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Pain Management in Postoperative Pediatric Craniotomy Patients: A Scoping Review
Get PDFPurpose/Background The pediatric craniotomy procedure is a complex and painful procedure that requires adequate pain management and frequent neurological assessments. Generally, evidence for pediatric pain management is severely lacking in research, and evidence for pediatric craniotomy patients is lacking even further. This scoping review aims to collect, condense, and review the current data in order to fuel future studies to establish more data, protocols, and evidence-based recommendations for analgesia in the pediatric craniotomy patient population.
Methods The studies selected were peer-reviewed, published in a medical or nursing journal, included study ages 0-21 years, or provided evidence on pediatric analgesia. Sources used include randomized controlled trials (RCT), systematic reviews, cohort studies, and qualitative studies. An excel spreadsheet and tables comparing the following data were created: age, gender, diagnosis, analgesia intra/post-operatively, pain scores for baseline and breakthrough pain, and the need for rescue pain medication. All data was reviewed and synthesized.
Results The results were variable. The studies provided no uniform recommendation for a specific protocol for pediatric craniotomy pain management. Many of the studies suggested the combination of non-opioid (acetaminophen) and opioid agents in order to decrease the use of opioids and provide better overall pain relief. NSAID use cannot be definitively recommended because safety standards have not yet been established. Due to their risk of respiratory and central nervous system depression opioids remain a major cause of adverse events post-craniotomy.
Implications for Nursing Practice Evidence supporting standardized analgesia is lacking for pediatric craniotomy patient. While studies continue to be conducted and published, medicine is behind in evidence-based recommendations for postoperative pediatric analgesia. Current available data supports concurrent use of opioid and non-opioid in pediatric post-operative pain management, and there is a strong foundation to support further research for a regimen that adequately manages pain and preserves neurological assessments
Cellular Dynamics and Disease Outcome of Type 3 Streptococcus pneumoniae Clinical Isolates Differ Between Strains
Get PDFStreptococcus pneumoniae is a bacterial pathogen that continues to be a major cause of disease around the world. It is not only the number one cause of bacterial pneumonia but also the cause of about 15% of the deaths of children under 5 around the world. There is a lot of research done on this organism, but with around 100 known serotypes and each one producing a unique capsule, there is still much more to be studied. The Etiology of Pneumonia in the Community (EPIC) study conducted by the CDC observed the burden of hospitalizations caused by pneumonia while determining the organism responsible. One of the most common organisms isolated from both children and adult patients was S. pneumoniae. To look further into these clinical isolates, we chose three different type 3 pneumococcal isolates and observed the immune cellular dynamics as well as capsule production, and saw that even with the same serotype immune responses can differ
Developing Targeted Therapies for T-cell Acute Lymphoblastic Leukemia
Get PDFIntroduction Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and risk-adapted chemotherapies have dramatically improved the outcomes of this disease. Compared to B-cell ALL, T-cell ALL (T-ALL) is more aggressive and has worse outcomes from chemotherapy. There is a great unmet need to develop biomarkers and novel targeted therapies for this type of cancer. Working together with internal and external collaborators, we performed a large-scale pharmacotyping assay in over 300 primary ALL samples. By combining pharmacotypying and genomic profiling of these samples, we identified a substantial T-ALL population that showed strong response to dasatinib, a known ABL1 inhibitor. Importantly, none of the T-ALL responders harbored BCR-ABL1 or fusions predicted to respond to ABL1 inhibitors. We identified differences in somatic genetic alterations between dasatinib responders and non-responders. For example, as the prevalence of NOTCH1 mutations and TCF7-SPI1 fusion is higher in dasatinib responders than non-responders, both of which are known to be associated with T-cell differentiation. Because clonal expansion often occurs during leukemogenesis, resulting in heterogeneity in the leukemia cell population and affecting dasatinib response. Therefore, we tested these hypotheses: 1) a subset of T-ALL cases responds to dasatinib in an ABL1-independent manner; 2) dasatinib sensitivity in T-ALL is associated with T-cell differentiation stage; 3) intra-tumoral heterogeneity in T-ALL affects dasatinib response; 4) dasatinib at the dosages used in pre-clinical models can reach desired drug exposure and effect in patients predicted by pharmacokinetic & pharmacodynamic (PK & PD) modeling; and 5) an LCK degradation approach can achieve better therapeutic efficacy than dasatinib in T-ALL. Methods We applied a network-based Bayesian Inference of Drivers (NetBID) algorithm using RNA-seq data to infer activity of each gene and identified drivers for dasatinib sensitivity. Genome-wide CRISPR/Cas9 screening, phosphorylation flow cytometry, and phosphorylation proteomics assays were employed to confirm the dependency and inhibitory effect of dasatinib on its therapeutic targets (dasatinib sensitivity drivers). In vitro differentiation assay using mouse hematopoietic stem cells validated the effect of T cell differentiation stages on dasatinib response. Single cell RNA sequencing was performed to determine the intra-tumor heterogeneity in T ALL. We performed pharmacokinetic and pharmacodynamic (PK & PD) studies using a patient-derived xenograft (PDX) model to predict the achievable drug exposure and lymphocyte-specific protein tyrosine kinase (LCK) inhibition in human. Mouse dasatinib exposure was measured by liquid chromatography–mass spectrometry (LC-MS), and LCK inhibition was quantified by western blotting, which was further used to predict the exposure-response relationship in patients. To develop novel T-ALL targeting approaches, we designed and synthesized a set of proteolysis targeting chimeras (PROTACs) to degrade LCK in T-ALL. Western blotting was used to measure the extent of degradation of LCK and other target proteins by PROTACs. Cell viability assays were performed in leukemia cell lines and PDX cells to determine cytotoxicity of PROTACs. We also performed kinome scan assay to determine the targeting spectrum of the lead PROTAC. Lastly, T-ALL PDX mouse models were used for PK & PD profiling and evaluation of in vivo drug efficacy
Role of Membrane Contact Sites in the Neuropathogenesis of GM1-Gangliosidosis
Get PDFBackground. GM1-ganglisidosis is a rare neurodegenerative lysosomal storage disease caused by the deficiency of the lysosomal enzyme β-GAL, resulting in the accumulation of its target substrate GM1. GM1, a glycosphingolipid found primarily in the PM of neurons, is known to modulate Ca2+ flux through its interactions with Ca2+ channels and Ca2+ binding proteins. GM1 is also known to promote neuritogenesis through the activation of phosphorylated TRKs, receptors for neurotrophic factors. Under disease conditions, GM1 accumulates not only in the PM but also in the intracellular membranes of organelles, altering their membrane composition and functions. Organelles are dynamic, constantly interacting with each other and the PM through specialized membrane microdomains, known as membrane contact sites (MCS). MCS have distinct protein and lipid composition and facilitate the transfer of lipids, proteins, metabolites and ions, such as Ca2+, between the organelles via non-vesicular transport. The two most studied MCS are those formed between the ER and mitochondria, known as mitochondrial-associated ER microdomains, or MAM, and those between the ER and PM, known as ER-PM junctions. These MCS are important for controlling Ca2+ homeostasis, through Ca2+ transporters and channels, and have been extensively studied for their role in phospholipid and cholesterol transport. These two lipids, along with glycosphingolipids, are the major lipid constituents of membranes; however, very little is known about the role of glycosphingolipids in MCS dynamics. Using a mouse model deficient for the lysosomal enzyme β-Gal, we have been able to study the role of GM1 in MCS formation and functions. GM1 accumulation was shown to increase the number of MAM tethering events. We have also shown that GM1 accumulates at the MAM triggering a phosphorylated IP3R-mediated ER Ca2+ depletion, resulting in the activation of the unfolded protein response. This efflux of Ca2+ is then buffered by the mitochondria, through the MAM, resulting in mitochondrial Ca2+ overload, activation of the caspase cascade and neuronal apoptosis. Purpose. Given the similar functions between the MAM and ER-PM junctions in Ca2+ dynamics and lipid transport, we sought to determine if GM1 accumulation at the respective membranes of β-Gal KO neurons would facilitate the formation of these MCS and alter the functions of the ER-PM junctions with respect to changes in Ca2+ regulated processes. We also aimed to test the efficacy of an ERT approach for ameliorating some of the neurodegenerative aspects of the GM1-gangliosidosis mice, using an RTB-conjugated recombinant β-Gal that has the ability to cross the blood brain barrier. Results. In the first set of results, we used TEM to demonstrate that β-Gal KO neurons have a significantly higher number of ER-PM junctions than WT neurons. This GM1-mediated phenomenon was also apparent in β-Gal KO primary neurons as well as GM1-
Prevention of Diabetes-Related Hospital Readmission Following Initial Diagnosis of Diabetes in Patients Over the Age of Fifty: A Scoping Review
Get PDFPurpose/Background: By reviewing multiple studies related to the treatment of patients with new diagnoses of diabetes, this scoping review will endeavor to determine which interventions, when implemented for patients over 50 years old which are newly diagnosed with type 2 diabetes, can decrease the likelihood of hospital readmission related to diabetes within 90 days when compared with those patients who did not receive or participate in follow-up.
Methods: For resources to be eligible to review they had to be from 2015 or after. Studies selected included patients over the age of 50 newly diagnosed with type 2 diabetes subject to interventions specifically designed to decrease readmission rates. Sources for this review were obtained through University of Tennessee Health Science Center Library online resources (EBSCO), Google scholar, and the National Institute of Health (PubMed). Demographic and pathophysiological data points considered included age, race, co-morbidities, socioeconomic status, and whether patients were covered by a health insurance plan. Dependent variables included number of readmissions, weight, hemoglobin A1C levels. Independent variables accounted for in the selection of studies were predischarge teaching, follow-up by telemedicine, outpatient or inpatient visit, med-to-bed by inpatient pharmacy, and inpatient dietary teaching and/or diabetes education.
Results: Three articles report telemedicine follow-up increasing the reduction of readmission. Seven articles report multidisciplinary follow-up increasing the reduction of readmission. Nine articles report discharge planning increasing the reduction of readmissions. Eleven articles report lifestyle modification increasing the reduction of readmissions. Seven articles report comorbidity improvement increasing the reduction of readmission.
Implications for Nursing Practice: Reducing diabetes readmissions will reduce healthcare costs, while improving patient outcomes. Improving the discharge process to decrease hospital readmission after the diagnosis of type 2 diabetes should be at the forefront of change for nurses and providers
Dexmedetomidine vs. Propofol in Postoperative Delirium Prevention
Get PDFPurpose/Background Postoperative delirium (POD) is an acute neurological condition affecting large numbers of surgical patients in various practice settings. Patients suffering from this condition face postoperative complications, increased lengths of stay, and tremendous financial burden. Understanding the contributing factors for POD, and how adjustments in intraoperative agents can prevent or reduce the incidence, is a crucial aspect of anesthesia practice. This scoping review will examine associations between POD and the intraoperative use of propofol versus dexmedetomidine with general anesthesia.
Methods Studies in this review were limited to peer-reviewed literature, published in medical and nursing journals within the last five years. All studies were in English and consisted of randomized controlled trials, systemic reviews, and meta-analyses. The studies compared a cohort of participants who received dexmedetomidine versus the mainstay agent, propofol, in the development of POD. Limitations were placed to assure that evidence was current, high quality, and relevant to the objectives.
Results Nine of the ten studies used in this research favored dexmedetomidine use over propofol in the reduction of POD. The one study excluded had equal occurrences of POD in both propofol and dexmedetomidine groups. The use of different levels of evidence in this research provides significant results for advocating for the use of dexmedetomidine over propofol in the reduction of POD.
Implications for Nursing Practice Dexmedetomidine has multiple promising implications for enhancing nursing practice. Unlike propofol, dexmedetomidine possesses analgesic properties, promoting postoperative recovery. Other advantages include reliable neurologic assessments, decreased POD, earlier extubation, decreased opioid administration, and earlier ambulation. These combined factors result in decreased overall length-of-stay and enhanced cost-effectiveness. If continued research supports these findings, future recommendation changes may suggest incorporating dexmedetomidine as the new standard of care for anesthetic protocols
Monitoring Adherence to HCV Screening Among the Baby Boomer Population
Get PDFPurpose/Background Chronic hepatitis C is currently the most common cause of liver disease in the United States and is associated with various complications that increase mortality and morbidity, yet many people go unidentified and thus untreated. The CDC created guidelines in 2012 for hepatitis C screening and testing among the baby boomer population due to their high rates of HCV infection and HCV-related mortality. Our project aimed to assess the adherence of hepatitis C screening, based on these CDC guidelines, of individuals within the baby boomer population (1945-1965) in the primary care setting through retrospective chart review.
Methods A 6-month retrospective chart review was performed identifying any patients presenting to the primary care clinic who were born between the years 1945-1965. Charts were reviewed for whether or not hepatitis C screening tests were ordered on these patients.
Results Thirty-one patients were identified based on our criteria and the average age of the individuals was 65.87 years old. Of these thirty-one patients, twenty-three (74%) were not screened for HCV and eight (26%) were screened for HCV.
Implications for Nursing Practice The results provided in this retrospective chart review indicate that a substantial number of patients in the baby boomer population were not screened for HCV. Through adherence to recommended guidelines, an initial HCV screen for every patient can significantly improve the identification and treatment of Hepatitis C in infected individuals
Effects of Sensory Intervention on Neurological Development in the Neonatal Intensive Care Unit: A Critically Appraised Topic
Get PDFThe final portfolio contains four research articles from both national and international journals. Study designs include a randomized clinical trial, a randomized control trial, a systematic review and meta-analysis, and an integrative review. All studies relate directly to components of the evidence-based practice question and will be used to recommend sensory intervention for neurological development of premature infants in the neonatal intensive care unit (NICU). One of the articles describes statistically significant effects. One of the articles describes both statistically significant and non-statistically significant effects of sensory intervention on neurological development of premature infants in the NICU. The other two articles describe non-statistically significant effects but included positive trends
On-treatment changes in pediatric parameningeal rhabdomyosarcoma treated with upfront proton therapy
Get PDFThe project is focused on the effects of longitudinal changes in patient and tumor anatomy on the delivered treatment plan during proton radiotherapy for the treatment of pediatric Para meningeal rhabdomyosarcoma. The study will investigate the effects of change on dose delivered to organs-at-risk near the tumor. This effort will extend the analysis of changes to the organs-at-risk to all the cases in the study and add an additional case meeting the study criteria
Using Digital Storytelling to Assess Patient Experience with Management of Diabetes in Everyday Life (MODEL) Study Intervention
Get PDFAfrican Americans are disproportionately affected by obesity-associated diabetes compared to their White counterparts. While social determinants of health may contribute to their poor health outcomes, studies have shown that pragmatic primary care-based interventions can be effective in improving the management of obesity-associated diabetes. The Management of Diabetes in Everyday Life (MODEL) is a pragmatic randomized comparative effectiveness trial of three approaches (health coaching, text-messaging, and enhanced usual care) to supporting medically underserved African American patients with uncontrolled diabetes in improving their self-care decisions. The purpose of this study is to assess the effect of the MODEL program participation on the lived experience and quality of life of MODEL program participants. This study seeks to understand the patients’ stories and how their lived experience, quality of life, and health has changed because of their participation in the MODEL program