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Impact of Spontaneous Breathing Trials on Reducing Ventilator-Associated Pneumonia in Adult Intubated Patients: A Scoping Review
Get PDFPurpose/Background For ventilated patients in the intensive care unit, ventilator-associated pneumonia (VAP) is a major source of morbidity. It is difficult to diagnose due to many of the diagnostic criteria being subjective, its clinical signs that are broad, and its association with various respiratory disorders. Hospitals have developed varying ventilator bundles in expectation to prevent the incidence of Ventilator-associate pneumonia. We performed scoping review to determine the impact of spontaneous breathing trials (SBT) on reducing VAP.
Methods From August to November of 2021, using the MEDLINE, ScienceDirect, and Scopus databases and MeSH search terms, we identified over 20,000 articles containing our keywords. Of those, thirty met our inclusion criteria, and ten were most relevant. The publication dates of the articles reviewed ranged from 2017-to 2021, were full-text, and were from peer-reviewed sources.
Results The publications reviewed utilized retrospective data analysis, a survey approach, or a randomized study design. Due to variations in terminology (i.e.: ventilator-associated pneumonia, ventilator-associated events) and clinical criteria, we cannot say spontaneous breathing trials alone reduce the patient\u27s diagnosis of VAP by a statistically significant amount.
Implications for Nursing Practice More research is needed to investigate the effects of spontaneous breathing trials alone on ventilator-associated pneumonia. So, providers should focus attention on addressing potential risk factors. The articles reviewed suggest ventilator bundles including SBT helped reduce days mechanically ventilated, therefore reducing risk. Subsequent plans are required, as spontaneous breathing trials are not appropriate for all patient populations. One article suggests subglottic secretion drainage systems and ETT cuff pressure control devices as devices to diminish risk
The Effect of Certified Diabetic Education on Hemoglobin A1C Levels in Patients with Type 2 Diabetes Mellitus
Get PDFPurpose/Background Type 2 Diabetes Mellitus (T2DM) is a nationwide growing epidemic which contributes to hundreds of billions of dollars a year in healthcare costs and can lead to significant health complications, such as disability or death. To prevent these complications, patients must maintain adequate blood glucose control by adhering to their treatment plan and adopting healthy lifestyle behaviors, including dietary modifications and exercise. Through Certified Diabetes Educators (CDE) and PharmDs, patients can be educated on proper self-management techniques. Current evidence shows that CDEs helped improve Hemoglobin A1C (HbA1c) levels.
Methods In this retrospective chart review, 29 charts of patients aged 18-65 diagnosed with T2DM who have received at least one diabetic education session from a PharmD/CDE were reviewed.
Results Between January 1, 2019 and August 31, 2021, 29 patients met eligibility criteria. A two-tailed paired samples t-test revealed a decrease in mean HbA1c pre- and post-intervention from 9.50 (SD = 2.3) to 8.64 (SD = 2.34). However, results were not statistically significant based on an alpha value of 0.05, t(28) =1.89, p = .069.
Implications for Nursing Practice While the data does not show a significant p-value, there was a detectable decrease in HbA1c in patients who were seen by a CDE. We believe this insignificant p-value was due to the low sample size and that a greater sample size would likely show more meaningful data. At this time, data demonstrates that the implementation of diabetic education, whether by a PharmD or CDE, is beneficial in the care of patients with T2DM
Targeting Protein Degradation to Uncover Novel Oncoprotein Drivers of Acute Leukemia
Get PDFAcute Lymphoblastic Leukemia (ALL), the most common childhood cancer and the second most common acute leukemia in adults, arises from clonal expansion of undifferentiated lymphoid precursor cells in bone marrow. Despite the extensive knowledge on its cytogenetic and molecular biology, ALL treatment remains highly challenging especially after relapse. Conventional chemotherapy has shown significant improvement in overall survival rates of pediatric patients up to 90%, however, treatment failure due to ALL relapse occurs in 15-20% of the cases. On the other hand, adults and elderly patients with ALL are considered difficult to treat populations with the 5-year overall survival of 30–40%. Small molecule induced protein degradation is a novel strategy that can be applied to currently undruggable targets and oncoproteins. In this paradigm, small molecule degraders (either Proteolysis Targeting Chimera (PROTAC) or Molecular Glue (MG)) redirect the cell’s endogenous ubiquitin proteasome system and induce ubiquitination of the target protein or non-native substrate of an E3 ligase (neosubstrate) and its subsequent proteasomal degradation. Recently, the Cereblon (CRBN) E3 ligase modulator, CC90009 was reported to show potent anti-tumor activity in acute myeloid leukemia (AML), leading to the identification of GSPT1 (G1 to S phase transition factor) as a CRBN neosubstrate. These findings suggest the potential of MGs to target unanticipated vulnerabilities in different malignancies. Here, using a structurally diverse and unique set of MGs (Molecular Glue Library (MGL)) with confirmed CRBN binding affinity, we sought to identify novel CRBN modulators through phenotypic and proteomic methods. Our screening of the MGL in a panel of representative acute leukemia cell lines, including the CRLF2 rearranged ALL cell line MHH-CALL-4 identified several active MGs with EC50 \u3c5 µM. A lenalidomide competition assay and MHH-CALL-4 CRBN knock-down cells confirmed the CRBN dependency of these MGs. Among these compounds, SJ6986, a thalidomide-driven sulfonamide showed potent cytotoxicity in over 10 ALL cell lines tested in vitro. TMT-MS proteomic analyses identified GSPT1/2 as the primary targets for this compound with high selectivity. We next tested SJ6986 activity in a panel of patient derived ALL xenografts (PDX) harboring rearrangement of IGH-CRLF2, EPOR, ATF7IP-JAK2 ex vivo. All the tested tumors were highly sensitive to SJ6986 with IC50 at nanomolar range. PK analyses in mice indicated rapid absorption and over 80% oral bioavailability for SJ6986. PD studies in an IGH CRLF2 PDX showed dose-dependent degradation of GSPT1 within 48 hours of treatment. Finally, we examined the anti-tumor activity of SJ6986 in 6 different PDX representative of high-risk subtypes of ALL including near haploid, low hypodiploid, CRLF2-rearranged and EPOR-rearranged, in vivo for 28 days. SJ6986 was able to dramatically decrease the tumor burden at 1 mg/kg dose in most of the tumor models. Collectively, these results affirm that SJ6986 is a novel CRBN modulator and a potential therapeutic agent by targeting GSPT1 protein with high selectivity and potency for the treatment of ALL
Effect of Early Mobilization on Length of Hospital Stay in COVID-19 Patients: A Critically Appraised Topic
Get PDFFor this project, we created a critically appraised topic to study the effects of early mobilization on length of hospital stay in COVID-19 patients in the ICU
Updates in the Pharmacologic Prophylaxis and Treatment of Invasive Candidiasis in the Pediatric and Neonatal Intensive Care Units
Get PDFPurpose of review The goal of this review was to provide an update on the prevention and treatment options for invasive candidiasis (IC) in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU).
Recent findings Studies have further validated the use of fluconazole for IC prophylaxis among high-risk patients in the NICU. It remains unclear if prophylaxis leads to resistance development and the ideal dosage regimen is still not clear. Recent studies have been published comparing caspofungin and micafungin to amphotericin B and illustrated similar efficacy outcomes in the NICU. Micafungin now has approval from the United States Food and Drug Administration (FDA) for use in infants \u3c 4 months of age. Prophylactic strategies in the PICU could include zinc and vitamin D. Anidulafungin has recent non-comparative data supporting use in pediatric patients older than 1 month of age and also has a recent FDA approval for use in children 1 month of age and older.
Summary Fluconazole prophylaxis remains a reasonable strategy in select NICU patients, although further analyses of resistance and the optimal dosage regimen are needed. Echinocandins are potential therapeutic options for non-meningitis or urinary tract infections in both the neonatal and pediatric population
Host-Pathogen Interactions During Leptospirosis in Male C3H/HeJ Mice
Get PDFLeptospirosis is a zoonotic disease transmitted from reservoir hosts like rodents to other animals and humans, who are incidental hosts. This infection is prevalent in the areas of Southeast Asia, Africa and South America. Inactivated Leptospira serovars vaccines are available in endemic areas but they have certain limitations such as serovar specificity and short-term protection. Antibiotics are effective treatment strategies useful at least during early stages of infection. Early diagnosis of Leptospirosis is difficult due to lack of accessible laboratory and point of care tests and due to clinical similarities with other diseases. Thus, it is important to understand host-Leptospira interactions which comprise host immunity, bacterial virulence, and pathogenesis. Transmission of Leptospira can occur directly or indirectly through environmental sources such as contaminated urine. Outbreaks have been reported from occupational exposure, natural disasters, and recreational activities. Immune responses during early or acute Leptospirosis remains unexplored. The host immunity plays an important role in combating Leptospira spp by involving different immunomodulators that activate specific immune cells. In our study, we investigated the early immune responses after pathogenic and saprophytic Leptospira infection. We observed an elevated chemo-cytokine response with pathogenic L. interrogans infection whereas only a few chemokines were upregulated during saprophytic L. biflexa infection. Moreover, pathogenic L. interrogans infection led to splenomegaly due to recruitment of major myeloid cells to the spleen. The innate immune response consisting of macrophages, neutrophils, NK cells effectively eradicated saprophytic L. biflexa, which did not disseminate in blood, whereas pathogenic Leptospira engaged the involvement of both innate and adaptive immune responses as the former is not sufficient to eradicate them. Consequently, pathogenic Leptospira further disseminates to different organs and promote to disease progression. Our results suggest that infection with pathogenic and saprophytic Leptospira is characterized by a differential immune response. The elevated immune response after L. biflexa exposure during early infection determined in the first study led us to posit that exposure to saprophytic Leptospira may act as an immune booster and could provide protection during subsequent pathogenic Leptospira infection. Our aim was to determine if pathogenic L. interrogans infection led to significant disease after single and double exposure of mice to saprophytic L. biflexa. We found that 75% of mice survived L. interrogans infection after single exposure to L. biflexa, while no deaths were observed in infected mice after double exposure to L. biflexa. An increase in IgG subsets suggested an antibody mediated response specific against L. interrogans. Immunophenotyping in spleen after double exposure to L. biflexa in infected mice showed an elevation in B cells, helper T cells with an increase in early effector and effector response with reduction in cytotoxic T cells. Thus, prior saprophytic L. biflexa exposure protected mice from infection with pathogenic L. interrogans serovar Copenhageni. Previous reports have suggested the possibility of venereal transmission of Leptospira in cattle, sheep, horse, and boars. Although, these studies have detected the presence of spirochetes and their viability in the testes and vaginal fluid of these animals such studies have not been performed in mice. Analysis of Leptospira dissemination and colonization of sex organs in rodents is of significant value as it queries the possibility of mammal-to-mammal venereal transmission. The aim of our study was to evaluate the presence and viability of Leptospira interrogans in testes of mice using models of infection that we previously developed. The aim of our study was to evaluate the presence and viability of Leptospira interrogans in testes of mice using models of infection that we previously developed. This was confirmed by qPCR for the Copenhageni serovar after lethal infection of C3H/HeJ mice. In this model, no histopathological changes were noticed in testis. We further studied persistence of serovar Copenhageni in C3H/HeJ testes after lethal and sublethal infection, with different doses of leptospires. No viable leptospires were recovered from testes of lethally infected mice. However, we found live culturable Leptospira in testes of sublethally infected mice at the acute phase but not at 15 days post infection, which corresponds to the chronic phase of renal colonization. The data suggest that colonization of testes with live and potentially infectious leptospires is transient and limited to the spirochetemic phase of infection. Further studies are necessary to evaluate if presence of Leptospira in testes of mice leads to excretion in semen and to venereal transmission to female mice
Sepsis: Do the Clinical Criteria Support the Medical Coding?
Get PDFBackground: Sepsis is a condition that can be very costly and very deadly. Diagnosing sepsis can be challenging as there is not one specific test that will identify whether a patient has sepsis and there are varying opinions as to the true definition of sepsis. The definition of sepsis used for this research is a combination of System Inflammatory Response Syndrome (SIRS) with an identified infection. Medical Coders must review the documentation provided in a medical record to accurately assign an ICD-10-CM code. Administrative data is then used to provide statistical information for research purposes. When coded data is not accurate, this leads to errors in administrative data and inaccuracies in research. Objectives: The main goal of this study was to identify the accuracy of medical coding for sepsis patients. There were six research questions that guided the research. These included 1) Are cases coded as sepsis that are not clinically supported as sepsis; 2) Are infection cases not coded as sepsis clinically supported as sepsis; 3) Are there any variances for certain physicians; 4) Are there any variances for certain physician specialties; 5) Are there any variances for certain payers; 6) Are there any variances for certain medical coders? Methods: We used a convenience sampling of patient records from 4th quarter 2019 from Erlanger Health Systems that were coded as sepsis and a sampling that were coded as an infection without sepsis. Research Design and Study Procedures: Following Institutional Review Board (IRB) approval from both Erlanger Health Systems and the University of Tennessee Health Science Center (UTHSC), a chart review was conducted. Clinical indicators identified in the created data abstraction tool were abstracted from the patient records. Results: Data analysis concluded that the accuracy rate of medical coding for the sepsis patient records based on the clinical documentation was 98.5%. Physician specialty and payer type had no impact on the accuracy of medical coding on these records. Data analysis concluded the accuracy rate of medical coding for the infection patient records based on clinical documentation was 59%. Logistical regression also identified there were no variances in the coding for the infection patients based on the payer type, medical coder years of inpatient coding experience and the medical coders education level. Analysis determined there was a variance in coding accuracy of the infection patients group based on physician specialty
Associations Between Postpartum Depression and Child Overweight and Obesity: Mediating Effect of Maternal Feeding Behaviors and Beliefs
Get PDFPurpose. Postpartum depression (PPD) is a mental condition that significantly affects 10% to 25% of women within the first year after the birth of their child. The mother-infant relationship is key to child growth. Previous studies have shown that PPD has a detrimental effect on children’s physical and psychological well-being as it affects the child through the mother’s parenting behavior. Depressed mothers show a lack of engagement with their children, which could extend to feeding practices influencing weight gain. The prevalence and severity of childhood overweight and obesity is a global public health problem. An increase in weight gain in infancy can be the initiation of childhood and adult overweight and obesity. We investigated the association between postpartum depression and child overweight and obesity, evaluating maternal feeding practices and beliefs as mediating factors in this relationship. Methods. We performed a secondary analysis on data from 1,425 mother/child dyads from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study that enrolled healthy pregnant women in Shelby County, Tennessee, from 2006 through 2011. We performed logistic regression analysis to investigate the relationship between PPD and child BMI trajectories from birth to 4-6 years, and child overweight and obesity at years 1, 2, 3, 4 – 6; multiple linear regression to investigate the relationship between PPD measured at 4 weeks and maternal feeding behaviors and beliefs as measured by the Infant Feeding Questionnaire (IFQ); and causal mediation analysis to investigate the association between PPD, maternal feeding behaviors and beliefs, and child overweight and obesity
Olfactory Processing in the Piriform Cortex of Awake, Freely Moving Mice
Get PDFThe piriform cortex (PC) has long been established as the primary cortical recipient of olfactory information in the mammalian brain. In rodents, information extracted from recordings of PC neurons can accurately decode the identity of odors, leading to delineation of PC as the primary cortical region involved in the formation of odor perception. Unfortunately, due to technical limitations, many of the prior studies establishing these coding principles were performed without the ability to track the responses of the same cells over time. Additionally, recordings have often relied on head-fixation to minimize diffusion of odor stimuli, limiting movement range and natural behavior of subjects in the process. The primary goal of the work presented in this dissertation was to expand on these prior studies by implementing tools to record from or manipulate conserved PC populations during naturalistic odor experience and odor-driven behavior. We found that, despite an immense volume of background PC activity in freely moving animals, odor responses can be isolated from recordings and contain sufficient information to decode odor identity within a session. Across days, however, the tuning of individual cells was often inconsistent, leading to decreases in classification accuracy. Importantly, attention to the odor was correlated with greater response consistency across days, indicating a role for behavioral state of the animal in modulating odor coding. Our results support recent evidence of representational drift in PC, but also indicate the possibility that animal behavior can influence response profiles. In a separate experiment, manipulation of olfactory bulb (OB) feedback from PC was unable to disrupt odor discrimination but did impair acquisition of a fear memory. This supports prior work from other labs indicating a role for PC in olfactory learning, expanding its role in olfactory processing. In total, this work highlights the need for more studies to clarify the coding strategies implemented by PC in olfactory processing
Mitophagy-Mediated Regulation of ROS Homeostasis During HSC Activation Contributes to Cell Fate
Get PDFThe ability of hematopoietic stem cells to self-renew and differentiate is required for the maintenance of all blood lineages under basal physiologic conditions and in response to inflammatory stress. The degradative capacity of the autophagy-lysosomal system is a determinant of hematopoietic stem cell (HSC) activation status with low autophagy predicting activation of HSCs, and autophagy deficiency causing the spontaneous loss of quiescence and HSC exhaustion. Although an increase in mitochondrial activity has been suggested as the cause of HSC depletion in autophagy-defective models, the contribution of mitophagy to HSC function remains to be elucidated. Here, we capitalized on the observation that HSCs lacking the mammalian Atg1 homologues, ULK1 and ULK2, have a defect in mitophagy but no significant impairment in basal flux through the autophagy pathways to explore the role of mitophagy in HSCs. Despite the comparable increase in mitochondrial content in HSCs lacking Ulk1/2 or Atg7 expression, Ulk1/2-deficiency failed to recapitulate the exhaustion of HSCs and associated multilineage cytopenia caused by the autophagy defect in Atg7-deficient HSCs that show high levels of reactive oxygen species (ROS) and a higher proportion of cycling cells at steady state. Mitophagy-defective HSCs aberrantly accrued ROS only upon HSC activation, sensitizing them to apoptosis, cell cycle delay, and/or differentiation, ultimately resulting in failure of the HSC population to expand appropriately in response to a variety of different inflammatory stimuli. Thus, a defect in mitophagy alone is not sufficient to activate HSCs, but rather disrupts ROS homeostasis upon activation of HSCs, thereby influencing cell fate. Our results highlight distinct contributions of basal autophagy and mitophagy in ROS homeostasis and HSC function