Clinical Care Research Articles

Abstract PO1-08-04: Universal Germline Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision Making

Abstract Background: Prior work from our group has shown a high rate of familial breast cancer (BC) among rural BC patients (pts), with 33% reporting > 1 first-degree family members with BC and 55% meeting NCCN germline genetic testing (GGT) criteria (Shelton CH et al. NC Med. J; 2022). In 2018, we increased GGT to include all BC pts and observed: 1) many pts were out-of-criteria per NCCN guidelines but had actionable pathogenic germline variants (PGVs) and 2) knowledge of GGT factored significantly into shared decision making by providers and patients, including for positive and negative results. Beginning in 2019, concurrent with the recommendation from the American Society of Breast Surgeons, we expanded this model of universal GGT to an IRB-approved study to measure the impact of prospective testing on shared decision-making. Herein we report the real-world implementation of universal GGT for patients with BC and genetics-informed treatment decision-making in a rural community practice. Methods: From 2019-2022 all BC pts at a small, rural community hospital were offered GGT. Demographics, clinical features, and GGT results were collected along with clinician-reported clinical recommendations for treatment based on GGT results. Descriptive statistics and two-tailed Fisher’s exact test were employed and significance was set at p< 0.05. Results: 210 BC pts were offered GGT and 192 (91%) underwent testing [97% female, 95% non-Hispanic White, mean age at diagnosis of 62, 75% Stage I], with all but 7 pts completing GGT before primary treatment decisions. 104 (54%) of patients were in-criteria (IC) and 88 (46%) out-of-criteria (OOC) with NCCN GGT guidelines. PGVs were identified in 25 pts (13%) and 15 genes, most commonly BRCA1/2 (5 pts), PALB2 (3), monoallelic MUTYH (3) and ATM, BARD1, CHEK2 (2 pts each). PGV frequencies were 15% in IC and 11% in OOC patients (p=0.495). 46 (24%) pts had only a variant of uncertain significance (VUS) results. 70% of patients had > 1 clinical management change based on their GGT results. Changes in breast surgery, uptake of risk-reducing bilateral salpingo-oophorectomy, surveillance and clinical follow-up were significantly higher in patients with PGV compared to those with VUS/negative results (p < 0.0001). Compared to those with negative results, patients with PGVs in BRCA1 and BRCA2 were significantly more likely to undergo bilateral mastectomy (BLM) while those with PGVs in other genes or with VUS were not significantly more likely to elect for BLM than those with negative results. Clinicians reported that return of GGT reinforced their recommendation for 73/138 (53%) of patients who underwent breast-conserving therapy. GGT results aided in radiation therapy strategy for 54% of pts, most often resulting in dose de-escalation (accelerated fractionation) for negative/VUS pts (Table). Conclusions: Universal GGT for patients with BC was successfully implemented in a rural community practice with >90% uptake. Treatment was enhanced in those with clinically actionable PGVs and de-escalated in those without PGVs. Universal GGT for patients with BC is feasible to implement as the standard of practice within rural populations, enabling optimization of clinical care to patients’ genetic profile and may reduce unnecessary healthcare resource utilization. Universal Germline Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision Making Changes in Radiation Therapy Strategy based on GGT Citation Format: Charles Shelton, Sarah Nielsen, Antonio Ruiz, Lauren Shelton, Karen Freas, Sarah Poll, Brandie Heald, Daniel Pineda-Alvarez, Edward Esplin, Rachel Ellsworth, Hannah Montgomery. Universal Germline Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision Making [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-08-04.

Abstract PO5-12-01: Characteristics of Patients Served by Participants in a Survivorship Navigator Learning Collaborative

Abstract Patient navigation is demonstrated to be a successful model for improving breast cancer screening and early detection, particularly for women in under-resourced communities. The effectiveness of this model has not yet been explored in cancer survivorship. Our research assesses the feasibility of community-based patient navigation after a breast cancer diagnosis. This analysis focuses on the role of patient navigators in providing community-based peer support for women living with breast cancer. We conducted an analysis of data from the Breast Cancer Survivorship Patient Navigator Virtual Learning Collaborative (VLC), a case-based, iterative, virtual training program designed to increase capacity of community-based patient navigators to support women diagnosed with breast cancer. Navigators participated in a 14-week practice-based curriculum focused on improving community support for breast cancer survivors. Each session included a brief lecture followed by a case presentation by a participant. Lecture topics include Breast Cancer 101, Psychosocial support, Treatment options, Clinical trials, Sexual Health, Palliative Care, Genetic Testing, and Trauma. All participants were asked to present at least one de-identified case for discussion, using an 55-item case presentation template. The template included data on patient demographics, diagnosis, treatment, and support. To encourage active learning, navigators were encouraged to present challenging cases for discussion focused on identifying solutions and providing peer support. This analysis focuses on the characteristics of patients presented by community navigators from January 2021 to May 2023. A total of 92 de-identified patient cases were presented by 71 patient navigators and community health workers. (Table 1) The majority of patients were diagnosed within 12 months (62%), with early stage (Stages I-III) disease (78%), and were in active treatment or had not yet started treatment (67%). More than half of the cases had tumors that were HR+ (54%) and nearly half were HER2- (43%); 9% of cases were triple negative and 9% were triple positive. Tumor characteristics were not reported for 27% of cases. Individuals diagnosed with metastatic breast cancer (MBC) compared with those diagnosed with early stage disease were more likely to be Black (59% v 39%), single (56% v 31%), not currently employed (100% v 46%), younger (average age 52 v 55 years old) and insured through Medicaid (56% v 17%) Individuals living with MBC relied more heavily on professional support compared to those diagnosed with early stage disease. The majority of MBC patients relied on the clinical care team (67%) and friends and family (67%) for support, with a large number also receiving support from faith-based organizations (56%), compared to those with early stage disease who relied on friends and family (90%) and the clinical care team (54%). Both groups relied on navigators (33% v 35%) and social workers (44% v 34%), while those with MBC relied more frequently on paid caregivers (44% v 3%), disability services (22% v 6%). The data indicates that individuals with MBC had more unmet needs, including practical support (55% v 33%) and disability (55% v 14%). Supportive care needs vary considerably based on stage of diagnosis, while community-based supportive services are often designed to meet the needs of those diagnosed with early stage disease. Community-based survivorship navigators more readily engage with patients with early stage disease who are newly diagnosed or in active treatment. Individuals with MBC have fewer community-based resources and are less likely to connect with a community-based navigator. Data from our Breast Cancer Survivorship Patient Navigator VLC points to the potential to identify gaps in community-based survivorship care. Future research should focus on expanding the reach of community navigators and ensuring community-based support for patients across all stages. Table 1 Demographics of Patients Presented at VLC Citation Format: Tamara Hamlish, Talia Holzman Castetllands. Characteristics of Patients Served by Participants in a Survivorship Navigator Learning Collaborative [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-01.

Evidence-based care for suicidality as an ethical and professional imperative: How to decrease suicidal suffering and save lives.

Suicide is a major public and mental health problem in the United States and around the world. According to recent survey research, there were 16,600,000 American adults and adolescents in 2022 who reported having serious thoughts of suicide (Substance Abuse and Mental Health Services Administration, 2023), which underscores a profound need for effective clinical care for people who are suicidal. Yet there is evidence that clinical providers may avoid patients who are suicidal (out of fear and perceived concerns about malpractice liability) and that too many rely on interventions (i.e., inpatient hospitalization and medications) that have little to no evidence for decreasing suicidal ideation and behavior (and may even increase risk). Fortunately, there is an emerging and robust evidence-based clinical literature on suicide-related assessment, acute clinical stabilization, and the actual treatment of suicide risk through psychological interventions supported by replicated randomized controlled trials. Considering the pervasiveness of suicidality, the life versus death implications, and the availability of proven approaches, it is argued that providers should embrace evidence-based practices for suicidal risk as their best possible risk management strategy. Such an embrace is entirely consistent with expert recommendations as well as professional and ethical standards. Finally, a call to action is made with a series of specific recommendations to help psychologists (and other disciplines) use evidence-based, suicide-specific, approaches to help decrease suicide-related suffering and deaths. It is argued that doing so has now become both an ethical and professional imperative. Given the challenge of this issue, it is also simply the right thing to do. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effectiveness of kangaroo mother care before clinical stabilisation versus standard care among neonates at five hospitals in Uganda (OMWaNA): a parallel-group, individually randomised controlled trial and economic evaluation

Preterm birth is the leading cause of death in children younger than 5 years worldwide. WHO recommends kangaroo mother care (KMC); however, its effects on mortality in sub-Saharan Africa and its relative costs remain unclear. We aimed to compare the effectiveness, safety, costs, and cost-effectiveness of KMC initiated before clinical stabilisation versus standard care in neonates weighing up to 2000 g. We conducted a parallel-group, individually randomised controlled trial in five hospitals across Uganda. Singleton or twin neonates aged younger than 48 h weighing 700-2000 g without life-threatening clinical instability were eligible for inclusion. We randomly assigned (1:1) neonates to either KMC initiated before stabilisation (intervention group) or standard care (control group) via a computer-generated random allocation sequence with permuted blocks of varying sizes, stratified by birthweight and recruitment site. Parents, caregivers, and health-care workers were unmasked to treatment allocation; however, the independent statistician who conducted the analyses was masked. After randomisation, neonates in the intervention group were placed prone and skin-to-skin on the caregiver's chest, secured with a KMC wrap. Neonates in the control group were cared for in an incubator or radiant heater, as per hospital practice; KMC was not initiated until stability criteria were met. The primary outcome was all-cause neonatal mortality at 7 days, analysed by intention to treat. The economic evaluation assessed incremental costs and cost-effectiveness from a disaggregated societal perspective. This trial is registered with ClinicalTrials.gov, NCT02811432. Between Oct 9, 2019, and July 31, 2022, 2221 neonates were randomly assigned: 1110 (50·0%) neonates to the intervention group and 1111 (50·0%) neonates to the control group. From randomisation to age 7 days, 81 (7·5%) of 1083 neonates in the intervention group and 83 (7·5%) of 1102 neonates in the control group died (adjusted relative risk [RR] 0·97 [95% CI 0·74-1·28]; p=0·85). From randomisation to 28 days, 119 (11·3%) of 1051 neonates in the intervention group and 134 (12·8%) of 1049 neonates in the control group died (RR 0·88 [0·71-1·09]; p=0·23). Even if policy makers place no value on averting neonatal deaths, the intervention would have 97% probability from the provider perspective and 84% probability from the societal perspective of being more cost-effective than standard care. KMC initiated before stabilisation did not reduce early neonatal mortality; however, it was cost-effective from the societal and provider perspectives compared with standard care. Additional investment in neonatal care is needed for increased impact, particularly in sub-Saharan Africa. Joint Global Health Trials scheme of the Department of Health and Social Care, Foreign, Commonwealth and Development Office, UKRI Medical Research Council, and Wellcome Trust; Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Development of palliative care clinical practice guidelines and referral care pathways for primary care practitioners in Pakistan

BackgroundDespite a large burden of life-limitingillness, there exists a dearth of services of palliative care in Pakistan. International guidelines have questionable applicability in Pakistan due to the socioeconomic differences. We generated a protocol describing the process of developing comprehensive palliative care guidelines and palliative care referral pathways for primary care practitioners to adopt in Pakistan.MethodsA GRADE-ADOLOPMENT approach with modification has been employed to create guidelines for a Pakistani context. The “National Comprehensive Cancer Network Guidelines Insights: Palliative Care, Version 2.2021” was used as the source guideline. Recommendations from the source guideline were reviewed by two local palliative care specialists to either “Adopt,” “Adapt” or “Exclude”. The finalized recommendations were incorporated into the local palliative care guideline. Clinical diagnosis and referral pathways were made from the finalized guideline. Any gaps in management found in the pathways were filled by taking existing recommendations from other credible guidelines.ResultsTwenty-seven recommendations were adopted without modification. No recommendations were deemed to be adapted and 15 were excluded. The referral care pathways created were reflective of the local guideline and included elements of initial assessment, preliminary management, reassessment, and referral. 6 additional recommendations were made.ConclusionThe described clinical practice guidelines and primary care clinical referral pathways will aid to standardize palliative care provision in Pakistan. These can be used by other resource constrained settings to develop guidelines within their own local context.

Tumor Size Is Not Everything: Advancing Radiomics as a Precision Medicine Biomarker in Oncology Drug Development and Clinical Care. A Report of a Multidisciplinary Workshop Coordinated by the RECIST Working Group.

Radiomics, the science of extracting quantifiable data from routine medical images, is a powerful tool that has many potential applications in oncology. The Response Evaluation Criteria in Solid Tumors Working Group (RWG) held a workshop in May 2022, which brought together various stakeholders to discuss the potential role of radiomics in oncology drug development and clinical trials, particularly with respect to response assessment. This article summarizes the results of that workshop, reviewing radiomics for the practicing oncologist and highlighting the work that needs to be done to move forward the incorporation of radiomics into clinical trials.

Management of Pediatric Intracranial Arteriovenous Malformations.

Pediatric intracranial arteriovenous malformations (AVMs) are challenging lesions managed by pediatric neurosurgeons. The high risk of hemorrhage and neurologic injury is compounded by the unique anatomy of each malformation that requires individualizing treatment options. This article reviews the current status of pediatric AVM epidemiology, pathophysiology and clinical care, with a specific focus on the rationale and methodology of surgical resection.

The learning experiences and career development expectations of Chinese nursing master's degree students: A qualitative investigation

AimTo explore the learning experiences and career development expectations of nursing master's degree students. BackgroundWith increasing demands for improved quality of life, there is a growing need for nursing graduate programs in clinical care. However, the existing training programs for nursing master's students in China require improvement. It is essential to analyze students' learning experiences, perceptions of the current status of nursing and expectations of the nursing profession to enhance and develop university training programs. DesignA descriptive qualitative study employing semi-structured interviews. MethodSemi-structured interviews were conducted with 14 nursing master's degree students. The data obtained were analyzed using Colaizzi's seven-step phenomenological analysis method. The study adhered to the consolidated criteria for reporting qualitative research (COREQ). ResultsThree main themes emerged from the analysis—Theme 1: Career expectations, encompassing motivations for pursuing the nursing master's program and career aspirations; Theme 2: Study experiences, including nursing professional ability, nursing management ability, self-awareness ability and moral literacy; Theme 3: Occupational dilemmas, encompassing the current challenges and coping strategies. ConclusionThe learning experiences of nursing master's students in universities are closely linked to their training programs. A disparity exists between students' career expectations and the actual employment landscape for nursing master's degree students.

Approach to postpancreatectomy care Impacts outcomes: Retrospective Validation of the PORSCH trial

BackgroundIn the recent PORSCH trial, a three-part postpancreatectomy care algorithm was employed with a near 50 ​% reduction in mortality. We hypothesized that clinical care congruent with this protocol would correlate with better outcomes in our patients. MethodsReal-world postoperative care was compared to the pathway described by the PORSCH trial and patients were assigned into groups based on congruence with its recommendations. The primary composite outcome (PCO) consisted of 90-day mortality, organ failure, and interventions for bleeding. ResultsOf 289 patients, care of 12 ​% was entirely congruent with the PORSCH algorithm. The PCO was recorded in 9 ​% of the PORSCH care group, 8 ​% of the Partial-PORSCH care group, and 19 ​% of the Non-PORSCH care group (p ​= ​0.044). Adverse outcomes were highest when pancreaticoduodenectomy patients received care incongruent with the algorithm's CT imaging recommendations. ConclusionsThese results add external validity to the principles of clinical care underlying the PORSCH algorithm.

Machine learning of ECG waveforms and cardiac magnetic resonance for response and survival after cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) can lead to marked symptom reduction and improved survival in selected patients with heart failure with reduced ejection fraction (HFrEF); however, many candidates for CRT based on clinical guidelines do not have a favorable response. A better way to identify patients expected to benefit from CRT that applies machine learning to accessible and cost-effective diagnostic tools such as the 12-lead electrocardiogram (ECG) could have a major impact on clinical care in HFrEF by helping providers personalize treatment strategies and avoid delays in initiation of other potentially beneficial treatments. This study addresses this need by demonstrating that a novel approach to ECG waveform analysis using functional principal component decomposition (FPCD) performs better than measures that require manual ECG analysis with the human eye and also at least as well as a previously validated but more expensive approach based on cardiac magnetic resonance (CMR). Analyses are based on five-fold cross validation of areas under the curve (AUCs) for CRT response and survival time after the CRT implant using Cox proportional hazards regression with stratification of groups using a Gaussian mixture model approach. Furthermore, FPCD and CMR predictors are shown to be independent, which demonstrates that the FPCD electrical findings and the CMR mechanical findings together provide a synergistic model for response and survival after CRT. In summary, this study provides a highly effective approach to prognostication after CRT in HFrEF using an accessible and inexpensive diagnostic test with a major expected impact on personalization of therapies.

Using AI to Improve Goal Concordant Care: Deep Dive into a 90-Day Mortality Model and Incorporation into Clinical Care (CO202C)

Using AI to Improve Goal Concordant Care: Deep Dive into a 90-Day Mortality Model and Incorporation into Clinical Care (CO202C)

Emulation of randomized trials of direct oral anticoagulants with claims data and implications for new Factor XI inhibitors.

Direct oral anticoagulants (DOACs) revolutionized the management of thromboembolic disorders. Clinical care may be further improved as Factor XIs undergo large-scale outcome trials. What role can non-randomized database studies play in expediting understanding of these drugs in clinical practice? The RCT-DUPLICATIVE Initiative emulated the design of eight DOAC randomized clinical trials (RCT) using non-randomized claims database studies. RCT study design parameters and measurements were closely emulated by the database studies and produced highly concordant results. The results of the single database study that did not meet all agreement metrics with the specific RCT it was emulating were aligned with a meta-analysis of six trials studying similar questions, suggesting the trial result was an outlier. Well-designed database studies using fit-for-purpose data came to the same conclusions as DOAC trials, illustrating how database studies could complement RCTs for Factor XI inhibitors-by accelerating insights in underrepresented populations, demonstrating effectiveness and safety in clinical practice, and testing broader indications.

Perceived misdiagnosis of psychiatric conditions in autistic adults

Many autistic people, particularly women, do not receive an autism diagnosis until adulthood, delaying their access to timely support and clinical care. One possible explanation is that autistic traits may initially be misinterpreted as symptoms of other psychiatric conditions, leading some individuals to experience misdiagnosis of other psychiatric conditions prior to their autism diagnosis. However, little is currently known about the frequency and nature of psychiatric misdiagnoses in autistic adults. Using data collected in the first half of 2019 from an ongoing longitudinal register of autistic adults in the Netherlands, this study explored the frequency of perceived psychiatric misdiagnoses before receiving an autism diagnosis. Gender differences were also explored. A sample of 1211 autistic adults (52.6% women, mean age 42.3 years), the majority of whom were Dutch and relatively highly educated, was evaluated. Results showed that 24.6% (n=298) of participants reported at least one previous psychiatric diagnosis that was perceived as a misdiagnosis. Personality disorders were the most frequent perceived misdiagnoses, followed by anxiety disorders, mood disorders, chronic fatigue syndrome/burnout-related disorders, and attention-deficit/hyperactivity disorder. Autistic women (31.7%) reported perceived misdiagnoses more frequently than men (16.7%). Women were specifically more likely than men to report perceived misdiagnoses of personality disorders, anxiety disorders, and mood disorders. Women also reported prior psychiatric diagnoses more often in general (65.8% versus 34.2% in men). Within the group of individuals with a prior diagnosis, perceived misdiagnoses were equally likely for men and women. One in four autistic adults, and one in three autistic women, reported at least one psychiatric diagnosis, obtained prior to being diagnosed with autism, that was perceived as a misdiagnosis. Inaccurate diagnoses are linked to long diagnostic pathways and delayed recognition of autism. These findings highlight the need for improved training of mental health practitioners, in order to improve their awareness of the presentation of autism in adulthood and of the complex relationship between autism and co-occurring conditions. The current study constitutes a first step towards showing that autistic adults, and particularly women, may be at greater risk of experiencing misdiagnoses. Future studies based on larger, more representative samples are required, to replicate current findings and provide more reliable estimates of the overall frequency of misdiagnoses as well as the frequency of misdiagnoses for specific psychiatric conditions. This study was made possible by funding from the Netherlands Organisation for Health Research and Development (ZonMW), project number 60-63600-98-834.

Unraveling molecular advancements in chordoma tumorigenesis and treatment response: a review of scientific discoveries and clinical implications.

Chordomas are tumors thought to originate from notochordal remnants that occur in midline structures from the cloves of the skull base to the sacrum. In adults, the most common location is the sacrum, followed by the clivus and then mobile spine, while in children a clival origin is most common. Most chordomas are slow growing. Clinical presentation of chordomas tend to occur late, with local invasion and large size often complicating surgical intervention. Radiation therapy with protons has been proven to be an effective adjuvant therapy. Unfortunately, few adjuvant systemic treatments have demonstrated significant effectiveness, and chordomas tend to recur despite intensive multimodal care. However, insight into the molecular underpinnings of chordomas may guide novel therapeutic approaches including selection for immune and molecular therapies, individualized prognostication of outcomes, and real-time noninvasive assessment of disease burden and evolution. At the genomic level, elevated levels of brachyury stemming from duplications and mutations resulting in altered transcriptional regulation may introduce druggable targets for new surgical adjuncts. Transcriptome and epigenome profiling have revealed promoter- and enhancer-dependent mechanisms of protein regulation, which may influence therapeutic response and long-term disease history. Continued scientific and clinical advancements may offer further opportunities for treatment of chordomas. Single-cell transcriptome profiling has further provided insight into the heterogeneous molecular pathways contributing to chordoma propagation. New technologies such as spatial transcriptomics and emerging biochemical analytes such as cell-free DNA have further augmented the surgeon-clinician's armamentarium by facilitating detailed characterization of intra- and intertumoral biology while also demonstrating promise for point-of-care tumor quantitation and assessment. Recent and ongoing clinical trials highlight accelerating interest to translate laboratory breakthroughs in chordoma biology and immunology into clinical care. In this review, the authors dissect the landmark studies exploring the molecular pathogenesis of chordoma. Incorporating this into an outline of ongoing clinical trials and discussion of emerging technologies, the authors aimed to summarize recent advancements in understanding chordoma pathogenesis and how neurosurgical care of chordomas may be augmented by improvements in adjunctive treatments.

Current updates in precision and personalized medicine in sepsis and trauma

Precision and personalized medicine remain an elusive but illustrious goal in the realm of critical care, particularly in the areas of trauma and sepsis. These aims specifically refer to data gathering, interpretation, and treatment application on an individualized basis in the clinical care of patients. Until now, personalized medicine has mainly remained focused on genetics and epigenetic phenomena and has propelled clinical care forward, especially in the field of oncology. Advances in technology and methodology continue to proliferate in early-phase research, and some of these advancements are well poised to break into the clinical sphere of critical care. Here, we describe 2 topics at the forefront of investigation with potent and imminent potential for clinical application.

Flushing and locking management related to central venous catheter occlusion rate among adult patients in acute care: a best practice implementation project.

A central venous catheter (CVC)-a type of central venous access device (CVAD)-is the most common intervention for critical illnesses. Obstruction of the CVC can lead to fatal consequences. Thus, it is critical to maintain catheter lumen patency. The CVC occlusion rate in a hospital in Taiwan was 33%. This project aimed to decrease the CVC occlusion rate in acute care. This project was conceptually informed by the JBI Evidence-Based Model of Healthcare, in particular, the conceptualization of evidence implementation as inclusive of context analysis, implementation, and evaluation of outcomes using evidence-based quality indicators. As part of the seven-phase implementation process, we used audit and feedback in a pre- and post-test design to measure baseline compliance. Based on the initial audit, we developed an implementation strategy responsive to the identified gaps in compliance. We then undertook a final audit to measure changes in compliance to evaluate our implementation effects. The JBI software, PACES, and the situational analysis software, GRiP, were used for data collection and implementation planning. There were six evidence-based criteria, with a sample size of 30 nurses for each criterion. The team carried out the project from September 2022 to January 2023. Post-implementation audit compliance rates increased to 100% for the following criteria: the organization had a standardized flushing and locking solution protocol (0%), the CVAD lumen was locked upon completion of the final flush (10%), a single-dose system was used for flushing and locking the CVAD (60%), and preservative-free 0.9% sodium chloride was used to flush the CVAD (60%). Furthermore, the CVC occlusion rate decreased from 33% to 5%. The project successfully decreased the rate of CVC occlusion and increased the competence of nurses in acute care settings. The implementation of best practices in clinical care should focus on leadership, cross-department coordination, education, and innovation.

Listening to patients, for the patients: The COVAD Study-Vision, organizational structure, and challenges.

The pandemic presented unique challenges for individuals with autoimmune and rheumatic diseases (AIRDs) due to their underlying condition, the effects of immunosuppressive treatments, and increased vaccine hesitancy. The COVID-19 vaccination in autoimmune diseases (COVAD) study, a series of ongoing, patient self-reported surveys were conceived with the vision of being a unique tool to gather patient perspectives on AIRDs. It involved a multinational, multicenter collaborative effort amidst a global lockdown. Leveraging social media as a research tool, COVAD collected data using validated patient-reported outcomes (PROs). The study, comprising a core team, steering committee, and global collaborators, facilitated data collection and analysis. A pilot-tested, validated survey, featuring questions regarding COVID-19 infection, vaccination and outcomes, patient demographics, and PROs was circulated to patients with AIRDs and healthy controls (HCs). We present the challenges encountered during this international collaborative project, including coordination, data management, funding constraints, language barriers, and authorship concerns, while highlighting the measures taken to address them. Collaborative virtual models offer a dynamic new frontier in medical research and are vital to studying rare diseases. The COVAD study demonstrates the potential of online platforms for conducting large-scale, patient-focused research and underscores the importance of integrating patient perspective into clinical care. Care of patients is our central motivation, and it is essential to recognize their voices as equal stakeholders and valued partners in the study of the conditions that affect them.

Implementation of a virtual community of practice to promote the empowerment of middle-aged people with multimorbidity: study protocol of a randomised controlled trial

IntroductionEmpowering people living with multimorbidity (multiple chronic conditions) to gain greater confidence in managing their health can enhance their quality of life. Education focused on self-management is a key tool...

A Simulation-Based Mastery Learning Curriculum Ensures Competency in Discussing Goals of Care for ICU Clinicians

A Simulation-Based Mastery Learning Curriculum Ensures Competency in Discussing Goals of Care for ICU Clinicians

Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy

The quality and quantity of tumor-infiltrating lymphocytes, particularly CD8+ Tcells, are important parameters for the control of tumor growth and response to immunotherapy. Here, we show in murine and human cancers that these parameters exhibit circadian oscillations, driven by both the endogenous circadian clock of leukocytes and rhythmic leukocyte infiltration, which depends on the circadian clock of endothelial cells in the tumor microenvironment. To harness these rhythms therapeutically, we demonstrate that efficacy of chimeric antigen receptor Tcell therapy and immune checkpoint blockade can be improved by adjusting the time of treatment during the day. Furthermore, time-of-day-dependent Tcell signatures in murine tumor models predict overall survival in patients with melanoma and correlate with response to anti-PD-1 therapy. Our data demonstrate the functional significance of circadian dynamics in the tumor microenvironment and suggest the importance of leveraging these features for improving future clinical trial design and patient care.