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Interventions to Improve Adherence to Recommended Diabetic Retinopathy Screening in Adult Patients with Diabetes Mellitus: A Scoping Review
Get PDFPurpose/Background Diabetic retinopathy (DR) is the leading cause of blindness in adults. Current guidelines recommend that all patients with type 2 diabetes mellitus (T2DM) have a DR screening (DRS) upon diagnosis of T2DM and then annually, but the adherence rate is only approximately 60%. This scoping review aims to evaluate the effectiveness of primary care providers (PCPs) employing strategies to increase compliance with annual DRS among adult patients with T2DM.
Methods Between September 2021 and January 2022, a literature review was performed to collect studies evaluating interventions to increase adherence to DRS. Individual searches of PubMed, SCOPUS, and CINAHL were completed using MeSh with the following keywords: diabetic retinopathies, primary healthcare, diabetic retinopathy screening, and others. 15 articles were potentially appropriate, then a rapid critical appraisal and in-depth discussion of these articles yielded a final selection of 7 articles. The goal was to demonstrate that interventions implemented by PCPs can increase adherence to DRS.
Results The articles included consisted of 4 randomized controlled trials, 2 clinical trials, and 1 systematic review. Per the articles, the most effective methods to increase the rate of DRS are behavior change techniques, improving general T2DM care, providing evidence-based informational leaflets about DR to patients, incorporating DRS into primary care appointments, and adding a point-of-care reminder to the electronic medical record. Interventions that did not improve adherence were financial incentives and printed reminders to the PCPs.
Implications for Nursing Practice The results of this scoping review highlight the difficulty of increasing the rate at which PCPs remind patients to screen for DR and increasing attendance of patients to DRS. Promising results indicate that interventions can be implemented to encourage improvement. PCPs can have a significant positive impact on the rate of patients developing DR, and this finding suggests that more research on the topic is valuable
Long-Acting Antipsychotic Injectables vs. Oral Antipsychotics: Comparing Compliance, Relapse, and Re-Hospitalization Rates
Get PDFPurpose/Background Psychosis is a psychiatric disorder characterized by hallucinations and delusions. These symptoms not only negatively impact a patient’s quality of life but can also make treatment compliance difficult. This lack of treatment compliance ultimately leads to higher relapse and re-hospitalization rates among this population. Thus, it is imperative that effective treatments are developed, utilized, and made readily available for patients. Antipsychotics are medications that block dopamine D2 receptors. These medications are used for psychosis to help to improve patient outcomes. Currently, two routes of antipsychotic administration are available, oral antipsychotics or long-acting antipsychotic injections (LAIs). Oral antipsychotic administration requires daily dosing to achieve optimal plasma concentrations, whereas LAIs may be given every 2-12 weeks (NAMI, 2016). This scoping review aims to review the literature and compare the compliance, relapse, and re-hospitalization rates of patients prescribed LAIs versus patients prescribed oral antipsychotics. The purpose of this scoping review is to determine if LAIs result in better compliance and lower relapse and re-hospitalization when compared to oral antipsychotics. This knowledge can help providers make an individualized, evidence-based decision when developing a treatment plan for patients who have psychosis.
Methods The selected studies had to meet the following criteria: be written in English, all its participants were at least eighteen years old and gave their consent in writing, they had diagnoses of schizophrenia, delusional disorder, bipolar disorder, or schizoaffective disorder, and that the studies focused on long-acting antipsychotic injectables and oral antipsychotics. In this study, an extensive literature review of peer-reviewed studies on oral antipsychotics versus long-acting injectables was performed from PubMed, JAMA, Cochrane library, and CINHAL databases, these sites were also used to obtain information on LAIs and oral antipsychotics within psychosis and psychosis-related disorders such as schizophrenia, schizoaffective disorder, delusional disorder, and bipolar disorder with psychotic features. In addition, other reputable websites, such as the National Alliance on Mental Health were utilized for statistics information. The studies taken as evidence had a recent publication date, high quality, and reliability. Data charting included essential information regarding the sources of data, such as participant demographics, diagnosis, medication type, and other variables such as discharge date, compliance rate, relapse rate, re-hospitalization rate, and length of re-hospitalization stay. All studies were grouped by diagnosis and medication type. Further compliance, relapse, and re-hospitalization rates were summarized, and the synthesis of results provided evidence to answer the study questions and to identify patterns.
Results Ten research articles were determined to meet the criteria for this scoping review. No significant differences were determined between long-acting and oral antipsychotic compliance, relapse, and re-hospitalization rates. Behavioral therapy intervention and minimal side effect profiles decrease the relapse and compliance rates (Sajatovic et al., 2017; Kashimoto et al., 2014). Missed doses decreased from 57.7% to 22%, while attitudes regarding both medication and treatment increased when behavioral therapy was utilized. After the behavioral therapy intervention, a 92.9% adherence rate was found in long-acting antipsychotic participants (Sajatovic et al., 2017). Though no significant difference existed between oral and long-acting injectable antipsychotics, specific guidelines to target barriers to adherence could be addressed. Behavioral therapy and increased education help patients feel empowered and autonomous in their treatment decisions.
Implications for Nursing Practice Benefits would come from further research to determine differences between LAIs and oral antipsychotics regarding compliance, relapse, and re-hospitalization rates. In addition, behavioral therapy and increased education should be implemented when prescribing either an oral or long-acting injectable antipsychotic to a patient experiencing psychosis to increase patient attitudes, empowerment and autonomy in their treatment can increase chances of compliance
Group Therapy for Adults with Hip Replacements
Get PDFThe purpose of our critically appraised topic is to synthesize the best current evidence regarding the feasibility of group occupational therapy and outcomes related to ADL performance. The final portfolio contains a total of four research articles. Study designs include two randomized control trials, one cohort design, and one systematic review. All studies related directly to the PICO question and were used to determine best evidence for the feasibility of group therapy of the older adult population who have hip replacements in a rehabilitation setting
Identification of Therapeutic Targets for Th17 Cell-Mediated Diseases
Get PDFHypersensitivity and autoimmune diseases are complex synergistic effect of environmental, genetic and other factors. T helper 17 (Th17) cells play a critical role in the immune pathology. Th17 cells are a group of specialized CD4+ T cells with potential pro-inflammatory function which are different from other T cells such as T helper 1 (Th1) cells or T helper 2 (Th2) cells. Th17 cell development and differentiation processes are strictly regulated through complex pathways. Th17 cells are characterized by secreting cytokines such as IL-17 and IL-22. Studies have shown that Th17 cells and IL-17 have been implicated in the pathogenesis of many hypersensitivity and autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Therefore, the study of Th17 cell differentiation and its regulatory mechanism will help with better understanding of the regulation of these diseases and may also potentially identify new targets for their treatment. In this study, we worked on two diseases: hypersensitivity pneumonitis (HP) and multiple sclerosis (MS). Both of them can be mediated by Th17 cells. HP is a hypersensitivity disease in the lung which may result in chronic lung fibrosis with high mortality. Corticosteroids such as prednisolone may help to control acute HP symptoms but may also produce side effects and not be effective to all patients. Because under the same environmental conditions not all exposed individuals get the diseases, the genetics may play an important role in HP. Our hypothesis is that severity and risk for developing HP will be most strongly influenced by genetic variants that are involved in regulation of the T cell response. Data from mouse inbred lines of BXD family were analyzed to identify the genes involved in susceptibility to HP and were used in the study of the mechanisms by which they contribute to the disease. We found that BXD strains exhibited variability in the T cell response to the development of HP and the expression level of Cdh2 was correlated with that of IL-17, which may contribute to inflammation in the lung and lung fibrosis. MS is an autoimmune disease occurring in the central nervous system (CNS) which may result in jeopardy of a patient’s lifespan. There is no cure for the disease, and the current treatment can only reduce the relapsing frequency and severity. Although the exact mechanism is unclear, one promising option is the use of high dose of intravenous immunoglobulin (IVIG). IVIG exhibits anti-inflammatory properties that are protective in autoimmune and inflammatory diseases. But it is still not the ideal treatment due to the large dosages and toxic effects. Gliknik lnc. developed fully recombinant IgG multimers as a therapeutic option for autoimmune diseases, called Stradomers. Our study found that the Stradomers could prevent the development of experimental autoimmune encephalitis (EAE), the mouse model of MS, with fewer Th17 cells infiltrated into the CNS. The therapeutic effect of Stradomers is dose-dependent and lower doses of Stradomers could delay the onset of EAE in our study. Overall, this dissertation addressed new feasible theoretical basis to prevent the development of HP and MS through Th17 pathways
A Cloning-Free Recyclable System for CRISPR-Cas9 Mediated Mutant and Reversion Construction in Candida albicans Clinical Isolates
Get PDFCandida albicans is a ubiquitous opportunistic fungal pathogen and one of the most prevalent causes of fungal diseases worldwide. The reference isolate SC5314 is one of the most widely used strains for both experimental and genetic studies, but it is becoming increasingly evident that genetic diversity in clinical isolates plays an important role in antifungal resistance, virulence, and pathogenicity. These recent discoveries highlight the need for genetic tools that are capable of investigating genes in multiple strain backgrounds. Here we build on the SAT1-flipper method and combine it with CRISPR-Cas9 technology to achieve cloning-free homozygous deletion in a single transformation event, followed by similarly efficient gene reversion. Short CRISPR RNAs (crRNAs) are combined with universal transactivating CRISPR RNA (tracrRNA) to form single guide RNA (sgRNA) that direct Cas9 to the target gene as part of the ribonucleoprotein (RNP) complex. To supplement the SAT1-flipper plasmid, we constructed an isogenic plasmid containing a C. albicans-optimized Hygromycin B resistance gene (CaHygB) in place of the SAT1 nourseothricin resistance gene to serve as repair templates. PCR-amplification of these cassettes with primers containing sequences homologous to the flanking regions of the target gene allow for high-efficiency homology-directed repair. We first targeted ADE2 for deletion, as homozygous deletion results in red pigmented colonies. In one transformation event, we achieved homozygous ADE2 deletion in SC5314 and a variety of clinical isolates (529L, JS15, SJCA1, and TW1) at a rate of nearly 100% when transformants were incubated on media containing both nourseothricin and hygromycin B. Gene reversion was similarly successful by engineering plasmids pDUP3 to contain the ADH1 terminator and an overlap extension PCR-mediated approach combined with CRISPR-Cas9 targeting at the NEUT5 locus. We also showed the efficacy of this method in deletion of the essential metabolic gene URA3 and the recyclability of the system by performing consecutive deletion of the morphology regulating genes CPH1 and EFG1. Thus, we have established an efficient, cloning-free, recyclable system for homozygous deletion and reversion across C. albicans isolates
Characterizing T Cell Features of Atypical Lymphocytes for the Optimization of Adoptive Immunotherapies
Get PDFT lymphocytes with atypical antigen targets or mechanisms or antigen recognition have been implemented into therapeutic approaches for the treatment of disease with auspicious results. Two such populations are regulatory T cells (Tregs) and CAR (chimeric antigen receptor-modified) T cells. The functional role of Tregs in the immune system is non-canonical, in that they prevent hyper-inflammation and resolve immunopathology by constraining conventional immune cell effector functions and producing mediators that promote tissue repair. Similarly, the targets of CAR T cells are also self-derived but are recognized through an engineered receptor designed to bypass the conventional mechanism of antigen-recognition. Despite their success in the clinic, additional studies are needed to identify cellular characteristics associated with optimal treatment success. For Tregs, the role of T cell receptor (TCR) specificity against disease-associated antigens is not clear due, in part, to a lack of comparative studies of TCR repertoires across diverse disease settings, which could inform which diseases would benefit from disease antigen-specific or disease antigen non-specific Treg-based cellular therapies. If disease antigen-specific, these studies can emphasize the need to identify additional Treg-associated antigens for \textit{ex vivo} expansion. For CAR T cells, the phenotypes linked to robust effector responses have not been thoroughly assessed due to limited access to patient samples throughout the entire course of treatment. To address these gaps, we have acquired TCR sequencing data of Tregs from varied disease contexts including acute infection, allergy, cancer, and autoimmunity, followed by integrated analysis of TCR repertoire and single-cell gene expression to comprehensively identify TCR features associated with disease-responsive Tregs and assess the potential relationship between the TCR and transcriptional fate. Secondly, we acquired both pre- and post-infusion CAR T cell samples from patients participating in the SJCAR19 clinical trial to track CAR T cell clonotypes upon infusion to identify signatures associated with optimal cytotoxicity and persistence. Treg TCRs sequenced from murine models of influenza (Flu), acute asthma (AS), non-small cell lung carcinoma (NSCLC), and type 1 diabetes (T1D) showed disease-specific repertoire features. Distinct repertoire features were identified in measures of clonality, gene segment usage, and amino amino acid similarity, and physicochemical properties. Surprisingly, despite the distinct repertoire characteristics, a high degree of repertoire sharing was displayed, especially across lung conditions, though generation probabilities suggest there is an increased likelihood of utilizing similar gene segments simply by chance. Treg TCR features may influence the heterogeneity of Treg phenotypes. Focusing on Tregs isolated from the lung of influenza-infected mice at 4, 7, 10, and 23 dpi and from the lungs of NSCLC mice, single-cell gene expression suggested converging functional gene expression profiles as influenza Tregs matured compared to NSCLC Tregs, wherein both 23dpi and NSCLC Tregs showed evidence of tissue-resident and tissue-reparative transcriptional profiles. To assess whether certain TCR features were associated with Treg transcriptional heterogeneity, we applied Clonotype Neighbor Graph Analysis (CoNGA) to identify clusters of cells based on simultaneous similarity in gene expression landscape and TCR amino acid sequence. CoNGA analysis identified 3 distinct Treg-associated gene expression clusters with high TCR similarity, suggesting that transcriptional heterogeneity in the Treg population is not driven by differences in TCR features, and likely, TCR specificity. Lastly, single-cell gene expression of pre- and post-infusion CAR T cells identified distinct transcriptional landscapes with pre-infusion CAR T cells displaying signatures of proliferation and post-infusion CAR T cells having largely acquired either a cytotoxic effector signature associated with expression granzymes and effector cytokines or a dysfunctional signature associated with cellular death and T cell exhaustion. Having identified CAR T cells with optimal effector responses, single-cell TCR data was utilized to identify pre-infusion cells clonally related to functional effector post-infusion CAR T cells, deemed effector precursors. Comparison of effector precursor gene expression to all other pre-infusion CAR T cells demonstrated higher expression of granzymes, \textit{GNLY}, and \textit{IFNG}, suggesting effector precursors were primed for optimal cytotoxic responses upon infusion. Using differential expression of genes encoding surface proteins, we demonstrated that effector precursors can be enriched in the pre-infusion sample to increase the proportion of ideal CAR T cells patients receive upon infusion. Taken together, these findings provide insight into TCR repertoires and subsequent functional association of these unconventional T cell populations, which will assist in the improvement of treatment strategies using Tregs or CAR T cells. Moreover, these data can be applied in the development of other T cell-based therapies, such as CAR-Tregs, by informing the role of the endogenous TCR in conditioning CAR-Treg phenotypes in distinct tissues and providing a novel method of leveraging the TCR to elucidate transcriptional signatures and surface phenotypes leading to optimal CAR-Treg responses
Investigating the Correlation Between LPR & Obesity
Get PDFObjectives: To determine whether Drug-Induced Sleep Endoscopy (DISE) findings of Laryngopharyngeal Reflux (LPR) correlate with obesity, gender, Epworth Sleepiness scale, and OSA severity.
Study design: Single center retrospective cohort study.
Methods: Patients greater than 18 years of age who underwent DISE by one surgeon at a tertiary care center from July 2016 to July 2022 were included. DISE findings, patient characteristics, demographics, polysomnogram(s), and Epworth Sleepiness Scale(s) were extracted. Fisher’s exact test was used to compare categorical variables, and independent sample t-test was used to compare continuous variables. All statistical analyses were performed using IBM SPSS Statistics 28.
Results: The study included 178 patients (60.87 years ± 11.54; 31.24 BMI ± 6.21). 38 patients had LPR, and 103 patients had a BMI\u3e30. LPR+ patients BMI was 33.11 ± 5.60, and LPR- patients BMI was 30.74 ± 6.28. There was a statistically significant relationship between obesity and LPR (p = 0.005). Additionally, obesity mild-moderately affected patients having LPR (d = .404). There was no statistically significant difference between LPR+ patients and ESS, AHI, and gender (p = .395, .174, & .302 respectively).
Conclusion: DISE aids in the diagnosis and evaluation of Obstructive Sleep Apnea (OSA) by simulating natural sleep. Using this highly precise diagnostic procedure, our study shows a relationship between findings of LPR in obese patients with obesity playing a small-medium role. There was no difference between LPR and ESS, AHI, and gender
Prophylactic Administration of Steroids and the Effect on Post-extubation Stridor: A Scoping Review
Get PDFPurpose/Background Stridor occurs due to laryngeal edema which arises when a patient has been intubated for an extended period of time. There are several factors that affect the degree of swelling. Post-extubation stridor signals that a patient requires reintubation because the airway is no longer patent. Corticosteroids, such as dexamethasone, can be used prior to extubation to minimize complications and overall length of stay if a patient is at high risk for stridor. This scoping review will evaluate the literature and the association between the use of prophylactic steroids on mechanically ventilated adult patients and the occurrence of post-extubation stridor.
Methods A literature review of eleven articles from the years 2007-2020 was conducted. The effect of prophylactic steroids on post-extubation stridor was examined. A summary of evidence table was constructed which included a total of 7,211 participants, with 3,683 being included in the intervention group and 3,428 being included in the control group. This data was used to determine whether the use of prophylactic steroids decreased the occurrence of reintubation due to laryngeal edema.
Results Out of the total 7,211 participants, with 50% receiving steroids (intervention group) and 50% receiving a placebo or nothing (control group), there was a 9.8% increase in laryngeal edema, stridor, and reintubation in the control groups versus the intervention groups. This suggests that the administration of prophylactic steroids decreases the occurrence of post-extubation stridor.
Implications for Nursing Practice The prophylactic administration of steroids can help decrease the incidence of reintubation due to post-extubation stridor. While the use of steroids remains a topic of controversy among healthcare professionals, the evidence supports the implementation of prophylactic steroids to decrease the risk of complications associated with prolonged intubation, laryngeal edema, and decrease the total length of ICU stay
Impact of Ante- and Postnatal Depression Screening in Women with HIV: A Scoping Review
Get PDFPurpose/Background Maternal depression has been identified as a strong predictor of poor prenatal care. Among pregnant women living with Human Immunodeficiency Virus (HIV), mental health-related factors such as depression could potentially undermine effective antiretroviral therapy (ART) adherence, increase mortality, and cause poor HIV viral suppression consequently impacting vertical transmission of HIV. This scoping review aims to identify existing knowledge regarding the impact of ante- and postnatal depression screening in women with HIV and to adduce the necessity for effective screening.
Methods A literature search was performed for studies with primary outcomes of depression screening within the context of ante- or postnatal timeframe. The authors individually screened relevant articles and collectively found 12 articles appropriate to include in this scoping review based on quality and relevancy to the research question. The study outcomes evaluated include maternal adherence to ART, CD4+ cell counts, infant outcomes, and maternal outcomes in relationship to ante- and postnatal depression.
Results Of the 12 studies meeting criteria for this review, two are Level I evidence, nine are Level II, and one is Level III. Eleven of the included studies showed statistically significant findings in at least one of the evaluated outcomes of this review. Based on the findings of this scoping review, it is demonstrated that ante- and postnatal depression screening of pregnant women with HIV will improve ART adherence as well as maternal and infant outcomes.
Implications for Nursing Practice Findings underscore the need to integrate routine screening for perinatal depression in women with HIV. A positive finding of depression from screening does have an impact on ART adherence, CD4+ count, and the wellbeing of ante-and postnatal women with HIV and their infant. Further research on this topic is needed to understand the implication of specific screening tools and the effect of timely recognition and treatment for this population