Eprenetapopt combined with venetoclax and azacitidine in TP53-mutated acute myeloid leukaemia: a phase 1, dose-finding and expansion study.

BACKGROUND: TP53-mutated acute myeloid leukaemia is associated with poor outcomes. Eprenetapopt (APR-246) is a first-in-class, small-molecule p53 reactivator. We aimed to evaluate the combination of eprenetapopt and venetoclax with or without azacitidine in patients with TP53-mutated acute myeloid leukaemia. METHODS: This phase 1, multicentre, open-label, dose-finding and cohort expansion study was done at eight academic research hospitals in the USA. Inclusion criteria were age of at least 18 years; at least one pathogenic TP53 mutation; treatment-naive acute myeloid leukaemia according to the 2016 WHO classification; an ECOG performance status of 0-2; and a life expectancy of at least 12 weeks. In dose-finding cohort 1 patients received previous therapy with hypomethylating agents for myelodysplastic syndromes. In dose-finding cohort 2, previous use of hypomethylating agents was not permitted. Treatment cycles were 28 days. Patients in cohort 1 received intravenous eprenetapopt 4·5 g/day on days 1-4 and oral venetoclax 400 mg/day on days 1-28; those in cohort 2 also received subcutaneous or intravenous azacitidine 75 mg/m2 on days 1-7. The expansion part of the study proceeded with patients enrolled as in cohort 2. Primary endpoints were safety in all cohorts (assessed in patients receiving at least one dose of assigned treatment) and complete response in the expansion cohort (assessed in patients who completed at least one treatment cycle and had at least one post-treatment clinical response assessment). The trial is registered with ClinicalTrials.gov, NCT04214860, and is complete. FINDINGS: Between Jan 3, 2020, and July 22, 2021, 49 patients were enrolled across all cohorts. Six patients were initially enrolled into each of dose-finding cohorts 1 and 2; after no dose-limiting toxicities were observed, cohort 2 was expanded to enrol an additional 37 patients. The median age was 67 years (IQR 59-73). 24 (49%) of 49 patients were female and 25 (51%) male, and 40 (82%) were White. At data cutoff (Oct 1, 2021), the median length of follow-up was 9·5 months (IQR 6·1-11·5). No dose-limiting toxicities were recorded and the recommended phase 2 dose for eprenetapopt combinations was 4·5 g/day on days 1-4. Across all patients, adverse events of grade 3 or worse occurring in at least 20% of patients were febrile neutropenia (23 [47%] of 49 patients), thrombocytopenia (18 [37%] patients), leukopenia (12 [25%] patients), and anaemia (11 [22%] patients). Treatment-related serious adverse events occurred in 13 (27%) of 49 patients and there was one (2%) treatment-related death (sepsis). 25 (64%, 95% CI 47-79) of 39 patients had an overall response with eprenetapopt and venetoclax with azacytidine; 15 (38%, 23-55) had a complete response. INTERPRETATION: Eprenetapopt and venetoclax with azacitidine had an acceptable safety profile and encouraging activity, supporting further frontline evaluation of this combination in the treatment of TP53-mutated acute myeloid leukaemia. FUNDING: Aprea Therapeutics.

Infusion Nursing.

With a focus on safety, these nurses manage all infusion needs.

A multi-year science research or engineering experience in high school gives women confidence to continue in the STEM pipeline or seek advancement in other fields: A 20-year longitudinal study.

There remains a large gender imbalance in the science, technology, engineering and mathematics (STEM) workforce deriving from a leaky pipeline where women start losing interest and confidence in science and engineering as early as primary school. To address this disparity, the Science Research & Engineering Program (SREP) at Hathaway Brown School was established in 1998 to engage and expose their all-female high school students to STEM fields through an internship-like multi-year research experience at partnering institutions. We compare data from existing Hathaway Brown School SREP alumnae records from 1998-2018 (n = 495) to Non-SREP students and national datasets (National Center for Educational Statistics, National Science Foundation, and US Census data) to assess how SREP participation may influence persistence in the STEM pipeline and whether SREP alumnae attribute differences in these outcomes to the confidence and skill sets they learned from the SREP experience. The results reveal that women who participate in the SREP are more likely to pursue a major in a STEM field and continue on to a STEM occupation compared to non-SREP students, national female averages, and national subsets. Participants attribute their outcomes to an increase in confidence, establishment of technical and professional skills, and other traits strengthened through the SREP experience. These data suggest that implementing similar experiential programs for women in science and engineering at the high school stage could be a promising way to combat the remaining gender gap in STEM fields.

MultiPole pacing in non-responders to cardiac resynchronization therapy: Results from the QP ExCELs/MPP sub-study.

BACKGROUND: Multisite LV stimulation therapy allows for stimulation of two different left ventricular pacing vectors within a single LV lead and may improve responsiveness to cardiac resynchronization therapy (CRT). This study prospectively evaluated the safety and efficacy of the MultiPole Pacing (MPP) feature in CRT non-responder patients. METHODS AND RESULTS: CRT non-responders with a standard CRT-D indication were eligible for enrollment into the MPP Sub-Study. Patient status, NYHA classification, Patient Global Assessment (PGA), and adverse events were collected at follow-up. A clinical composite score (CCS) was determined at the 6 month follow-up visit. The primary objective was defined as the proportion of patients with an improved CCS. Safety was evaluated as freedom from MPP system related adverse events requiring additional invasive intervention to resolve. A total of 53 patients were enrolled across 26 U.S. centers. The cumulative follow-up duration was 24.1 years. CCS was improved in 35.6% of patients (p < .0001 when compared to a performance goal of 3%) after 6 months of MPP therapy. When incorporating patient feedback into a modified CCS, 60.0% of patients showed an improvement. Three patients (5.7%) experienced hospitalization for heart failure, and three patient deaths occurred over the follow-up period. No MPP system-related events were reported for an AE-free rate of 100% (95% CI 93.28% to 100.0%). CONCLUSIONS: The results of this small, non-randomized study suggest that the MPP feature is safe, and may be effective at converting a percentage of CRT non-responders to responders. Larger, randomized studies are needed to confirm this result.

Utilization and programming of an automatic MRI recognition feature for cardiac rhythm management devices.

BACKGROUND: Cardiac implantable electronic devices (CIED)-ie, pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices-have recently been designed to allow for patients to safely undergo magnetic resonance imaging (MRI) when specific programming is implemented. MRI AutoDetect is a feature that automatically switches CIED's programming into and out of an MR safe mode when exposed to an MRI environment. OBJECTIVE: The purpose was to analyze de-identified daily remote transmission data to characterize the utilization of the MRI AutoDetect feature. METHODS: Home Monitoring transmission data collected from MRI AutoDetect-capable devices were retrospectively analyzed to determine the workflow and usage in patients experiencing an MRI using the MRI AutoDetect feature. RESULTS: Among 48,756 capable systems, 2197 devices underwent an MRI using the MRI AutoDetect feature. In these 2197 devices, the MRI AutoDetect feature was used a total of 2806 times with an average MRI exposure of 40.83 minutes. The majority (88.9%) of MRI exposures occurred on the same day as the MRI AutoDetect programming. A same day post-MRI exposure follow-up device interrogation was performed 8.6% of the time. A device-related complaint occurred within 30 days of the MRI exposure in 0.25% of MRI exposures using MRI AutoDetect but with no adverse clinical outcome. CONCLUSION: As a result of automation in device programming, the MRI AutoDetect feature eliminated post-MRI device reprogramming in 91.4% of MRI exposures and, while less frequent, allowed for pre-MRI interrogations prior to the day of the MRI exposure-reducing resource utilization and creating workflow flexibility.

The Role of Nursing Leadership in Ensuring a Healthy Workforce in Corrections.

In Canada, responsibility for corrections is divided between federal, provincial and territorial governments, with nurses being the largest group of healthcare professionals working in correctional institutions (penitentiaries, jails, prisons, correctional centres and secure correctional treatment centres) across the country. Correctional institutions are among the most challenging workplace settings for nurses, as they face competing tensions between the provision of quality care and strict security requirements for safety. They also experience unique workforce issues with high reports of burnout and emotional exhaustion. Nursing leadership at all levels of the correctional system is critical in creating work environments that optimize workplace well-being and minimize burnout. The purpose of this paper is to discuss the role of nursing leadership in facilitating and enabling a healthy workforce in corrections. Minimal research has examined leadership and healthy work environments in correctional institutions. Several authors have, however, discussed transformational leadership as a strategy to positively influence correctional nursing practice. In this article, we expand on this previous work to describe the full range leadership model and how it can be used to form the foundation of effective leadership and support the creation of healthy work environments in the correctional context.

Novel two-lead cardiac resynchronization therapy system provides equivalent CRT responses with less complications than a conventional three-lead system: Results from the QP ExCELs lead registry.

INTRODUCTION: The novel two-lead cardiac resynchronization therapy (CRT)-DX system utilizes a floating atrial dipole on the implantable cardioverter-defibrillator lead, and when implanted with a left ventricular (LV) lead, offers a two-lead CRT system with AV synchrony. This study compared complication rates and CRT response among subjects implanted with a two-lead CRT-DX system to those subjects implanted with a standard three-lead CRT-D system. METHODS AND RESULTS: A total of 240 subjects from the Sentus QP-Extended CRT Evaluation with Quadripolar Left Ventricular Leads postapproval study were selected to identify 120 matched pairs based on similar demographic characteristics using a Greedy algorithm. The complication-free rate was evaluated as the primary endpoint. All-cause mortality, heart failure hospitalizations, device diagnostic data, New York Heart Association (NYHA) class improvement, and defibrillator therapy were evaluated from clinical data, in-office interrogations, and remote monitoring throughout the follow-up period. Complication-free survival favored the CRT-DX group with 92.5% without a major complication compared to 85.0% in the CRT-D cohort (P = .0495; 95% confidence interval: 0.1%-14.9%) over a mean follow-up of 1.3 and 1.4 years, respectively. Incidence of all-cause mortality, heart failure hospitalizations, NYHA changes at 6 months postimplant, and percent of LV pacing during CRT therapy were similar in both device cohorts. Inappropriate shocks were more frequent in the CRT-D cohort with 5.8% of subjects receiving an inappropriate shock vs 0.8% in the CRT-DX cohort. CONCLUSION: The results of this subanalysis demonstrate that the CRT-DX system can provide similar CRT responses and significantly fewer complications when compared to a similar cohort with a conventional three-lead CRT-D system.

BioMonitor 2 in-office setting insertion safety and feasibility evaluation with device functionality assessment: results from the prospective cohort BioInsight study.

BACKGROUND: Insertable cardiac monitors are utilized for the diagnosis of arrhythmias and traditionally have been inserted within hospitals. Recent code updates allow for reimbursement of office-based insertions; however, there is limited information regarding the resources and processes required to support in-office insertions. We sought to determine the safety and feasibility of in-office insertion of the BioMonitor 2 and better understand in-office procedures, including patient selection, pre-insertion protocols, resource availability, and staff support. METHODS: Patients meeting an indication for a rhythm monitor were prospectively enrolled into this single-arm, non-randomized trial. All patients underwent insertion in an office setting. Two follow-up visits at days 7 and 90 were required. Information on adverse events, device performance, office site preparations, and resource utilization were collected. RESULTS: Eighty-two patients were enrolled at six sites. Insertion was successful in all 77 patients with an attempt. Oral anticoagulation was stopped in 20.8% of patients and continued through insertion in 23.4%, while prophylactic antibiotics were infrequently utilized (37.7% of study participants). On average, the procedure required a surgeon plus two support staff and 35 min in an office room to complete the 8.4 min insertion procedure. The mean R-wave amplitude was 0.77 mV at insertion and 0.67 mV at 90-days with low noise burden (2.7%). There were no procedure related complications. Two adverse events were reported (event rate 2.7% [95% CI 0.3, 9.5%]). CONCLUSIONS: In-office insertion of the BioMonitor 2 is safe and feasible. Devices performed well with high R-wave amplitudes and low noise burden. These results further support shifting cardiac monitor insertions to office-based locations. TRIAL REGISTRATION: clinicaltrials.gov, NCT02756338. Registered 29 April 2016.

AnaLysIs of Both sex and device specific factoRs on outcomes in pAtients with non-ischemic cardiomyopathy (BIO-LIBRA): Design and clinical protocol.

BACKGROUND: Outcomes of patients with nonischemic cardiomyopathy and low ejection fraction implanted with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT-D), especially in contemporary, real-life cohorts, are not fully understood. OBJECTIVE: We aimed to better characterize outcomes of death and ventricular tachyarrhythmias in patients with nonischemic cardiomyopathy, implanted with an ICD or CRT-D, and specifically assess differences by sex. METHODS: The AnaLysIs of Both Sex and Device Specific FactoRs on Outcomes in PAtients with Non-Ischemic Cardiomyopathy (BIO-LIBRA) study was designed to prospectively assess outcomes of device-treated ventricular tachyarrhythmias and all-cause mortality events in nonischemic cardiomyopathy patients, indicated for an ICD or CRT-D implantation for the primary prevention of sudden cardiac death (SCD), with a specific focus on sex differences. We will enroll a total of 1000 subjects across 50 U.S. sites and follow patients for up to 3 years. RESULTS: The primary objective of BIO-LIBRA is to evaluate the combined risk of all-cause mortality and treated ventricular tachycardia (VT) or ventricular fibrillation (VF) events by subject sex and by implanted device type. We will also assess all-cause mortality, VT or VF alone, cardiac death, and SCD in the total cohort, as well as by subject sex and by the implanted device type. In addition, the previously validated Seattle Proportional Risk Model (SPRM) will be used to compare the SPRM predicted incidence of SCD to the observed incidence. CONCLUSIONS: The BIO-LIBRA study will provide novel and contemporary information regarding outcomes in patients with a NICM who receive a defibrillator.

The Acceptability and Feasibility of Implementing an Online Educational Intervention With Nurses in a Provincial Prison Context.

BACKGROUND: Correctional nursing requires a strong knowledge base with access to continuing education (CE) to maintain and enhance competencies. Nurses working in provincial prisons have reported many challenges in accessing CE, with online learning being identified as a potential solution. Limited research was found, however, which examined the correctional context in the development and delivery of online learning for nurses. The purpose of this study was to develop an online educational intervention tailored to correctional nurses and determine the feasibility and acceptability of implementing the intervention in a provincial prison context. METHODS: A sequential mixed methods study was conducted. Participants included nurses from three correctional settings in the province of Ontario, Canada. Semistructured interviews examined contextual factors and educational needs. Delphi surveys determined the educational topic. Preintervention and postintervention questionnaires examined the context, educational content, and intervention's acceptability and feasibility. RESULTS: The online intervention focused on mental health and addictions with two 30-minute webinars delivered back-to-back over 15 weeks. Respondents expressed satisfaction with the convenience of online learning at work using short webinars, as well as the topics, relevance of information, and teaching materials, but dissatisfaction with presentation style. The feasibility of the intervention was limited by access to technology, time to attend, education space, and comfort with technology. DISCUSSION: The findings from this study provide insight to guide the future development of online CE for correctional nurses. If changes are made within correctional facilities in collaboration with nurses and managers, online learning holds the potential to facilitate access to ongoing professional development.

Genetically enhancing the expression of chemokine domain of CX3CL1 fails to prevent tau pathology in mouse models of tauopathy.

BACKGROUND: Fractalkine (CX3CL1) and its receptor (CX3CR1) play an important role in regulating microglial function. We have previously shown that Cx3cr1 deficiency exacerbated tau pathology and led to cognitive impairment. However, it is still unclear if the chemokine domain of the ligand CX3CL1 is essential in regulating neuronal tau pathology. METHODS: We used transgenic mice lacking endogenous Cx3cl1 (Cx3cl1-/-) and expressing only obligatory soluble form (with only chemokine domain) and lacking the mucin stalk of CX3CL1 (referred to as Cx3cl1105Δ mice) to assess tau pathology and behavioral function in both lipopolysaccharide (LPS) and genetic (hTau) mouse models of tauopathy. RESULTS: First, increased basal tau levels accompanied microglial activation in Cx3cl1105Δ mice compared to control groups. Second, increased CD45+ and F4/80+ neuroinflammation and tau phosphorylation were observed in LPS, hTau/Cx3cl1-/-, and hTau/Cx3cl1105Δ mouse models of tau pathology, which correlated with impaired spatial learning. Finally, microglial cell surface expression of CX3CR1 was reduced in Cx3cl1105Δ mice, suggesting enhanced fractalkine receptor internalization (mimicking Cx3cr1 deletion), which likely contributes to the elevated tau pathology. CONCLUSIONS: Collectively, our data suggest that overexpression of only chemokine domain of CX3CL1 does not protect against tau pathology.

Disease Progression-Dependent Effects of TREM2 Deficiency in a Mouse Model of Alzheimer's Disease.

Neuroinflammation is an important contributor to Alzheimer's disease (AD) pathogenesis, as underscored by the recent identification of immune-related genetic risk factors for AD, including coding variants in the gene TREM2 (triggering receptor expressed on myeloid cells 2). Understanding TREM2 function promises to provide important insights into how neuroinflammation contributes to AD pathology. However, studies so far have produced seemingly conflicting results, with reports that amyloid pathology can be both decreased and increased in TREM2-deficient AD mouse models. In this study, we unify these previous findings by demonstrating that TREM2 deficiency ameliorates amyloid pathology early, but exacerbates it late in disease progression in the APPPS1-21 mouse model of AD. We also demonstrate that TREM2 deficiency decreases plaque-associated myeloid cell accumulation by reducing cell proliferation, specifically late in pathology. In addition, TREM2 deficiency reduces myeloid cell internalization of amyloid throughout pathology, but decreases inflammation-related gene transcript levels selectively late in disease progression. Together, these results suggest that TREM2 plays distinct functional roles at different stages in AD pathology. SIGNIFICANCE STATEMENT: Alzheimer's disease (AD) is a devastating neurodegenerative disorder and there are currently no effective treatments that modify disease progression. However, the recent identification of genetic risk factors for AD promises to provide new insight into AD biology and possible new therapeutic targets. Among these risk factors, variants in the gene TREM2 (triggering receptor expressed on myeloid cells 2) confer greatly elevated risk for developing the disease. We demonstrate that TREM2 deficiency has opposing effects on AD-related pathologies at early and late stages of disease progression, unifying previous work in the field. In addition, we examine how TREM2 affects the function of the brain immune cell populations in which it is expressed throughout disease progression to understand possible mechanisms underlying its differential impacts on pathology.

Healthcare Utilizing Deliberate Discussion Linking Events (HUDDLE): A Systematic Review.

The phenomenon, "huddle moments," can be described as a preparatory briefing among healthcare providers for the purpose of collaborating, exchanging information, and bringing awareness to patient safety concerns. A historical background of huddle communication is described and a systematic literature review was conducted on preoperative briefing and huddle communication. The article also describes a need for increased interprofessional collaboration education in anesthesia and a need for leadership to support initiatives that improve patient safety. The purpose of this article is to provide a systematic review of huddle communication and give future evidence-based recommendations on how the huddle can be used in healthcare as well as how to roll out use of the HUDDLE acronym: Healthcare, Utilizing, Deliberate, Discussion, Linking, Events.

TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer's disease mouse models.

Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer's disease (AD) and other neurodegenerative diseases. However, the cell types and mechanisms underlying TREM2's involvement in neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated on myeloid cells surrounding amyloid deposits in AD mouse models and human AD tissue. TREM2 was detected on CD45(hi)Ly6C(+) myeloid cells, but not on P2RY12(+) parenchymal microglia. In AD mice deficient for TREM2, the CD45(hi)Ly6C(+) macrophages are virtually eliminated, resulting in reduced inflammation and ameliorated amyloid and tau pathologies. These data suggest a functionally important role for TREM2(+) macrophages in AD pathogenesis and an unexpected, detrimental role of TREM2 in AD pathology. These findings have direct implications for future development of TREM2-targeted therapeutics.

Phase I dose escalation study of lestaurtinib in patients with myelofibrosis.

We performed a multicenter, investigator initiated, phase I dose escalation study of the oral multi-kinase inhibitor lestaurtinib in patients with JAK2V617F positive myelofibrosis, irrespective of baseline platelet count. A total of 34 patients were enrolled. Dose-limiting toxicities were observed in three patients overall, at the 100 mg (n = 1) and 160 mg (n = 2) twice-daily dose levels. The maximum tolerated dose was 140 mg twice daily. Gastrointestinal toxicity was the most common adverse event. Sixteen patients were evaluable for response at 12 weeks. Seven patients had clinical improvement by International Working Group - Myeloproliferative Neoplasms Research and Treatment criteria. Meaningful reductions in JAK2V617F allele burden were not observed. To measure JAK2 inhibition in vivo, plasma from treated patients was assayed for its ability to inhibit phosphorylation of signal transducer and activator of transcription 5 (STAT5): doses lower than 140 mg had variable and incomplete inhibition. In this phase I study, although gastrointestinal adverse events were common, significant clinical activity with lestaurtinib was observed (ClinicalTrials.gov identifier: NCT00668421).

MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis.

From 2007 to 2011, 66 patients with primary myelofibrosis or myelofibrosis (MF) preceded by essential thrombocythemia or polycythemia vera were enrolled into a prospective phase 2 clinical trial of reduced-intensity allogeneic hematopoietic stem cell transplantation (AHSCT), Myeloproliferative Disorder Research Consortium 101 trial. The study included patients with sibling donors (n = 32) receiving fludarabine/melphalan (FluMel) as a preparative regimen and patients with unrelated donors (n = 34) receiving conditioning with FluMel plus anti-thymocyte globulin (ATG). Patient characteristics in the 2 cohorts were similar. Engraftment occurred in 97% of siblings and 76% of unrelated transplants, whereas secondary graft failure occurred in 3% and 12%, respectively. With a median follow-up of 25 months for patients alive, the overall survival (OS) was 75% in the sibling group (median not reached) and 32% in the unrelated group (median OS: 6 months, 95% confidence interval [CI]: 3, 25) (hazard ratio 3.9, 95% CI: 1.8,8.9) (P < .001). Nonrelapse mortality was 22% in sibling and 59% in unrelated AHSCT. Survival correlated with type of donor, but not with the degree of histocompatibility match, age, or JAK2(V617F) status. In patients with MF with sibling donors, AHSCT is an effective therapy, whereas AHSCT from unrelated donors with FluMel/ATG conditioning led to a high rate of graft failure and limited survival. This trial was registered at www.clinicaltrials.gov as #NCT00572897.

Exploring work-life issues in provincial corrections settings.

Correctional nurses hold a unique position within the nursing profession as their work environment combines the demands of two systems, corrections and health care. Nurses working within these settings must be constantly aware of security issues while ensuring that quality care is provided. The primary role of nurses in correctional health care underscores the importance of understanding nurses' perceptions about their work. The purpose of this study was to examine the work environment of nurses working in provincial correctional facilities. A mixed-methods design was used. Interviews were conducted with 13 nurses and healthcare managers (HCMs) from five facilities. Surveys were distributed to 511 nurses and HCMs in all provincial facilities across the province of Ontario, Canada. The final sample consisted of 270 nurses and 27 HCMs with completed surveys. Participants identified several key issues in their work environments, including inadequate staffing and heavy workloads, limited control over practice and scope of practice, limited resources, and challenging workplace relationships. Work environment interventions are needed to address these issues and subsequently improve the recruitment and retention of correctional nurses.

Correctional nursing: a study protocol to develop an educational intervention to optimize nursing practice in a unique context.

BACKGROUND: Nurses are the primary healthcare providers in correctional facilities. A solid knowledge and expertise that includes the use of research evidence in clinical decision making is needed to optimize nursing practice and promote positive health outcomes within these settings. The institutional emphasis on custodial care within a heavily secured, regulated, and punitive environment presents unique contextual challenges for nursing practice. Subsequently, correctional nurses are not always able to obtain training or ongoing education that is required for broad scopes of practice. The purpose of the proposed study is to develop an educational intervention for correctional nurses to support the provision of evidence-informed care. METHODS: A two-phase mixed methods research design will be used. The setting will be three provincial correctional facilities. Phase one will focus on identifying nurses' scope of practice and practice needs, describing work environment characteristics that support evidence-informed practice and developing the intervention. Semi-structured interviews will be completed with nurses and nurse managers. To facilitate priorities for the intervention, a Delphi process will be used to rank the learning needs identified by participants. Based on findings, an online intervention will be developed. Phase two will involve evaluating the acceptability and feasibility of the intervention to inform a future experimental design. DISCUSSION: The context of provincial correctional facilities presents unique challenges for nurses' provision of care. This study will generate information to address practice and learning needs specific to correctional nurses. Interventions tailored to barriers and supports within specific contexts are important to enable nurses to provide evidence-informed care.

Effect of rate-adaptive pacing on performance and physiological parameters during activities of daily living in the elderly: results from the CLEAR (Cylos Responds with Physiologic Rate Changes during Daily Activities) study.

AIMS: For most elderly pacemaker patients, evaluation of rate-adaptive pacing using treadmill and bicycle tests is impractical and not representative of typical daily activities. This study was designed to compare the performance and physiological response of the closed-loop stimulation (CLS) rate-adaptive sensor to accelerometer (XL) and no rate sensor (DDD) during typical daily activity testing. METHODS AND RESULTS: Subjects recently implanted with a Cylos pacemaker completed timed activities of daily life testing, which included walking, sweeping, and standing from a seated position. Activity performance and physiological response from each sensor mode was evaluated for subjects requiring ≥80% pacing. Overall, 74 subjects needed ≥80% pacing during at least one test. An increase in the area swept (CLS vs. XL, 1.67 m(2) difference, P = 0.009; CLS vs. DDD, 1.59 m(2) difference, P = 0.025) and a decrease in the prevalence of orthostatic hypotension (OH) after standing 1 min (CLS vs. XL, odds ratio = 0.16, P = 0.006; CLS vs. DDD, odds ratio = 0.18, P = 0.012) was observed in the CLS mode as compared with XL and DDD. No statistical difference in walk distance was observed between CLS and XL or CLS and DDD. CONCLUSION: In acute testing, as compared with XL and DDD, CLS provides a more physiological response during the performance of activities of daily living for subjects with ≥80% pacing. This is clinically reflected in better performance during the sweep test as well as a decrease in the prevalence of OH in our elderly population. Clinicaltrials.gov identifier: NCT00355797.

Identification of blood culture isolates directly from positive blood cultures by use of matrix-assisted laser desorption ionization-time of flight mass spectrometry and a commercial extraction system: analysis of performance, cost, and turnaround time.

Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry represents a revolution in the rapid identification of bacterial and fungal pathogens in the clinical microbiology laboratory. Recently, MALDI-TOF has been applied directly to positive blood culture bottles for the rapid identification of pathogens, leading to reductions in turnaround time and potentially beneficial patient impacts. The development of a commercially available extraction kit (Bruker Sepsityper) for use with the Bruker MALDI BioTyper has facilitated the processing required for identification of pathogens directly from positive from blood cultures. We report the results of an evaluation of the accuracy, cost, and turnaround time of this method for 61 positive monomicrobial and 2 polymicrobial cultures representing 26 species. The Bruker MALDI BioTyper with the Sepsityper gave a valid (score, >1.7) identification for 85.2% of positive blood cultures with no misidentifications. The mean reduction in turnaround time to identification was 34.3 h (P < 0.0001) in the ideal situation where MALDI-TOF was used for all blood cultures and 26.5 h in a more practical setting where conventional identification or identification from subcultures was required for isolates that could not be directly identified by MALDI-TOF. Implementation of a MALDI-TOF-based identification system for direct identification of pathogens from blood cultures is expected to be associated with a marginal increase in operating costs for most laboratories. However, the use of MALDI-TOF for direct identification is accurate and should result in reduced turnaround time to identification.