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Tenecteplase has been shown to be non-inferior to alteplase for the treatment of acute ischemic stroke within 4.5 hours of stroke onset. While not formally approved by regulatory authorities, many jurisdictions have transitioned to using tenecteplase for routine stroke treatment because it is simpler to use and has cost advantages.
Methods:
We report a three-phase time-series analysis over 2.5 years and the process for transition from use of alteplase to tenecteplase for the routine treatment of acute ischemic stroke from a system-wide perspective involving an entire province. The transition was planned and implemented centrally. Data were collected in clinical routine, arising from both administrative sources and a prospective stroke registry, and represent real-world outcome data. Data are reported using standard descriptive statistics.
Results:
A total of 1211 patients were treated with intravenous thrombolysis (477 pre-transition using alteplase, 180 transition period using both drugs, 554 post-transition using tenecteplase). Baseline characteristics, adverse events and outcomes were similar between epochs. There were four dosing errors with tenecteplase, including providing the cardiac dose to two patients. There were no instances of major hemorrhage associated with dosing errors.
Discussion:
The transition to using intravenous tenecteplase for stroke treatment was seamless and resulted in identical outcomes to intravenous alteplase.
Seed genebanks must maintain collections of healthy seeds and regenerate accessions before seed viability declines. Seed shelf life is often characterized at the species level; however, large, unexplained variation among genetic lines within a species can and does occur. This variation contributes to unreliable predictions of seed quality decline with storage time. To assess variation of seed longevity and aid in timing regeneration, ten varieties of pea (Pisum sativum L.), chickpea (Cicer arietinum L.) and lentil (Lens culinaris Medikus subsp. culinaris) from the Australian Grains Genebank were stored at moderate temperature (20°C) and moisture (7–11% water, relative humidity [RH] ~30%) and deterioration was assessed by yearly germination tests for 20 years. Decline in germination was fit to a sigmoidal model and the time corresponding to 50% germination (P50) was used to express seed longevity for each genetic line. The feasibility of using RNA fragmentation to assess changed seed health was measured using RNA integrity number (RIN) from RNA extracted from seeds that were stored for 13 and 20 years. Seed lots of legume grains that maintained high survival throughout the 20 years (i.e. they aged slower than other lines) had higher RIN than samples that degraded faster. RIN was lower in embryonic axes compared with cotyledons in the more deteriorated samples, perhaps indicating that axes exhibit symptoms of ageing sooner than cotyledons. Overall, RIN appears to be associated with longevity indicators of germination for these legumes and indicating that RIN decline can be used to assess ageing rate, which is needed to optimize viability monitoring.
Objectives: Older people with care needs are often supported by their older care-partners (50+). Over time, the increased demand in care needs can result in the care partner placing their own health needs aside. This study was aimed at establishing and piloting a novel co-designed Carer Health and Wellbeing Service (CHWS) that offers multidisciplinary (social work, psychology, occupational therapy, and physiotherapy) one-to-one support to care partners.
Methods: We conducted a pre-post 6-month study design including qualitative and quantitative Methods. Consenting individuals attending the CHWS completed five measures pre- and post- their interaction with the CHWS: Carer Support Needs Assessment Tool (CSNAT); Preparedness for Caregiving Scale (PCS); Family Appraisal of Caregiving Questionnaire (FACQ); EuroQoL Five Dimension Five Level Scale (EQ-5D-5L); and Health Economics Survey.
Results: Service operation commenced 1 day/week in March 2024 with 16 participants to date. Preliminary pre- service use indicates care partners feel underprepared for the carer role (particularly emotionally and psychologically), experience high levels of guilt when addressing their own care needs and are unsure about how to advocate or navigate the existing support system. Care partners have been coached to identify, prioritize, and address their current health and wellbeing needs. Additional findings regarding the implementation of the CHWS will be reported in this presentation.
Conclusions: The preliminary sample presents several emotional and psychological needs that need addressing. These will inform the type of support services to be provided as part of the CHWS, which will also be presented at the conference.
Although pediatric cancer often causes significant stress for families, most childhood cancer survivors are resilient and do not exhibit severe or lasting psychopathology. Research demonstrates some survivors may report benefit-finding or positive outcomes following this stressful life event. However, considerably less research has included families of children who are unlikely to survive their illness. Thus, this study investigated benefit-finding among parents and their children with advanced cancer, as well as associated demographic and medical factors.
Methods
Families (N = 72) of children with advanced cancer (ages 5–25) were recruited from a large pediatric hospital. Advanced cancer was defined as relapsed or refractory disease, an estimated prognosis of <60%, or referral to end-of-life care. Participants completed a demographic survey and the Benefit Finding Scale at enrollment.
Results
Children, mothers, and fathers reported moderate to high benefit-finding scores. Correlations between family members were weak and non-significant. Children reported significantly higher benefit-finding than fathers. Demographic and medical factors were not associated with benefit-finding in children, mothers, or fathers.
Significance of results
Families of children with advanced cancer reported moderate to high benefit-finding regardless of background or medical factors. Children identified benefits of their cancer experience independent of the experiences of their mothers and fathers. Larger studies should continue to examine factors associated with positive and negative outcomes in the context of childhood cancer to inform interventions.
To characterize caregiver experiences in the context of advanced pediatric cancer by identifying individual (i.e., demographic factors, stress) and family context factors (i.e., family roles, social support) associated with caregiver strain.
Methods
Families of children (ages 5–25) with advanced cancer (i.e., physician-estimated prognosis < 60%, relapsed/refractory disease) were recruited from a large children’s hospital. Mothers (n = 55; 87% White) and fathers (n = 30; 83% White) reported on their caregiver strain, cancer-specific stress, general stress, social support, division of 7 family roles (e.g., medical care of ill child, household chores), and their satisfaction with each role.
Results
Parents reported moderate caregiver strain, cancer-specific stress, and general stress, and high social support and satisfaction with family roles. Fathers reported family roles were shared equally, whereas mothers reported either sharing roles or completing them independently. When accounting for income and partnership status, greater caregiver strain for mothers was associated with greater general stress, greater satisfaction with family roles, and lower social support. For fathers, greater caregiver strain was associated only with greater cancer-specific stress.
Significance of results
In the context of advanced pediatric cancer, fathers may experience caregiver strain as cancer-specific stress increases, whereas mothers’ strain may depend on broader family and social factors. Psychosocial providers should address general and cancer-specific stress within families, and provide resources for enhancing mothers’ social support. Additional research is needed with larger, more diverse samples to inform future intervention approaches.
A gap in the literature exists pertaining to a global research nurse/research midwife resources and communication skill set necessary to engage with participants of diverse populations and geographic regions in the community or home-based conduct of decentralized clinical trials.
Aims:
An embedded mixed methods study was conducted to examine research nurse/research midwife knowledge base, experiences, and communication skill sets pertaining to decentralized trials across global regions engaged in remote research: the USA, Republic of Ireland, United Kingdom, and Australia.
Methods:
An online survey was deployed across international research nurse/research midwife stakeholder groups, collecting demographics, decentralized trial experience, barriers and facilitators to optimal trial conduct, and the self-perceived communication competence (SPCC) and interpersonal communication competence (IPCC) instruments.
Results:
86 research nurses and research midwives completed the survey across all countries: The SPCC and IPCC results indicated increased clinical research experience significantly correlated with increased SPCC score (p < 0.05). Qualitative content analysis revealed five themes: (1) Implications for Role, (2) Safety and Wellbeing, (3) Training and Education, (4) Implications for Participants, and (5) Barriers and Facilitators.
Conclusions:
Common trends and observations across the global sample can inform decentralized trial resource allocation and policy pertaining to the research nurse/research midwife workforce. This study demonstrates shared cultural norms of research nursing and midwifery across varied regional clinical trial ecosystems.
Adolescents with cancer often experience significant symptom burden and aggressive treatment near end-of-life. Increased adolescent involvement in care and decision-making may benefit health outcomes. Limited research has examined factors associated with adolescents’ involvement in care in the context of advanced disease. Thus, we examined the impact of background factors and decision-making perceptions on both adolescents’ involvement in care and their desired change in involvement.
Methods
Adolescents with advanced cancer (<60% survival or refractory/relapsed disease), ages 10–23 (n = 41; Mage = 15.37), were recruited approximately 1 month after diagnosis to complete measures of decision-making perceptions and their family role. Hierarchical regressions examined the contributions of background factors and decision-making perceptions to adolescents’ frequency and desired involvement in their care. Qualitative interviews regarding decision-making were analyzed using deductive analysis.
Results
The model examining frequency of involvement in care was significant, F(5,34) = 3.12, p = .02, R2= .31. Older age was the only significant predictor (β = .13, p= .003). The model examining desired involvement was non-significant, F(5,34) = 2.22, p = .075. Qualitative analysis indicated that (1) older adolescents have more involvement in decision-making, (2) collaborative decision-making occurred between the adolescent and extended family, and (3) adolescents trusted others to make decisions. Integration of qualitative and quantitative data revealed congruence in findings.
Significance of results
Adolescents with advanced cancer, who consider how decisions directly impact them and prefer greater autonomy, may be more involved in their medical care. Research is needed to identify other longitudinal predictors of decision-making and involvement in care. Providers should consider encouraging families to communicate their preferences and engage in shared decision-making.
Hospitals play a significant and important role in funding high-cost medicines so patients can access treatments they need. High-cost medicines are often specialty medicines, which contribute to a significant and increasing portion of the hospital budget. It is imperative that these expensive medicines are governed and managed with a fair, standardized evidence-based process. We aim to provide a framework for Drugs and Therapeutics Committees (DTCs).
Methods
During 2021, Guiding Principles were developed following a literature review and survey of current practices by DTCs in Australia. An Expert Advisory Group (EAG) was convened, comprising individuals with expertise in quality use of medicines, evidence-based medicine and medicines governance. The guiding principles were drafted by the EAG, in consultation with a range of stakeholders and relevant external organizations. All feedback was collated, reviewed and discussed to refine the content of the final Guiding Principles released in January 2022.
Results
Seven overarching principles provide key recommendations for the governance of high-cost medicines:
(i) A definition of high‑cost medicines should be determined and clearly articulated for use by each medicines governance committee.
(ii) Review of high-cost medicines requires members with relevant expertize to facilitate good and effective decision-making.
(iii) The committee should engage directly with the applicant prior to review to ensure a full understanding of the rationale for the request.
(iv) consistent, robust and transparent procedure for the assessment of high-cost medicine applications should be defined and implemented for use by each medicines governance committee to ensure fair process.
(v) Ethical considerations fundamentally underpin deliberations around high-cost medicines.
(vi) The decisions and outcomes of the decision making should be transparent and appropriately communicated to the various audiences.
(vii) The high-quality assessment of high-cost medicines requires appropriate training and resourcing.
Conclusions
These national Guiding Principles promote consistent, evidence-based use of high-cost medicines and provide a framework for DTCs to assess and achieve effective governance for the quality use of high‑cost medicines.
In contrast to high-volume medicines prescribed by general practitioners, low-volume highly specialized medicines have not been supported by national quality use of medicine (QUM) programs in Australia. The first area addressed has focused on optimizing use of biological disease-modifying antirheumatic drugs (bDMARDs).
Methods
The program was designed, developed and implemented in partnership with nine consortium member organizations and four affiliate organizations representing consumer and clinical audiences, program development expertize and implementation capability. The common agenda for the collective impact approach was to achieve better health outcomes for people with inflammatory arthritis, inflammatory bowel disease and plaque psoriasis. Multidisciplinary expert working groups reviewed formative QUM research and agreed on objectives, audiences, messages and interventions. Interventions were selected based on identified barriers, enablers and behavioral drivers, informed by the Theoretical Domains Framework. Interventions were co-designed and tested with end-users. Marketing and promotion activity supported implementation of all interventions through consortium channels and networks. Evaluation includes process, impact and outcome measures, and a realist evaluation of the academic detailing.
Results
Program objectives were to optimize: (i) first-line therapy before bDMARD use; (ii) first-choice bDMARDs; (iii) biosimilar prescribing and dispensing; (iv) bDMARD dosage; (v) glucocorticoid and analgesic use. Over 60 interventions supporting key messages for each objective were developed for audiences: consumers; rheumatologists, gastroenterologists, dermatologists; pharmacists; drug and therapeutic committees. Interventions implemented between September 2020 and September 2022 included: consumer decision aids, action plans, fact sheets, lived experience videos; living guidelines and evidence summaries; guidance/position statements for hospitals, podcasts, webinars, online learning; prescribing feedback reports; and academic detailing. Uptake of interventions has largely met targets and surveys have demonstrated shifts in specialist and consumer knowledge and behavior in line with key messages and objectives. Realist and outcome evaluation is ongoing.
Conclusions
Our experience demonstrates the value of a consortium of stakeholder organizations, with different expertise and interests but agreed goals and roles, working together to progress the quality use of highly specialized drugs.
In this chapter I argue that Adam Smith’s moral, social and economic thought was influenced by both Stoic and Epicurean sources with surprising and fruitful results. Although these schools of thought conflicted in most respects, Smith adopted and adapted elements from each to creatively construct a kind of ‘benign-realist’ social science able to explain the order of the human universe while comprehending humans as they really were rather than as we might wish them to be. By combining the Stoic idea that all of nature is both divine and benign with a pragmatic Epicurean moral psychology, Smith not only reconciles his own realist intuitions with his sincere faith in a designed universe, but produces a compelling account of how economies and societies should operate. I show this by exploring how Smith responded to the Stoic and Epicurean approaches to virtue, self-interest, benevolence, justice and our obligations to others, especially strangers and foreigners. I also explore how he applied an Epicurean sensibility to reimagine Stoic cosmopolitanism.
This article aims to explore the ethical issues arising from attempts to diversify genomic data and include individuals from underserved groups in studies exploring the relationship between genomics and health. We employed a qualitative synthesis design, combining data from three sources: 1) a rapid review of empirical articles published between 2000 and 2022 with a primary or secondary focus on diversifying genomic data, or the inclusion of underserved groups and ethical issues arising from this, 2) an expert workshop and 3) a narrative review. Using these three sources we found that ethical issues are interconnected across structural factors and research practices. Structural issues include failing to engage with the politics of knowledge production, existing inequities, and their effects on how harms and benefits of genomics are distributed. Issues related to research practices include a lack of reflexivity, exploitative dynamics and the failure to prioritise meaningful co-production. Ethical issues arise from both the structure and the practice of research, which can inhibit researcher and participant opportunities to diversify data in an ethical way. Diverse data are not ethical in and of themselves, and without being attentive to the social, historical and political contexts that shape the lives of potential participants, endeavours to diversify genomic data run the risk of worsening existing inequities. Efforts to construct more representative genomic datasets need to develop ethical approaches that are situated within wider attempts to make the enterprise of genomics more equitable.
This qualitative study examined how families share information and feelings about advanced pediatric cancer from the perspective of both parents and children, as well as how these perspectives vary by child developmental stage.
Methods
Participants (24 mothers, 20 fathers, 23 youth [children and adolescents]) were from a larger longitudinal study at an academic pediatric hospital. Eligible youth had advanced cancer (physician-estimated prognosis of <60%, relapse, or refractory disease), were aged 5–19 years (>8 years old to participate independently), had an English-speaking parent, and lived within 140 miles of the hospital. Interviews were completed at enrollment and asked how families share information and emotions about the child’s cancer as a family.
Results
Saturation was reached at 20 interviews for mothers, fathers, and youth. Analyses revealed 4 major themes: (A) parents managing cancer-related information based on child age/developmental stage and processing styles of family members; (B) parents withholding poor prognosis information and emotions to maintain positivity; (C) lack of personal and familial emotion sharing; and (D) emotion sharing among their family and externally. Both parents and youth endorsed themes A, C, and D, but only parents endorsed theme B. Adolescents endorsed more themes than children. Parents of children (as opposed to adolescents) endorsed theme A more.
Significance of results
Although both parents and youth with advanced cancer were generally willing to talk about treatment, emotions were not consistently shared. Perspectives varied depending on the child’s developmental stage. Clinicians should assess parent and child information and emotion-sharing needs and provide individualized support to families regarding communication about advanced cancer.
Pain following surgery for cardiac disease is ubiquitous, and optimal management is important. Despite this, there is large practice variation. To address this, the Paediatric Acute Care Cardiology Collaborative undertook the effort to create this clinical practice guideline.
Methods:
A panel of experts consisting of paediatric cardiologists, advanced practice practitioners, pharmacists, a paediatric cardiothoracic surgeon, and a paediatric cardiac anaesthesiologist was convened. The literature was searched for relevant articles and Collaborative sites submitted centre-specific protocols for postoperative pain management. Using the modified Delphi technique, recommendations were generated and put through iterative Delphi rounds to achieve consensus
Results:
60 recommendations achieved consensus and are included in this guideline. They address guideline use, pain assessment, general considerations, preoperative considerations, intraoperative considerations, regional anaesthesia, opioids, opioid-sparing, non-opioid medications, non-pharmaceutical pain management, and discharge considerations.
Conclusions:
Postoperative pain among children following cardiac surgery is currently an area of significant practice variability despite a large body of literature and the presence of centre-specific protocols. Central to the recommendations included in this guideline is the concept that ideal pain management begins with preoperative counselling and continues through to patient discharge. Overall, the quality of evidence supporting recommendations is low. There is ongoing need for research in this area, particularly in paediatric populations.
To describe the clinical impact of healthcare-associated (HA) respiratory syncytial virus (RSV) in hospitalized adults.
Design:
Retrospective cohort study within a prospective, population-based, surveillance study of RSV-infected hospitalized adults during 3 respiratory seasons: October 2017–April 2018, October 2018–April 2019, and October 2019–March 2020.
Setting:
The study was conducted in 2 academically affiliated medical centers.
Patients:
Each HA-RSV patient (in whom RSV was detected by PCR test ≥4 days after hospital admission) was matched (age, sex, season) with 2 community-onset (CO) RSV patients (in whom RSV was detected ≤3 days of admission).
Methods:
Risk factors and outcomes were compared among HA-RSV versus CO-RSV patients using conditional logistic regression. Escalation of respiratory support associated with RSV detection (day 0) from day −2 to day +4 was explored among HA-RSV patients.
Results:
In total, 84 HA-RSV patients were matched to 160 CO-RSV patients. In HA-RSV patients, chronic kidney disease was more common, while chronic respiratory conditions and obesity were less common. HA-RSV patients were not more likely to be admitted to an ICU or require mechanical ventilation, but they more often required a higher level of care at discharge compared with CO-RSV patients (44% vs 14%, respectively). Also, 29% of evaluable HA-RSV patients required respiratory support escalation; these patients were older and more likely to have respiratory comorbidities, to have been admitted to intensive care, and to die during hospitalization.
Conclusions:
HA-RSV in adults may be associated with escalation in respiratory support and an increased level of support in living situation at discharge. Infection prevention and control strategies and RSV vaccination of high-risk adults could mitigate the risk of HA-RSV.
Neurocognitive testing may advance the goal of predicting near-term suicide risk. The current study examined whether performance on a Go/No-go (GNG) task, and computational modeling to extract latent cognitive variables, could enhance prediction of suicide attempts within next 90 days, among individuals at high-risk for suicide.
Method
136 Veterans at high-risk for suicide previously completed a computer-based GNG task requiring rapid responding (Go) to target stimuli, while withholding responses (No-go) to infrequent foil stimuli; behavioral variables included false alarms to foils (failure to inhibit) and missed responses to targets. We conducted a secondary analysis of these data, with outcomes defined as actual suicide attempt (ASA), other suicide-related event (OtherSE) such as interrupted/aborted attempt or preparatory behavior, or neither (noSE), within 90-days after GNG testing, to examine whether GNG variables could improve ASA prediction over standard clinical variables. A computational model (linear ballistic accumulator, LBA) was also applied, to elucidate cognitive mechanisms underlying group differences.
Results
On GNG, increased miss rate selectively predicted ASA, while increased false alarm rate predicted OtherSE (without ASA) within the 90-day follow-up window. In LBA modeling, ASA (but not OtherSE) was associated with decreases in decisional efficiency to targets, suggesting differences in the evidence accumulation process were specifically associated with upcoming ASA.
Conclusions
These findings suggest that GNG may improve prediction of near-term suicide risk, with distinct behavioral patterns in those who will attempt suicide within the next 90 days. Computational modeling suggests qualitative differences in cognition in individuals at near-term risk of suicide attempt.
To reduce both inappropriate testing for and diagnosis of healthcare-onset (HO) Clostridioides difficile infections (CDIs).
Design:
We performed a retrospective analysis of C. difficile testing from hospitalized children before (October 2017–October 2018) and after (November 2018–October 2020) implementing restrictive computerized provider order entry (CPOE).
Setting:
Study sites included hospital A (a ∼250-bed freestanding children’s hospital) and hospital B (a ∼100-bed children’s hospital within a larger hospital) that are part of the same multicampus institution.
Methods:
In October 2018, we implemented CPOE. No testing was allowed for infants aged ≤12 months, approval of the infectious disease team was required to test children aged 13–23 months, and pathology residents’ approval was required to test all patients aged ≥24 months with recent laxative, stool softener, or enema use. Interrupted time series analysis and Mann-Whitney U test were used for analysis.
Results:
An interrupted time series analysis revealed that from October 2017 to October 2020, the numbers of tests ordered and samples sent significantly decreased in all age groups (P < .05). The monthly median number of HO-CDI cases significantly decreased after implementation of the restrictive CPOE in children aged 13–23 months (P < .001) and all ages combined (P = .003).
Conclusion:
Restrictive CPOE for CDI in pediatrics was successfully implemented and sustained. Diagnostic stewardship for CDI is likely cost-saving and could decrease misdiagnosis, unnecessary antibiotic therapy, and overestimation of HO-CDI rates.
There is a need for a paradigm shift across mental health in primary care to improve the lives of millions of Europeans. To contribute to this paradigm shift, the European Forum for Primary Care (EFPC-MH) working group for Mental Health, produced a Position Paper for Primary Care Mental Health outlining 14 themes that needed prioritizing. These themes were developed and discussed interactively during the EFPC conferences between 2012 and 2019. The Position Paper on Mental Health gives direction to the necessary improvements over the next ten years. The themes vary from preferable healthcare model to the social determinants highlighting issues such as inequalities. The Statement of Mental Health in Primary Care will be established in cooperation with fellow organizations.
Characterizing non-lethal damage within dry seeds may allow us to detect early signs of ageing and accurately predict longevity. We compared RNA degradation and viability loss in seeds exposed to stressful conditions to quantify relationships between degradation rates and stress intensity or duration. We subjected recently harvested (‘fresh’) ‘Williams 82’ soya bean seeds to moisture, temperature and oxidative stresses, and measured time to 50% viability (P50) and rate of RNA degradation, the former using standard germination assays and the latter using RNA Integrity Number (RIN). RIN values from fresh seeds were also compared with those from accessions of the same cultivar harvested in the 1980s and 1990s and stored in the refrigerator (5°C), freezer (−18°C) or in vapour above liquid nitrogen (−176°C). Rates of viability loss (P50−1) and RNA degradation (RIN⋅d−1) were highly correlated in soya bean seeds that were exposed to a broad range of temperatures [holding relative humidity (RH) constant at about 30%]. However, the correlation weakened when fresh seeds were maintained at high RH (holding temperature constant at 35°C) or exposed to oxidizing agents. Both P50−1 and RIN⋅d−1 parameters exhibited breaks in Arrhenius behaviour near 50°C, suggesting that constrained molecular mobility regulates degradation kinetics of dry systems. We conclude that the kinetics of ageing reactions at RH near 30% can be simulated by temperatures up to 50°C and that RNA degradation can indicate ageing prior to and independent of seed death.
Pediatric long-term care facilities were surveyed to assess infection control and antimicrobial stewardship practices. Policies mandated by the Centers of Medicare and Medicaid Services (CMS) were included. Only 40% of sites reported implementing >90% of surveyed CMS policies. The survey also identified several gaps in non–CMS-mandated policies.