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1.
Proc Natl Acad Sci U S A ; 119(15): e2110846119, 2022 04 12.
Article in English | MEDLINE | ID: mdl-35385353

ABSTRACT

Ebola virus (EBOV) disease is characterized by lymphopenia, breach in vascular integrity, cytokine storm, and multiorgan failure. The pathophysiology of organ involvement, however, is incompletely understood. Using [18F]-DPA-714 positron emission tomography (PET) imaging targeting the translocator protein (TSPO), an immune cell marker, we sought to characterize the progression of EBOV-associated organ-level pathophysiology in the EBOV Rhesus macaque model. Dynamic [18F]-DPA-714 PET/computed tomography imaging was performed longitudinally at baseline and at multiple time points after EBOV inoculation, and distribution volumes (Vt) were calculated as a measure of peripheral TSPO binding. Using a mixed-effect linear regression model, spleen and lung Vt decreased, while the bone marrow Vt increased over time after infection. No clear trend was found for liver Vt. Multiple plasma cytokines correlated negatively with lung/spleen Vt and positively with bone marrow Vt. Multiplex immunofluorescence staining in spleen and lung sections confirmed organ-level lymphoid and monocytic loss/apoptosis, thus validating the imaging results. Our findings are consistent with EBOV-induced progressive monocytic and lymphocytic depletion in the spleen, rather than immune activation, as well as depletion of alveolar macrophages in the lungs, with inefficient reactive neutrophilic activation. Increased bone marrow Vt, on the other hand, suggests hematopoietic activation in response to systemic immune cell depletion and leukocytosis and could have prognostic relevance. In vivo PET imaging provided better understanding of organ-level pathophysiology during EBOV infection. A similar approach can be used to delineate the pathophysiology of other systemic infections and to evaluate the effectiveness of newly developed treatment and vaccine strategies.


Subject(s)
Hemorrhagic Fever, Ebola , Positron-Emission Tomography , Receptors, GABA , Animals , Biomarkers/metabolism , Disease Models, Animal , Hemorrhagic Fever, Ebola/diagnostic imaging , Hemorrhagic Fever, Ebola/pathology , Lung/pathology , Macaca mulatta , Positron-Emission Tomography/methods , Pyrazoles/metabolism , Pyrimidines/metabolism , Receptors, GABA/metabolism , Spleen/pathology
2.
Nucleic Acids Res ; 50(D1): D211-D221, 2022 01 07.
Article in English | MEDLINE | ID: mdl-34570238

ABSTRACT

Small non-coding RNAs (sncRNAs) are pervasive regulators of physiological and pathological processes. We previously developed the human miRNA Tissue Atlas, detailing the expression of miRNAs across organs in the human body. Here, we present an updated resource containing sequencing data of 188 tissue samples comprising 21 organ types retrieved from six humans. Sampling the organs from the same bodies minimizes intra-individual variability and facilitates the making of a precise high-resolution body map of the non-coding transcriptome. The data allow shedding light on the organ- and organ system-specificity of piwi-interacting RNAs (piRNAs), transfer RNAs (tRNAs), microRNAs (miRNAs) and other non-coding RNAs. As use case of our resource, we describe the identification of highly specific ncRNAs in different organs. The update also contains 58 samples from six tissues of the Tabula Muris collection, allowing to check if the tissue specificity is evolutionary conserved between Homo sapiens and Mus musculus. The updated resource of 87 252 non-coding RNAs from nine non-coding RNA classes for all organs and organ systems is available online without any restrictions (https://www.ccb.uni-saarland.de/tissueatlas2).


Subject(s)
MicroRNAs/genetics , RNA, Long Noncoding/genetics , RNA, Small Interfering/genetics , RNA, Small Nuclear/genetics , RNA, Small Nucleolar/genetics , RNA, Transfer/genetics , Software , Animals , Atlases as Topic , Female , Humans , Internet , Male , Mice , MicroRNAs/classification , MicroRNAs/metabolism , Organ Specificity , RNA, Long Noncoding/classification , RNA, Long Noncoding/metabolism , RNA, Small Interfering/classification , RNA, Small Interfering/metabolism , RNA, Small Nuclear/classification , RNA, Small Nuclear/metabolism , RNA, Small Nucleolar/classification , RNA, Small Nucleolar/metabolism , RNA, Transfer/classification , RNA, Transfer/metabolism , Transcriptome
3.
J Infect Dis ; 228(Suppl 4): S322-S336, 2023 10 03.
Article in English | MEDLINE | ID: mdl-37788501

ABSTRACT

The mass production of the graphics processing unit and the coronavirus disease 2019 (COVID-19) pandemic have provided the means and the motivation, respectively, for rapid developments in artificial intelligence (AI) and medical imaging techniques. This has led to new opportunities to improve patient care but also new challenges that must be overcome before these techniques are put into practice. In particular, early AI models reported high performances but failed to perform as well on new data. However, these mistakes motivated further innovation focused on developing models that were not only accurate but also stable and generalizable to new data. The recent developments in AI in response to the COVID-19 pandemic will reap future dividends by facilitating, expediting, and informing other medical AI applications and educating the broad academic audience on the topic. Furthermore, AI research on imaging animal models of infectious diseases offers a unique problem space that can fill in evidence gaps that exist in clinical infectious disease research. Here, we aim to provide a focused assessment of the AI techniques leveraged in the infectious disease imaging research space, highlight the unique challenges, and discuss burgeoning solutions.


Subject(s)
COVID-19 , Communicable Diseases , Humans , Artificial Intelligence , Pandemics , Diagnostic Imaging/methods , Communicable Diseases/diagnostic imaging
4.
Nucleic Acids Res ; 49(W1): W397-W408, 2021 07 02.
Article in English | MEDLINE | ID: mdl-33872372

ABSTRACT

Analyzing all features of small non-coding RNA sequencing data can be demanding and challenging. To facilitate this process, we developed miRMaster. After the analysis of over 125 000 human samples and 1.5 trillion human small RNA reads over 4 years, we present miRMaster 2 with a wide range of updates and new features. We extended our reference data sets so that miRMaster 2 now supports the analysis of eight species (e.g. human, mouse, chicken, dog, cow) and 10 non-coding RNA classes (e.g. microRNAs, piRNAs, tRNAs, rRNAs, circRNAs). We also incorporated new downstream analysis modules such as batch effect analysis or sample embeddings using UMAP, and updated annotation data bases included by default (miRBase, Ensembl, GtRNAdb). To accommodate the increasing popularity of single cell small-RNA sequencing data, we incorporated a module for unique molecular identifier (UMI) processing. Further, the output tables and graphics have been improved based on user feedback and new output formats that emerged in the community are now supported (e.g. miRGFF3). Finally, we integrated differential expression analysis with the miRNA enrichment analysis tool miEAA. miRMaster is freely available at https://www.ccb.uni-saarland.de/mirmaster2.


Subject(s)
RNA, Small Untranslated/chemistry , Sequence Analysis, RNA/methods , Animals , Cattle , Dementia/genetics , Dogs , Humans , Mice , MicroRNAs , RNA, Small Untranslated/metabolism , Rats , Software
5.
Nucleic Acids Res ; 48(W1): W521-W528, 2020 07 02.
Article in English | MEDLINE | ID: mdl-32374865

ABSTRACT

Gene set enrichment analysis has become one of the most frequently used applications in molecular biology research. Originally developed for gene sets, the same statistical principles are now available for all omics types. In 2016, we published the miRNA enrichment analysis and annotation tool (miEAA) for human precursor and mature miRNAs. Here, we present miEAA 2.0, supporting miRNA input from ten frequently investigated organisms. To facilitate inclusion of miEAA in workflow systems, we implemented an Application Programming Interface (API). Users can perform miRNA set enrichment analysis using either the web-interface, a dedicated Python package, or custom remote clients. Moreover, the number of category sets was raised by an order of magnitude. We implemented novel categories like annotation confidence level or localisation in biological compartments. In combination with the miRBase miRNA-version and miRNA-to-precursor converters, miEAA supports research settings where older releases of miRBase are in use. The web server also offers novel comprehensive visualizations such as heatmaps and running sum curves with background distributions. We demonstrate the new features with case studies for human kidney cancer, a biomarker study on Parkinson's disease from the PPMI cohort, and a mouse model for breast cancer. The tool is freely accessible at: https://www.ccb.uni-saarland.de/mieaa2.


Subject(s)
MicroRNAs/metabolism , Software , Animals , Biomarkers , Breast Neoplasms/genetics , Carcinoma, Renal Cell/genetics , Disease Progression , Female , Humans , Kidney Neoplasms/genetics , Mice , Parkinson Disease/genetics , Workflow
6.
J Infect Dis ; 221(Suppl 4): S419-S430, 2020 05 11.
Article in English | MEDLINE | ID: mdl-31687756

ABSTRACT

Nipah virus (NiV) is an emerging virus associated with outbreaks of acute respiratory disease and encephalitis. To develop a neurological model for NiV infection, we exposed 6 adult African green monkeys to a large-particle (approximately 12 µm) aerosol containing NiV (Malaysian isolate). Brain magnetic resonance images were obtained at baseline, every 3 days after exposure for 2 weeks, and then weekly until week 8 after exposure. Four of six animals showed abnormalities reminiscent of human disease in brain magnetic resonance images. Abnormalities ranged from cytotoxic edema to vasogenic edema. The majority of lesions were small infarcts, and a few showed inflammatory or encephalitic changes. Resolution or decreased size in some lesions resembled findings reported in patients with NiV infection. Histological lesions in the brain included multifocal areas of encephalomalacia, corresponding to known ischemic foci. In other regions of the brain there was evidence of vasculitis, with perivascular infiltrates of inflammatory cells and rare intravascular fibrin thrombi. This animal model will help us better understand the acute neurological features of NiV infection and develop therapeutic approaches for managing disease caused by NiV infection.


Subject(s)
Central Nervous System Infections/virology , Chlorocebus aethiops , Disease Models, Animal , Henipavirus Infections/virology , Nipah Virus/physiology , Aerosols , Animals , Central Nervous System Infections/pathology , Female , Henipavirus Infections/pathology , Male , Viral Load
7.
Value Health ; 21(7): 839-842, 2018 07.
Article in English | MEDLINE | ID: mdl-30005756

ABSTRACT

OBJECTIVE: Evidence-based recommendations for the a priori estimation of sample size are needed for qualitative concept elicitation (CE) interview studies in clinical outcome assessment (COA) instrument development. Saturation is described as the point at which no new data is expected to emerge from the conduct of additional qualitative interviews. STUDY DESIGN: A retrospective evaluation of 26 CE interview studies conducted with patients between 2006 and 2013 was completed to assess the point at which saturation of concept was achieved in each study. METHODS: For each of the 26 interview studies, saturation of symptom concepts was assessed by dividing the sample into quartiles and then comparing the number of responses elicited from the first 25% of participants to the next 25% of participants, from the first 50% of participants to the next 25% of participants, and then from the first 75% of participants to the last 25% of participants. The number of interviews required to achieve saturation was documented for each study and then summarized across studies. RESULTS: Findings indicate that 84% of symptom concepts emerged by the 10th interview, 92% emerged by the 15th interview, 97% emerged by the 20th interview, and 99% by the 25th interview. CONCLUSIONS: Results provide practical guidance for estimating the number of interviews that may be needed to achieve saturation in a qualitative CE interview study for COA instrument development; address an important gap in qualitative research for the development of COAs in the context of medical product development; and offer useful information for study design and implementation.


Subject(s)
Concept Formation , Interviews as Topic , Patient Outcome Assessment , Qualitative Research , Research Subjects/psychology , Sample Size , Surveys and Questionnaires , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
8.
BMC Health Serv Res ; 18(1): 168, 2018 03 07.
Article in English | MEDLINE | ID: mdl-29514631

ABSTRACT

BACKGROUND: Healthcare organizations increasingly are focused on providing care which is patient-centered rather than disease-focused. Yet little is known about how best to transform the culture of care in these organizations. We sought to understand key organizational factors for implementing patient-centered care cultural transformation through an examination of efforts in the US Department of Veterans Affairs. METHODS: We conducted multi-day site visits at four US Department of Veterans Affairs medical centers designated as leaders in providing patient-centered care. We conducted qualitative semi-structured interviews with 108 employees (22 senior leaders, 42 middle managers, 37 front-line providers and 7 staff). Transcripts of audio recordings were analyzed using a priori codes based on the Consolidated Framework for Implementation Research. We used constant comparison analysis to synthesize codes into meaningful domains. RESULTS: Sites described actions taken to foster patient-centered care in seven domains: 1) leadership; 2) patient and family engagement; 3) staff engagement; 4) focus on innovations; 5) alignment of staff roles and priorities; 6) organizational structures and processes; 7) environment of care. Within each domain, we identified multi-faceted strategies for implementing change. These included efforts by all levels of organizational leaders who modeled patient-centered care in their interactions and fostered willingness to try novel approaches to care amongst staff. Alignment and integration of patient centered care within the organization, particularly surrounding roles, priorities and bureaucratic rules, remained major challenges. CONCLUSIONS: Transforming healthcare systems to focus on patient-centered care and better serve the "whole" patient is a complex endeavor. Efforts to transform healthcare culture require robust, multi-pronged efforts at all levels of the organization; leadership is only the beginning. Challenges remain for incorporating patient-centered approaches in the context of competing priorities and regulations. Through actions within each of the domains, organizations may begin to truly transform to patient-driven care.


Subject(s)
Delivery of Health Care/organization & administration , Hospitals, Veterans/organization & administration , Organizational Culture , Patient-Centered Care/organization & administration , Health Services Research , Humans , Leadership , United States , United States Department of Veterans Affairs
9.
J Gen Virol ; 97(8): 1942-1954, 2016 08.
Article in English | MEDLINE | ID: mdl-27166137

ABSTRACT

We previously demonstrated that small-particle (0.5-3.0 µm) aerosol infection of rhesus monkeys (Macaca mulatta) with cowpox virus (CPXV)-Brighton Red (BR) results in fulminant respiratory tract disease characterized by severe lung parenchymal pathology but only limited systemic virus dissemination and limited classic epidermal pox-like lesion development (Johnson et al., 2015). Based on these results, and to further develop CPXV as an improved model of human smallpox, we evaluated a novel large-particle aerosol (7.0-9.0 µm) exposure of rhesus monkeys to CPXV-BR and monitored for respiratory tract disease by serial computed tomography (CT). As expected, the upper respiratory tract and large airways were the major sites of virus-induced pathology following large-particle aerosol exposure. Large-particle aerosol CPXV exposure of rhesus macaques resulted in severe upper airway and large airway pathology with limited systemic dissemination.


Subject(s)
Aerosols , Cowpox virus/pathogenicity , Cowpox/pathology , Cowpox/virology , Disease Models, Animal , Respiratory Tract Infections/pathology , Respiratory Tract Infections/virology , Animals , Macaca mulatta , Respiratory Tract Infections/diagnostic imaging , Tomography, X-Ray Computed
10.
Adv Skin Wound Care ; 29(5): 226-38; quiz E1, 2016 May.
Article in English | MEDLINE | ID: mdl-27089151

ABSTRACT

PURPOSE: To present findings of a study of institutional factors related to pressure ulcer (PrU) prevention in Veterans Health Administration nursing homes. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Identify the study's design, process, and purpose.2. List the factors pertaining to sites with improving performance. OBJECTIVES: Important gaps exist in the knowledge of how to achieve successful, sustained prevention of pressure ulcers (PrUs) in nursing homes. This study aimed to address those gaps by comparing nursing leadership and indirect care staff members' impressions about the context of PrU prevention in facilities with improving and declining PrU rates. SETTING: The study was conducted in a sample of 6 Veterans Health Administration nursing homes (known as community living centers) purposively selected to represent a range of PrU care performance. DESIGN AND PARTICIPANTS: One-time 30-minute semistructured interviews with 23 community living center staff were conducted. Qualitative interview data were analyzed using an analytic framework containing (a) a priori analytic constructs based on the study's conceptual framework and (b) sections for emerging constructs. MAIN RESULTS: Analysis revealed 6 key concepts differentiating sites with improving and declining PrU care performance. These concepts were (1) structures through which the change effort is initiated; (2) organizational prioritization, alignment, and support; (3) improvement culture; (4) clarity of roles and responsibilities; (5) communication strategies; and (6) staffing and clinical practices. Results also pointed to potential contextual facilitators of and barriers to successful PrU prevention. CONCLUSIONS: Leadership's visible prioritization of and support for PrU prevention and the initiation of PrU prevention activities through formal structures were the most striking components represented at sites with improving performance, but not at ones where performance declined. Sites with improving performance were more likely to align frontline staff and leadership goals for PrU prevention.


Subject(s)
Nursing, Team/organization & administration , Outcome Assessment, Health Care , Pressure Ulcer/prevention & control , Primary Prevention/organization & administration , Wound Healing/physiology , Aged , Aged, 80 and over , Female , Homes for the Aged/organization & administration , Humans , Interviews as Topic , Long-Term Care/organization & administration , Male , Nursing Homes/organization & administration , Pressure Ulcer/nursing , Qualitative Research , Quality Improvement , Risk Assessment , Skin Care/standards
11.
Ann Pharmacother ; 49(2): 189-95, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25429093

ABSTRACT

BACKGROUND: Clinical pharmacists (CPs) with a scope of practice operate as direct care providers and health care team members. Research often focuses on one role or the other; little is understood about the dynamic relationship between roles in practice settings. OBJECTIVE: To identify the challenges CPs face in balancing dual roles as direct care providers and health care team members and the implications for CP effectiveness and quality of care. METHODS: Pharmacists were interviewed with a primary purpose of informing an implementation effort. Besides the implementation, there were emergent themes regarding the challenges posed for CPs in negotiating dual roles. This study is, therefore, a secondary analysis of semistructured interviews and direct observation of 48 CPs, addressing this phenomenon. Interview data were entered into NVivo 10 and systematically analyzed using an emergent thematic coding strategy. RESULTS: Pharmacists describe role ambiguity, where they perform as direct providers or team members simultaneously or in quick succession. They note the existence of a "transaction cost," where switching causes loss of momentum or disruption of work flow. Additionally, pharmacists feel that fellow providers lack an understanding of what they do and that CP contributions are not evaluated accurately by other health professionals. CONCLUSION: It is a challenge for CPs to balance the distinct roles of serving as collaborators and primary providers. Frequent role switching is not conducive to optimal work efficiency or patient care. Our findings suggest concrete steps that medical centers can take to improve both CP worklife and quality of patient care.


Subject(s)
Cooperative Behavior , Patient Care Team , Pharmacy Service, Hospital/methods , Attitude of Health Personnel , Humans , Pharmacists , Professional Role , Qualitative Research
12.
Brain ; 137(Pt 10): 2823-33, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25070511

ABSTRACT

Accumulating neuroscience evidence indicates that human intelligence is supported by a distributed network of frontal and parietal regions that enable complex, goal-directed behaviour. However, the contributions of this network to social aspects of intellectual function remain to be well characterized. Here, we report a human lesion study (n = 144) that investigates the neural bases of social problem solving (measured by the Everyday Problem Solving Inventory) and examine the degree to which individual differences in performance are predicted by a broad spectrum of psychological variables, including psychometric intelligence (measured by the Wechsler Adult Intelligence Scale), emotional intelligence (measured by the Mayer, Salovey, Caruso Emotional Intelligence Test), and personality traits (measured by the Neuroticism-Extraversion-Openness Personality Inventory). Scores for each variable were obtained, followed by voxel-based lesion-symptom mapping. Stepwise regression analyses revealed that working memory, processing speed, and emotional intelligence predict individual differences in everyday problem solving. A targeted analysis of specific everyday problem solving domains (involving friends, home management, consumerism, work, information management, and family) revealed psychological variables that selectively contribute to each. Lesion mapping results indicated that social problem solving, psychometric intelligence, and emotional intelligence are supported by a shared network of frontal, temporal, and parietal regions, including white matter association tracts that bind these areas into a coordinated system. The results support an integrative framework for understanding social intelligence and make specific recommendations for the application of the Everyday Problem Solving Inventory to the study of social problem solving in health and disease.


Subject(s)
Brain Mapping/methods , Emotional Intelligence/physiology , Problem Solving/physiology , Social Problems , Cerebral Cortex/physiology , Craniocerebral Trauma/pathology , Executive Function , Humans , Image Processing, Computer-Assisted , Intelligence , Nerve Net/anatomy & histology , Nerve Net/physiology , Neuropsychological Tests , Personality , Psychometrics , Regression Analysis , Tomography, X-Ray Computed , Vietnam Conflict , Wechsler Scales
13.
BMC Health Serv Res ; 15: 62, 2015 Feb 14.
Article in English | MEDLINE | ID: mdl-25890333

ABSTRACT

BACKGROUND: Contextual elements have significant impact on uptake of health care innovations. While existing conceptual frameworks in implementation science suggest contextual elements interact with each other, little research has described how this might look in practice. To bridge this gap, this study identifies the interconnected patterns among contextual elements that influence uptake of an anticoagulation clinic improvement initiative. METHODS: We completed 51 semi-structured interviews and ethnographic observations across five case study sites involved in an evidence-based practice (EBP) quality improvement initiative. We analyzed data in NVivo 10 using an a priori approach based on the Promoting Action on Research Implementation in Health Services (PARIHS) model and an emergent thematic analysis. RESULTS: Key contextual elements, such as leadership, teamwork, and communication, interacted with each other in contributing to site-level uptake of the EBP, often yielding results that could not be predicted by looking at just one of these elements alone. Sites with context conducive to change in these areas predictably had high uptake, while sites with uniformly weak contextual elements had low uptake. Most sites presented a mixed picture, with contextual elements being strongly supportive of change in some areas and weak or moderate in others. In some cases, we found that sites with strong context in at least one area only needed to have adequate context in other areas to yield high uptake. At other sites, weak context in just one area had the potential to contribute to low uptake, despite countervailing strengths. Even a site with positive views of EBPs could not succeed when context was weak. CONCLUSION: Interrelationships among different contextual elements can act as barriers to uptake at some sites and as facilitators at others. Accounting for interconnections among elements enables PARIHS to more fully describe the determinants of successful implementation as they operate in real-world settings.


Subject(s)
Cooperative Behavior , Diffusion of Innovation , Evidence-Based Practice , Quality Improvement , Delivery of Health Care/standards , Health Services Research , Humans , Interdisciplinary Communication , Interviews as Topic , Leadership , Organizational Case Studies , Qualitative Research
14.
Pediatr Blood Cancer ; 61(9): 1598-602, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24753394

ABSTRACT

BACKGROUND: Pirfenidone, an oral anti-inflammatory, antifibrotic agent with activity in idiopathic pulmonary fibrosis, may mediate anti-tumor activity in neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PN) by inhibition of fibroblast proliferation and collagen synthesis. The primary objective of this open label, single arm phase II trial was to evaluate the activity of pirfenidone in children and young adults with inoperable PN. PROCEDURE: Patients (3-21 years) with NF1-related progressive PN received pirfenidone at the previously determined optimal dose (500 mg/m(2) orally, q8h) on a continuous dosing schedule (one cycle = 28 days). Volumetric MRI analysis was used to assess response. Progression was defined as ≥ 20% PN volume increase compared to baseline. Pirfenidone would be considered active if it doubled the median time to progression (TTP) compared to the TTP on the placebo arm of a phase II trial with the farnesyltransferase inhibitor tipifarnib, which used near identical eligibility criteria. Toxicities, objective response rate, and quality of life (QOL) also were evaluated. RESULTS: Thirty-six patients were enrolled and tolerated pirfenidone well with intermittent nausea and vomiting as the most frequent toxicities. A dose reduction was required in only three patients. The median TTP for pirfenidone was 13.2 months compared to 10.6 months for the placebo control group from the tipifarnib trial (two-tailed P = 0.92; one-tailed P = 0.46). No objective responses were observed. CONCLUSIONS: Pirfenidone was well tolerated, but did not demonstrate activity as defined in this trial and does not warrant further evaluation in children with NF1 and progressive PN.


Subject(s)
Antineoplastic Agents/therapeutic use , Neurofibroma, Plexiform/drug therapy , Neurofibromatosis 1/drug therapy , Pyridones/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adolescent , Adult , Child , Child, Preschool , Disease Progression , Female , Follow-Up Studies , Humans , Male , Neoplasm Staging , Neurofibroma, Plexiform/mortality , Neurofibroma, Plexiform/pathology , Neurofibromatosis 1/mortality , Neurofibromatosis 1/pathology , Prognosis , Quality of Life , Survival Rate , Time Factors , Young Adult
15.
Cereb Cortex ; 23(7): 1663-72, 2013 Jul.
Article in English | MEDLINE | ID: mdl-22669970

ABSTRACT

Mental paper folding is a complex measure of visuospatial ability involving a coordinated sequence of mental transformations and is often considered a measure of mental ability. The literature is inconclusive regarding the precise neural architecture that underlies performance. We combined the administration of the Armed Forces Qualification Test boxes subtest measuring mental paper folding ability, with a voxel-based lesion symptom mapping approach to identify brain regions associated with impaired mental paper folding ability. Using a large sample of subjects with penetrating traumatic brain injury and defined lesions studied over 2 time points, roughly 15 and 35 years post-injury, enabled us to answer the causal questions regarding mental paper folding impairment. Our results revealed that brain injury significantly exacerbates the decline of performance on mental paper folding tasks over time. Our study adds novel neuropsychological and neuroimaging support for parietal lobe involvement; specifically the right inferior parietal lobule (Broadmann's Area [BA] 40) and the left parahippocampal region (BAs 19, 36). Both areas were consistently associated with mental paper folding performance and demonstrate that the right parietal lobe and the left parahippocampal gyrus play an integral role in mental paper folding tasks.


Subject(s)
Head Injuries, Penetrating/pathology , Hippocampus/pathology , Neuropsychological Tests , Parietal Lobe/pathology , Follow-Up Studies , Head Injuries, Penetrating/psychology , Hippocampus/injuries , Humans , Male , Middle Aged , Parietal Lobe/injuries , Task Performance and Analysis , Tomography, X-Ray Computed , Veterans
16.
Article in English | MEDLINE | ID: mdl-39164184

ABSTRACT

Novel strategies are needed to improve low rates of lung cancer screening (LCS) in the US. Seeking to determine hospitalists' perspectives on leveraging hospitalizations to identify patients eligible for LCS, we performed qualitative interviews with eight hospitalists from two hospitals within a large integrated healthcare system. The interviews used semi-structured questions to assess (1) knowledge and practice of general screening and LCS guidelines from the United States Preventive Services Task Force (USPSTF), (2) identification of smoking history, and (3) hospitalists' views on how data obtained during hospitalization may be utilized to improve general screening and LCS post hospitalization. We ultimately reached the conclusion that hospitalists would support a dedicated program to identify hospitalized patients eligible for LCS and facilitate testing after discharge. Efforts to identify patients and arrange subsequent screening should be performed by team members outside the inpatient team.

17.
J Thromb Haemost ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39128654

ABSTRACT

BACKGROUND: Inpatient and extended post-discharge thromboprophylaxis of COVID-19 patients remain suboptimal despite antithrombotic guidelines. OBJECTIVES: To determine whether a novel electronic health record (EHR)-agnostic clinical decision support (CDS) tool incorporating IMPROVE-DD VTE scores increases appropriate inpatient and extended post-discharge thromboprophylaxis and improves outcomes in COVID-19 inpatients. METHODS: This post-hoc analysis of the IMPROVE-DD cluster randomized trial evaluated thromboprophylaxis CDS among COVID-19 inpatients at four New York hospitals between December 21, 2020, and January 21, 2022. Hospitals were randomized 1:1 to CDS (intervention, N=2), versus no CDS (usual care, N=2). The primary outcome was rate of appropriate thromboprophylaxis. Secondary outcomes included rates of major thromboembolism, all-cause and VTE-related readmissions and death, major bleeding (MB), and all-cause mortality 30 days post-discharge. RESULTS: 2,452 COVID-19 inpatients were analyzed (1,355 CDS; 1,097 no CDS). Mean age was 73.7 ± 9.37 years; 50.1% of participants were male. CDS adoption was 96.8% (intervention group). CDS was associated with increased appropriate at-discharge extended thromboprophylaxis (42.6% versus 28.8%, odds ratio [OR] 1.83, 95% Confidence Interval [CI] 1.39 - 2.41, p<0.001). CDS was associated with reduced VTE (OR 0.54, 95% CI 0.39-0.75, p<0.001), arterial thromboembolism (OR 0.10, 95% CI 0.01-0.81, p=0.01), total TE (OR 0.50, 95% CI 0.36-0.69, p<0.001), and 30-day all-cause readmission/death (OR 0.78, 95% CI 0.62-0.99, p=0.04). There were no differences in MB, VTE-related readmissions/death, or all-cause mortality. CONCLUSION: EHR-agnostic CDS incorporating IMPROVE-DD VTE scores had high adoption, was associated with increased appropriate at-discharge extended thromboprophylaxis, and reduced TE and all-cause readmission/death without increasing MB in COVID-19 inpatients.

18.
JAMIA Open ; 7(3): ooae064, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39091509

ABSTRACT

Objective: Our objective was to determine the feasibility and preliminary efficacy of a behavioral nudge on adoption of a clinical decision support (CDS) tool. Materials and Methods: We conducted a pilot cluster nonrandomized controlled trial in 2 Emergency Departments (EDs) at a large academic healthcare system in the New York metropolitan area. We tested 2 versions of a CDS tool for pulmonary embolism (PE) risk assessment developed on a web-based electronic health record-agnostic platform. One version included behavioral nudges incorporated into the user interface. Results: A total of 1527 patient encounters were included in the trial. The CDS tool adoption rate was 31.67%. Adoption was significantly higher for the tool that included behavioral nudges (39.11% vs 20.66%; P < .001). Discussion: We demonstrated feasibility and preliminary efficacy of a PE risk prediction CDS tool developed using insights from behavioral science. The tool is well-positioned to be tested in a large randomized clinical trial. Trial Registration: Clinicaltrials.gov (NCT05203185).

19.
Med Care ; 51(3 Suppl 1): S62-6, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23407015

ABSTRACT

BACKGROUND: Vulnerable populations face difficulties accessing and using the internet and personal health record (PHR) systems for health-related purposes. Populations disconnected from the internet also tend to be disconnected from health care services. OBJECTIVES: To develop and evaluate an intervention to increase skills in health-related internet and PHR use for vulnerable populations with limited computer and internet experience. RESEARCH DESIGN: Preevaluation and postevaluation using quantitative surveys, semistructured interviews, focus groups, and ethnographic observation. SUBJECTS: Fourteen low-income Veterans receiving care at Veterans Affairs medical centers for human immunodeficiency virus or hepatitis C. MEASURES: Internet and PHR use, self-efficacy, patient activation, disease knowledge, predictors of medication adherence. RESULTS: At follow-up one (FU1), mean number of internet for health features used increased from 1.57 to 4.07 (P<0.001) as did number of PHR features, from 0.36 to 2.00 (P<0.001). Mean self-efficacy increased at FU1, from 7.12 to 8.60, (P=0.009) and was maintained at follow-up two (FU2). Patient activation increased only at FU2, from 3.42 to 3.61 (P=0.03). Disease specific knowledge showed borderline increase at FU1, from 67.9% to 72.2% (P=0.05), whereas there were no changes in predictors of medication adherence. Qualitative findings underscored the interest in using internet and PHRs and their contribution to increased engagement in care. Training cost per participant was $287. CONCLUSIONS: Group training of vulnerable patients represents a cost-effective method to increase internet and PHR skills, and improve patient confidence in finding health-related information, making online health-related transactions, and interacting with health care providers.


Subject(s)
HIV Infections/therapy , Health Records, Personal , Hepatitis C/therapy , Internet , Patient Education as Topic , Veterans , Vulnerable Populations , Female , Focus Groups , Follow-Up Studies , Health Knowledge, Attitudes, Practice , Hospitals, Veterans , Humans , Interviews as Topic , Male , Medication Adherence , Middle Aged , Patient Education as Topic/economics , Poverty , Program Development , Program Evaluation , Self Efficacy , Surveys and Questionnaires , United States
20.
Sex Transm Dis ; 40(4): 341-5, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23486502

ABSTRACT

Nurse-initiated HIV rapid testing (NRT) increases testing/receipt of results compared with traditional testing. We implemented NRT in primary care clinics at 2 Veterans Affairs hospitals.At site 1, 2364 tests were conducted; 5 HIV positives were identified. At site 2, 2522 tests were conducted; 9 HIV positives were identified. Success varied across demographic/clinical strata.


Subject(s)
AIDS Serodiagnosis/methods , HIV Seropositivity/diagnosis , HIV Seropositivity/epidemiology , Mass Screening/nursing , Primary Health Care , Female , HIV Antibodies/immunology , HIV Seropositivity/immunology , HIV Seropositivity/nursing , Humans , Male , Middle Aged , Prevalence , United States/epidemiology , United States Department of Veterans Affairs , Veterans/statistics & numerical data
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