28232 research outputs found
Sort by
Validation of the Observer-Reported Communication Ability (ORCA) Measure for Individuals With Angelman Syndrome.
No full textThere is a critical need for high-quality clinical outcome assessments to capture the important aspects of communication ability of individuals with Angelman syndrome (AS). To center the perspective of caregivers, our team developed the novel Observer-Reported Communication Ability (ORCA) measure using best practice guidelines, with the goal of developing a measure that could be administered to caregivers directly without the need for a certified administrator for use in clinical trials. To refine the draft measure, we conducted two rounds of cognitive interviews with 24 caregivers and a quantitative study including 249 caregivers. The results from both studies support the overall content validity, construct validity, and the reliability of the ORCA measure for individuals with AS > 2 years old for use in research contexts. Future work should explore the responsiveness of ORCA measures to changes over time in a diverse sample
Quality Outcomes Database Spine Care Project 2012-2020: milestones achieved in a collaborative North American outcomes registry to advance value-based spine care and evolution to the American Spine Registry.
No full textThe Quality Outcomes Database (QOD), formerly known as the National Neurosurgery Quality Outcomes Database (N2QOD), was established by the NeuroPoint Alliance (NPA) in collaboration with relevant national stakeholders and experts. The overarching goal of this project was to develop a centralized, nationally coordinated effort to allow individual surgeons and practice groups to collect, measure, and analyze practice patterns and neurosurgical outcomes. Specific objectives of this registry program were as follows: "1) to establish risk-adjusted national benchmarks for both the safety and effectiveness of neurosurgical procedures, 2) to allow practice groups and hospitals to analyze their individual morbidity and clinical outcomes in real time, 3) to generate both quality and efficiency data to support claims made to public and private payers and objectively demonstrate the value of care to other stakeholders, 4) to demonstrate the comparative effectiveness of neurosurgical and spine procedures, 5) to develop sophisticated 'risk models' to determine which subpopulations of patients are most likely to benefit from specific surgical interventions, and 6) to facilitate essential multicenter trials and other cooperative clinical studies." The NPA has launched several neurosurgical specialty modules in the QOD program in the 7 years since its inception including lumbar spine, cervical spine, and spinal deformity and cerebrovascular and intracranial tumor. The QOD Spine modules, which are the primary subject of this paper, have evolved into the largest North American spine registries yet created and have resulted in unprecedented cooperative activities within our specialty and among affiliated spine care practitioners. Herein, the authors discuss the experience of QOD Spine programs to date, with a brief description of their inception, some of the key achievements and milestones, as well as the recent transition of the spine modules to the American Spine Registry (ASR), a collaboration between the American Association of Neurological Surgeons and the American Academy of Orthopaedic Surgeons (AAOS)
We both led Medicare and Medicaid. Biden’s vaccine mandate for health-care workers must stand.
No full textAnkle osteoarthritis: comprehensive review and treatment algorithm proposal.
No full textAnkle osteoarthritis (OA) is much less frequent than knee or hip OA, but it can be equally disabling, greatly affecting the quality of life of the patients. Approximately 80% of ankle OA is post-traumatic, mainly secondary to malleolar fractures, being another of the main causes untreated in chronic instability. The average age of the patient affected by ankle OA is around 50 years, being therefore active patients and in working age who seek to maintain mobility and remain active. The authors conducted a comprehensive review of the conservative, medical, and surgical treatment of ankle OA. Initial conservative treatment is effective and should be attempted in any stage of OA. From a pharmacological point of view, non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular infiltrations can produce temporary relief of symptoms. After the failure of conservative-medical treatment, two large groups of surgical treatment have been described: joint-preserving and joint-sacrificing procedures. In the early stages, only periarticular osteotomies have enough evidence to recommend in ankle OA with malalignment. Both ankle arthrodesis and ankle replacement can produce satisfactory functional results if correctly indicated in the final stages of the disease. Finally, the authors propose a global treatment algorithm that can aid in the decision-making process
Leveraging Fungal and Human Calcineurin-Inhibitor Structures, Biophysical Data, and Dynamics To Design Selective and Nonimmunosuppressive FK506 Analogs.
No full textCalcineurin is a critical enzyme in fungal pathogenesis and antifungal drug tolerance and, therefore, an attractive antifungal target. Current clinically accessible calcineurin inhibitors, such as FK506, are immunosuppressive to humans, so exploiting calcineurin inhibition as an antifungal strategy necessitates fungal specificity in order to avoid inhibiting the human pathway. Harnessing fungal calcineurin-inhibitor crystal structures, we recently developed a less immunosuppressive FK506 analog, APX879, with broad-spectrum antifungal activity and demonstrable efficacy in a murine model of invasive fungal infection. Our overarching goal is to better understand, at a molecular level, the interaction determinants of the human and fungal FK506-binding proteins (FKBP12) required for calcineurin inhibition in order to guide the design of fungus-selective, nonimmunosuppressive FK506 analogs. To this end, we characterized high-resolution structures of the Mucor circinelloides FKBP12 bound to FK506 and of the Aspergillus fumigatus, M. circinelloides, and human FKBP12 proteins bound to the FK506 analog APX879, which exhibits enhanced selectivity for fungal pathogens. Combining structural, genetic, and biophysical methodologies with molecular dynamics simulations, we identify critical variations in these structurally similar FKBP12-ligand complexes. The work presented here, aimed at the rational design of more effective calcineurin inhibitors, indeed suggests that modifications to the APX879 scaffold centered around the C15, C16, C18, C36, and C37 positions provide the potential to significantly enhance fungal selectivity. IMPORTANCE Invasive fungal infections are a leading cause of death in the immunocompromised patient population. The rise in drug resistance to current antifungals highlights the urgent need to develop more efficacious and highly selective agents. Numerous investigations of major fungal pathogens have confirmed the critical role of the calcineurin pathway for fungal virulence, making it an attractive target for antifungal development. Although FK506 inhibits calcineurin, it is immunosuppressive in humans and cannot be used as an antifungal. By combining structural, genetic, biophysical, and in silico methodologies, we pinpoint regions of the FK506 scaffold and a less immunosuppressive analog, APX879, centered around the C15 to C18 and C36 to C37 positions that could be altered with selective extensions and/or deletions to enhance fungal selectivity. This work represents a significant advancement toward realizing calcineurin as a viable target for antifungal drug discovery
The Biblical Odes and the Text of the Christian Bible: A Reconsideration of the Impact of Liturgical Singing on the Transmission of the Gospel of Luke
No full textThe role of glucosylsphingosine as an early indicator of disease progression in early symptomatic type 1 Gaucher disease.
No full textGaucher disease (GD), a lysosomal storage disorder caused by β-glucocerebrosidase deficiency, results in the accumulation of glucosylceramide and glucosylsphingosine. Glucosylsphingosine has emerged as a sensitive and specific biomarker for GD and treatment response. However, limited information exists on its role in guiding treatment decisions in pre-symptomatic patients identified at birth or due to a positive family history. We present two pediatric patients with GD1 and highlight the utility of glucosylsphingosine monitoring in guiding treatment initiation
Patients with adult spinal deformity treated operatively report greater baseline pain and disability than patients treated nonoperatively; however, deformities differ between age groups.
No full textStudy designMulticenter, prospective analysis of consecutive patients with adult spinal deformity (ASD).ObjectiveIdentify age-related radiographical parameters associated with poor health-related quality of life (HRQOL) and treatment preferences for ASD.Summary of background dataPatients with ASD report discrepant severities of disability. Understanding age-associated differences for reported disability and treatment preferences may improve ASD evaluation and treatment.MethodsBaseline demographic, radiographical, and HRQOL values were evaluated in a multicenter, prospective cohort of consecutive patients with ASD.Inclusion criteriaASD, age more than 18 years, and no prior spine surgery. Patients were grouped into those treated operatively (OP) or nonoperatively (NON) and stratified into 3 age groups: G1, 50 years or less; G2, 50 to 65 years; G3, 65 years or more. HRQOL measures included Scoliosis Research Society-22r questionnaire, Oswestry Disability Index, and Short Form-36 Health Survey.ResultsFour hundred ninety-seven patients (OP = 156, NON = 341) with a mean age of 50.4 years met inclusion criteria. The OP group was older (53.3 vs. 49.0 yr), had larger scoliosis (49.3° vs. 43.3°), larger sagittal vertical axis (SVA, 33.2 vs. 13.7 mm), greater pelvic incidence-lumbar lordosis mismatch (6.6°vs. 3.1°), and worse HRQOL scores than the NON group, respectively (P ConclusionPoor HRQOL uniformly determined operative treatment for ASD. Spinal deformities differed between age groups. Younger OP had larger scoliosis but similar SPA and SVA than NON. Older OP had similar scoliosis but worse SVA than NON. Age-associated differences for poor HRQOL must be considered when evaluating patients with ASD.Level of evidence2
Performance of the Bronchoalveolar Lavage Fluid Aspergillus Galactomannan Lateral Flow Assay With Cube Reader for Diagnosis of Invasive Pulmonary Aspergillosis: A Multicenter Cohort Study.
No full textBackgroundThe Aspergillus Galactomannan Lateral Flow Assay (LFA) is a rapid test for the diagnosis of invasive aspergillosis (IA) that has been almost exclusively evaluated in patients with hematologic malignancies. An automated digital cube reader that allows for quantification of results has recently been added to the test kits.MethodsWe performed a retrospective multicenter study on bronchoalveolar lavage fluid (BALF) samples obtained from 296 patients with various underlying diseases (65% without underlying hematological malignancy) who had BALF galactomannan (GM) ordered between 2013 and 2019 at the University of California, San Diego, the Medical University of Graz, Austria, and the Mannheim University Hospital, Germany.ResultsCases were classified as proven (n = 2), probable (n = 56), putative (n = 30), possible (n = 45), and no IA (n = 162). The LFA showed an area under the curve (AUC) of 0.865 (95% confidence interval [CI] .815-.916) for differentiating proven/probable or putative IA versus no IA, with a sensitivity of 74% and a specificity of 83% at an optical density index cutoff of 1.5. After exclusion of GM as mycological criterion for case classification, diagnostic performance of the LFA was highly similar to GM testing (AUC 0.892 vs 0.893, respectively). LFA performance was consistent across different patient cohorts and centers.ConclusionsIn this multicenter study the LFA assay from BALF demonstrated good diagnostic performance for IA that was consistent across patient cohorts and locations. The LFA may serve a role as a rapid test that may replace conventional GM testing in settings where GM results are not rapidly available
Taking a Fresh Look at Clean Air Act Standards: The Role of Retrospective Review in Achieving Health and Climate Benefits
No full textMany sections of the Clean Air Act (CAA) require the U.S. Environmental Protection Agency (EPA) to retrospectively, and often periodically, review and potentially revise its standards. The paper examines the implementation of the retrospective “residual risk” review provision of CAA 112 to suggest improvements to EPA’s implementation of retrospective review for air toxics standards. By streamlining the review process for low-risk source categories and increasing stakeholder involvement, EPA can meet its statutory requirements while achieving greater risk reductions with fewer resources. The analysis of CAA 112 retrospective review can also inform EPA’s efforts to utilize CAA 111 to reduce greenhouse gas (GHG) emissions. Efficient periodic review of CAA 111 standards would allow traditional command-and-control regulations to effectively address climate change in a rapidly changing regulatory environment