Conectar
Chronic venous insufficiency (CVI) is a chronic lower limb progressive disorder with significant burden. Graduated compression therapy is the gold-standard treatment, but its underutilisation, as indicated in recent literature, may be contributing to the growing burden of CVI. The aim of this systematic review is to determine the reasons for poor compliance in patients who are prescribed graduated compression therapy in the management of chronic venous insufficiency. A systematic review of the literature was conducted to identify the reasons for non-compliance in wearing graduated compression therapy in the management of chronic venous insufficiency. The keyword search was conducted through Medline, PubMed, CINAHL, Cochrane library, AMED, and Embase databases from 2000 to April 2023. Qualitative and quantitative studies were included with no study design or language limits imposed on the search. The study populations were restricted to adults aged over 18 years, diagnosed with chronic venous insufficiency. Of the 856 studies found, 80 full-text articles were reviewed, with 14 being eligible for the review. Due to the variability in study designs, the results were summarised rather than subjected to meta-analysis. There are five main overarching themes for non-compliance, which are physical limitations, health literacy, discomfort, financial issues, and psychosocial issues with emerging sub-themes. Graduated compression therapy has the potential to reduce the burden of chronic venous insufficiency if patients are more compliant with their prescription.
This scoping review aimed to identify and map the available information on the nutrition care process in older adults with delirium to analyse and summarise key concepts, and gaps, including the barriers and enablers to providing nutrition care for this group.
Scoping review.
This review was conducted in accordance with the JBI methodology for scoping reviews. Published and grey sources in English were considered.
Databases searched were CINAHL, Medline, Embase, JBI Evidence-based Practice, Scopus, ProQuest and Google. The initial search was conducted from October 2021 to March 2022 and repeated in October 2023.
The database search identified 1561 articles, 186 underwent full-text review and 17 articles were included. The grey literature search identified eight articles. Malnutrition and delirium were identified as mutually reinforcing, and nutrition strategies were included as part of multicomponent interventions for delirium management. There was no mention of barriers or enablers to nutrition care and minimal descriptive or empirical data available to guide nutrition care processes in this group.
This scoping review revealed a need for further research into nutrition care processes in older patients with delirium, in particular the barriers and enablers, to inform appropriate management strategies in this vulnerable group.
Providing nutrition care for older patients with delirium is important and further practical guidance could help patients, healthcare staff and families.
This scoping review yielded instructive data suggesting that delirium is an important risk factor for malnutrition and vice versa, which leads to poor patient and health service outcomes.
This scoping review adhered to relevant EQUATOR guidelines and used the Preferred Reporting Items For Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR).
No patient or public contribution.
Previous studies have shown the COVID-19 pandemic was associated with reductions in volume across a spectrum of non-SARS-CoV-2 hospitalizations. In the present study, we examine the impact of the pandemic on patient safety and quality of care.
This is a retrospective population-based study of discharge abstracts.
We applied a set of nationally validated indicators for measuring the quality of inpatient care to hospitalizations in Ontario, Canada between January 2010 and December 2022. We measured 90-day mortality after selected types of higher risk admissions (such as cancer surgery and cardiovascular emergency) and the rate of patient harm events (such as delirium, pressure injuries and hospital-acquired infections) occurring during the hospital stay.
A total 13,876,377 hospitalization episodes were captured. Compared with the pre-pandemic period, and independent of SARS-CoV-2 infection, the pandemic period was associated with higher rates of mortality after bladder cancer resection (adjusted risk ratio [aRR] 1.20 (1.07–1.34)) and open repair for abdominal aortic aneurysm (aRR 1.45 (1.06–1.99)). The pandemic was also associated with higher rates of delirium (adjusted odds ratio [aOR] 1.04 (1.02–1.06)), venous thromboembolism (aOR 1.10 (1.06–1.13)), pressure injuries (aOR 1.28 (1.24–1.33)), aspiration pneumonitis (aOR 1.15 (1.12–1.18)), urinary tract infections (aOR 1.02 (1.01–1.04)), Clostridiodes difficile infection (aOR 1.05 (1.02–1.09)), pneumothorax (aOR 1.08 (1.03–1.13)), and use of restraints (aOR 1.12 (1.10–1.14)), but was associated with lower rates of viral gastroenteritis (aOR 0.22 (0.18–0.28)). During the pandemic, SARS-CoV-2-positive admissions were associated with a higher likelihood of various harm events.
The COVID-19 pandemic was associated with higher rates of patient harm for a wide range of non-SARS-CoV-2 inpatient populations.
Understanding which quality measures are improving or deteriorating can help health systems prioritize quality improvement initiatives.
No patient or public contribution.
by Juan P. Wisnivesky, Nikita Agrawal, Jyoti Ankam, Adam Gonzalez, Alex Federman, Steven B. Markowitz, Janette M. Birmingham, Paula J. Busse
BackgroundPost-traumatic stress disorders (PTSD) is associated with worse asthma outcomes in individuals exposed to the World Trade Center (WTC) site.
Research questionDo WTC workers with coexisting PTSD and asthma have a specific inflammatory pattern that underlies the relationship with increased asthma morbidity?
Study design and methodsWe collected data on a cohort of WTC workers with asthma recruited from the WTC Health Program. Diagnosis of PTSD was ascertained with a Structured Clinical Interview for DSM-5 (Diagnostic and Statistical Manuel of Mental Disorders) and the severity of PTSD symptoms was assessed with the PTSD Checklist 5. We obtained blood and sputum samples to measure cytokines levels in study participants.
ResultsOf the 232 WTC workers with diagnosis of asthma in the study, 75 (32%) had PTSD. PTSD was significantly associated with worse asthma control (p = 0.002) and increased resource utilization (p = 0.0002). There was no significant association (p>0.05) between most blood or sputum cytokines with PTSD diagnosis or PCL-5 scores both in unadjusted and adjusted analyses.
InterpretationOur results suggest that PTSD is not associated with blood and sputum inflammatory markers in WTC workers with asthma. These findings suggest that other mechanisms likely explain the association between PTSD and asthma control in WTC exposed individuals.
by Gerik W. Tushoski-Alemán, Kelly M. Herremans, Patrick W. Underwood, Ashwin Akki, Andrea N. Riner, Jose G. Trevino, Song Han, Steven J. Hughes
BackgroundPancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins.
MethodsTissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples.
ResultsOur findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC.
ConclusionIn this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.
In 2018, the American College of Obstetricians and Gynecologists recommended low-dose aspirin to prevent the onset of pre-eclampsia among women who were at high risk. Factors influencing women’s acceptance of this recommendation span multiple sectors and levels. Understanding how these factors interact will help stakeholders design effective population-level intervention strategies. Our study aims to identify and map relationships among factors influencing the medication decisions of pregnant women at risk of hypertensive disorders.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines will be followed for this review. A research librarian developed a comprehensive search strategy to retrieve published and unpublished English studies after 1 January 1980, involving factors that influence pregnant women’s uptake and adherence to medication for gestational hypertensive disorders. This literature includes perceptions, patterns, acceptance, refusal, tendencies, probability and service utilisation. We will search PubMed, Embase, Web of Science and CINAHL. Reference lists of the selected papers will be searched manually to identify more relevant studies. A two-stage independent screening, consisting of title and abstract screening, followed by full-text screening, will be conducted by two independent reviewers to identify eligible articles. Extracted data will be recorded in a customised variable extraction form and input into a Microsoft Access database. The PRISMA-ScR will be used to guide the presentation of the results, which will be presented in a table and causal map to demonstrate the relationships between extracted variables and medication uptake and adherence. A conceptual simulation model will be formulated to validate the logic of the relationships between variables and identify knowledge gaps. Lastly, experts and stakeholders will be invited to critique and comment on the results.
This study does not require ethical approval. The full review results will be presented at a relevant conference and submitted to a peer-reviewed scientific journal for publication.
To explore the lived experiences of mature female students undertaking a Bachelor of Nursing (Adult) programme in the UK, to gain insight into the challenges and barriers faced by students and investigate the factors that support students who have considered leaving, to stay and continue with their studies.
There is a global shortage of nurses and challenges exist in ensuring that enough nurses are available to provide care in the complex and rapidly changing care environments. Initiatives introduced to increase the number of Registered Nurses (RN), include increasing the number of students enrolled on pre-registration nursing programmes. However, the success of this intervention is contingent on the number of students who go on to complete their course.
This qualitative study employed Interpretative Phenomenological Analysis (IPA), which provided a methodological framework and analytical approach to enable an exploration of participants' individual and shared lived experiences.
Eight female, mature students at the end of their second year of a Bachelor of Nursing (Adult) programme at a Higher Education Institution in South Wales participated in semi-structured, face-to-face interviews, which were analysed idiographically before group-level analysis was undertaken.
The analysis revealed three superordinate themes: ‘Ambition to become a Registered Nurse’; ‘Jugging Roles’ and ‘Particular Support Needs for a Particular Student’.
Each student had a unique history, their past and present social and psychological experiences were multifaceted and complex. These differences resulted in varying degrees of resilience and motivations to continue their studies. These findings are important for ensuring that services develop and provide effective support to maximize retention and, ultimately, increase the number of students entering the RN workforce.
No patient or public contribution.
This research expands on current literature regarding the needs of mature female students, a growing student nurse demographic. Every student had a dynamic set of circumstances and demonstrated that the identification of ‘at-risk’ students, purely based on demographics or information on a Curriculum Vitae, is problematic and potentially futile. This knowledge could be used to tailor University support systems and inform curriculum development and support systems for maximizing student retention. These findings are important for ensuring that services continue to develop and provide effective support to maximize retention and completion and, ultimately, increase the number of students entering the Nursing and Midwifery Council register.
Hospitals are experiencing a nursing shortage crisis that is expected to worsen over the next decade. Acute care settings, which manage the care of very complex patients, need innovations that lessen nurses' workload burden while ensuring safe patient care and outcomes. Thus, a pilot study was conducted to evaluate the feasibility of implementing a large-scale acute care telenurse program, where a hospital-employed telenurse would complete admission and discharge processes for hospitalized patients virtually. In 3 months, almost 9000 (67%) of patient admissions and discharges were conducted by an acute care telenurse, saving the bedside nurse an average of 45 minutes for each admission and discharge. Preliminary benefits to the program included more uninterrupted time with patients, more complete hospital admission and discharge documentation, and positive patient and nurse feedback about the program. by Jaecy K. Banther-McConnell, Thanchira Suriyamongkol, Samuel M. Goodfellow, Robert A. Nofchissey, Steven B. Bradfute, Ivana Mali
Orthohantaviruses are diverse zoonotic RNA viruses. Small mammals, such as mice and rats are common chronic, asymptomatic hosts that transmit the virus through their feces and urine. In North America, hantavirus infection primarily causes hantavirus cardiopulmonary syndrome (HCPS), which has a mortality rate of nearly 36%. In the United States of America, New Mexico (NM) is leading the nation in the number of HCPS-reported cases (N = 129). However, no reported cases of HCPS have occurred within eastern NM. In this study, we assessed the prevalence of Sin Nombre virus (SNV) in rodent assemblages across eastern NM, using RT-qPCR. We screened for potential rodent hosts in the region, as well as identified areas that may pose significant infection risk to humans. We captured and collected blood and lung tissues from 738 rodents belonging to 23 species. 167 individuals from 16 different species were positive for SNV RNA by RT-qPCR, including 6 species unreported in the literature: Onychomys leucogaster (Northern grasshopper mouse), Dipodomys merriami (Merriam’s kangaroo rat), Dipodomys ordii (Ord’s kangaroo rat), Dipodomys spectabilis (Banner-tailed kangaroo rat), Perognathus flavus (Silky pocket mouse), and Chaetodipus hispidus (Hispid pocket mouse). The infection rates did not differ between sexes or rodent families (i.e., Cricetidae vs. Heteromyidae). Generalized linear model showed that disturbed habitat types positively influenced the prevalence of SNV at sites of survey. Overall, the results of this study indicate that many rodent species in east New Mexico have the potential to maintain SNV in the environment, but further research is needed to assess species specific infectivity mechanisms and potential risk to humans.The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS), part of National Disease Registration Service in National Health Service England, quality assures, curates and analyses individual data on the pregnancies, fetuses, babies, children and adults with congenital anomalies and rare diseases across England. The congenital anomaly (CA) register provides a resource for patients and their families, clinicians, researchers and public health professionals in furthering the understanding of CAs.
NCARDRS registers CAs occurring in babies born alive and stillborn, fetal losses and terminations in England. NCARDRS collects data from secondary and tertiary healthcare providers, private providers and laboratories covering fetal medicine, maternity or paediatric services. Data describe the pregnancy, mother, baby and anomaly. Established in 2015, NCARDRS expanded CA registration coverage from 22% of total births in England in 2015 to national coverage, which was achieved in 2018. Prior to 2015, data collection was performed independently by regional registers in England; these data are also held by NCARDRS.
NCARDRS registers approximately 21 000 babies with CAs per year with surveillance covering around 600 000 total births, the largest birth coverage for a CA register globally. Data on prevalence, risk factors and survival for children with CAs are available. Data have been used in several peer-reviewed publications. Birth prevalence statistics, including public health indicators such as the association with maternal age, infant and perinatal mortality, are published annually. NCARDRS supports clinical audit for screening programmes and service evaluation.
NCARDRS provides a valuable resource for the understanding of the epidemiology, surveillance, prevention and treatment of CAs. Currently, approximately 21 000 new registrations of babies or fetuses with suspected or confirmed CAs are added each year. Identifiers are collected, enabling linkage to routinely collected healthcare and population statistics, further enhancing the value of the data.
by Steven Habbous, David Gomez, David Urbach, Erik Hellsten
IntroductionWe examine trends in inguinal hernia repairs with respect to the COVID-19 pandemic and secular trends in Ontario, Canada.
MethodsThis was a retrospective cohort study. Hernia repairs performed January 1, 2010-December 31, 2022 were captured from health administrative inpatient and outpatient databases. Patients managed in three clinical settings were examined: public hospital in-patient, semi-private hospital in-patient (Shouldice Hospital), and public hospital out-patient. We examined the effect of the COVID-19 pandemic on surgical volumes, clinical setting, patient characteristics by setting, time from diagnosis until surgery, hospital length-of-stay, and patient outcomes (90-day readmissions, 1-year reoperations). We used multivariable logistic regression to examine whether patient outcomes were comparable between the COVID-19 period and the pre-pandemic period, adjusted sociodemographic and clinical factors. Shouldice Hospital is the only semi-private hospital in Ontario specializing in hernia repair (patients pay for the mandated admission, but not for the procedure).
ResultsDuring the pandemic (March 2020-December 2022), there were 8,162 fewer (15%) scheduled inguinal hernia repairs than expected, but the age-sex standardized rate of urgent repairs remained unchanged. Shouldice Hospital performed more surgeries in the COVID-19 era than pre-pandemic and had a shorter average LOS by 24 hours, despite treating more patients with older age, higher ASA score [adjusted odds ratio (aOR) 2.13 (1.93–2.35) III vs I-II] and greater comorbidity [aOR 1.36 (1.08–1.70) for 2 vs none] than pre-pandemic. Patients treated in the COVID-19 era experienced a longer time until surgery, being the longest in 2022 (median 133 days). Ninety-day readmissions and 1-year reoperations were lower in the COVID-19 era and lower for patients receiving surgery at Shouldice Hospital.
ConclusionDuring the COVID-19 pandemic, there were 8,162 fewer scheduled hernia repairs than expected, longer wait-times until surgery, shorter length-of-stay, and more patients with comorbidities, but outcomes were not worse compared with the pre-pandemic period.
by Ashley G. Holtz, Troy L. Lowe, Yusuke Aoki, Yutaro Kubota, Robert M. Hoffman, Steven G. Clarke
The methionine addiction of cancer cells is known as the Hoffman effect. While non-cancer cells in culture can utilize homocysteine in place of methionine for cellular growth, most cancer cells require exogenous methionine for proliferation. It has been suggested that a biochemical basis of this effect is the increased utilization of methionine for S-adenosylmethionine, the major methyl donor for a variety of cellular methyltransferases. Recent studies have pointed to the role of S-adenosylmethionine-dependent protein arginine methyltransferases (PRMTs) in cell proliferation and cancer. To further understand the biochemical basis of the methionine addiction of cancer cells, we compared protein arginine methylation in two previously described isogenic cell lines, a methionine-addicted 143B human osteosarcoma cell line and its less methionine-dependent revertant. Previous work showed that the revertant cells were significantly less malignant than the parental cells. In the present study, we utilized antibodies to detect the asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) products of PRMTs in polypeptides from cellular extracts and purified histone preparations of these cell lines fractionated by SDS-PAGE. Importantly, we observed little to no differences in the banding patterns of ADMA- and SDMA-containing species between the osteosarcoma parental and revertant cell lines. Furthermore, enzymatic activity assays using S-adenosyl-ʟ-[methyl-3H] methionine, recombinantly purified PRMT enzymes, cell lysates, and specific PRMT inhibitors revealed no major differences in radiolabeled polypeptides on SDS-PAGE gels. Taken together, these results suggest that changes in protein arginine methylation may not be major contributors to the Hoffman effect and that other consequences of methionine addiction may be more important in the metastasis and malignancy of osteosarcoma and potentially other cancers.by Abel Fekadu Dadi, Vincent He, Georgina Nutton, Jiunn-Yih Su, Steven Guthridge
BackgroundPositive early development is critical in shaping children’s lifelong health and wellbeing. Identifying children at risk of poor development is important in targeting early interventions to children and families most in need of support. We aimed to develop a predictive model that could inform early support for vulnerable children.
MethodsWe analysed linked administrative records for a birth cohort of 2,380 Northern Territory children (including 1,222 Aboriginal children) who were in their first year of school in 2015 and had a completed record from the Australian Early Development Census (AEDC). The AEDC measures early child development (school readiness) across five domains of development. We fitted prediction models, for AEDC weighted summary scores, using a Partial Least Square Structural Equation Model (PLS-SEM) considering four groups of factors–pre-pregnancy, pregnancy, known at birth, and child-related factors. We first assessed the models’ internal validity and then the out-of-sample predictive power (external validity) using the PLSpredict procedure.
ResultWe identified separate predictive models, with a good fit, for Aboriginal and non-Aboriginal children. For Aboriginal children, a significant pre-pregnancy predictor of better outcomes was higher socioeconomic status (direct, β = 0.22 and indirect, β = 0.16). Pregnancy factors (gestational diabetes and maternal smoking (indirect, β = -0.09) and child-related factors (English as a second language and not attending preschool (direct, β = -0.28) predicted poorer outcomes. Further, pregnancy and child-related factors partially mediated the effects of pre-pregnancy factors; and child-related factors fully mediated the effects of pregnancy factors on AEDC weighted scores. For non-Aboriginal children, pre-pregnancy factors (increasing maternal age, socioeconomic status, parity, and occupation of the primary carer) directly predicted better outcomes (β = 0.29). A technical observation was that variance in AEDC weighted scores was not equally captured across all five AEDC domains; for Aboriginal children results were based on only three domains (emotional maturity; social competence, and language and cognitive skills (school-based)) and for non-Aboriginal children, on a single domain (language and cognitive skills (school-based)).
ConclusionThe models give insight into the interplay of multiple factors at different stages of a child’s development and inform service and policy responses. Recruiting children and their families for early support programs should consider both the direct effects of the predictors and their interactions. The content and application of the AEDC measurement need to be strengthened to ensure all domains of a child’s development are captured equally.
by Hamed Keramati, Adelaide de Vecchi, Ronak Rajani, Steven A. Niederer
Accurate velocity reconstruction is essential for assessing coronary artery disease. We propose a Gaussian process method to reconstruct the velocity profile using the sparse data of the positron emission particle tracking (PEPT) in a biological environment, which allows the measurement of tracer particle velocity to infer fluid velocity fields. We investigated the influence of tracer particle quantity and detection time interval on flow reconstruction accuracy. Three models were used to represent different levels of stenosis and anatomical complexity: a narrowed straight tube, an idealized coronary bifurcation with stenosis, and patient-specific coronary arteries with a stenotic left circumflex artery. Computational fluid dynamics (CFD), particle tracking, and the Gaussian process of kriging were employed to simulate and reconstruct the pulsatile flow field. The study examined the error and uncertainty in velocity profile reconstruction after stenosis by comparing particle-derived flow velocity with the CFD solution. Using 600 particles (15 batches of 40 particles) released in the main coronary artery, the time-averaged error in velocity reconstruction ranged from 13.4% (no occlusion) to 161% (70% occlusion) in patient-specific anatomy. The error in maximum cross-sectional velocity at peak flow was consistently below 10% in all cases. PEPT and kriging tended to overestimate area-averaged velocity in higher occlusion cases but accurately predicted maximum cross-sectional velocity, particularly at peak flow. Kriging was shown to be useful to estimate the maximum velocity after the stenosis in the absence of negative near-wall velocity.Brief interventions that reduce suicide risk following youth’s experience with acute care due to suicidality are needed.
The study will use a three-arm randomised controlled trial designed to test the effectiveness of the Safety Planning Intervention with structured follow-up (SPI+) and the Collaborative Assessment and Management of Suicidality (CAMS) compared with enhanced usual care. The primary outcomes measure will be suicidal events, defined as death by suicide, attempted suicide, preparatory acts toward imminent suicidal behaviour or suicidal ideation resulting in a change in emergency evaluation or inpatient admission. Secondary measures will be the number of suicide attempts and severity of suicidal ideation. The experimental interventions, SPI+ and CAMS, consist of up to eight sessions over approximately 8 weeks that are designed to manage (SPI+) or treat (CAMS) patient-identified ‘drivers’ of suicidal thoughts and behaviours. Mechanisms and moderators of change will be evaluated to understand treatment impacts.
This study has been approved by the Seattle Children’s Institutional Review Board and is monitored by external agencies including the University of Washington Institute for Translational Health Sciences, and a National Institute of Mental Health (NIMH)-appointed Data Safety and Monitoring Board. Trial results will help establish evidence towards safe and effective treatment strategies for youth transitioning from acute to outpatient care due to a suicidal crisis. The data will be shared with the NIMH Data Archives and disseminated through publications and conferences.
by Chao Li, Zhong Liu, Justin Anderson, Zhongyu Liu, Liping Tang, Yao Li, Ning Peng, Jianguo Chen, Xueming Liu, Lianwu Fu, Tim M. Townes, Steven M. Rowe, David M. Bedwell, Jennifer Guimbellot, Rui Zhao
A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.Little research exists on how risk scores are used in counselling. We examined (a) how Breast Cancer Risk Assessment Tool (BCRAT) scores are presented during counselling; (b) how women react and (c) discuss them afterwards.
Consultations were video-recorded and participants were interviewed after the consultation as part of the NRG Oncology/National Surgical Adjuvant Breast and Bowel Project Decision-Making Project 1 (NSABP DMP-1).
Two NSABP DMP-1 breast cancer care centres in the USA: one large comprehensive cancer centre serving a high-risk population and an academic safety-net medical centre in an urban setting.
Thirty women evaluated for breast cancer risk and their counselling providers were included.
Participants who were identified as at increased risk of breast cancer were recruited to participate in qualitative study with a video-recorded consultation and subsequent semi-structured interview that included giving feedback and input after viewing their own consultation. Consultation videos were summarised jointly and inductively as a team.tThe interview material was searched deductively for text segments that contained the inductively derived themes related to risk assessment. Subgroup analysis according to demographic variables such as age and Gail score were conducted, investigating reactions to risk scores and contrasting and comparing them with the pertinent video analysis data. From this, four descriptive categories of reactions to risk scores emerged. The descriptive categories were clearly defined after 19 interviews; all 30 interviews fit principally into one of the four descriptive categories.
Risk scores were individualised and given meaning by providers through: (a) presenting thresholds, (b) making comparisons and (c) emphasising or minimising the calculated risk. The risk score information elicited little reaction from participants during consultations, though some added to, agreed with or qualified the provider’s information. During interviews, participants reacted to the numbers in four primary ways: (a) engaging easily with numbers; (b) expressing greater anxiety after discussing the risk score; (c) accepting the risk score and (d) not talking about the risk score.
Our study highlights the necessity that patients’ experiences must be understood and put into relation to risk assessment information to become a meaningful treatment decision-making tool, for instance by categorising patients’ information engagement into types.
The objective of this study is to investigate early-to-late postdoctoral clinical academic progression and the experiences of NIHR Clinical Lectureship (CL) fellows, considering enablers and barriers to success, and identifying the factors associated with immediate progression to a clinical academic role following completion of the award.
Datasets of CL awardees across the UK.
For semistructured interviews, n=40 CL awardees that had finished their award within the previous 5 years. For quantitative analysis, n=1226 completed or currently active CL awardees.
The responses from the semistructured interviews to the defined questions on experiences during the award, postaward progression, and enablers and barriers to academic progression. Other primary outcome measures were quantitative data on first destinations postaward, demographic data, and whether an awardee had previously held an NIHR Academic Clinical Fellowship (ACF) or was a recipient of the Academy of Medical Sciences (AMS) Starter Grant.
CL awardees identified numerous benefits to the award, with the majority achieving their aims. Most awardees progressed to a clinical academic role; however, some returned to a clinical only position, citing concerns around the time pressure associated with balancing clinical and academic responsibilities, and the competition to attain further postdoctoral awards. The region of the award partnership, year of award end and success in applying for an AMS Starter Grant were associated with progression to a clinical academic role. Gender, holding an ACF and having a craft or non-craft specialty had no independent statistical association with clinical academic progression.
The CL is a valued element of the Integrated Academic Pathway. By addressing issues around later postdoctoral progression opportunities, responding to challenges experienced by CLs, and by understanding the factors identified in this study associated with clinical academic progression, it should be possible to increase the proportion of CLs that become fully independent clinical academic research leaders.
1226 NIHR CLs active or completed on the award between 2006 and 2020.
To map out the primary research studies relating to how virtual reality (VR) has been used to distract children and young people with long-term conditions from pain or pruritus.
Pharmacologic treatment of chronic pain and pruritus may have side effects; hence, non-invasive non-pharmacological treatments are being sought.
The scoping review followed the methodology recommended by the Joanna Briggs Institute, PAGER framework and PRISMA-ScR checklist. The protocol was registered with the Open Science Registration on 14 February 2022 https//doi.org/10.17605/OSF.IO/K2R93.
Five databases (Medline, CINAHL, PsycINFO, Web of Science and Scopus) were searched. Data were extracted from primary research studies published between 2000 and 2022 involving children and adolescent populations (<21 years) with a long-term condition that had an element of enduring pruritus and/or pain.
Of 464 abstracts screened, 35 full-text papers were assessed with 5 studies meeting the eligibility criteria. Three main themes emerged from the included studies: (1) Improvements in pain and daily functioning; (2) positive perceptions of VR and (3) accessibility and feasibility of VR. No papers were found on the effect of VR on alleviating pruritus.
VR is feasible, acceptable, and safe for children and adolescents with chronic pain in a range of long-term conditions and offers promise as an adjunctive treatment for improving chronic pain and quality of life. No studies were identified that targeted pruritis or measured pruritis outcomes; thus, the effects of VR for pruritis are unknown. There is a need for rigorously designed, randomised controlled trials to test the clinical and cost-effectiveness of VR interventions for chronic pain and pruritis in children and adolescents. The use of the PAGER (Patterns, Advances, Gaps, Evidence for Practice and Research Recommendations) framework for scoping reviews helped to structure analysis and findings and identify research gaps.
VR interventions offer promise in improving chronic pain related to long-term conditions.
FreshRSS 