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Updated Sunday, 07 March 2021

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Faheem Handoo ◽  
Yuyao Liu ◽  
Sonja G. Schütz ◽  
Ronald D. Chervin ◽  
Ivo D. Dinov

Background: Obstructive sleep apnea (OSA) occurs when the airway is repeatedly blocked during sleep, resulting in frequent brief awakenings throughout the night. OSA has been found to increase the risk of many cardiovascular diseases, especially heart failure (HF). HF with reduced, preserved, and borderline ejection fraction (HFrEF, HFpEF, and HFbEF) are three subtypes common in OSA patients. The aim of this study is to further explore the relationship between OSA and HF and the influence of specific OSA measures. Methods: Electronic medical data was collected from health histories, echocardiograms, and polysomnography studies. Observations were sorted into three categories based on left ventricular ejection fraction: HFpEF (n=334), HFrEF (n=77), and HFbEF (n=37). Multinomial logistic regression was then conducted to determine the relative risk of HFpEF and HFrEF from each variable as compared to the baseline HFbEF. Results: Pacemaker presence, previous stroke, BMI, and a measure of left ventricular dysfunction (LVD), called relative wall thickness, all raised the risk of HFpEF compared to HFbEF, while another LVD measure, left ventricular end-systolic dimension, reduced it. These factors also increased risk for HFrEF, except for previous stroke and pacemaker presence, which were not significant. Relevant OSA metrices included average blood oxygen saturation and three measures of sleep apnea severity, named central apnea index, hypopnea index per hour, and the Epworth Sleepiness Scale (ESS). These all decreased relative HFpEF risk, other than ESS, which raised it. Conclusions: As was expected, several standard HF predictors increased the risk of both types of HF. Surprisingly, few OSA indices had the same effect. This suggests that targeting specific OSA markers may not be effective in treating patients with any of these HF types. Future work could involve the influence of OSA and its indices on mortality, or the responses of these indicators to treatment, both topics with limited previous findings.


2020 ◽  
Vol 3 ◽  
Author(s):  
Walter Fitschen ◽  
Sikandar Khan ◽  
Heidi Lindroth ◽  
Sophia Wang ◽  
Sundus Imran ◽  
...  

Background: Delirium is a common post-operative complication for patients who undergo esophagectomy. The pathophysiology of delirium is poorly understood, limiting therapeutic options. To advance our pathophysiologic understanding, we conducted this study to evaluate the association of protein expression with postoperative delirium.  Methods: A case-control study was performed using blood samples from the PEPOD randomized clinical control trial (NCT02213900). 52 patients (26 cases with delirium, 26 control)  who were >18 years old, spoke English, and underwent esophagectomy were included, while those with schizophrenia, Parkinson’s, alcohol abuse, neuroleptic malignant syndrome, haloperidol allergy, and severe dementia were excluded. Samples were from pre-op and post-op day 1. Delirium was assessed for using the Confusion Assessment Method for the Intensive Care Unit and Richmond Agitation Sedation Scale, while the severity was assessed using DRS-R-68. Proteomic analysis was performed using TMT 10ples isobaric labels. Proteome Discoverer and STRING web-based tools were used for bioinformatic analyses, and the Wilcoxon-Mann-Whitney Odds (WMWodds) test was used to report between-group differences in protein abundance ratios.  Results: 52 samples (26 cases, 26 controls) were analyzed for this study. Elevated protein abundance ratios of Coagulation factor IX (Median (IQR): 1.18 (1.08-1.28) p=0.047) and Mannosyl-oligosaccharide 1,2-alpha-mannosidase (Median (IQR): 1.50 (1.35-1.60) p=0.049) were noted in patients that developed delirium. Elevated protein abundance ratios of angiotensinogen (Median (IQR): 1.19 (1.14-1.23) p=0.038), ceruloplasmin (Median (IQR): 1.02 (0.98-1.08) p=0.038), and Complement C2 (Median (IQR): 1.01 (0.96-1.08) p=0.016) were noted in control patients. Protein abundance ratios for Complement C2 (Spearman rs=0.31, 95%CI [-0.55, -0.02]) and Mannosyl-oligosaccharide 1,2-alpha-mannosidase (rs=0.61, 95%CI [0.29, 0.81]) were associated with the severity of delirium in case patients.   Conclusions: Changes in proteins associated with coagulation, inflammation, and protein handling were identified. These could be evaluated in future studies to develop tools for predicting onset and severity of post-operative delirium. 


2020 ◽  
Vol 3 ◽  
Author(s):  
Emily Freeman ◽  
Yiqiang Song ◽  
Katie Allen ◽  
Siu Hui ◽  
Eneida Mendonca

Background: Social and health inequities place marginalized populations at increased risk of contracting the novel coronavirus 2019 (COVID-19). While COVID-19 literature continues to accumulate, there remains a lack of comprehensive epidemiological data on COVID-19 in children. The study aims to identify demographic trends in disease severity amongst COVID-19 positive pediatric patients.     Methods: We analyzed the medical records of 2217 laboratory-confirmed COVID-19 pediatric patients, ages 0-18, across Indiana. Working with Regenstrief Institute Center of Biomedical Informatics, data was extracted from the databases of Indiana Network for Patient Care, Indiana University Health, and Eskenazi Health from February 28th, 2020 to July 13th, 2020. Factors of interest were age, race, and ethnicity. The study assessed the clinical outcome of disease severity which was defined by one of the following clinical designations: outpatient management exclusively, emergency care without hospital admission, non-pediatric intensive care unit (PICU) hospitalization, PICU hospitalization, and death.     Results: The laboratory confirmed COVID-19 pediatric cohort was composed of 12.2% (N= 270) Black or African American, 49.3% (N=1094) white, and 3.2% (N= 71) American Indian/Alaska Native, Asian/Pacific Islander, and Multiracial combined group. 34.4% of Black or African American patients required emergency (12.2%) or inpatient care (22.2%) while 24.4% white patients required emergency (7.0%) or inpatient care (17.3%). 17.6% of the cohort was 0-5 years old, 24.8% was 6-12 years old, and 57.6% was 13-18 years old. 30.9% of the 0-5 age group required emergency or inpatient care while the percentages of the 6-12 age group and 13-18 age group requiring emergency or inpatient care were 20.6% and 18.9%, respectively.      Conclusion:  While our data is preliminary and requires additional validation, our exploration of racial and age disproportionalities in pediatric coronavirus severity serves to expand on the current COVID-19 literature and understanding of this virus.  


2020 ◽  
Vol 3 ◽  
Author(s):  
Myranda Grismore ◽  
Nicole Fowler

Background/Hypothesis:  The 16 million unpaid caregivers serving individuals with Alzheimer’s disease and related dementias (ADRD) are more likely to participate in medical decision-making than caregivers of older adults with other chronic conditions. Their decisions may reflect the patient’s severity of cognitive impairment and life expectancy. Analysis of the relationship between these two factors is needed to improve the prognostic information provided to caregivers. ADRD severity can be measured using the Dementia Severity Rating Scale (DSRS), a validated, informant-based multiple-choice questionnaire that assesses functional and cognitive abilities. Life expectancy can be estimated using the Schonberg Index (SI), a validated, predictive mortality index. We hypothesize that DSRS and SI scores will be correlated.    Methods:  A retrospective analysis of data from 230 dyads enrolled in the Decisions about Cancer Screening in Alzheimer’s Disease (DECAD) study was performed. The DECAD study is an ongoing randomized controlled trial enrolling dyads of older women with ADRD and their caregivers to test the benefits of a mammography decision aid. In the study, caregivers completed the DSRS and SI questions. DSRS and SI scores were compared using linear regression analysis. Additionally, 20 DECAD interviews were qualitatively evaluated to explore themes of medical decision-making among ADRD caregivers.    Results:  DSRS scores and SI scores were weakly correlated, yielding an R2 value of 0.1. Interviews revealed that caregivers most frequently considered physician advice, comorbidity status, and patient preferences in decision-making. 67% of moderate ADRD caregivers and 36% of mild ADRD caregivers cited cognitive impairment severity as an influential factor.    Conclusions/Implications:  Further analysis controlling for time since diagnosis will better establish the relationship between DSRS and SI scores. The resulting increase in accuracy of ADRD prognostic information will aid physicians and caregivers in medical decision-making. Furthermore, understanding what influences caregiver decisions will allow for the provision of improved guidance from physicians. 


2020 ◽  
Vol 3 ◽  
Author(s):  
Kayla Harpold ◽  
Hong-Ming Zhou ◽  
Radomir Slominski ◽  
Leroy Seymour ◽  
Maria Bell ◽  
...  

Inflammation is an integral aspect of skin wound healing; however, the mechanisms that regulate inflammatory cascades in this context are not well defined. To better understand how skin inflammation impacts wound healing, we developed an ex vivo skin culture system to model key aspects of the inflammatory phase of wound healing. In this model, a defined set of proinflammatory cytokines and chemokines, mirroring those produced in wounds in vivo, are produced when mouse or human skin biopsies are cultured ex vivo.  We refer to this pattern of cytokine and chemokine induction as the skin injury-induced inflammatory response. Previous studies in our laboratory demonstrated this response is initiated by the cytokine, interleukin 1 alpha (IL-1α). To understand the cellular sources and targets of IL-1α during the skin injury-induced inflammatory response, skin biopsies from mouse tail skin were cultured ex vivo for 8 hours followed by processing for single cell RNA sequencing (scRNAseq). Using bioinformatic software, R, and the package, Seurat, analysis of scRNAseq data from this experiment identified 22 distinct cell population clusters. While no populations exhibited significant expression of Il1a transcripts, multiple cell populations expressed Il1r1 transcripts, which encodes the ligand-specific subunit of the IL-1 receptor.  Notably, fibroblast, endothelial cell and stromal cell clusters were characterized by expression of Il1r1 and the skin injury-induced inflammatory response transcripts Il6, Cxcl1 and/or Csf3. Furthermore, Reactome Pathway Analysis suggested the Il-1 signaling axis was activated in these cell populations. This information provides a basis for future studies to understand how IL-1 signaling in fibroblasts, endothelial cells and stromal cells impacts wound healing in vivo, which could in turn lead to novel therapeutic approaches to clinically relevant outcomes.  


2020 ◽  
Vol 3 ◽  
Author(s):  
Alaina Johnston ◽  
Takefumi Komiya

Background and Hypothesis:  Non-Small Cell Lung Cancer (NSCLC) constitutes the largest proportion of lung cancers and is the foremost cause of mortality associated with cancer around the world. Of patients with non-small cell lung cancer, approximately 15% of Caucasians and 30% of Asians have activating mutations in the epidermal growth factor receptor (EGFR) gene. Numerous studies have indicated increased progression free survival after treatment with tyrosine kinase inhibitors (TKI). However, the most efficacious combination of drugs, whether TKIs, chemotherapy, or anti-angiogenesis, is still unknown. This literature review will be constructed to determine whether tyrosine kinase inhibitor targeted therapy in combination with chemotherapy or anti-angiogenesis drugs is more effective in prolonging progression free survival in EGFR-mutated NSCLC as opposed to tyrosine kinase inhibitor targeted therapy alone.    Project Methods:  The methodology of this proposed literature review is an online search of PubMed, Journal of Clinical Oncology, and important scientific conferences. The treatment interventions consist of tyrosine kinase inhibitor targeted therapy in combination with chemotherapy and tyrosine kinase inhibitor targeted therapy alone. The projected outcome is an increase in progression free survival and overall survival. The proposed data analysis consists of constructing a forest plot in order to display the results.    Results:  The results are expected to support the hypothesis, that combination treatment with TKI and chemotherapy will allow patients with an opportunity to prolong their progression-free survival. The forest plot is expected to indicate a progression-free survival hazard ratio that favors combination therapy. P-values will be included to indicate statistically significant results.    Conclusion and Potential Impact:  The importance of finding the answer to this hypothesis is that it will improve treatment outcomes for patients with NSCLC. It will provide patients with a strong alternative to chemotherapy or tyrosine kinase inhibitor therapy alone. Most importantly, it will provide patients with an avenue to increase their progression-free survival. 


2020 ◽  
Vol 3 ◽  
Author(s):  
Kimberly Jones ◽  
Erin Jefferson ◽  
Brian Henriksen

Background/Objective: Type 2 diabetes affects 8.5% of adults over the age of 18 and costs the United States an average of 327 billion dollars per year. Two diets, the ketogenic diet and the vegan diet have both been shown to promote weight loss as well as reduce A1c’s in individuals with type 2 diabetes. Ketogenic diets are best defined as high fat, low carbohydrate diets that induce a state of nutritional ketosis. Vegan diets are centered around the consumption of legumes, fruits, vegetables, and whole grains. All animal-derived products including gelatin are avoided. The primary goal of this study is to determine whether the vegan diet is non-inferior to the ketogenic diet in the reduction of hemoglobin A1c levels in adults with type 2 diabetes.     Methods: A total of 120 participants between the ages of 18 and 70 who have an A1c between 6.5 and 10.0 will randomly be assigned to either the vegan or ketogenic diet groups. Dietary interventions will be implemented for a total of 24 weeks. Hemoglobin A1c levels will be measured at weeks 0, 12, and 24 and values will be compared using the repeated-measures analysis of variance test to determine if there is a significant difference between groups.   Expected results: It is expected that both groups will experience a decrease in their hemoglobin A1c levels, but that a more significant reduction will occur in those following the vegan diet. Weight loss is also an anticipated side effect in both groups.  Conclusion/Potential impact: This study has the potential to provide individuals with a more cost-effective management strategy to medication therapy in type 2 diabetes. Choosing to adopt healthier dietary practices will ultimately lead to better blood glucose control and a lower likelihood of developing diabetic complications.  


2020 ◽  
Vol 3 ◽  
Author(s):  
David Karnani ◽  
Eric White

Background/Hypothesis:  Cardiac implantable electronic devices (CIED) include permanent pacemakers (PPM), implantable cardioverter defibrillators (ICD), and cardiac resynchronization therapy (CRT). Both ICDs and dual chamber PPMs are two-lead systems; whereas, CRT is a three-lead system. Indications for CIEDs include arrythmia, risk of sudden cardiac death and AV block. From 1993 to 2003, over 4 million CIEDs were implanted. With the upward trend in the rate of CIED implantations, the post-operative infection burden has increased concurrently. Device related infections are a serious complication of CIED implants. They are associated with a significant increase in the rate of mortality as well as a significant increase in financial burden. We hypothesize two-lead systems will have significantly lower rate of infection than three-lead devices   Methods:  This study will be a retrospective review of patient charts who are hospitalized in the Parkview Health medical system in Fort Wayne, Indiana over a three-year period. All patients who have received a CIED during that time frame will be included in the study. Patients will be categorized by specific implant type and recorded as developing post-operation infection or not. Demographic and health status data will also be collected and analyzed for correlation with the development of device related infection.   Results:  Our results will compare the device related infection rate for two-lead versus three lead systems, as well as the infection rate for each type of CIED. We also expect to find results which support a correlation between specific patient demographics and patient health factors.    Conclusion and Impact:  The results of this study will serve as a guide for identifying high risk procedures and patients. The objective is to provide providers with guidelines for the use of post-operative prophylaxis in order to reduce the incidence of CIED-related infection.


2020 ◽  
Vol 3 ◽  
Author(s):  
Jaibir Khera ◽  
Shaun Grannis ◽  
Suranga Kasthurirathne

Background and Hypothesis: Healthcare data is increasingly fragmented across multiple points of care due to increased specialization of healthcare services and mobility of patient populations [1]. The Indiana Network for Patient Care (INPC) plays a pivotal role in capturing, standardizing, and integrating comprehensive datasets[2]. Currently, the INPC receives medication data from a variety of sources. However, some of these sources are costly and may be incomplete and/or inaccurate. We aim to characterize the degree to which additional claims data can augment or replace existing INPC medication data. Our hypothesis is that the new claims datasets will provide additional medication information for patients in the INPC.  Methods: Data analysts extracted and formatted a claims data sample for analysis. Individuals from the sample dataset were then mapped to INPC data using global person identifiers. The resulting analysis was split into two phases.   Phase 1: To provide an initial high-level assessment of overlap and complementarity between INPC and new claims data, we computed the number of patients captured in each data source. Patients were classified into five groups as illustrated in Figure 1. To investigate Medicare usage, we also stratified datasets by patient age: less than 65 and 65 and older.   Figure 1: Venn diagram illustrating medication claims data analysis approach. Several subgroups  among the INPC will be compared to existing pharmacy claims and new claims data sources.  Phase 2: Investigation of data quality on a clinical use case. These datasets will be used to investigate the current state of the opioid epidemic in Indiana.   Results: With the completion of phase 1, we expect to characterize the current state of claims data across each of the patient groups, and how they influence data quality within the INPC.  Discussion. The quality and completeness of medication data currently available via the INPC in unclear. Our efforts add clarity to the current status of these datasets, and how they can be augmented for increased research and clinical productivity.    Citations  [1] Stange, K.C., The problem of fragmentation and the need for integrative solutions. The Annals of Family Medicine. 7(2):100-103, 2009.  [2] McDonald, C. J., Overhage, J. M., Barnes, M., Schadow, G., Blevins, L., Dexter, P. R., ... & INPC Management Committee. (2005). The Indiana network for patient care: a working local health information infrastructure. Health affairs, 24(5), 1214-1220. 


2020 ◽  
Vol 3 ◽  
Author(s):  
Taylor Kleyn ◽  
Michael Francis ◽  
Andrew Visco ◽  
Tom Hummer

Background and Hypothesis:   People with schizophrenia often experience impairments with episodic memory (EM). Due in part to a lack of understanding regarding the neural mechanisms of EM, there are no effective treatments. Recent research indicates that the precuneus may be associated with EM impairment. Repetitive transcranial magnetic stimulation (rTMS) is a commonly employed intervention for treatment resistant depression, but its potential for investigating other psychiatric disorders such as schizophrenia is unclear. We hypothesize that, compared to sham stimulation, 1 Hz rTMS will decrease precuneus activity and 20 Hz rTMS will increase precuneus activity during an EM task.    Experimental Design:   Seven patients with early phase psychosis underwent a baseline fMRI scan during an EM recognition task that required participants to accurately identify which images were previously shown (targets) or not shown (foils). Next, participants had three separate rTMS sessions targeting the precuneus, each one week apart, in a randomized order: inhibitory (1 Hz) rTMS, excitatory (20Hz) rTMS, and sham stimulation. Each rTMS session was immediately followed by fMRI during the EM task.    Results:   We currently remain blind to the conditions because the study is ongoing. Participants had relatively lower accuracy during foil trials in one treatment session. During this same session, precuneus activity was relatively stronger to foils than targets, compared to other treatment sessions. These preliminary results suggest that rTMS applied to the precuneus may impact episodic memory and related brain activity in early psychosis    Conclusion and Potential Impact:   Data from this study will help determine whether targeting the precuneus with rTMS impacts functional activation in patients with schizophrenia during EM tasks. Additionally, relationships between EM performance and changes in precuneus activity will be identified. If effective, rTMS may represent a novel treatment for EM deficits in schizophrenia.  


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