Medicine and Health Sciences Commons^™

Tracking The Evolving Role Of Artificial Intelligence In Implementation Science: Protocol For A Living Scoping Review Of Applications, Evaluation Approaches And Outcomes [Version 2; Peer Review: 2 Approved], Guillaume Fontaine, Byron J Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: Artificial intelligence (AI) offers significant opportunities to improve the field of implementation science by supporting key activities such as evidence synthesis, contextual analysis, and decision-making to promote the adoption and sustainability of evidence-based practices. This living scoping review aims to: (1) map applications of AI in implementation research and practice; (2) identify evaluation approaches, reported outcomes, and potential risks; and (3) synthesize reported research gaps and opportunities for advancing the use of AI in implementation science.

METHODS: This scoping review will follow the Joanna Briggs Institute (JBI) methodology and the Cochrane guidance for living systematic reviews. A living scoping …

Piezo1-Mediated Calcium Influx Transiently Alters Nuclear Mechanical Properties Via Actin Remodeling In Chondrocytes, Jaquelin M Garcia-Castorena, Rosa Riester, Miranda Gamino-Ornelas, Nikitha Ada, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

Mechanosensation allows cells to generate intracellular signals in response to mechanical cues from their environment. Previous research has demonstrated that mechanical stress can alter the mechanical properties of the nucleus, affecting gene transcription, chromatin methylation, and nuclear mechanoprotection during mechanical loading. PIEZO1, a mechanically gated Ca

Barriers And Facilitators To Implementing A Single-Visit, Screen-And-Treat Approach With Thermal Ablation For Cervical Cancer Prevention In Kenya, Harriet Fridah Adhiambo, Thomas Odeny, Et Al.

2020-Current year OA Pubs

Cervical cancer continues to be a major global threat to women's health, with approximately 660,000 women diagnosed annually, 94% of whom are in low- and middle-income countries (LMICs). The high disease burden in LMICs is partly due to suboptimal adoption and widespread implementation of effective preventive interventions. This study explored drivers of implementation success and failure for a future single-visit, screen, and treat approach with thermal ablation (SV-SAT + TA), referred to as TIBA in Kenya. Guided by the Consolidated Framework for Implementation Research (CFIR framework), we conducted in-depth interviews with 34 participants (frontline health workers, health facility managers, and …

Depression And Weight Loss Trajectories During An Integrated Behavioral Intervention: Within-Treatment Analysis Of The Rainbow Trial, Bailey W. Osweiler, Daphne Lew, Nan Lv, Jun Ma, Thomas G. Kannampallil

2020-Current year OA Pubs

INTRODUCTION: Depression and obesity are two of the most common chronic conditions among US adults. The Research Aimed at Improving Both Mood and Weight (RAINBOW) study was the first randomized clinical trial to demonstrate the effectiveness of an integrated behavioral treatment for depression and obesity. We aimed to characterize the trajectories of both depression symptoms and weight loss during the RAINBOW intervention.

METHODS: Participants (N = 201) randomly assigned to the RAINBOW treatment arm who provided serial data on depression symptoms (via the 9-item Patient Health Questionnaire [PHQ9]) and self-measured weight were included. Group-Based Multi-Trajectory Modeling is a statistical technique …

Anticodon-Edited Trna Enables Translational Readthrough Of Col4a5 Premature Termination Codons, Kohei Omachi, Joseph J. Porter, John D. Lueck, Jeffrey H. Miner

2020-Current year OA Pubs

Alport syndrome is caused by variants in COL4A3, COL4A4, or COL4A5, which encode the α3α4α5 chains of type IV collagen. These variants result in defects in the glomerular basement membrane (GBM) and impaired kidney function. Nonsense variants result in truncated proteins lacking the NC1 domain, thereby preventing proper GBM assembly and function and causing the most severe forms of the disease. Restoring full-length protein expression represents a potential therapeutic strategy for Alport syndrome and related disorders. Anticodon-edited transfer RNAs (ACE-tRNAs), which promote premature termination codon (PTC) readthrough, have shown promise in diseases such as cystic fibrosis, but their application in …

Efficacy And Safety Of Dostarlimab In Combination With Chemotherapy In Patients With Dmmr/Msi-H Primary Advanced Or Recurrent Endometrial Cancer In A Phase 3, Randomized, Placebo-Controlled Trial (Engot-En6-Nsgo/Gog-3031/Ruby), Matthew A Powell, Carolyn Mccourt, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial.

METHODS: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with …

Early Changes In Spatiotemporal Dynamics Of Remapped Circuits And Global Networks Predict Functional Recovery After Stroke In Mice, Ryan M Bowen, Jake Lee, Brendon Wang, Keith R Lohse, Hanyang Miao, Jonah A Padawer-Curry, Asher J Albertson, Eric C Landsness, Adam Q Bauer, Jin-Moo Lee

2020-Current year OA Pubs

SIGNIFICANCE: Stroke is the leading cause of chronic disability in the United States. How stroke size affects post-stroke repair and recovery is poorly understood.

AIM: We aim to investigate the effects of stroke size on early repair patterns and determine how early changes in neuronal circuits and networks predict functional outcomes after stroke.

APPROACH: We used wide-field optical imaging, photothrombosis, and the cylinder-rearing assay to examine changes in neuronal circuit and network activity in the context of functional recovery after stroke.

RESULTS: Larger strokes ablating

CONCLUSIONS: These results suggest that diffuse patterns of remapping, and desynchronization and hyperconnectivity of cortical …

De Novo Lipid Synthesis In Cardiovascular Tissue And Disease, Tariq J Khan, Clay F Semenkovich, Mohamed A Zayed

2020-Current year OA Pubs

Most tissues have the capacity for endogenous lipid synthesis. A crucial foundational pathway for lipid synthesis is de novo lipid synthesis (DNL), a ubiquitous and complex metabolic process that occurs at high levels in the liver, adipose and brain tissue. Under normal physiological conditions, DNL is vital in converting excess carbohydrates into fatty acids. DNL is linked to other pathways, including the endogenous synthesis of phospholipids and sphingolipids. However, abnormal lipid synthesis can contribute to various pathologies and clinical conditions. Experimental studies involving dietary restriction and in vivo genetic modifications provide compelling evidence demonstrating the significance of lipid synthesis in …

Treatment Of Hereditary Hemorrhagic Telangiectasias With Sclerotherapy: A Case Series, Jenny Ji, Andrew M Peterson, Jay F Piccirillo

2020-Current year OA Pubs

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is characterized by abnormal blood vessel formation. One treatment for HHT-related arteriovenous malformations (AVMs) is sclerotherapy, which collapses the blood vessels by irritating the endothelial lining.

METHODS: This case series describes two HHT patients undergoing in-office sodium tetradecyl sulfate sclerotherapy for non-nasal telangiectasias and AVMs. The first patient had AVMs on the red lip while the second patient had an AVM and several telangiectasias on the tongue.

RESULTS: Both patients' AVMs required only one treatment visit and were no longer noticeable within a week. Neither of the patients had any side effects from treatment.

CONCLUSION: …

Expert Consensus On The Diagnosis And Management Of Digoxin Toxicity, Jason B Hack, Sue Wingate, Ron Zolty, Michael W Rich, Paul J Hauptman

2020-Current year OA Pubs

While there has been a decline in the use of digoxin in patients with heart failure and atrial fibrillation, acute and chronic digoxin toxicity remains a significant clinical problem. Digoxin's narrow therapeutic window and nonspecific signs and symptoms of toxicity create clinical challenges and uncertainty around the diagnostic criteria of toxicity and responsive treatment choices for the bedside clinician. A systematic review of published literature on digoxin toxicity (34,587 publications over 6 decades, with 114 meeting inclusion criteria) was performed to develop 33 consensus statements on diagnostic and therapeutic approaches which were then evaluated through a modified Delphi process involving …

Nutcracker Syndrome (A Delphi Consensus), Floor Heilijgers, Suresh Vedantham, Et Al.

2020-Current year OA Pubs

BACKGROUND: Nutcracker syndrome (NCS) describes the symptomatic compression of the left renal vein between the aorta and superior mesenteric artery. Whereas asymptomatic compression is a common radiological finding, patients with NCS can report a range of symptoms. There are no specific diagnostic criteria and interventions include a range of open surgical and endovascular procedures. Therefore, we wished to develop an international consensus document covering aspects of diagnosis, management, and follow-up for patients with NCS.

METHODS: A three-stage modified Delphi consensus was performed. A steering committee developed 37 statements covering 3 categories for patients with NCS: diagnosis, management, and follow-up. These …

Acquired Ductopenia: An Insight Into Imaging Findings, Rachita Khot, Nathan R Shelman, Daniel R Ludwig, Rashmi T Nair, Mark A Anderson, Sudhakar K Venkatesh, Raj Mohan Paspulati, Rex A Parker, Christine O Menias

2020-Current year OA Pubs

Hepatic ductopenia is a pathologic diagnosis characterized by a decrease in the number of intrahepatic bile ducts as a consequence of various underlying etiologies. Some etiologies, such as primary sclerosing cholangitis, primary biliary cholangitis, and ischemic cholangitis, often have distinctive imaging findings. In contrast, other causes such as chronic rejection following liver transplantation, drug-induced biliary injury, infection, malignancy such as lymphoma, and graft-versus-host disease may only have ancillary or non-specific imaging findings. Thus, diagnosing ductopenia in conditions with nonspecific imaging findings requires a multidimensional approach, including clinical evaluation, serological testing, imaging, and liver histology to identify the underlying cause. These …

Validating A Novel Measure For Assessing Patient Openness And Concerns About Using Artificial Intelligence In Healthcare, Bryan A Sisk, Alison L Antes, Sunny C Lin, Paige Nong, James M Dubois

2020-Current year OA Pubs

OBJECTIVES: Patient engagement is critical for the effective development and use of artificial intelligence (AI)-enabled tools in learning health systems (LHSs). We adapted a previously validated measure from pediatrics to assess adults' openness and concerns about the use of AI in their healthcare.

STUDY DESIGN: Cross-sectional survey.

METHODS: We adapted the 33-item "Attitudes toward Artificial Intelligence in Healthcare for Parents" measure for administration to adults in the general US population (AAIH-A), recruiting participants through Amazon's Mechanical Turk (MTurk) crowdsourcing platform. AAIH-A assesses openness to AI-driven technologies and includes 7 subscales assessing participants' openness and concerns about these technologies. The openness …

Head-To-Head Preclinical Treatment Design Prioritizes Promising Therapies For Neurofibromatosis Type 1 Optic Glioma Clinical Translation, Talia Eligator, Jit Chatterjee, Shintaro Yamada, Anthony Kirchner, Hareesh B Nair, Jason R Fangusaro, David H Gutmann

2020-Current year OA Pubs

BACKGROUND: Authenticated preclinical brain tumor models provide unprecedented opportunities to evaluate next-generation treatments. However, some therapies with robust anti-tumor activity in mice fail in human trials, highlighting the need to better prioritize candidates for clinical translation. Herein, we implemented a head-to-head preclinical strategy using a well-characterized murine model of NF1-optic pathway glioma (

METHODS:

RESULTS: While all agents restored normal tissue architecture, reduced ON proliferation, and decreased TME soluble mediator and tumor cell marker RNA expression, only lamotrigine and mirdametinib also reduced ON volume. Everolimus, lamotrigine, and HBS-101 restored RNFL thickness to wild-type levels, whereas carboplatin showed a trend towards …

Colorectal Cancer Incidence Trends In Younger Versus Older Adults: An Analysis Of Population-Based Cancer Registry Data, Hyuna Sung, Rebecca L Siegel, Mathieu Laversanne, Chenxi Jiang, Eileen Morgan, Mariam Zahwe, Yin Cao, Freddie Bray, Ahmedin Jemal

2020-Current year OA Pubs

BACKGROUND: Previous studies have shown that colorectal cancer incidence is increasing among younger adults (aged < 50 years) in multiple high-income western countries in contrast with stabilising or decreasing trends in incidence in older adults (aged ≥50 years). This study aimed to investigate contemporary colorectal cancer incidence trends in younger adults versus older adults.

METHODS: Colorectal cancer incidence data, including year of diagnosis, sex, and 5-year age group for 50 countries and territories, were extracted from the WHO-International Agency for Research on Cancer Cancer Incidence in Five Continents Plus database. The Human Development Index 2022 was retrieved from the United Nations Development Programme and grouped into very high (>0·80), high (0·70-0·79), medium (0·55-0·69), and low (< 0·55) categories. Age-standardised incidence rates (ASR) per 100 000 person-years of early-onset (diagnosed between ages 25 to 49 years) and late-onset (diagnosed between ages 50 to 74 years) colorectal cancer (ICD 10th revision, C18-20), diagnosed between 1943-2003 and 2015-17, were calculated using the direct method and Segi-Doll world standard population). The primary study objective was to examine contemporary colorectal cancer incidence trends in younger adults versus older adults using data until 2017 from 50 countries and territories. Temporal trends were visualised and quantified with joinpoint regression, stratified by age at diagnosis (25-49 years or 50-74 years). Average annual percentage changes (AAPC) were estimated.

FINDINGS: In the most recent 5 years (2013-17 for all countries analysed, except for Japan [2011-15], Spain [2012-16], and Costa Rica [2012-16]), …

Surgeon Interpretation Of Patient-Reported Outcome Measures In Upper Extremity Osteoarthritis, Rick S. Looman, Koen Oude Nijhuis, Sina Ramtin, David Ring, Daniel A. London, Ryan Calfee, Niels Brinkman, Science Of Variation Group

2020-Current year OA Pubs

PURPOSE: Measures that quantify levels of pain intensity, incapability, symptoms of distress, and unhelpful thinking were designed as research tools. We studied how surgeons interpret and act on these scores in the care of individual patients.

METHODS: In an online experiment, 67 upper limb specialists from the Science of Variation Group reviewed 10 fictious patient scenarios of trapeziometacarpal, wrist and elbow osteoarthritis (OA) and randomized elements of radiographic severity, levels of discomfort and incapability, deprivation index score (social health), and levels of distress and unhelpful thinking (mental health). Multilevel mixed-effects linear regression identified patient factors associated with surgeon concern, enthusiasm …

Thalamic And Visual Network Dysfunction Relates To Tremor Response In Thalamic Deep Brain Stimulation, Aimee E Morris, Babatunde Adeyemo, Meghan C Campbell, Abraham Z Snyder, Joel S Perlmutter, Jonathan W Mink, Scott A Norris

2020-Current year OA Pubs

BACKGROUND: Essential tremor (ET) is the most common movement disorder in adults, but its pathogenesis is incompletely understood. Deep brain stimulation of the ventral intermediate thalamic nucleus (VIM DBS) provides effective treatment for medically-refractory cases. We aimed to determine how pre-surgical resting-state functional connectivity (FC) in medically-refractory ET relates to VIM DBS clinical response.

METHODS: We analyzed resting-state FC MRI in 21 participants with medically-refractory ET who subsequently underwent VIM DBS and 34 matched controls. We applied rigorous quality assurance to minimize motion artifact. Whole-brain correlation matrices were computed across 300 cortical, subcortical, and cerebellar regions and compared across groups …

Development Of A High-Throughput Platform For Quantitation Of Histone Modifications On A New Qtof Instrument, Emily Zahn, Yixuan Xie, Xingyu Liu, Rashmi Karki, Richard M Searfoss, Francisca N De Luna Vitorino, Joanna K Lempiäinen, Joanna Gongora, Zongtao Lin, Chenfeng Zhao, Zuo-Fei Yuan, Benjamin A Garcia

2020-Current year OA Pubs

Histone post-translational modifications (PTMs) regulate gene expression patterns through epigenetic mechanisms. The five histone proteins (H1, H2A, H2B, H3, and H4) are extensively modified, with over 75 distinct modification types spanning more than 200 sites. Despite strong advances in mass spectrometry (MS)-based approaches, identification and quantification of modified histone peptides remains challenging because of factors, such as isobaric peptides, pseudo-isobaric PTMs, and low stoichiometry of certain marks. Here, we describe the development of a new high-throughput method to identify and quantify over 150 modified histone peptides by LC-MS. Fast gradient microflow liquid chromatography and variable window sequential windows acquisition of …

Caregiver Worry About Covid-19 As A Predictor Of Social Mitigation Behaviours And Sars-Cov-2 Infection In A 12-City U.S. Surveillance Study Of Households With Children, Steven M Brunwasser, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Understanding compliance with COVID-19 mitigation recommendations is critical for informing efforts to contain future infectious disease outbreaks. This study tested the hypothesis that higher levels of worry about COVID-19 illness among household caregivers would predict lower (a) levels of overall and discretionary social exposure activities and (b) rates of household SARS-CoV-2 infections.

METHODS: Data were drawn from a surveillance study of households with children (

RESULTS: Caregivers with high enrollment levels of worry about COVID-19 illness were more likely to reduce direct social contact outside the household, particularly during the U.S.'s most deadly pandemic wave. Households of caregivers with …

Sample Ascertainment And Recruitment Sources In The Accelerating Medicines Partnership Schizophrenia Program, Jean Addington, Daniel Mamah, Et Al.

2020-Current year OA Pubs

BACKGROUND: This paper presents the recruitment sources of clinical high-risk (CHR) and community controls (CC) from the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program, which aims to study various clinical variables and biomarkers in 2040 CHR and 652 CC participants.

METHODS: A total of 1640 CHR and 514 CC had recruitment source data. The Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the SIPS was utilized to assess CHR criteria and severity of attenuated psychotic symptoms (APSs), and the Global Functioning: Social Scale was used for social functioning. Participants were recruited through various …

Sociodemographic Factors Predict Outcomes And Reveal Spatial Tumor Patterns In Glioblastoma, Patrick H Luckett, Michael Olufawo, Noah Naddaff-Slocum, Ki Yun Park, Bidhan Lamichhane, Donna Dierker, Gabriel Trevino Verastegui, John J Lee, Peter Yang, Albert Kim, Omar H Butt, Milan G Chheda, Abraham Z Snyder, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Glioblastoma (GBM) is the deadliest malignant glioma of the central nervous system. Postsurgical functional impairment correlates with survival and is estimated using metrics such as extent and location of resection. This study uses machine learning to evaluate the predictive ability of baseline sociodemographic and lifestyle factors for forecasting postoperative functional outcomes in GBM patients.

METHODS: Glioblastoma patients (

RESULTS: Utilizing decision trees with age, SVI/SES, sex, tobacco use, alcohol use, obesity, and race as predictors, we achieved 88% accuracy in classifying median KPS and 85% accuracy in classifying KPS slope. Socioeconomic factors were the strongest predictors. Age, sex, and …

Recombinant Human Alpha-N-Acetylglucosamine-6-Sulfatase Delivered To Sanfilippo D Mice With Repeated Intracerebroventricular Injections Corrects Cns Pathology, Grant L. Austin, Feng Wang, Steven Q. Le, Alexander Sorensen, Shan Li, Lai C. Foong, Srikanth Singamsetty, Jill Wood, Tsui-Fen Chou, Patricia I. Dickson

2020-Current year OA Pubs

Mucopolysaccharidosis type IIID (MPS IIID; Sanfilippo D) is caused by biallelic pathogenic variants in N-acetylglucosamine-6-sulfatase (GNS), which participates in catabolism of heparan sulfate (HS) glycosaminoglycans. Characterization of MPS IIID disease at a cellular level has not been robustly achieved. We used unbiased quantitative proteomics to establish a cellular phenotype for MPS IIID mice. Recombinant human GNS (rhGNS), a variant of which previously demonstrated single dose efficacy in MPS IIID human fibroblasts and in MPS IIID neonatal mice, was used to establish a repeat dosing schedule to treat MPS IIID mice. Adult Gns KO mice or heterozygous carriers were treated via …

Novel Loci For Triglyceride/Hdl-C Ratio Longitudinal Change Among Subjects Without T2d, Lihua Wang, Siyu Wang, Jason A Anema, Vaha A Moghaddam, Yanli Lu, Shiow Lin, E Warwick Daw, Allison L Kuipers, Iva Miljkovic, Michael Brent, Gary J Patti, Bharat Thygarajan, Joseph M Zmuda, Michael A Province, Ping An

2020-Current year OA Pubs

Triglyceride (TG)/HDL-C ratio (THR) is a surrogate predictor of hyperinsulinemia. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among nondiabetic Europeans from the Long Life Family Study (n = 1,384). Subjects with diabetes or on dyslipidemia medications were excluded. ΔTHR was derived using growth curve modeling and adjusted for age, sex, field centers, and principal components. GWAS used a linear mixed model accounting for familial relatedness. GWLS employed haplotype-based identity-by-descent estimation with 0.5 cM average spacing. Heritability of ΔTHR was moderate (46%). Our GWAS identified a …

Examining And Classifying Reasons For Missing Viral Loads Among Adults Living With Hiv: An Extended Outcome Investigation And Ascertainment Approach In Western Kenya, Harriet Fridah Adhiambo, Jayne Lewis-Kulzer, Edwin Nyagesoa, Sarah Gimbel, Eliud Akama, Dorothy Mangale, Lina Montonya, Ingrid Eshun-Wilson, Sarah Iguna, Everlyne Nyandieka, Elizabeth Bukusi, Lisa Abuogi, Thomas Odeny, Maya L. Petersen, Elvin H. Geng

2020-Current year OA Pubs

Gaps in HIV RNA monitoring persist globally impeding the ability to determine clinical progress and outcomes. This study systematically evaluated provider (e.g., guideline non-adherence), system (e.g., laboratory error) and participant-level (e.g., refusal) drivers of missed viral load (VL) monitoring measurements among people with HIV in Kenya. Adults aged 18-65 years were followed across five health facilities in Kenya as part of a clinical trial (NCT#02338739) where HIV RNA monitoring was done routinely. Instances of missed VL despite being indicated per Kenyan guidelines were identified. An algorithm for assessing root causes of missing HIV RNA was developed and generalized linear models …

Vagus Nerve Stimulation In Treatment-Resistant Depression: A One-Year, Randomized, Sham-Controlled Trial, Charles R Conway, Christopher L Kriedt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Few treatments are available for individuals with marked treatment-resistant depression (TRD).

OBJECTIVE: Evaluate the safety and effectiveness of FDA-approved adjunctive vagus nerve stimulation (VNS) in patients with marked TRD.

METHODS: This 12-month, multicenter, double-blind, sham-controlled trial included 493 adults with marked treatment-resistant major depression who were randomized to active or no-stimulation sham VNS for 12 months. The primary outcome was percent time in response across months 3-12, with response defined as a ≥50 % change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS). Several secondary endpoints were evaluated.

RESULTS: Overall, 88.4 % of participants completed the trial. Percent …

Effects Of Vagus Nerve Stimulation On Daily Function And Quality Of Life In Markedly Treatment-Resistant Major Depression: Findings From A One-Year, Randomized, Sham-Controlled Trial, A John Rush, Charles R Conway, Et Al.

2020-Current year OA Pubs

BACKGROUND: Depression treatments aim to minimize symptom burden and optimize quality of life (QoL) and psychosocial function.

OBJECTIVE: Compare the effects of adjunctive versus sham vagus nerve stimulation (VNS) on QoL and function in markedly treatment-resistant depression (TRD).

METHODS: In this multicenter, double-blind, sham-controlled trial, 493 adults with TRD and ≥4 adequate but unsuccessful antidepressant treatment trials (current episode) were randomized to active (n = 249) or sham (n = 244) VNS (plus treatment as usual) over a 12-month observation period. Quarterly outcomes included QoL with the Q-LES-Q, Mini-Q-LES-Q, and EQ-5D-5L, and function with the WHODAS 2.0 and Work Productivity …

Exploring Factors Contributing To Patient Decision-Making In The Care Journey To Elective Hernia Care In Kenya, Helen W. Li, Jesse Kiprono Too, Sarah Nyanchama Nyariki, Charles Nathan Nessle, Sara Malone, Rachel Matsumoto, Teddy Ashibende Aurah, Jeffrey A. Blatnik, Joanna Hunter-Squires, Ivan Seno Saruni

2020-Current year OA Pubs

BACKGROUND: Capacity for elective general surgical care is an important reflection of a health system's ability to meet a population's surgical needs and is currently known to be inadequate in many low- and middle-income countries. Patient agency is a key, understudied factor which shapes how and when patients ultimately decide to engage with formal care. Understanding factors which influence patient care seeking activity can have important implications for how current and future health systems may be utilized. This study aims to explore how patients approach the navigation and triage of their elective hernia condition within the Kenyan surgical care system. …

Rethinking Immune Check Point Inhibitors Use In Liver Transplantation: Implications And Resistance, Vivian Ortiz, Emilien Loeuillard

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, including the two most common liver tumors, hepatocellular carcinoma and cholangiocarcinoma, but their use in the peri-transplantation period is controversial. ICI therapy aims to heighten cytotoxic T lymphocytes response against tumors. However, tumor recurrence is common owing to tumor immune response escape involving ablation of CTL response by interfering with antigen presentation, triggering CLT apoptosis and inducing epigenetic changes that promote ICI therapy resistance. ICI can also affect tissue resident memory T cell population, impact tolerance in the post-transplant period, and induce acute inflammation risking graft survival post-transplant. Their interaction with immunosuppression …

Poor Sleep Is Common In Treatment-Resistant Late-Life Depression And Associated With Poorer Antidepressant Response: Findings From The Optimum Clinical Trial, Michael S B Mak, Marie Anne Gebara, Eric J Lenze, Daniel M Blumberger, Patrick J Brown, Pilar Cristancho, Alastair J Flint, Jordan F Karp, Helen Lavretsky, J Philip Miller, Charles F Reynolds 3rd, Steven P Roose, Benoit H Mulsant, Sarah T Stahl

2020-Current year OA Pubs

BACKGROUND: Adults with treatment-resistant late-life depression (TRLLD) have high rates of sleep problems; however, little is known about the occurrence and change in sleep during pharmacotherapy of TRLLD. This analysis examined: (1) the occurrence of insufficient sleep among adults with TRLLD; (2) how sleep changed during pharmacotherapy; and (3) whether treatment outcomes differed among participants with persistent insufficient sleep, worsened sleep, improved sleep, or persistent sufficient sleep.

METHODS: Secondary analysis of data from 634 participants age 60+ years in the OPTIMUM clinical trial for TRLLD. Sleep was assessed using the sleep item from the Montgomery-Asberg Depression Rating Scale at the …

Molecular Regulation And Therapeutic Targeting Of Vldl Production In Cardiometabolic Disease, Kendall H Burks, Nathan O Stitziel, Nicholas O Davidson

2020-Current year OA Pubs

There exists a complex relationship between steatotic liver disease (SLD) and atherosclerotic cardiovascular disease (CVD). CVD is a leading cause of morbidity and mortality among individuals with SLD, particularly those with metabolic dysfunction-associated SLD (MASLD), a significant proportion of whom also exhibit features of insulin resistance. Recent evidence supports an expanded role of very low-density lipoprotein (VLDL) in the pathogenesis of CVD in patients, both with and without associated metabolic dysfunction. VLDL represents the major vehicle for exporting neutral lipid from hepatocytes, with each particle containing one molecule of apolipoproteinB100 (APOB100). VLDL production becomes dysregulated under conditions characteristic of MASLD …