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To develop a theoretical understanding of the transition to survivorship in older adult blood cancer survivors.
Qualitative research employing Classic Glaserian Grounded Theory methods.
Purposive and theoretical sampling recruited 17 participants via Leukaemia & Lymphoma Society© Community webpages (65–83 years) from across the US and Canada. Data from individual semi-structured interviews using HIPPA-compliant Zoom© were analysed from September 2020 to March 2021.
Participants' main concern was losing their sense of self and reclaiming self was the core category. The substantive theory of Reclaiming Self-Balancing on a Tightrope Across Time is a six-phase transition process to survivorship: receiving a blood cancer diagnosis, finding bearings, reclaiming self, persevering through, realizing a transition and living in a new reality.
The transition to survivorship in older adult blood cancer survivors is a complex process because of age and disease type.
Age-related aspects of one's sense of self and its relation to health, well-being and quality of life, as older adult blood cancer survivors advance into older age need further research. Ageism and its impact on cancer survivorship care in older adults should also be explored.
What problem did the study address?: Existing theoretical frameworks do not explain the complex process of transition to survivorship for older adult blood cancer survivors. What were the main findings?: A substantive theory Reclaiming Self-Balancing on a Tightrope Across Time is a six-phase transition process from cancer diagnosis to survivorship characterized by an uncertain and liminal nature. Where and on whom will the research have an impact?: Understanding how older adults experience the transition to survivorship can inform age-appropriate person-centered nursing practices and healthcare policies specific to their needs.
COREQ.
No patient or public contribution.
Equity, diversity and inclusion (EDI) in the healthcare field are crucial in meeting the healthcare needs of a progressively diverse society. In fact, a diverse healthcare workforce enables culturally sensitive care, promotes health equity and enhances the understanding of various needs and patients’ viewpoints, potentially resulting in more effective patient treatment and improved patient outcomes. Despite this, information on the effectiveness of policies or programmes promoting EDI in health institutions is scarce. The objective of this systematic review is to assess the effects and outcomes of EDI programmes in healthcare institutions.
We will conduct Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of studies on EDI programmes and describe their effects and outcomes in healthcare institutions. We will search PubMed, Scopus, Web of Science, CINAHL and PsycINFO databases. Selected studies will include randomised control trials (RCTs), non-RCTs and cross-sectional studies published either in English or French. Quality appraisal of studies and a narrative synthesis of extracted data will be conducted as well as a meta-analysis if possible. The quality of evidence in this review will be assessed by the Grades of Recommendation, Assessment, Development and Evaluation.
We anticipate that this systematic review will reveal information on the effect of EDI programmes and their outcomes in healthcare institutions. We expect this information will provide insights that will lead to improvements in designing EDI policies and programmes in healthcare institutions.
No ethical clearance is required for this study as no primary data will be collected. The final manuscript will be submitted to a journal for publication. In addition to this, the results of the study will also be disseminated through conference presentations to inform the research and clinical practice.
This protocol has been registered with the International Prospective Register of Systematic Reviews; registration number CRD42024502781.
by YanXiao Zhao, Basyarah Hamat, Tao Wang, SongEn Wang, Leah Ling Li Pang
AimsIn order to explore new consumer demands for Chinese tea set products, propose an innovative tea set product design and evaluation method to improve the user experience and satisfaction of the produced tea sets, thereby promoting the development of the tea set market and the promotion of tea culture.
MethodsFirstly, grounded theory (GT) was used to analyze interview data to extract consumer demand indicators and construct a design evaluation hierarchical model. Secondly, the Analytical Hierarchy Process (AHP) was used to calculate the weights of the indicators, determine their priority of importance, and obtain several indicators that have a greater impact on the tea set design to guide innovative design practice. Lastly, the tea set design schemes were evaluated using the fuzzy comprehensive evaluation method to select the optimal design scheme and also to act as a guideline for further design optimization.
ConclusionThis study explores the innovative design and evaluation method for tea set products based on GT-AHP-FCE and validates the feasibility of this approach through a practical example of tea set design inspired by “The Classic of Mountains and Seas.”. It provides innovative theoretical and practical guidance for designers of subsequent tea set products and also provides a new path for the inheritance and innovation of traditional culture.
Objetivo: identificar las necesidades humanas básicas de las embarazadas de alto riesgo hospitalizadas con base en la Teoría de Wanda Horta. Método: investigación asistencial realizada con dieciséis gestantes de alto riesgo hospitalizadas en una maternidad de referencia en Ceará entre septiembre y noviembre de 2019. Se recolectó información a través de diario de campo y ficha de caracterización de las gestantes y registros de necesidades humanas básicas. Los resultados se analizaron mediante estadística descriptiva simple y un enfoque integral a la luz del marco de Wanda Horta. Resultados: las gestantes presentaron necesidades psicobiológicas, psicosociales y psicoespirituales, siendo prevalentes: ausencia de actividades de ocio, inseguridad emocional, escaso conocimiento, sueño y descanso perjudicados, y actividades físicas restringidas por indicación de descanso. Consideraciones finales: se cree que el razonamiento crítico y el juicio clínico de los enfermeros se centraron en la individualidad de las gestantes, identificando necesidades en los tres niveles propuestos por la teoría, apuntando caminos para cualificar el cuidado de enfermería a las gestantes de alto riesgo.
This study aimed to evaluate the predictive value of admission D-dimer levels for in-hospital mortality in patients with COVID-19 and acute ischaemic stroke.
Cohort (prospective).
Tertiary referral hospital in the capital city of Indonesia conducted from June to December 2021.
60 patients with acute ischaemic stroke and COVID-19 were included. Patients were classified into D-dimer groups (low and high) according to a 2 110 ng/mL cut-off value, determined via receiver operating characteristic analysis.
The primary outcome was in-hospital mortality, with admission D-dimer levels as the major predictor. Secondary outcomes included associations between other demographic and clinical variables and the admission D-dimer value. Kaplan-Meier method was used to carry out survival analysis, with univariable and multivariable Cox regression performed to assess the association of D-dimer levels and other confounding variables (including demographic, clinical and laboratory parameters) with in-hospital mortality.
The findings demonstrated an association between elevated admission D-dimer levels (≥2 110 ng/mL) and an increased likelihood of death during hospitalisation. The adjusted HR was 14.054 (95% CI 1.710 to 115.519; p=0.014), demonstrating an increase in mortality risk after accounting for confounders such as age and diabetes history. Other significant predictors of mortality included a history of diabetes and increased white blood cell count.
Admission D-dimer levels may be a useful predictive indicator for the likelihood of death during hospitalisation in individuals with COVID-19 and acute ischaemic stroke.
The COVID-19 pandemic accelerated changes to clinical research methodology, with clinical studies being carried out via online/remote means. This mixed-methods study aimed to identify which digital tools are currently used across all stages of clinical research by stakeholders in clinical, health and social care research and investigate their experience using digital tools.
Two online surveys followed by semistructured interviews were conducted. Interviews were audiorecorded, transcribed and analysed thematically.
To explore the digital tools used since the pandemic, survey participants (researchers and related staff (n=41), research and development staff (n=25)), needed to have worked on clinical, health or social care research studies over the past 2 years (2020–2022) in an employing organisation based in the West Midlands region of England (due to funding from a regional clinical research network (CRN)). Survey participants had the opportunity to participate in an online qualitative interview to explore their experiences of digital tools in greater depth (n=8).
Six themes were identified in the qualitative interviews: ‘definition of a digital tool in clinical research’; ‘impact of the COVID-19 pandemic’; ‘perceived benefits/drawbacks of digital tools’; ‘selection of a digital tool’; ‘barriers and overcoming barriers’ and ‘future digital tool use’. The context of each theme is discussed, based on the interview results.
Findings demonstrate how digital tools are becoming embedded in clinical research, as well as the breadth of tools used across different research stages. The majority of participants viewed the tools positively, noting their ability to enhance research efficiency. Several considerations were highlighted; concerns about digital exclusion; need for collaboration with digital expertise/clinical staff, research on tool effectiveness and recommendations to aid future tool selection. There is a need for the development of resources to help optimise the selection and use of appropriate digital tools for clinical research staff and participants.
The aim of this scoping review was to provide an overview of current research into topical oxygen therapies including the under-researched singlet oxygen for wound healing. A scoping review was undertaken using five databases. After duplicates and ineligible studies were excluded, 49 studies were included for a narrative review. Out of the included 49 studies, 45 (91.8%) were published in the past 10 years (2013–2023) with 32 (65.3%) published in the past 5 years (2018–2023). Eight of the studies were systematic reviews and/or meta-analysis and 18 were RCTs. The search identified zero human RCTs on singlet oxygen, but one human cohort study and five studies in animals. There is evidence that topical oxygen therapy may be useful for the treatment of chronic wounds, mainly diabetic foot ulcers. Singlet oxygen has shown potential, but would need further confirmation in controlled human trials, including more research to understand the bio-properties.
Time is a fundamental component of acute stroke and transient ischaemic attack (TIA) care, thus minimising prehospital delays is a crucial part of the stroke chain of survival. COVID-19 restrictions were introduced in Ireland in response to the pandemic, which resulted in major societal changes. However, current research on the effects of the COVID-19 pandemic on prehospital care for stroke/TIA is limited to early COVID-19 waves. Thus, we aimed to investigate the effect of the COVID-19 pandemic on ambulance time intervals and suspected stroke/TIA call volume for adults with suspected stroke and TIA in Ireland, from 2018 to 2021.
We conducted a secondary data analysis with a quasi-experimental design.
We used data from the National Ambulance Service in Ireland. We defined the COVID-19 period as ‘1 March 2020–31 December 2021’ and the pre-COVID-19 period ‘1 January 2018–29 February 2020’.
We compared five ambulance time intervals: ‘allocation performance’, ‘mobilisation performance’, ‘response time’, ‘on scene time’ and ‘conveyance time’ between the two periods using descriptive and regression analyses. We also compared call volume for suspected stroke/TIA between the pre-COVID-19 and COVID-19 periods using interrupted time series analysis.
We included all suspected stroke/TIA cases ≥18 years who called the National Ambulance Service from 2018 to 2021.
40 004 cases were included: 19 826 in the pre-COVID-19 period and 19 731 in the COVID-19 period. All ambulance time intervals increased during the pandemic period compared with pre-COVID-19 (p
A ’shock' like a pandemic has a negative impact on the prehospital phase of care for time-sensitive conditions like stroke/TIA. System evaluation and public awareness campaigns are required to ensure maintenance of prehospital stroke pathways amidst future healthcare crises. Thus, this research is relevant to routine and extraordinary prehospital service planning.
Co-creation approaches, such as co-design and co-production, aspire to power-sharing and collaboration between service providers and service users, recognising the specific insights each group can provide to improve health and other public services. However, an intentional focus on equity-based approaches grounded in lived experience and epistemic justice is required considering entrenched structural inequities between service-users and service-providers in public and institutional spaces where co-creation happens.
This paper presents a Charter of tenets and principles to foster a new era of ‘Equity-based Co-Creation’ (EqCC).
The Charter is based on themes heard during an International Forum held in August 2022 in Ontario, Canada, where 48 lived experience experts and researchers were purposively invited to deliberate challenges and opportunities in advancing equity in the co-creation field.
The Charter’s seven tenets—honouring worldviews, acknowledging ongoing and historical harms, operationalising inclusivity, establishing safer and brave spaces, valuing lived experiences, ‘being with’ and fostering trust, and cultivating an EqCC heartset/mindset—aim to promote intentional inclusion of participants with intersecting social positions and differing historic oppressions. This means honouring and foregrounding lived experiences of service users and communities experiencing ongoing structural oppression and socio-political alienation—Black, Indigenous and people of colour; disabled, Mad and Deaf communities, women, 2S/LGBTQIA+ communities, people perceived to be mentally ill and other minoritised groups—to address epistemic injustice in co-creation methodologies and practice, thereby providing opportunities to begin to dismantle intersecting systems of oppression and structural violence.
Each Charter tenet speaks to a multilayered, multidimensional process that is foundational to shifting paradigms about redesigning our health and social systems and changing our relational practices. Readers are encouraged to share their reactions to the Charter, their experiences implementing it in their own work, and to participate in a growing international EqCC community of practice.
To explore parents' perceptions/experiences of help-seeking for unsettled baby behaviours, including views and experiences of obtaining advice from primary healthcare professionals.
Semi-structured qualitative interviews.
Recruitment occurred via social media, general practice and health visiting teams. Remote semi-structured interviews were conducted with parents of babies. Babies were under 12 months old at time of interview, and parents had perceived unsettled baby behaviours in their first 4 months of life. Interviews were transcribed and data analysed using reflexive thematic analysis.
Based on interviews with 25 mothers, four main themes were developed. ‘The need for answers’ highlighted parental uncertainty about what constitutes normal baby behaviour, leading to help-seeking from multiple sources. ‘The importance of health professionals’ and ‘Experiencing health professional support’ identified perceptions about limited access, communication, mixed advice and how these influenced parental perception/management of behaviours. ‘Foundations to help-seeking’ highlighted important roles of social support and online help for valued shared experiences, emotional and practical support.
Health professional access and advice are important to parents, despite the increasing role of online help and importance of social support. More support and improved access to reliable sources of information is needed for parents.
Findings will inform future research and clinical practice to address parental uncertainties. Qualitative research with front-line health professionals is necessary.
Findings can inform the development of resources to support professionals/families managing unsettled babies.
Standards for Reporting Qualitative Research.
A public contributor was involved throughout all stages of the research. Emerging findings were discussed at a parent group.
Addressing parental uncertainties is important; about what is normal, non-pharmacological approaches and when pharmacological intervention is required. A digital information/self-management intervention may be useful for parents/clinicians.
To systemically identify and synthesize information on health professionals’ and students’ perceptions regarding the development needs of incident reporting software.
A systematic review of qualitative studies.
A database search was conducted using Medline, CINAHL, Scopus, Web of Science and Medic without time or language limits in February 2023.
A total of 4359 studies were identified. Qualitative studies concerning the perceptions of health professionals and students regarding the development needs of incident reporting software were included, based on screening and critical appraisal by two independent reviewers. A thematic synthesis was conducted.
From 10 included studies, five analytical themes were analysed. Health professionals and students desired the following improvements or changes to incident reporting software: (1) the design of reporting software, (2) the anonymity of reporting, (3) the accessibility of reporting software, (4) the classification of fields and answer options and (5) feedback and tracking of reports. Wanted features included suitable reporting forms for various specialized fields that could be integrated into existing hospital information systems. Rapid, user-friendly reporting software using multiple reporting platforms and with flexible fields and predefined answer options was preferred. While anonymous reporting was favoured, the idea of reporting serious incidents with both patient and reporter names was also suggested.
Health professionals and students provided concrete insights into the development needs for reporting software. Considering the underreporting of healthcare cases, the perspectives of healthcare professionals must be considered while developing user-friendly reporting tools. Reporting software that facilitates the reporting process could reduce underreporting.
The ENTREQ reporting guideline was used to support the reporting of this systematic review.
There was no patient or public contribution.
The protocol is registered in the International Prospective Register of Systematic Reviews with register number CRD42023393804.
by Koen M.F. Gorgels, Senna C.J.L. van Iersel, Sylvia F.A. Keijser, Christian J.P.A. Hoebe, Jacco Wallinga, Albert J. van Hoek
Measuring the severity of the disease of SARS-CoV-2 is complicated by the lack of valid estimations for the prevalence of infection. Self-administered rapid antigen diagnostic tests (Ag-RDTs) were available in the Netherlands since March 2021, requiring confirmation by reverse-transcription polymerase chain reaction (RT-PCR) for positive results. We explored the possibility of utilizing the positive predictive value (PPV) of Ag-RDTs to estimate SARS-CoV-2 prevalence. We used data from all Public Health service testing facilities between 3 May 2021 and 10 April 2022. The PPV was calculated by dividing the number of positive RT-PCR results by the total number of confirmation tests performed, and used to estimate the prevalence and compared with the number of COVID-19 hospital admissions. In total 3,599,894 cases were included. The overall PPV was 91.8% and 88.8% were symptomatic. During our study period, the estimated prevalence ranged between 2–22% in symptomatic individuals and 2–14% in asymptomatic individuals, with a correlation between the estimated prevalence and hospital admissions two weeks later (r = 0.68 (p
by Sonal Singh, Noelle M. Cocoros, Xiaojuan Li, Kathleen M. Mazor, Mary T. Antonelli, Lauren Parlett, Mark Paullin, Thomas P. Harkins, Yunping Zhou, Paula A. Rochon, Richard Platt, Inna Dashevsky, Carly Massino, Cassandra Saphirak, Sybil L. Crawford, Jerry H. Gurwitz
ContextPotentially inappropriate prescribing of medications in older adults, particular those with dementia, can lead to adverse drug events including falls and fractures, worsening cognitive impairment, emergency department visits, and hospitalizations. Educational mailings from health plans to patients and their providers to encourage deprescribing conversations may represent an effective, low-cost, “light touch”, approach to reducing the burden of potentially inappropriate prescription use in older adults with dementia.
ObjectivesThe objective of the Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer’s Disease (D-PRESCRIBE-AD) trial is to evaluate the effect of a health plan based multi-faceted educational outreach intervention to community dwelling patients with dementia who are currently prescribed sedative/hypnotics, antipsychotics, or strong anticholinergics.
MethodsThe D-PRESCRIBE-AD is an open-label pragmatic, prospective randomized controlled trial (RCT) comparing three arms: 1) educational mailing to both the health plan patient and their prescribing physician (patient plus physician arm, n = 4814); 2) educational mailing to prescribing physician only (physician only arm, n = 4814); and 3) usual care (n = 4814) among patients with dementia enrolled in two large United States based health plans. The primary outcome is the absence of any dispensing of the targeted potentially inappropriate prescription during the 6-month study observation period after a 3-month black out period following the mailing. Secondary outcomes include dose-reduction, polypharmacy, healthcare utilization, mortality and therapeutic switching within targeted drug classes.
ConclusionThis large pragmatic RCT will contribute to the evidence base on promoting deprescribing of potentially inappropriate medications among older adults with dementia. If successful, such light touch, inexpensive and highly scalable interventions have the potential to reduce the burden of potentially inappropriate prescribing for patients with dementia.ClinicalTrials.gov Identifier: NCT05147428.
This study sought to determine the prevalence and associated factors of hepatitis B virus (HBV) infection ever in life and chronic HBV infection in Armenia.
A population-based cross-sectional seroprevalence study combined with a phone survey of tested individuals.
All administrative units of Armenia including 10 provinces and capital city Yerevan.
The study frame was the general adult population of Armenia aged ≥18 years.
The participants were tested for anti-HBV core antibodies (anti-HBc) and HBV surface antigen (HBsAg) using third-generation enzyme immunoassays. In case of HBsAg positivity, HBV DNA and hepatitis D virus (HDV) RNA PCR tests were performed. Risk factors of HBV infection ever in life (anti-HBc positivity) and chronic HBV infection (HBsAg positivity) were identified through fitting logistic regression models.
The seroprevalence study included 3838 individuals 18 years and older. Of them, 90.7% (3476 individuals) responded to the phone survey. The prevalence of anti-HBc positivity was 14.1% (95% CI 13.1% to 15.2%) and HBsAg positivity 0.8% (95% CI 0.5% to 1.1%). The viral load was over 10 000 IU/mL for 7.9% of HBsAg-positive individuals. None of the participants was positive for HDV. Risk factors for HBsAg positivity included less than secondary education (aOR=6.44; 95% CI 2.2 to 19.1), current smoking (aOR=2.56; 95% CI 1.2 to 5.6), and chronic liver disease (aOR=8.44; 95% CI 3.0 to 23.7). In addition to these, risk factors for anti-HBc positivity included age (aOR=1.04; 95% CI 1.04 to 1.05), imprisonment ever in life (aOR=2.53; 95% CI 1.41 to 4.56), and poor knowledge on infectious diseases (aOR=1.32; 95% CI 1.05 to 1.67), while living in Yerevan (vs provinces) was protective (aOR=0.74; 95% CI 0.59 to 0.93).
This study provided robust estimates of HBV markers among general population of Armenia. Its findings delineated the need to revise HBV testing and treatment strategies considering higher risk population groups, and improve population knowledge on HBV prevention.
Critically ill patients are at high risk of acquiring ventilator-associated pneumonia (VAP), which occurs in approximately 20% of mechanically ventilated patients. VAP results either from aspiration of pathogen-contaminated oropharyngeal secretions or contaminated biofilms that form on endotracheal tubes (ETTs) after intubation. VAP results in increased duration of mechanical ventilation, increased intensive care unit and hospital length of stay, increased risk of death and increased healthcare costs. Because of its impact on patient outcomes and the healthcare system, VAP is regarded as an important patient safety issue and there is an urgent need for better evidence on the efficacy of prevention strategies. Modified ETTs that reduce aspiration of oropharyngeal secretions with subglottic secretion drainage or reduce the occurrence of biofilm with a coating of ceragenins (CSAs) are available for clinical use in Canada. In this implementation study, we will evaluate the efficacy of these two types of Health Canada-licensed ETTs on the occurrence of VAP, and impact on patient-centred outcomes.
In this ongoing, pragmatic, prospective, longitudinal, interrupted time, cross-over implementation study, we will compare the efficacy of a CSA-coated ETT (CeraShield N8 Pharma) with an ETT with subglottic secretion drainage (Taper Guard, Covidien). The study periods consist of four alternating time periods of 11 or 12 weeks or a total of 23 weeks for each ETT. All patients intubated with the study ETT in each time period will be included in an intention-to-treat analysis. Outcomes will include VAP incidence, mortality and health services utilisation including antibiotic use and length of stay.
This study has been approved by the Health Sciences Research Ethics Board at Queen’s University. The results of this study will be actively disseminated through manuscript publication and conference presentations.
This study aims to (1) introduce the emergent concept of the retrograde plunge experienced by people living with Alzheimer's disease and (2) illustrate how nurses can accompany those experiencing this phenomenon, as well as their family and formal carers, using the seven-phase inquiry process proposed by Smith and Liehr.
Discursive paper.
After describing the phenomenon and the Story Theory, the 7-phase Inquiry Process presents the fictional story of Mrs. Lurie, a nursing home resident.
Story theory allows nurses to accompany Mrs. Lurie. The emergent concept of retrograde plunge is explained. Different tools such as genograms, story paths and eco-maps are presented. This discussion demonstrates how some perspectives can contribute to a better description of the retrograde plunge phenomenon. The narrative care approach can help give voices to people experiencing retrograde phenomena. The adoption of a perspective that considers embodied language could help to better understand the needs of a person.
There is a lack of consistency and uniformity regarding the understanding of the retrograde phenomenon. This impacts the quality of care for people and the scientific knowledge, research and education of healthcare professionals. This issue should be addressed in future studies.
This article shows how story theory helps nurses accompany those facing a retrograde plunge phenomenon, helps them tell their own stories and finds a way to resolve the situation.
This article paves the way for further developments that must now be realized by the international community of experts involved in the care of people with Alzheimer's disease, from practical, academic and research perspectives.
No patient or public was involved in the design or drafting of the discursive paper.
The retrograde plunge is a phenomenon in which people living with Alzheimer's disease return to their past lives and re-experience with certain events. The retrograde plunge is a well-known concept that is poorly described in scientific literature and is sometimes misunderstood by families and professional caregivers. This discursive article explains the retrograde plunge phenomenon experienced by people living with Alzheimer's disease.
This article demonstrates how story theory helps nurses and families support people with retrograde plunges. This highlights the lack of consistency and uniformity in this phenomenon, which has implications for the quality of care, education and research. Story theory and the seven-phase inquiry process proposed by Smith and Liehr (in Middle-range theory for nursing, Springer Publishing Company, 2023) help to better understand and explain the retrograde plunge phenomenon.
This article advances nurses' knowledge in the different fields of practice, teaching and research. This article proposes links among the retrograde plunge phenomenon, embodied language and narrative care approach; this could offer further ways to develop nursing knowledge. This study has the potential to advance the knowledge of practice and education and offers new opportunities for research.
There was no trial or protocol registration as this article is a discussion.
by Harikrishnan Vijayakumar Sreelatha, Hamza Palekkodan, Ansar Fasaludeen, Lissy K. Krishnan, Klas S. P. Abelson
Usage and reporting of analgesia in animal models of spinal cord injury (SCI) have been sparse and requires proper attention. The majority of experimental SCI research uses rats as an animal model. This study aimed to probe into the effects of some commonly used regimens with NSAIDs and opioids on well-being of the rats as well as on the functional outcome of the model. This eight-week study used forty-two female Wistar rats (Crl: WI), randomly and equally divided into 6 treatment groups, viz. I) tramadol (5mg/kg) and buprenorphine (0.05mg/kg); II) carprofen (5mg/kg) and buprenorphine (0.05mg/kg); III) carprofen (5mg/kg); IV) meloxicam (1mg/kg) and buprenorphine (0.05mg/kg); V) meloxicam (1mg/kg); and VI) no analgesia (0.5 ml sterile saline). Buprenorphine was administered twice daily whereas other treatments were given once daily for five days post-operatively. Injections were given subcutaneously. All animals underwent dental burr-assisted laminectomy at the T10-T11 vertebra level. A custom-built calibrated spring-loaded 200 kilodynes force deliverer was used to induce severe SCI. Weekly body weight scores, Rat Grimace Scale (RGS), and dark-phase home cage activity were used as markers for well-being. Weekly Basso Beattie and Bresnahan (BBB) scores served as markers for functionality together with Novel Object Recognition test (NOR) at week 8 and terminal histopathology using area of vacuolisation and live neuronal count from the ventral horns of spinal cord. It was concluded that the usage of analgesia improved animal wellbeing while having no effects on the functional aspects of the animal model in comparison to the animals that received no analgesics.
by Ursula Just, Helmut Burtscher, Sylvia Jeratsch, Meike Fischer, Carol Stocking, Jens Preussner, Mario Looso, Ralf Schwanbeck, Stefan Günther, Ralf Huss, Lynne Mullen, Thomas Braun
Brain metastasis leads to increased mortality and is a major site of relapse for several cancers, yet the molecular mechanisms of brain metastasis are not well understood. In this study, we established and characterized a new leukemic cell line, FIA10, that metastasizes into the central nervous system (CNS) following injection into the tail vein of syngeneic mice. Mice injected with FIA10 cells developed neurological symptoms such as loss of balance, tremor, ataxic gait and seizures, leading to death within 3 months. Histopathology coupled with PCR analysis clearly showed infiltration of leukemic FIA10 cells into the brain parenchyma of diseased mice, with little involvement of bone marrow, peripheral blood and other organs. To define pathways that contribute to CNS metastasis, global transcriptome and proteome analysis was performed on FIA10 cells and compared with that of the parental stem cell line FDCP-Mix and the related FIA18 cells, which give rise to myeloid leukemia without CNS involvement. 188 expressed genes (RNA level) and 189 proteins were upregulated (log2 ratio FIA10/FIA18 ≥ 1) and 120 mRNAs and 177 proteins were downregulated (log2 ratio FIA10/FIA18 ≤ 1) in FIA10 cells compared with FIA18 cells. Major upregulated pathways in FIA10 cells revealed by biofunctional analyses involved immune response components, adhesion molecules and enzymes implicated in extracellular matrix remodeling, opening and crossing the blood-brain barrier (BBB), molecules supporting migration within the brain parenchyma, alterations in metabolism necessary for growth within the brain microenvironment, and regulators for these functions. Downregulated RNA and protein included several tumor suppressors and DNA repair enzymes. In line with the function of FIA10 cells to specifically infiltrate the brain, FIA10 cells have acquired a phenotype that permits crossing the BBB and adapting to the brain microenvironment thereby escaping immune surveillance. These data and our model system FIA10 will be valuable resources to study the occurrence of brain metastases and may help in the development of potential therapies against brain invasion.
Acute heart failure (HF) is a major cause of unplanned hospitalisation characterised by excess body water. A restriction in oral fluid intake is commonly imposed on patients as an adjunct to pharmacological therapy with loop diuretics, but there is a lack of evidence from traditional randomised controlled trials (RCTs) to support the safety and effectiveness of this intervention in the acute setting.
This study aims to explore the feasibility of using computer alerts within the electronic health record (EHR) system to invite clinical care teams to enrol patients into a pragmatic RCT at the time of clinical decision-making. It will additionally assess the effectiveness of using an alert to help address the clinical research question of whether oral fluid restriction is a safe and effective adjunct to pharmacological therapy for patients admitted with fluid overload.
THIRST (Randomised Controlled Trial within the electronic Health record of an Interruptive alert displaying a fluid Restriction Suggestion in patients with the treatable Trait of congestion) Alert is a single-centre, parallel-group, open-label pragmatic RCT embedded in the EHR system that will be conducted as a feasibility study at an National Health Service (NHS) hospital in London. The clinical care team will be invited to enrol suitable patients in the study using a point-of-care alert with a target sample size of 50 patients. Enrolled patients will then be randomised to either restricted or unrestricted oral fluid intake. Two primary outcomes will be explored (1) the proportion of eligible patients enrolled in the study and (2) the mean difference in oral fluid intake between randomised groups. A series of secondary outcomes are specified to evaluate the effectiveness of the alert, adherence to the randomised treatment allocation and the quality of data generated from routine care, relevant to the outcomes of interest.
This study was approved by Riverside Research Ethics Committee (Ref: 22/LO/0889) and will be published on completion.
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