Medicine and Health Sciences Commons^™

Redefining And Revisiting Cost Estimates Of Routine Art Care In Zambia: An Analysis Of Ten Clinics, Austin Tucker, Tannia Tembo, Radhika P Tampi, Jacob Mutale, Mpande Mukumba-Mwenechanya, Anjali Sharma, David W Dowdy, Carolyn B Moore, Elvin Geng, Charles B Holmes, Izukanji Sikazwe, Hojoon Sohn

2020-Current year OA Pubs

INTRODUCTION: Accurate costing is key for programme planning and policy implementation. Since 2011, there have been major changes in eligibility criteria and treatment regimens with price reductions in ART drugs, programmatic changes resulting in clinical task-shifting and decentralization of ART delivery to peripheral health centres making existing evidence on ART care costs in Zambia out-of-date. As decision makers consider further changes in ART service delivery, it is important to understand the current drivers of costs for ART care. This study provides updates on costs of ART services for HIV-positive patients in Zambia.

METHODS: We evaluated costs, assessed from the health …

Diroximel Fumarate Demonstrates An Improved Gastrointestinal Tolerability Profile Compared With Dimethyl Fumarate In Patients With Relapsing-Remitting Multiple Sclerosis: Results From The Randomized, Double-Blind, Phase Iii Evolve-Ms-2 Study, Robert T Naismith, Et Al.

2020-Current year OA Pubs

BACKGROUND: Diroximel fumarate (DRF) is a novel oral fumarate approved in the USA for relapsing forms of multiple sclerosis. DRF is converted to monomethyl fumarate, the pharmacologically active metabolite of dimethyl fumarate (DMF). DRF 462 mg and DMF 240 mg produce bioequivalent exposure of monomethyl fumarate and are therefore expected to have similar efficacy/safety profiles; the distinct chemical structure of DRF may contribute to its tolerability profile.

OBJECTIVES: The objective of this study was to compare the gastrointestinal tolerability of DRF and DMF over 5 weeks in patients with relapsing-remitting multiple sclerosis.

METHODS: EVOLVE-MS-2 was a phase III, randomized, double-blind, …

Toward Actionable Practice Parameters For "Dual Diagnosis": Principles Of Assessment And Management For Co-Occurring Psychiatric And Intellectual/Developmental Disability, John N Constantino, Shae Strom, Michael Bunis, Cy Nadler, Teresa Rodgers, Julia Lepage, Connie Cahalan, Amber Stockreef, Lucas Evans, Rachel Jones, Alyssa Wilson

2020-Current year OA Pubs

PURPOSE OF REVIEW: Although treatment algorithms and parameters for best practice are readily available for all major syndromes of psychiatric impairment, the occurrence of psychiatric syndromes in individuals with intellectual and developmental disability (IDD) invokes serious contextual challenges for interpretation of symptoms, diagnosis, and optimization of treatment, both for clinicians and for the service sectors in which care and support of individuals with IDD are delivered. Recognizing that there exist very few definitive resources for best practice under the circumstance of this form of "dual diagnosis," the Missouri Department of Mental Health convened an expert panel to conduct a focused …

Hypothalamic Orexin And Mechanistic Target Of Rapamycin Activation Mediate Sleep Dysfunction In A Mouse Model Of Tuberous Sclerosis Complex, Bo Zhang, Dongjun Guo, Lirong Han, Nicholas Rensing, Akiko Satoh, Michael Wong

2020-Current year OA Pubs

Tuberous sclerosis complex (TSC) is a genetic disease related to hyperactivation of the mechanistic target of rapamycin (mTOR) pathway and manifested by neurological symptoms, such as epilepsy and sleep disorders. The pathophysiology of sleep dysfunction is poorly understood and is likely multifactorial, but may involve intrinsic biological regulators in the brain. Here, we characterized a mouse model of sleep disorders in TSC and investigated mechanisms of sleep dysfunction in this conditional knockout model involving inactivation of the Tsc1 gene in neurons and astrocytes (Tsc1

Treatment Of Atopic Dermatitis With Ruxolitinib Cream (Jak1/Jak2 Inhibitor) Or Triamcinolone Cream, Brian S Kim, Michael D Howell, Kang Sun, Kim Papp, Adnan Nasir, Michael E Kuligowski, Incb 18424-206 Study Investigators

2020-Current year OA Pubs

BACKGROUND: Atopic dermatitis (AD) is a highly pruritic chronic inflammatory skin disorder. Ruxolitinib, a selective inhibitor of Janus kinase 1 and Janus kinase 2, potently suppresses cytokine signaling involved in AD pathogenesis.

OBJECTIVE: We sought to evaluate the efficacy and safety of ruxolitinib (RUX) cream in adults with AD.

METHODS: In this phase 2 study (NCT03011892), 307 adult patients with AD, an Investigator's Global Assessment score of 2 or 3 (mild or moderate), and 3% to 20% affected body surface area were equally randomized for 8 weeks of double-blind treatment to RUX (1.5% twice daily [BID], 1.5% once daily [QD], …

Negative Pressure Wound Therapy With Instillation: International Consensus Guidelines Update., Paul J Kim, Christopher E Attinger, Thomas Constantine, Brett D Crist, Elizabeth Faust, Christoph R Hirche, Lawrence A Lavery, Valerie J Messina, Norihiko Ohura, Laurie J Punch, Garrett A Wirth, Ibby Younis, Luc Téot

2020-Current year OA Pubs

The use of negative pressure wound therapy with instillation and dwell time (NPWTi-d) has gained wider adoption and interest due in part to the increasing complexity of wounds and patient conditions. Best practices for the use of NPWTi-d have shifted in recent years based on a growing body of evidence and expanded worldwide experience with the technology. To better guide the use of NPWTi-d with all dressing and setting configurations, as well as solutions, there is a need to publish updated international consensus guidelines, which were last produced over 6 years ago. An international, multidisciplinary expert panel of clinicians was …

A Characterization Of Gaucher Ips-Derived Astrocytes: Potential Implications For Parkinson's Disease, Elma Aflaki, Barbara K Stubblefield, Ryan P Mcglinchey, Benjamin Mcmahon, Daniel S Ory, Ellen Sidransky

2020-Current year OA Pubs

While astrocytes, the most abundant cells found in the brain, have many diverse functions, their role in the lysosomal storage disorder Gaucher disease (GD) has not been explored. GD, resulting from the inherited deficiency of the enzyme glucocerebrosidase and subsequent accumulation of glucosylceramide and its acylated derivative glucosylsphingosine, has both non-neuronopathic (GD1) and neuronopathic forms (GD2 and 3). Furthermore, mutations in GBA1, the gene mutated in GD, are an important risk factor for Parkinson's disease (PD). To elucidate the role of astrocytes in the disease pathogenesis, we generated iAstrocytes from induced pluripotent stem cells made from fibroblasts taken from controls …

Glopid-R Report On Chikungunya, O'Nyong-Nyong And Mayaro Virus, Part 5: Entomological Aspects, L. Pezzi, M. S. Diamond, Et Al.

2020-Current year OA Pubs

The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) chikungunya (CHIKV), o'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group has been established to investigate natural history, epidemiology and clinical aspects of infection by these viruses. Here, we present a report dedicated to entomological aspects of CHIKV, ONNV and MAYV. Recent global expansion of chikungunya virus has been possible because CHIKV established a transmission cycle in urban settings using anthropophilic vectors such as Aedes albopictus and Aedes aegypti. MAYV and ONNV have a more limited geographic distribution, being confined to Africa (ONNV) and central-southern America (MAYV). ONNV is probably maintained through …

Cryo-Em Structure Of Nucleotide-Bound Tel1atm Unravels The Molecular Basis Of Inhibition And Structural Rationale For Disease-Associated Mutations, Luke A Yates, Rhys M Williams, Sarem Hailemariam, Rafael Ayala, Peter Burgers, Xiaodong Zhang

2020-Current year OA Pubs

Yeast Tel1 and its highly conserved human ortholog ataxia-telangiectasia mutated (ATM) are large protein kinases central to the maintenance of genome integrity. Mutations in ATM are found in ataxia-telangiectasia (A-T) patients and ATM is one of the most frequently mutated genes in many cancers. Using cryoelectron microscopy, we present the structure of Tel1 in a nucleotide-bound state. Our structure reveals molecular details of key residues surrounding the nucleotide binding site and provides a structural and molecular basis for its intrinsically low basal activity. We show that the catalytic residues are in a productive conformation for catalysis, but the phosphatidylinositol 3-kinase-related …

Toward Improving Practices For Submission Of Diagnostic Tissue Blocks For National Cancer Institute Clinical Trials, Hala Makhlouf, Mark A Watson, Heather A Lankes, Carol Weil, Maura Dickler, Michael Birrer, Christopher Moskaluk, Nilsa C Ramirez, Nader Okby, Edgar Alonsozana, Mark Barnes, Edward B Goldman, Rebecca Enos, Irina Lubensky

2020-Current year OA Pubs

OBJECTIVES: The National Cancer Institute (NCI) National Clinical Trials Network performs phase II and III clinical trials, which increasingly rely on the submission of diagnostic formalin-fixed, paraffin-embedded tissue blocks for biomarker assessment. Simultaneously, advances in precision oncology require that clinical centers maintain diagnostic specimens for ancillary, standard-of-care diagnostics. This has caused tissue blocks to become a limited resource for advancing the NCI clinical trial enterprise and the practice of modern molecular pathology.

METHODS: The NCI convened a 1-day workshop of multidisciplined experts to discuss barriers and strategic solutions to facilitate diagnostic block submission for clinical trial science, from the perspective …

Genomic Profiling Of Circulating Tumor Dna From Cerebrospinal Fluid To Guide Clinical Decision Making For Patients With Primary And Metastatic Brain Tumors, Lori A Ramkissoon, Sonika Dahiya, Et Al.

Open Access Publications

Despite advances in systemic therapies for solid tumors, the development of brain metastases remains a significant contributor to overall cancer mortality and requires improved methods for diagnosing and treating these lesions. Similarly, the prognosis for malignant primary brain tumors remains poor with little improvement in overall survival over the last several decades. In both primary and metastatic central nervous system (CNS) tumors, the challenge from a clinical perspective centers on detecting CNS dissemination early and understanding how CNS lesions differ from the primary tumor, in order to determine potential treatment strategies. Acquiring tissue from CNS tumors has historically been accomplished …

Personality Traits As Markers Of Psychosis Risk In Kenya: Assessment Of Temperament And Character, Daniel Mamah, C Robert Cloninger, Victoria N Mutiso, Isaiah Gitonga, Albert Tele, David M Ndetei

2020-Current year OA Pubs

Specific personality traits have been proposed as a schizophrenia-related endophenotype and confirmed in siblings at risk for psychosis. The relationship of temperament and character with psychosis has not been previously investigated in Africa. The study was conducted in Kenya, and involved participants at clinical high-risk (CHR) for psychosis (

How Do Subjective Health Literacy Measures Work In Young Adults? Specifying "Online" Or "Paper-Based" Forms Impacts Results, Mary C Politi, Courtney M Goodwin, Kimberly A Kaphingst, Xuechen Wang, Angela Fagerlin, Lindsay N Fuzzell, Sydney E Philpott-Streiff

2020-Current year OA Pubs

No abstract provided.

Prognostic Impact Of Cdkn2a/B Deletion, Tert Mutation, And Egfr Amplification On Histological And Molecular Idh-Wildtype Glioblastoma, Sirui Ma, Soumon Rudra, Jian L Campian, Sonika Dahiya, Gavin P Dunn, Tanner Johanns, Michael Goldstein, Albert H Kim, Jiayi Huang

2020-Current year OA Pubs

BACKGROUND: We aimed to evaluate the clinical outcomes of molecular glioblastoma (mGBM) as compared to histological GBM (hGBM) and to determine the prognostic impact of

METHODS: IDH-wildtype GBM patients treated with radiation therapy (RT) between 2012 and 2019 were retrospectively analyzed. mGBM was defined as grade II-III IDH-wildtype astrocytoma without histological features of GBM but with one of the following molecular alterations:

RESULTS: Of the 367 eligible patients, the median follow-up was 11.7 months. mGBM and hGBM did not have significantly different OS (median: 16.6 vs 13.5 months, respectively,

CONCLUSION: Criteria for mGBM may require further refinement and validation.

Improving The Implementation And Sustainment Of Evidence-Based Practices In Community Mental Health Organizations: A Study Protocol For A Matched-Pair Cluster Randomized Pilot Study Of The Collaborative Organizational Approach To Selecting And Tailoring Implementation Strategies (Coast-Is), Byron J Powell, Amber D Haley, Sheila V Patel, Lisa Amaya-Jackson, Beverly Glienke, Mellicent Blythe, Rebecca Lengnick-Hall, Stacey Mccrary, Rinad S Beidas, Cara C Lewis, Gregory A Aarons, Kenneth B Wells, Lisa Saldana, Mary M Mckay, Morris Weinberger

2020-Current year OA Pubs

BACKGROUND: Implementing and sustaining evidence-based programs with fidelity may require multiple implementation strategies tailored to address multi-level, context-specific barriers and facilitators. Ideally, selecting and tailoring implementation strategies should be guided by theory, evidence, and input from relevant stakeholders; however, methods to guide the selection and tailoring of strategies are not well-developed. There is a need for more rigorous methods for assessing and prioritizing implementation determinants (barriers and facilitators) and linking implementation strategies to determinants. The Collaborative Organizational Approach to Selecting and Tailoring Implementation Strategies (COAST-IS) is an intervention designed to increase the effectiveness of evidence-based practice implementation and sustainment. COAST-IS …

Aging And Efficacy Of Disease-Modifying Therapies In Multiple Sclerosis: A Meta-Analysis Of Clinical Trials, Yinan Zhang, Natalia Gonzalez Caldito, Afsaneh Shirani, Amber Salter, Gary Cutter, William Culpepper, Mitchell Wallin, Peter Kosa, Bibiana Bielekova, Fred Lublin, Olaf Stuve

2020-Current year OA Pubs

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for the treatment of disease activity and are effective in reducing relapses and new magnetic resonance imaging (MRI) lesions. However, disease activity generally subsides with time, and age-dependent changes in DMT efficacy are not well-established. We aimed to investigate whether age impacts the efficacy of DMTs in treating disease activity in patients with relapsing-remitting MS (RRMS).

Methods: DMT efficacy related to age was assessed through a meta-analysis of clinical trials that evaluated the efficacy of DMTs in RRMS patients as measured by reductions in the annualized relapse rate (ARR), new …

Physician Attitudes Towards-And Adoption Of-Mobile Health, Tracie Kong, Mary Morgan Scott, Yang Li, Cynthia Wichelman

2020-Current year OA Pubs

OBJECTIVE: Smartphone apps and mobile devices are an emerging method of healthcare data collection. This study sought to understand how physicians currently view mobile health (mHealth) technologies and use them in patient care.

METHODS: A total of 186 physicians affiliated with Washington University School of Medicine in St. Louis, Missouri, USA completed a survey in 2016 regarding their current implementation of mHealth technologies for patient care and support for further development.

RESULTS: More than half of respondents were willing to discuss health apps and mobile devices with patients. However, most were not currently recommending them to patients. Apps/devices that encouraged …

Semi-Automated Segmentation Of The Lateral Periventricular Regions Using Diffusion Magnetic Resonance Imaging, Albert M Isaacs, Rowland H Han, Christopher D Smyser, David D Limbrick, Joshua S Shimony

2020-Current year OA Pubs

The lateral ventricular perimeter (LVP) of the brain is a critical region because in addition to housing neural stem cells required for brain development, it facilitates cerebrospinal fluid (CSF) bulk flow and functions as a blood-CSF barrier to protect periventricular white matter (PVWM) and other adjacent regions from injurious toxins. LVP injury is common, particularly among preterm infants who sustain intraventricular hemorrhage or post hemorrhagic hydrocephalus and has been associated with poor neurological outcomes. Assessment of the LVP with diffusion MRI has been challenging, primarily due to issues with partial volume artifacts since the LVP region is in close proximity …

2019 Hrs/Ehra/Aphrs/Lahrs Expert Consensus Statement On Catheter Ablation Of Ventricular Arrhythmias, Edmond M Cronin, Phillip Cuculich, Et Al.

2020-Current year OA Pubs

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the …

Who Benefits From A Prostate Rectal Spacer? Secondary Analysis Of A Phase Iii Trial, Thomas J. Quinn, Walter Bosch, Et Al.

2020-Current year OA Pubs

PURPOSE: Previously a phase III trial of a hydrogel rectal spacer during prostate radiation therapy found decreased toxicity and a clinically significant improvement in bowel quality of life (QOL) at 3 years by the Expanded Prostate Cancer Index. We performed a secondary analysis to identify men less likely to benefit.

METHODS AND MATERIALS: Clinical and dosimetric data for the 222 patients enrolled on the SpaceOAR phase III trial were analyzed. The volume of rectum treated to 70 Gy (V70) and the quantitative analysis of normal tissue effects in the clinic (QUANTEC) rectal dose goals were used as surrogates for clinical …

Histopathologic Findings In Malignant Peripheral Nerve Sheath Tumor Predict Response To Radiotherapy And Overall Survival, Calixto-Hope G Lucas, Harish N Vasudevan, William C Chen, Stephen T Magill, Steve E Braunstein, Line Jacques, Sonika Dahiya, Fausto J Rodriguez, Andrew E Horvai, Arie Perry, Melike Pekmezci, David R Raleigh

2020-Current year OA Pubs

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive and poorly understood malignant neoplasm. Even in the setting of multimodal therapy, the clinical course of MPNST is frequently marked by metastatic conversion and poor overall prognosis, with optimal treatment paradigms for this rare tumor unknown.

METHODS: We reviewed the medical records and histopathology of 54 consecutive patients who were treated at University of California San Francisco between 1990 and 2018.

RESULTS: Our cohort consisted of 24 male and 30 female patients (median age 38 years). Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) sarcoma grading criteria segregated …