ABSTRACT
The clinical impact of any therapy requires the product be safe and effective. Gammaretroviral vectors pose several unique risks, including inadvertent exposure to replication competent retrovirus (RCR) that can arise during vector manufacture. The US FDA has required patient monitoring for RCR, and the National Gene Vector Biorepository is an NIH resource that has assisted eligible investigators in meeting this requirement. To date, we have found no evidence of RCR in 338 pre-treatment and 1,595 post-treatment blood samples from 737 patients associated with 60 clinical trials. Most samples (75%) were obtained within 1 year of treatment, and samples as far out as 9 years after treatment were analyzed. The majority of trials (93%) were cancer immunotherapy, and 90% of the trials used vector products produced with the PG13 packaging cell line. The data presented here provide further evidence that current manufacturing methods generate RCR-free products and support the overall safety profile of retroviral gene therapy.
Subject(s)
Retroviridae , Virus Replication , Humans , Retroviridae/genetics , Genetic Vectors/genetics , Cell Line , Genetic Therapy/adverse effectsABSTRACT
BACKGROUND: Therapeutic relational connection (TRC) in telehealth is a new concept that refers to the intentional use of relationship connection between health care providers and their patients as both parties work toward a therapeutic aim. It has been demonstrated that TRC positively affects patient-centered outcomes including adherence, self-management, and satisfaction with care. What is not known are best practices for establishing TRC during telehealth visits. The rapid emergence of telehealth during the COVID-19 pandemic has identified a number of challenges. These challenges include lack of human contact, distance creating mistrust, the inability to rely on nonverbal communication, and a sense of depersonalization. Training for health care providers in these interpersonal communication skills needed to establish TRC during telehealth visits is needed. OBJECTIVE: This paper aims to explore the evolutionary concept of TRC in telehealth. The purpose of this paper is to provide a concept analysis of TRC during telehealth interactions between providers and patients through a comprehensive review of the existing published literature. METHODS: Rodgers' evolutionary concept analysis method was used to guide this study. PubMed, Embase, PsycINFO, and CINAHL were used to search for relevant publications. An integrative review strategy aided by Rayyan software was used to identify a final sample of 13 papers for analysis. RESULTS: The proposed definition of TRC in telehealth is the experience of a mutually responsive patient-provider relationship that is built on mutual respect and understanding and informed by cultural humility, presence, empathy, and the ability to effectively evaluate patient concerns to work toward a therapeutic aim. The key attributes of TRC in telehealth are the provider's ability to evaluate patient concerns, interpersonal communication, cultural humility, mutual trust and respect, presence, empathy, and building relationships. Clinical presence, proper environment, knowledge about the use of technology (both patient and provider), use of verbal and nonverbal communication, and knowledge about community and culture are important antecedents of TRC. Consequences of TRC include improved communication resulting in mutual respect and caring, adherence to follow-up recommendations, increased coping, collaborative decision-making, and satisfaction with care. CONCLUSIONS: Telehealth visits necessitate alternative approaches to establishing TRC as compared to in-person clinic visits. With the rapid expansion of telehealth platforms and a heightened acceptance of the technology, there is a need to integrate knowledge and provide a clear conceptualization of TRC in telehealth as TRC has been demonstrated to result in positive patient-centered outcomes. Identifying the attributes and antecedents of TRC in telehealth allows us the opportunity to develop guidelines and educational interventions aimed at training health care providers in the skills needed to establish TRC during telehealth visits.
Subject(s)
COVID-19 , Telemedicine , Humans , Pandemics , Health Personnel , Professional-Patient RelationsABSTRACT
BACKGROUND: Deciding on a disease modifying therapy (DMT) for the treatment of pediatric onset multiple sclerosis (POMS) often presents a challenge to families. Parents are often overwhelmed by DMT choices, but they desire to be an integral part of the decision making process for their child. There is no standard approach for how best to involve families in this process. The aim of this study was to describe the experience of decision making related to the use of disease modifying therapy in parents of children and adolescents with POMS. METHODS: The research aim was addressed using a descriptive survey design. Participants were recruited from the Pediatric MS and Related Disorders Program at Boston Children's Hospital as well as from the Pediatric Multiple Sclerosis Alliance online Facebook group. RESULTS: Overall, fewer than half of parents felt very satisfied with the DMT they chose for their child with POMS (44%). Parental satisfaction with the decision making process increased with a high level of control of the process (p < 0.0001), satisfaction with communication (p < 0.0001), and feeling supported by the healthcare provider (p < 0.0001). PRACTICE IMPLICATIONS: Healthcare providers should recognize the importance of the role of the family in the decision making process and how this directly impacts health outcomes. An open discussion at the time of DMT education should involve identification of family values and preferences. The use of online decision support tools have a valuable role in determining family preferences. CONCLUSION: There is an opportunity of healthcare providers to foster shared decision making practices to improve satisfaction among parents of children and adolescents with POMS. Healthcare providers should work closely with families to identify and incorporate their personal preferences for their role in the decision making process. Future research should include the testing of decision support tools for decision making in POMS.
Subject(s)
Decision Making, Shared , Multiple Sclerosis , Adolescent , Child , Decision Making , Humans , Multiple Sclerosis/drug therapy , Parents , Professional-Family RelationsABSTRACT
Exposure to replication-competent lentivirus (RCL) is a theoretical safety concern for individuals treated with lentiviral gene therapy. For certain ex vivo gene therapy applications, including cancer immunotherapy trials, RCL detection assays are used to screen the vector product as well as the vector-transduced cells. In this study, we reviewed T cell products screened for RCL using methodology developed in the National Gene Vector Biorepository. All trials utilized third-generation lentiviral vectors produced by transient transfection. Samples from 26 clinical trials totaling 460 transduced cell products from 375 subjects were evaluated. All cell products were negative for RCL. A total of 296 of the clinical trial participants were screened for RCL at least 1 month after infusion of the cell product. No research subject has shown evidence of RCL infection. These findings provide further evidence attesting to the safety of third-generation lentiviral vectors and that testing T cell products for RCL does not provide added value to screening the lentiviral vector product.
Subject(s)
Genetic Vectors/genetics , Lentivirus/genetics , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Virus Replication/genetics , Adoptive Transfer , Cell Line , Follow-Up Studies , Genetic Therapy , Humans , Lentivirus/physiology , Transduction, GeneticABSTRACT
Background: Hand hygiene and its significance for reducing the spread of infection is well evidenced and has been brought into sharp focus following the COVID-19 pandemic. Although a crucial clinical skill in ensuring safe healthcare, little is known regarding nursing students' effectiveness of hand hygiene practice. Aim: The aim of this study was to evaluate the impact of an educational intervention on hand hygiene practice, designed by the research team for first year pre-registration nursing students. Particular emphasis was placed upon hand drying technique and time. Methodology: 825 nursing students were observed and assessed for their hand hygiene practice in a clinical suite at a university setting. Nursing students were observed for compliance against set outcome measures involving hand hygiene preparation, hand and wrist washing technique, hand drying technique and time. Data were analysed quantitatively using SPSS. Results: The educational intervention had a significant impact on the clinical skills learning of nursing students. 779 students passed the assessment at the first attempt (94.4%). Of the 46 students that failed to meet the necessary criteria, 45 satisfied the criteria at the second attempt; giving an overall optimal compliance of 99.9%. 99.6% of students complied with recommended hand drying standards. Conclusion: This study offers an important contribution to the development and delivery of nursing education programmes. The educational intervention improved compliance with recommended hand hygiene technique and practice. Lack of attention to hand drying may negate effective hand hygiene in healthcare.
ABSTRACT
We evaluated the use of the Product Enhanced Reverse Transcriptase (PERT) assay as a means of detecting virus in retroviral vectors products pseudotyped with Gibbon Ape Leukemia Virus (GALV) and Vesicular Stomatitis Virus G (VSVG) envelopes. PERT provides greater standardization than the S+/L- assay which has been used extensively in virus detection. A challenge is that PERT will also detect residual retroviral vectors as vector particles contain reverse transcriptase. Vector products were cultured for 3 weeks on HEK293 cells to amplify any potential virus. In addition, vector supernatant and end-of-production cells were spiked with GALV to evaluate for inhibition by the test article. Results of PERT and the S+/L- assay were compared. PERT and S+/L- assays were both effective in detecting virus. Vector supernatants were negative at the end of 3 weeks of culture by PERT for both GAVL and VSVG pseudotyped vector. In contrast, end-of-production cells were positive by PERT due to persistent vector producing cells. A one-week culture of cell-free media obtained at the 3 weeks timepoint allowed distinction of virus-free test articles from those with virus. The PERT assay is suitable for detecting replication competent retrovirus in vector products pseudotyped with GALV and VSVG envelopes.
ABSTRACT
Lentiviral vectors are now in clinical trials for a variety of inherited and acquired disorders. A challenge for moving any viral vector into the clinic is the ability to screen the vector product for the presence of replication-competent virus. Assay development for replication-competent lentivirus (RCL) is particularly challenging because recombination of vector packaging plasmids and cellular DNA leading to RCL has not been reported with the current viral vector systems. Therefore, the genomic structure of a RCL remains theoretical. In this report, we describe a highly sensitive RCL assay suitable for screening vector product and have screened large-scale vector supernatant, cells used in vector production, and cells transduced with clinical grade vector. We discuss the limitations and challenges of the current assay, and suggest modifications that may improve the suitability of this assay for screening US Food and Drug Administration (US FDA)-licensed products.
Subject(s)
Genetic Vectors/isolation & purification , Genetic Vectors/standards , Lentivirus/isolation & purification , Virus Replication , Cell Line , Enzyme-Linked Immunosorbent Assay/methods , Genetic Vectors/genetics , Genetic Vectors/therapeutic use , HEK293 Cells , HIV Core Protein p24/immunology , Humans , Lentivirus/genetics , Quality Control , Recombination, Genetic , Reference Standards , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND: Poor nutrition is one of the leading risk factors for preventable chronic diseases in the United States. Nutrition counseling has been shown to improve clinical outcomes in the adult primary care setting. Nurse practitioners (NPs) can help fill the critical need for nutrition counseling, yet little is known about their role providing nutrition counseling. PURPOSE: To describe the primary care NP's experience in providing nutrition counseling to adult patients in primary care practice. METHODS: Qualitative descriptive study design. Data were collected through virtual semi-structured interviews with 18 board-certified primary care NPs. Interviews were audio-recorded, de-identified, transcribed verbatim, and analyzed. Data collection and analysis took place concurrently and continued until data saturation was achieved. RESULTS: Five themes emerged from NPs' descriptions of their experiences in providing nutrition counseling to adult patients in primary care practice: (1) role of nutrition counseling in NP primary care practice; (2) developing NP self-efficacy in nutrition counseling; (3) nutrition counseling is more than the provision of information; (4) emotional aspect of nutrition; and (5) barriers to behavior change. CONCLUSIONS: Findings suggest that although NPs understand the importance of nutrition counseling in primary care practice and provide it in some capacity, its continuance is limited by multiple barriers. Future research should evaluate ways to enhance NPs' preparedness to provide nutrition counseling, assess specific resources and tools to aid in nutrition counseling, and determine best practices for communication when delivering nutrition counseling. IMPLICATIONS FOR PRACTICE: Future interventions have the potential to positively affect patients' dietary practices and improve clinical outcomes.
Subject(s)
Nurse Practitioners , Adult , Communication , Counseling , Humans , Nurse Practitioners/psychology , Primary Health Care , Qualitative Research , United StatesABSTRACT
Objective: The purpose was to understand college students' motivations for the use and discontinued use of fitness related technology (FRT) in relation to their physical activity behaviors. Participants: Participants were undergraduate students (n = 22) who were eligible if they were between 18-24 years of age (emerging adulthood) and current or previous users of FRT. Methods: Qualitative descriptive design was used with semi-structured interviews conducted virtually. Thematic analysis was used to analyze the data. Results: Participants discussed four themes; (1) Motivations for physical activity, (2) Motivations for using FRT, (3) Social connection improves accountability for physical activity, and (4) The ups and downs of FRT goal setting and data display. Conclusions: Best practice guidelines need to be established for the use of FRT along with approaches to promote physical activity among this population. Additional research is needed to identify reasons for discontinuation of use and to develop potential interventions to promote sustained engagement with FRT.
ABSTRACT
Parents of children with epilepsy, like parents of children with many other chronic conditions, are faced with a constant feeling of uncertainty about their child's condition. This uncertainty can lead to a decreased ability to cope as evidenced by increased stress levels, negative mood states, and impaired family functioning. Because altered coping in the parent may have a profound negative impact on the child's psychosocial adjustment to living with a chronic condition, it is important to identify ways to facilitate positive coping skills in the parent. The purpose of this review was to critically analyze the existing literature related to the challenges associated with parenting a child who has epilepsy. Interventions geared toward facilitating coping in parents will also be reviewed, and gaps in the literature will be identified. Lastly, future implications for nursing research will be discussed.
Subject(s)
Adaptation, Psychological , Clinical Nursing Research , Epilepsy/nursing , Epilepsy/psychology , Family Nursing/methods , Parents/psychology , Adult , Child , Humans , Stress, Psychological/nursing , Stress, Psychological/psychologyABSTRACT
The National Gene Vector Biorepository (NGVB) program has been highly accessed by gene therapy investigators. The reagent repository has distributed over 1,000 reagents to 397 investigators. The Pharmacology/Toxicology Archive contains over 36,000 specimens from a variety of adeno-associated virus (AAV), adenoviral, and other pharmacology/toxicology studies. NGVB also maintains a searchable database of gene therapy pharmacology/toxicology studies to promote data sharing. NGVB has provided Food and Drug Administration (FDA)-mandated replication-competent virus testing for over 70 clinical trials. From 2008 to 2018, there have been 114 publications acknowledging the NGVB. It is unlikely that any other National Institutes of Health (NIH)-funded program has served as many gene therapy investigators as the NGVB.
Subject(s)
Biological Specimen Banks , Clinical Laboratory Services , Genetic Therapy , Genetic Vectors , Laboratories , Biological Specimen Banks/organization & administration , Clinical Laboratory Services/organization & administration , Community Health Services/organization & administration , Databases, Factual , Genetic Vectors/classification , Genetic Vectors/genetics , Humans , Laboratories/organization & administrationABSTRACT
Lentiviral vectors are being used in a growing number of clinical applications, including T cell immunotherapy for cancer. As this new technology moves forward, a safety concern is the inadvertent recombination and subsequent development of a replication-competent lentivirus (RCL) during the manufacture of the vector material. To assess this risk, regulators have required screening of T cell products infused into patients for RCL. Since vector particles have many of the proteins and nucleotide sequences found in RCL, a biologic assay has proven the most sensitive method for RCL detection. As regulators have required screening of up to 108 cells per T cell product, this method described a procedure for assessing RCL contamination of large-volume T cell products.
Subject(s)
Genetic Vectors/genetics , Immunotherapy, Adoptive/standards , Lentivirus/genetics , Neoplasms/immunology , Neoplasms/therapy , T-Lymphocytes , Transduction, Genetic , Biological Assay , Cell Line , Clinical Trials as Topic , Humans , Immunotherapy, Adoptive/methods , Neoplasms/pathology , Quality Assurance, Health Care , Quality Control , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Virus ReplicationABSTRACT
Healthcare providers are often faced with ethical dilemmas when making treatment decisions for a child with neurological impairment. Problems may stem from the fact that the wishes of the family may be in opposition to what the healthcare team feels is in the best interest of the child. There are many factors that need to be considered when determining treatment options for the child with neurological impairment. Nurses are in a unique position to advocate for the involvement of the child's family in making these difficult decisions.
Subject(s)
Brain Diseases/nursing , Nurse's Role , Pediatric Nursing/ethics , Withholding Treatment/ethics , Child , Decision Making , Humans , Practice Guidelines as Topic , Quality of LifeABSTRACT
Infection presents a significant risk for immunocompromised patients. To reduce this risk, various precautions can be implemented and these may affect patients' quality of life. Such precautions are controversial, with varying practices being adopted by different hospitals. This article aims to enhance nurses' knowledge about the current evidence on the interventions designed to reduce the rate of infection in immunocompromised patients who are in hospital.
Subject(s)
Immunocompromised Host , Infection Control/methods , Antineoplastic Agents/adverse effects , Diet , Environment, Controlled , Humans , Neoplasms/drug therapy , Neoplasms/nursing , Neutropenia/chemically induced , Neutropenia/nursingABSTRACT
This study interviewed parents to understand families' experience with pediatric onset multiple sclerosis (POMS), which make up 2.7% to 10.5% of all MS cases. 21 sets of parents of children with a confirmed diagnosis of POMS were recruited from two pediatric MS centers. Families experienced stress from the uncertainty prior to diagnosis, anxiety over symptoms and possible progression of the disease, frustrations with the uncertain effects of disease-modifying treatments (DMTs), and difficulties with injections. Families had to cope with cognitive and physical effects of POMS at school, decisions about expectations and independence for the child, and extra demands POMS placed on the family. Most parents reported benefitting from support from physicians, the National Multiple Sclerosis Society, and the MS community. Families had benefitted from DMTs, and, despite the stresses, most had adapted successfully to the illness. Advice from interviewees to other parents and recommendations for improving family support are presented.
ABSTRACT
BACKGROUND: Scholarship is a hallmark of all professions and includes research and practice scholarship. Building the science for practice and care is a major responsibility of each profession. METHODS: The purpose of this article is to define clinical science as it applies to neuroscience nursing as well as to establish the foundation for the work of the Clinical Science Committee of the American Association of Neuroscience Nursing. CONCLUSIONS: Research scholars conduct investigations for discovery of new knowledge. Practice scholars develop clinical knowledge through clinical practice and experience and an inquiring mindset that questions why and how certain methods or processes contribute to the achievement of certain outcomes; they look for better ways to improve processes of care and practice that will achieve optimal evidence-based outcomes. Scholarship in both research and practice domains is critical to the advancement of neuroscience nursing. Many opportunities exist for neuroscience nurses to contribute to clinical science.
Subject(s)
Evidence-Based Practice , Fellowships and Scholarships , Neuroscience Nursing , Nursing Research , Humans , Science , United StatesABSTRACT
Replication-competent retrovirus (RCR) is a safety concern for individuals treated with retroviral gene therapy. RCR detection assays are used to detect RCR in manufactured vector, transduced cell products infused into research subjects, and in the research subjects after treatment. In this study, we reviewed 286 control (n = 4) and transduced cell products (n = 282) screened for RCR in the National Gene Vector Biorepository. The transduced cell samples were submitted from 14 clinical trials. All vector products were previously shown to be negative for RCR prior to use in cell transduction. After transduction, all 282 transduced cell products were negative for RCR. In addition, 241 of the clinical trial participants were also screened for RCR by analyzing peripheral blood at least 1 month after infusion, all of which were also negative for evidence of RCR infection. The majority of vector products used in the clinical trials were generated in the PG13 packaging cell line. The findings suggest that screening of the retroviral vector product generated in PG13 cell line may be sufficient and that further screening of transduced cells does not provide added value.
ABSTRACT
BACKGROUND: Parents of children with epilepsy and other neurological conditions live with a feeling of constant uncertainty. The uncertainty associated with caring for a child with a neurological condition produces stress, which leads to decreased parental belief in caregiving skills, anxiety, and depression, ultimately altering parental functioning resulting in an increase in child behavioral problems. The stress associated with caring for children with neurological conditions is unlike caring for children with other chronic conditions. Neurological conditions are unpredictable, and there are often no warning signs before an acute event. This unpredictability accompanied with stigma results in social isolation and impacts family functioning. In addition, children with neurological conditions have a higher rate of psychological comorbidities and behavior problems when compared with children with other chronic conditions. This produces an additional burden on the parents and family. STUDY DESIGN: This randomized controlled trial tested the efficacy of the Creating Opportunities for Parent Empowerment intervention for parents of children with epilepsy and other neurological conditions. This intervention was administered at three intervals: (a) during hospital admission, (b) 3 days after hospital discharge by telephone, and (c) 4-6 weeks after hospital discharge. RESULTS: Forty-six parents of children admitted to the inpatient neuroscience unit at Boston Children's Hospital participated in the study. Several study limitations resulted in an inadequate sample size to obtain the power necessary to reach statistically significant results for most of the research questions. A one-between, one-within multivariate analysis of variance revealed that the main effect of time was significant for differences in state anxiety for both the usual care group and the intervention group, F(1, 20) = 9.86, p = .005, indicating that state anxiety for both groups combined was more pronounced during the hospitalization. A one-between, one-within multivariate analysis of variance showed that the effect of the interaction between time and group was significant for internalized behavior assessment system score only (p = .037) because the usual care group reported a significant decrease in internalizing behavior scores in their children over time. CONCLUSIONS: Findings from this study have significant implications for clinical practice and future research. Parents of children with neurological conditions often struggle to manage a constant feeling of uncertainty in their daily lives. Nurses possess the knowledge and expertise necessary to identify the psychosocial needs of these parents and provide education and support as needed. Future research should focus on designing interventions to meet the needs of these families and develop strategies to help improve the quality of life for both the parent and child living with a neurological condition.
Subject(s)
Adaptation, Psychological , Chronic Disease , Epilepsy , Parents/education , Power, Psychological , Adolescent , Adult , Brief Psychiatric Rating Scale , Child , Child, Preschool , Humans , Middle Aged , Nervous System Diseases , Stress, Psychological/etiologyABSTRACT
The product-enhanced reverse transcriptase (PERT) assay has been used to detect reverse transcriptase (RT) activity associated with retroviruses. Although the PERT assay has been proposed as a method for detection of replication-competent retrovirus (RCR) and lentivirus (RCL), it has not been rigorously compared with existing methods for RCR and RCL detection. We have assessed the PERT assay for detection of RCL and RCR that may contaminate lentiviral and retroviral vectors and compared it with published methods for RCL (p24gag ELISA/gag PCR) and RCR (S+/L-) detection. Our results suggest that the PERT assay is as sensitive as p24gag ELISA and gag PCR for detection of replication-competent HIV-1 in an RCL detection assay. Comparison of detection of replication-competent retroviruses, GALV and RD114, by extended S+/L- and PERT assays indicates that both assays can detect 1 IU of each virus. Our findings suggest that the PERT assay can be used for RCL and RCR testing of a variety of retroviral vectors regardless of the structure, sequence, and envelope of the vectors.
Subject(s)
Biological Assay , Lentivirus , RNA-Directed DNA Polymerase/analysis , Virus Replication , Biological Assay/methods , Lentivirus/chemistry , Lentivirus/genetics , RNA-Directed DNA Polymerase/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Virus Replication/geneticsABSTRACT
BACKGROUND: Hydatidiform moles occur in approximately 1 in 1,500 pregnancies; however, early miscarriages or spontaneous abortions may not be correctly identified as molar pregnancies due to poor differentiation of chorionic villi. METHODS: The current clinical testing algorithm used for the detection of hydatidiform moles uses a combination of morphological analysis and p57 immunostaining followed by ploidy testing to establish a diagnosis of either a complete or partial molar pregnancy. We review here 198 referrals for fluorescence in situ hybridization (FISH) ploidy testing, where the initial diagnosis based on morphology is compared to the final diagnosis based on a combination of morphology, FISH and p57 immunohistochemical (IHC) staining. RESULTS: Approximately 40% of cases were determined to be genetically abnormal, but only 28.8% of cases were diagnosed as molar pregnancies. The underestimation of complete molar pregnancies and those with androgenetic inheritance was also found to be likely using conventional diagnostic methods, as atypical p57 staining was observed in approximately 10% of cases. CONCLUSIONS: Our findings suggest that a revised approach to testing products of conception is necessary, with cases screened according to their clinical history in order to distinguish molar pregnancy referrals from hydropic pregnancies.