have previously been considered a marker of axonal injury. The linear appearance and location of some traumatic microbleeds suggests a vascular origin. The aims of this study were to: (i) identify and characterize traumatic microbleeds in patients with acute traumatic brain injury; (ii) determine whether appearance of traumatic microbleeds predict clinical outcome; and (iii) describe the pathology underlying traumatic microbleeds in an index patient. Patients presenting to the emergency department following acute head trauma who received a head CT were enrolled within 48 h of injury and received a research MRI. Disability was defined using Glasgow Outcome Scale-Extended ≤6 at follow-up. All magnetic resonance images were interpreted prospectively and were used for subsequent analysis of traumatic microbleeds. Lesions on T2* MRI were stratified based on 'linear' streak-like or 'punctate' petechial-appearing traumatic microbleeds. The brain of an enrolled subject imaged acutely was procured following death for evaluation of traumatic microbleeds using MRI targeted pathology methods. Of the 439 patients enrolled over 78 months, 31% (134/439) had evidence of punctate and/or linear traumatic microbleeds on MRI. Severity of injury, mechanism of injury, and CT findings were associated with traumatic microbleeds on MRI. The presence of traumatic microbleeds was an independent predictor of disability (P < 0.05; odds ratio = 2.5). No differences were found between patients with punctate versus linear appearing microbleeds. Post-mortem imaging and histology revealed traumatic microbleed co-localization with iron-laden macrophages, predominately seen in perivascular space. Evidence of axonal injury was not observed in co-localized histopathological sections. Traumatic microbleeds were prevalent in the population studied and predictive of worse outcome. The source of traumatic microbleed signal on MRI appeared to be iron-laden macrophages in the perivascular space tracking a network of injured vessels. While axonal injury in association with traumatic microbleeds cannot be excluded, recognizing traumatic microbleeds as a form of traumatic vascular injury may aid in identifying patients who could benefit from new therapies targeting the injured vasculature and secondary injury to parenchyma.

Sex-specific Association of Matrix Metalloproteinases with Secondary Injury and Outcomes after Intracerebral Hemorrhage.

OBJECTIVE: Intracerebral hemorrhage affects approximately 2 million individuals per year. While the incidence is roughly equal in men and women, few studies have examined the influence of sex on secondary injury and associated long-term functional outcomes. Matrix metalloproteinases (MMPs) promote vessel rupture and worsen outcomes by potentiating blood-brain barrier breakdown after injury. We hypothesized that different MMP isoform levels would be predictive of injury severity, secondary injury, and long-term functional outcomes in males and females, respectively. METHODS: We examined the levels of MMP isoforms in serum samples from a prospective patient biobank (n = 55). Baseline clinical, radiographic, and laboratory data were also analyzed. RESULTS: We found that MMP-1 (P = .036), MMP-2 (P = .014), MMP-3 (P < .001), and MMP-9 (P = .02) levels gradually increased over time in male patients until 10 DPI. In female patients, we found a different pattern of activation: MMP-8 (P = .02) was the only isoform that significantly changed with time, which reached a peak at 3-5 days postinjury. Several MMP isoforms correlated with markers of secondary injury in female patients (all P < .05). Additionally, serum levels of MMP-3 (P = .011) in males and MMP-10 (P = .044) in females were significantly associated with long-term functional outcomes in a sex-specific manner. CONCLUSIONS: This is the first sex-specific study to examine serum MMP levels and their correlation with clinicoradiologic measures after intracerebral hemorrhage, and identifies potential biomarkers of secondary injury and long-term outcomes in both sexes.

Detection of Anterior Circulation Large Artery Occlusion in Ischemic Stroke Using Noninvasive Cerebral Oximetry.

BACKGROUND AND PURPOSE: Large artery occlusion (LAO) in ischemic stroke requires recognition and triage to an endovascular stroke treatment center. Noninvasive LAO detection is needed to improve triage. METHODS: Prospective study to test whether noninvasive cerebral oximetry can detect anterior circulation LAO in acute stroke. Interhemispheric ΔBrSO2 in LAO was compared with controls. RESULTS: In LAO stroke, mean interhemispheric ΔBrSO2 was -8.3±5.8% (n=19), compared with 0.4±5.8% in small artery stroke (n=17), 0.4±6.0% in hemorrhagic stroke (n=14), and 0.2±7.5% in subjects without stroke (n=19) (P<0.001). Endovascular stroke treatment reduced the ΔBrSO2 in most LAO subjects (16/19). Discrimination of LAO at a -3% ΔBrSO2 cut had 84% sensitivity and 70% specificity. Addition of the G-FAST clinical score (gaze-face-arm-speech- time) to the BrSO2 measure had 84% sensitivity and 90% specificity. CONCLUSIONS: Noninvasive cerebral oximetry may help detect LAO in ischemic stroke, particularly when combined with a simple clinical scoring system.

Pedunculopontine Nucleus Cholinergic Deficiency in Cervical Dystonia.

BACKGROUND: The etiology of cervical dystonia is unknown. Cholinergic abnormalities have been identified in dystonia animal models and human imaging studies. Some animal models have cholinergic neuronal loss in the striatum and increased acetylcholinesterase activity in the pedunculopontine nucleus. OBJECTIVES: The objective of this study was to determine the presence of cholinergic abnormalities in the putamen and pedunculopontine nucleus in cervical dystonia human brain donors. METHODS: Formalin-fixed brain tissues were obtained from 8 cervical dystonia and 7 age-matched control brains (controls). Pedunculopontine nucleus was available in only 6 cervical dystonia and 5 controls. Neurodegeneration was evaluated pathologically in the putamen, pedunculopontine nucleus, and other regions. Cholinergic neurons were detected using choline acetyltransferase immunohistochemistry in the putamen and pedunculopontine nucleus. Putaminal cholinergic neurons were quantified. A total of 6 cervical dystonia patients and 6 age-matched healthy controls underwent diffusion tensor imaging to determine if there were white matter microstructural abnormalities around the pedunculopontine nucleus. RESULTS: Decreased or absent choline acetyltransferase staining was identified in all 6 pedunculopontine nucleus samples in cervical dystonia. In contrast, strong choline acetyltransferase staining was present in 4 of 5 pedunculopontine nucleus controls. There were no differences in pedunculopontine nucleus diffusion tensor imaging between cervical dystonia and healthy controls. There was no difference in numbers of putaminal cholinergic neurons between cervical dystonia and controls. CONCLUSIONS: Our findings suggest that pedunculopontine nucleus choline acetyltransferase deficiency represents a functional cholinergic deficit in cervical dystonia. Structural lesions and confounding neurodegenerative processes were excluded by absence of neuronal loss, gliosis, diffusion tensor imaging abnormalities, and beta-amyloid, tau, and alpha-synuclein pathologies. © 2018 International Parkinson and Movement Disorder Society.

The Impact of Quality Assurance Initiatives and Workplace Policies and Procedures on HIV/AIDS-Related Stigma Experienced by Patients and Nurses in Regions with High Prevalence of HIV/AIDS.

Stigma is commonly experienced by people living with HIV/AIDS and by those providing care to HIV/AIDS patients. Few intervention studies have explored the impact of workplace policies and/or quality improvement on stigma. We examine the contribution of health care workplace policies, procedures and quality assurance initiatives, and self- and peer-assessed individual nurse practices, to nurse-reported HIV/AIDS-stigma practices toward patients living with HIV/AIDS and nurses in health care settings. Our sample of survey respondents (n = 1157) included managers (n = 392) and registered/enrolled nurses (n = 765) from 29 facilities in 4 countries (South Africa, Uganda, Jamaica, Kenya). This is one of the first studies in LMIC countries to use hierarchical linear modeling to examine the contributions of organizational and individual factors to HIV/AIDS stigma. Based on our results, we argue that organizational interventions explicitly targeting HIV/AIDS stigma are required to reduce the incidence, prevalence and morbidity of HIV/AIDS.

African and Caribbean Nurses' Decisions about HIV Testing: A Mixed Methods Study.

Nurses in Jamaica, Kenya, South Africa, and Uganda are at risk for occupational exposure to HIV. Little is known about the experiences and policy supports related to nurses having themselves tested for the virus. This article reports a mixed-methods study about contextual influences on nurses' decision-making about HIV testing. Individual and focus group interviews, as well as a questionnaire on workplace polices and quality assurance and a human resource management assessment tool provided data. Fear of a positive diagnosis and stigma and lack of confidentiality along with gaps in the policy environment contributed to indecision about testing. There were significant differences in policy supports among countries. Institutional support must be addressed if improvements in HIV testing for health care workers are going to be effectively implemented. Future work is required to better understand how HRM policies intersect to create conditions of perceived vulnerability for HIV positive staff.

A need to improve the assessment of environmental hazards for falls on stairs and in bathrooms: results of a scoping review.

BACKGROUND: Falls occurring on stairs or in bathrooms are associated with a high risk of injuries among older adults. Home environmental assessments are frequently used to guide fall-prevention interventions. The aims of this review were to describe how, where, by whom, and for whom environmental hazard checklists are used, and to examine the characteristics of environmental hazard assessment checklists with specific attention to features of bathrooms and stairs/steps assessed in them. METHODS: Studies published before January 5, 2018, were identified using several databases. Publications reporting the use and/or evaluation of environmental hazard checklists were eligible if they assessed bathrooms or stairs/steps in homes of older adults (≥65 years). Content analysis was conducted on publications that provided a complete list of specific environmental hazards assessed. Checklist items related to bathrooms and stairs/steps were extracted and categorized as structural or non-structural and as objective or subjective. RESULTS: 1119 studies were appraised. A pool of 136 published articles and 4 checklists from the grey literature were included in this scoping review. Content analysis was conducted on 42 unique checklists. There was no widely used checklist and no obvious consensus definition of either environmental hazards overall or of single hazards listed in checklists. Checklists varied greatly with respect to what rooms were assessed, whether or not outdoor stair/steps hazards were assessed, and how responses were coded. Few checklists examined person-environment fit. The majority of checklists were not oriented towards structural hazards in bathrooms. Although the majority of checklists assessing stair/steps hazards evaluated structural hazards, most features assessed were not related to the construction geometry of stairs/steps. Objective features of bathrooms and stairs/steps that would deem them safe were rarely specified. Rather, adequacy of their characteristics was mostly subjectively determined by the evaluator with little or no guidance or training. CONCLUSION: The lack of standard definitions and objective criteria for assessing environmental hazards for falls is limiting meaningful cross-study comparisons and slowing advances in this field. To inform population health interventions aimed at preventing falls, such as building code regulations or municipal housing by-laws, it is essential to include objectively-assessed structural hazards in environmental checklists.

Examining the relationships between walkability and physical activity among older persons: what about stairs?

BACKGROUND: Walkability is considered an important dimension of healthy communities. However, variable associations between measures of walkability and physical activity have been observed, particularly among older persons. Given the challenges older persons may have navigating stairs on walking routes, the presence of stairs may be an explanatory factor for these mixed associations. The purposes of this scoping review were to determine whether studies examining the relationship between walkability and physical activity included items that assessed stairs and what relationships were found. METHODS: Systematic reviews were identified by entering search terms into five database search engines. Eligibility criteria were: a) published between 2008 and 2017, b) examined the relationship between walkability and physical activity, c) included a focus on persons aged 65 years and older, and d) written in English. The full articles for all primary studies included in eligible systematic reviews were then retrieved. Duplicates were removed. Information about where the study took place, walkability measures used, types of walkability data obtained (objective and/or subjective) and questions asked about stairs were extracted from the full text articles. RESULTS: Eleven systematic reviews were identified; seven were eligible. After removing duplicates, 289 primary studies remained for review. Measures of neighborhood walkability were present in 205 studies; a minority (n = 5, 2.4%) included items about stairs. No information was obtained on the structural features of the stairs. CONCLUSIONS: The presence of stairs may deter older persons (and others) from walking outdoors. Standard measures to document the presence and characteristics of stairs, and sampling approaches to select stairs for assessment are needed. The inclusion of these measures would augment the utility and comparability of studies examining relationships between walkability and physical activity and better inform planning and policy decisions.

Stigma and intersectionality: a systematic review of systematic reviews across HIV/AIDS, mental illness, and physical disability.

BACKGROUND: Stigma across HIV/AIDS, mental illness, and physical disability can be co-occurring and may interact with other forms of stigma related to social identities like race, gender, and sexuality. Stigma is especially problematic for people living with these conditions because it can create barriers to accessing necessary social and structural supports, which can intensify their experiences with stigma. This review aims to contribute to the knowledge on stigma by advancing a cross-analysis of HIV/AIDS, mental illness, and physical disability stigma, and exploring whether and how intersectionality frameworks have been used in the systematic reviews of stigma. METHODS: A search of the literature was conducted to identify systematic reviews which investigated stigma for HIV/AIDS, mental illness and/or physical disability. The electronic databases MEDLINE, CINAHL, EMBASE, COCHRANE, and PsycINFO were searched for reviews published between 2005 and 2017. Data were extracted from eligible reviews on: type of systematic review and number of primary studies included in the review, study design study population(s), type(s) of stigma addressed, and destigmatizing interventions used. A keyword search was also done using the terms "intersectionality", "intersectional", and "intersection"; related definitions and descriptions were extracted. Matrices were used to compare the characteristics of reviews and their application of intersectional approaches across the three health conditions. RESULTS: Ninety-eight reviews met the inclusion criteria. The majority (99%) of reviews examined only one of the health conditions. Just three reviews focused on physical disability. Most reviews (94%) reported a predominance of behavioural rather than structural interventions targeting stigma in the primary studies. Only 17% of reviews used the concept and/or approach of intersectionality; all but one of these reviews examined HIV/AIDS. CONCLUSIONS: The lack of systematic reviews comparing stigma across mental illness, HIV/AIDS, and physical disability indicates the need for more cross-comparative analyses among these conditions. The integration of intersectional approaches would deepen interrogations of co-occurring social identities and stigma.

Development of measurable indicators to enhance public health evidence-informed policy-making.

BACKGROUND: Ensuring health policies are informed by evidence still remains a challenge despite efforts devoted to this aim. Several tools and approaches aimed at fostering evidence-informed policy-making (EIPM) have been developed, yet there is a lack of availability of indicators specifically devoted to assess and support EIPM. The present study aims to overcome this by building a set of measurable indicators for EIPM intended to infer if and to what extent health-related policies are, or are expected to be, evidence-informed for the purposes of policy planning as well as formative and summative evaluations. METHODS: The indicators for EIPM were developed and validated at international level by means of a two-round internet-based Delphi study conducted within the European project 'REsearch into POlicy to enhance Physical Activity' (REPOPA). A total of 82 researchers and policy-makers from the six European countries (Denmark, Finland, Italy, the Netherlands, Romania, the United Kingdom) involved in the project and international organisations were asked to evaluate the relevance and feasibility of an initial set of 23 indicators developed by REPOPA researchers on the basis of literature and knowledge gathered from the previous phases of the project, and to propose new indicators. RESULTS: The first Delphi round led to the validation of 14 initial indicators and to the development of 8 additional indicators based on panellists' suggestions; the second round led to the validation of a further 11 indicators, including 6 proposed by panellists, and to the rejection of 6 indicators. A total of 25 indicators were validated, covering EIPM issues related to human resources, documentation, participation and monitoring, and stressing different levels of knowledge exchange and involvement of researchers and other stakeholders in policy development and evaluation. CONCLUSION: The study overcame the lack of availability of indicators to assess if and to what extent policies are realised in an evidence-informed manner thanks to the active contribution of researchers and policy-makers. These indicators are intended to become a shared resource usable by policy-makers, researchers and other stakeholders, with a crucial impact on fostering the development of policies informed by evidence.

Thrombelastography Suggests Hypercoagulability in Patients with Renal Dysfunction and Intracerebral Hemorrhage.

BACKGROUND: The objective of this study was to quantify coagulopathy using thrombelastography (TEG) in patients with renal dysfunction and intracerebral hemorrhage (ICH). METHODS: We reviewed patients admitted with spontaneous ICH between November 2009 and May 2015. TEG was performed at the time of admission. Creatinine clearance (CCr) was calculated using the Cockroft-Gault equation. Patients were divided into 2 groups based on normal (CCr ≥ 90) or reduced renal function (CCr < 90). Multivariable regression models were conducted to compare the differences of TEG components. RESULTS: A total of 120 patients were included in the analysis. The normal CCr group was younger (56.1 versus 62.3 years, P < .01), was more often male (73.6% versus 53.7%, P = .03), and had higher mean admission hemoglobin (14.2 versus 13.2 mEq/L, P < .01) than the reduced renal function group. The 2 groups were similar with respect to antiplatelet or anticoagulant use, coagulation studies, and baseline ICH volume. Following multivariate analysis, the reduced renal function group was found to have shorter K (1.5 versus 2.2 min, P = 004), increased angle (66 versus 62.2 degrees, P = .04), increased MA (67.3 versus 62.3, P = .02), and increased G (11.3 versus 9.9 dynes/cm2, P = .04) compared with the normal group. Mortality, poor functional outcome (modified Rankin Scale score 4-6), hematoma enlargement, hospital length of stay, and surgical interventions were not different between the 2 groups. CONCLUSIONS: Patients with ICH and reduced CCr display faster clotting rate and increased clot strength, suggesting that patients with renal dysfunction present with a relatively hypercoagulable state based on TEG parameters thought to reflect platelet activity.

Implementing Comprehensive Primary Care Referral Tracking in a Patient-Centered Medical Home.

The Patient-Centered Medical Home care model emphasizes efficient, coordinated care distributed among interdisciplinary team members. One key function to care coordination is referral/test tracking. This study evaluated the referral practices in a nurse-managed Patient-Centered Medical Home primary care clinic. The major findings corroborate the need for a well-organized referral-tracking system that is centralized and contains safety nets to reduce the number of delayed or missed referrals.