Clinical Action Research Articles

P-572 Circadian serum progesterone variations on the day of frozen embryo transfer in a modified natural cycle protocol

Abstract Study question Does a circadian variation of serum progesterone (P) on the frozen embryo transfer (FET) day in a modified natural cycle (mNC) exist? Summary answer A statistically significant diurnal variation of serum P on the day of a FET in a mNC protocol exists. What is known already In recent years, the proportion of FET cycles has increased dramatically. To further optimize pregnancy outcomes after FET, recent studies have focused on serum luteal P levels in both natural and artificially prepared FET cycles. Despite the different cut-off values proposed to define low serum P in the natural cycle, it is generally accepted that lower serum P values (<10ng/ml) around the day of FET are associated with negative reproductive outcomes. However, a single serum P measurement on the day of FET is not reliable given that P levels are prone to diurnal fluctuations and are impacted by patients’ characteristics. Study design, size, duration A prospective cohort study was conducted in a single fertility center including 22 patients performing a single blastocyst mNC-FET from August 2022 to August 2023.Serum P levels were measured on the day of transfer at 08:00h,12:00h,16:00h and 20:00h.Differences between P levels were compared using the Wilcoxon signed-rank test.The sample size was calculated to detect a difference of 15% between the first and last P measurements with a 5% false-positive rate and a 95% confidence interval. Participants/materials, setting, methods Patients with a normal BMI, between 18 and 40 years old, without uterine diseases were eligible. Patients utilizing donated oocytes were excluded. The mNC-FET protocol implied monitoring the normal ovarian cycle and triggering ovulation with an injection of 250 mcg of choriogonadotropin alfa when a pre-ovulatory follicle (16-20 mm diameter)was visualized. The blastocyst was transferred seven days later. The patients were not supplemented with exogenous P at any moment before the day of the FET. Main results and the role of chance The mean age and BMI of the study population were 33.6 ± 3.8 years and 22.7 ± 1.8 kg/m2, respectively. Mean P values at 08:00h,12:00h,16:00h, and 20:00h were 14.6 ± 4.5ng/ml, 14.7 ± 4.1ng/ml, 12.9 ± 3.5ng/ml, and 14.6 ± 4.3ng/ml, respectively. The mean P levels at 16:00h were statistically significantly lower compared to all other time points (p < 0.05:p= 0.007 between P at 8:00h and 16:00h;p = 0.003 between P at 12:00h and 16:00h;p=0.007 between P at 16:00h and 20:00h). Absence of a statistically significant fluctuation was observed between P values at the other time points (p = 0.88 between P at 8:00h and 12:00h;p=0.96 between P at 8:00h and 20:00h;p=0.83 between P at 12:00h and 20:00h). This study confirms the existence of an intra-day variation of serum P on the day of mNC-FET, with lower values at 16:00h. This highlights the importance of standardizing P measurement on the day of FET; we propose this should always be assessed in the morning to be more reliable and to allow the time to prescribe additional exogenous progesterone if lower P values (<10ng/ml) are detected. This standardization would allow fertility clinics around the world to compare their results and develop internationally recognized treatment protocols. Limitations, reasons for caution The study’s main limitation include the small sample size that may cause a bias when results are extrapolated to a larger subfertile population undergoing mNC-FET. Ideally, larger prospective trials including a more heterogeneous patient population would be necessary to validate our findings. Wider implications of the findings This study demonstrates the existence of a diurnal fluctuation of serum P on the mNC-FET day highlighting the importance of a standardized time point for its measurement.This is important when clinical actions, like additional exogenous P supplementation, are considered when encountering P values lower than 10ng/ml on the FET day. Trial registration number NCT05511272

A theoretical framework for identifying sociocultural factors that influence nurses' compliance with early warning systems for acute clinical deterioration: A cross-sectional survey

BackgroundSystematic adoption of early warning systems in healthcare settings is dependent on the optimal and reliable application by the user. Psychosocial issues and hospital culture influence clinicians' patient safety behaviours. Objective(i) To examine the sociocultural factors that influence nurses' EWS compliance behaviours, using a theory driven behavioural model and (ii) to propose a conceptual model of sociocultural factors for EWS compliance behaviour. DesignA cross-sectional survey. SettingNurses employed in public hospitals across Queensland, Australia. ParticipantsUsing convenience and snowball sampling techniques eligible nurses accessed a dedicated web site and survey containing closed and open-ended questions. 291 nurses from 60 hospitals completed the survey. MethodsQuantitative data were analysed using ANOVA or t-tests to test differences in means. A series of path models based on the theory were conducted to develop a new model. Directed or theory driven content analysis informed qualitative data analysis. ResultsNurses report high levels of previous compliance behaviour and strong intentions to continue complying in the future (M=4.7; SD 0.48). Individual compliance attitudes (β 0.29, p<.05), perceived value of escalation (β 0.24, p<.05) and perceived ease or difficulty complying with documentation (β −0.31, p<.05) were statistically significant, predicting 24% of variation in compliance behaviour. Positive personal charting beliefs (β 0.14, p<.05) and subjective norms both explain higher behavioural intent indirectly through personal attitudes. High ratings of peer charting beliefs indirectly explain attitudes through subjective norms (β 0.20, p<.05). Perceptions of control over one's clinical actions (β −0.24, p<.05) and early warning system training (β −0.17, p<.05) directly contributed to fewer difficulties complying with documentation requirements. Prior difficulties when escalating care (β −0.31, p<.05) directly influenced the perceived value of escalating. ConclusionsThe developed theory-based conceptual model identified sociocultural variables that inform compliance behaviour (documenting and escalation protocols). The model highlights areas of clinical judgement, education, interprofessional trust, workplace norms and cultural factors that directly or indirectly influence nurses' intention to comply with EWS protocols. Extending our understanding of the sociocultural and system wide factors that hamper nurses' use of EWSs and professional accountability has the potential to improve the compliance behaviour of staff and subsequently enhance the safety climate attitudes of hospitals. Tweetable abstractA newly developed model reports nurse's personal attitudes, peer influence, perceived difficulties encountered documenting and escalation beliefs all predict early warning system compliance behaviour.

Provision and evaluation of explanations within an automated planning-based approach to solving the multimorbidity problem

The multimorbidity problem involves the identification and mitigation of adverse interactions that occur when multiple computer interpretable guidelines are applied concurrently to develop a treatment plan for a patient diagnosed with multiple diseases. Solving this problem requires decision support approaches which are difficult to comprehend for physicians. As such, the rationale for treatment plans generated by these approaches needs to be provided. Objective:To develop an explainability component for an automated planning-based approach to the multimorbidity problem, and to assess the fidelity and interpretability of generated explanations using a clinical case study. Methods:The explainability component leverages the task-network model for representing computer interpretable guidelines. It generates post-hoc explanations composed of three aspects that answer why specific clinical actions are in a treatment plan, why specific revisions were applied, and how factors like medication cost, patient’s adherence, etc. influence the selection of specific actions. The explainability component is implemented as part of MitPlan, where we revised our planning-based approach to support explainability. We developed an evaluation instrument based on the system causability scale and other vetted surveys to evaluate the fidelity and interpretability of its explanations using a two dimensional comparison study design. Results:The explainability component was implemented for MitPlan and tested in the context of a clinical case study. The fidelity and interpretability of the generated explanations were assessed using a physician-focused evaluation study involving 21 participants from two different specialties and two levels of experience. Results show that explanations provided by the explainability component in MitPlan are of acceptable fidelity and interpretability, and that the clinical justification of the actions in a treatment plan is important to physicians. Conclusion:We created an explainability component that enriches an automated planning-based approach to solving the multimorbidity problem with meaningful explanations for actions in a treatment plan. This component relies on the task-network model to represent computer interpretable guidelines and as such can be ported to other approaches that also use the task-network model representation. Our evaluation study demonstrated that explanations that support a physician’s understanding of the clinical reasons for the actions in a treatment plan are useful and important.

Designing cancer screening trials for reduction in late-stage cancer incidence

ABSTRACT Before implementing a biomarker test for early cancer detection into routine clinical care, the test must demonstrate clinical utility, that is, the test results should lead to clinical actions that positively affect patient-relevant outcomes. Unlike therapeutical trials for patients diagnosed with cancer, designing a randomized controlled trial (RCT) to demonstrate the clinical utility of an early detection biomarker with mortality and related endpoints poses unique challenges. The hurdles stem from the prolonged natural progression of the disease and the lack of information regarding the time-varying screening effect on the target asymptomatic population. To facilitate the study design of screening trials, we propose using a generic multistate disease history model and derive model-based effect sizes. The model links key performance metrics of the test, such as sensitivity, to primary endpoints like the incidence of late-stage cancer. It also incorporates the practical implementation of the biomarker-testing program in real-world scenarios. Based on the chronological time scale aligned with RCT, our method allows the assessment of study powers based on key features of the new program, including the test sensitivity, the length of follow-up, and the number and frequency of repeated tests. The calculation tool from the proposed method will enable practitioners to perform realistic and quick evaluations when strategizing screening trials for specific diseases. We use numerical examples based on the National Lung Screening Trial to demonstrate the method.

Feasibility and Effectiveness of the Implementation of Anxiety Screening for Adolescents in a Primary Care Setting.

The United States Preventive Services Task Force recommended routine anxiety screening for children and adolescents in 2022. This study describes the feasibility of routine anxiety screening in a primary care practice.It further examines the effects of routine anxiety screening on anxiety diagnoses and provider behavior in a setting in which anxiety screening was implemented five years in advance of the national guidelines. During the first year of implementation, approximately 80% of patients were screened, and 17% of screens were positive.A retrospective chart review of patients with positive screens found that the majority of positive screens led to a new diagnosis of anxiety and that half of newly diagnosed patients were prescribed an intervention. Screening was associated with an increase in diagnoses of anxiety disorders in the studied population from 9.6% to 13.3% (p<0.0001). Following the initial implementation, screening rates continued to rise, with an eventual plateau of >90%. Anxiety screening in the pediatric primary care setting is feasible and sustainable and led to increased provider recognition of anxiety and meaningful clinical action.

The Home-Based Experiences of Palliative and Hospice Care for Children and Caregivers (EXPERIENCE) Measure: Evaluation of Psychometric Properties

ContextHome-based pediatric palliative and hospice care (PPHC) supports the hundreds of thousands of children with serious illness and complex care needs and their families in the home setting. Considerable variation, however, exists in the provision and quality of home-based PPHC in the U.S. Ensuring equitable, high-quality home-based PPHC for all children requires the evaluation of families’ care experiences and assessment of whether these experiences are aligned with their needs and priorities. ObjectivesTo evaluate the psychometric properties of the previously developed 23-item home-based PPHC EXPERIENCE Measure for use with families of children receiving home-based PPHC in the United States. MethodsParticipants included families recruited from the Children's Hospital of Philadelphia, Courageous Parents Network, and several other hospital- and community-based PPHC programs across the U.S. who provide home-based PPHC services. Participants completed the EXPERIENCE Measure at baseline and again at retest. We evaluated the factor structure of the EXPERIENCE Measure, as well as evidence regarding score reliability and validity. ResultsEighty-two family participants completed the baseline and 53 completed the retest questionnaire from 15 states across the U.S. We found evidence for the score reliability and validity of a four-domain EXPERIENCE measure. ConclusionThe EXPERIENCE Measure is a tool with evidence for reliable and valid scores to evaluate family-reported home-based PPHC experiences at the time care is being received. Future work will evaluate the usability (i.e., acceptability, feasibility, and clinical actionability) of EXPERIENCE, including the sensitivity of the instrument to change over time and its impact on real-time clinical actions.

PCR16 Clinical Actions Generated By Remote Symptom Alerts and Electronic Patient-Reported Outcomes (ePROs) in Real-World Breast Cancer Practice

PCR16 Clinical Actions Generated By Remote Symptom Alerts and Electronic Patient-Reported Outcomes (ePROs) in Real-World Breast Cancer Practice

App Engagement as a Predictor of Weight Loss in Blended-Care Interventions: Retrospective Observational Study Using Large-Scale Real-World Data.

Early weight loss is an established predictor for treatment outcomes in weight management interventions for people with obesity. However, there is a paucity of additional, reliable, and clinically actionable early predictors in weight management interventions. Novel blended-care weight management interventions combine coach and app support and afford new means of structured, continuous data collection, informing research on treatment adherence and outcome prediction. Against this backdrop, this study analyzes app engagement as a predictor for weight loss in large-scale, real-world, blended-care interventions. We hypothesize that patients who engage more frequently in app usage in blended-care treatment (eg, higher logging activity) lose more weight than patients who engage comparably less frequently at 3 and 6 months of intervention. Real-world data from 19,211 patients in obesity treatment were analyzed retrospectively. Patients were treated with 3 different blended-care weight management interventions, offered in Switzerland, the United Kingdom, and Germany by a digital behavior change provider. The principal component analysis identified an overarching metric for app engagement based on app usage. A median split informed a distinction in higher and lower engagers among the patients. Both groups were matched through optimal propensity score matching for relevant characteristics (eg, gender, age, and start weight). A linear regression model, combining patient characteristics and app-derived data, was applied to identify predictors for weight loss outcomes. For the entire sample (N=19,211), mean weight loss was -3.24% (SD 4.58%) at 3 months and -5.22% (SD 6.29%) at 6 months. Across countries, higher app engagement yielded more weight loss than lower engagement after 3 but not after 6 months of intervention (P3 months<.001 and P6 months=.59). Early app engagement within the first 3 months predicted percentage weight loss in Switzerland and Germany, but not in the United Kingdom (PSwitzerland<.001, PUnited Kingdom=.12, and PGermany=.005). Higher age was associated with stronger weight loss in the 3-month period (PSwitzerland=.001, PUnited Kingdom=.002, and PGermany<.001) and, for Germany, also in the 6-month period (PSwitzerland=.09, PUnited Kingdom=.46, and PGermany=.03). In Switzerland, higher numbers of patients' messages to coaches were associated with higher weight loss (P3 months<.001 and P6 months<.001). Messages from coaches were not significantly associated with weight loss (all P>.05). Early app engagement is a predictor of weight loss, with higher engagement yielding more weight loss than lower engagement in this analysis. This new predictor lends itself to automated monitoring and as a digital indicator for needed or adapted clinical action. Further research needs to establish the reliability of early app engagement as a predictor for treatment adherence and outcomes. In general, the obtained results testify to the potential of app-derived data to inform clinical monitoring practices and intervention design.

Efficacy of the Cardiac Implantable Electronic Device Multisensory Triage-HF Algorithm in Heart Failure Care: A Real-World Clinical Experience.

Heart failure (HF) admissions are burdensome, and the mainstay of prevention is the timely detection of impending fluid retention, creating a window for medical treatment intensification. This study evaluated the accuracy and performance of a Triage-HF-guided carepath in real-world ambulatory HF patients in daily clinical practice. In this prospective, observational study, 92 adult HF patients (71 males (78%), with a median age of 69 [IQR 59-75] years) with the Triage-HF algorithm activated in their cardiac implantable electronic devices (CIEDs), were monitored. Following high-risk alerts, an HF nurse contacted patients to identify signs and symptoms of fluid retention. The sensitivity and specificity were 83% and 97%, respectively. The positive predictive value was 89%, and negative predictive value was 94%. The unexplained alert rate was 0.05 alerts/patient year, and the false negative rate was 0.11 alerts/patient year. Ambulatory diuretics were initiated or escalated in 77% of high-risk alert episodes. In 23% (n = 6), admission was ultimately required. The median alert handling time was 2 days. Fifty-eight percent (n = 18) of high-risk alerts were classified as true positives in the first week, followed by 29% in the second-third weeks (n = 9), and 13% (n = 4) in the fourth-sixth weeks. Common sensory triggers included an elevated night ventricular rate (84%), OptiVol (71%), and reduced patient activity (71%). The CIED-based Triage-HF algorithm-driven carepath enables the timely detection of impending fluid retention in a contemporary ambulatory setting, providing an opportunity for clinical action.

Current treatment for spondyloarthritis: focus on netakimab. A review

Spondyloarthritis (SpA) is a group of rheumatic diseases that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA) and a number of other diseases. SpA lead to a significant social problem, since it is a common pathology that debuts mainly at a young age, significantly impairing the ability to work and the ability to social contacts of the most active part of the population. For all the main types of chronic progressive SpA, biological agents (biologics) are of great importance in patients with persistent activity despite standard treatment, especially in the case of predominantly axial involvement, since in this case it is actually the only option for effective treatment, in addition to the constant use of non-steroidal anti-inflammatory drugs (NSAIDs). Over the past decade, interleukin-17A (IL-17A) inhibitors have taken the first place in therapy of SpA, because, according to modern ideas about pathogenesis, IL-17A may be a key target for therapeutic intervention in SpA. In terms of ensuring availability for Russian patients with SpA, it is of particular importance to the introduction of the original medication from the group of IL-17A inhibitors Netakimab (NTK). This review presents data from randomized clinical trials of NTK phases I, II and III in AS and PsA also post-registration observational studies of phase IV, including analysis of subpopulations of patients of special interest, in particular, patients with psoriatic spondylitis. NTK demonstrated high effectiveness in the treatment of SpA both in randomized clinical trials and in clinical practice. The drug is characterized by a rapid onset of clinical action and persistent maintenance of the achieved improvement, a complex effect on various manifestations of the disease, is able to have a structure-modifying effect and slow down the progression of both the erosive process and osteoproliferation. The safety profile of NTK is generally typical for the entire group of IL-17 inhibitors. The drug has low immunogenicity, which allows us to count on the possibility of many years of effective use. Resolutions of expert councils on the use of NTK in AS and PsA support the inclusion of this drug in clinical guidelines.

The future is now: Implementation of standard of care, preemptive pharmacogenomic testing in patients with gastrointestinal cancers.

1546 Background: Preemptive germline pharmacogenomic (PGx) testing provides insight into the safety of high-risk chemotherapy and effective use of supportive care medications in gastrointestinal (GI) cancers. Advances in clinical practice guidelines and clinician support have accelerated the appetite for PGx testing, particularly for drugs with severe adverse reactions. The objective of this study was to assess operational outcomes associated with end-to-end electronic health record (EHR) integration of standard of care, preemptive multigene PGx testing in patients with GI cancers. Methods: Patients in two UCHealth GI oncology clinics were tested for five PGx genes related to 5-fluorouracil (5-FU, DPYD), irinotecan ( UGT1A1), and supportive care therapies ( CYP2C19, CYP2D6, CYP2C9). The PGx test order was embedded in all GI oncology treatment plans. Patient samples were genotyped, and PGx results were returned as discrete data to the EHR. Automated clinical decision support (CDS) tools provided PGx-guided recommendations at the point of prescribing. We leveraged the EPIS process framework and evaluated operational outcomes such as number of patients tested, lab turnaround time, patients with actionable phenotypes, and number of CDS alerts and clinical actions. Results: The analysis included 89 patients who received results for DPYD/UGT1A1 and 83 patients who received results for supportive care genes. Among samples tested, DPYD/UGT1A1 and supportive care gene results were returned to the EHR in an average of 4.7 ± 2 days (range 1-8) and 17.3 ± 3 days (range 9-24), respectively. The number of patients with abnormal phenotypes, defined as poor metabolizers for UGT1A1 and any non-normal phenotypes for the other genes, were UGT1A1, n=10 (11.2%); DPYD, n=4 (4.5%); CYP2C19, n=43 (51.8%); CYP2D6, n=31 (41.3%; 8 uninterpretable results); and CYP2C9, n=19 (22.9%). This equated to 14/89 (15.7%) and 68/83 (81.9%) patients having an abnormal result for DPYD/UGT1A1 and at least one supportive care gene, respectively. CDS alerts fired for 32 drug-gene interactions for 25 distinct patients. Of the alerts, 7 (21.9%) were for 5-FU or irinotecan, which showed for 7/89 patients (7.9%); 25 (78.1%) were for supportive care medications, which showed for 23/83 patients (27.7%). There were 9 clinical actions taken in response to the PGx alerts, 7 (77.8%) for 5-FU or irinotecan and 2 (22.2%) for supportive care drugs. Appropriate clinical actions were taken for 100% of patients with 5-FU or irinotecan drug-gene interactions. Conclusions: End-to-end EHR integration of PGx testing and prescribing guidance facilitated clinician adoption of preemptive, standard of care multigene PGx testing, with test results driving important medication changes. Future studies will evaluate the impact of PGx testing on clinical outcomes and cost effectiveness metrics in this population.

Implementation and preliminary efficacy of a risk stratification system +/- patient-reported outcomes monitoring for patients with hospital-diagnosed advanced lung cancer.

11095 Background: Risk stratification systems may improve quality of care for patients with advanced lung cancer (ALC) by identifying those at high risk of rehospitalization and directing them to supportive care. The purpose of this study was to evaluate the implementation and preliminary efficacy of a risk-based system, with/without electronic patient-reported outcome (ePRO) symptom monitoring, to trigger supportive care for patients with hospital-diagnosed ALC. Methods: In this single-site, non-randomized, pragmatic study, patients in an academic center with hospital-diagnosed ALC were stratified to low or high risk using an established tool. High-risk patients were referred to two-pronged supportive care: patient navigation and outpatient palliative care. Eligible patients were recruited for 3 months of ePRO symptom monitoring coupled with provider alerts. Healthcare utilization was assessed at 90 days post-discharge. Program feasibility and acceptability were assessed using percent of eligible supportive care referrals made and completed, enrollment rates in ePROs, ePRO completion, and notifications to providers of concerning symptoms. Preliminary efficacy was defined as percentage of concerning ePRO symptoms resulting in new clinical action and 90-day readmissions. Results: At the time of interim analysis, 49 patients had been assessed with 48/49 (98%) identified as high risk. Patients had a mean age of 66 years, and were non-Hispanic, 51% male, and 22% Black. Patient navigation referral (92%) and completion (88%) was high. Palliative care referral (89%) and completion (45%) was lower. 14/39 (36%) of eligible patients enrolled in ePRO symptom monitoring, with competing priorities or feeling overwhelmed as the primary reasons for non-participation. Patient-level ePRO completion ranged from 0-100% (mean 53%). Nearly all (97%) concerning symptoms were reported to the clinical team; 27% of these resulted in new clinical action. By 90 days, 16/37 (43%) had hospital readmissions. Conclusions: Patient navigation was feasible and acceptable in patients with hospital-diagnosed ALC. However, there are ongoing barriers to implementation of post-hospitalization ePRO symptom monitoring and palliative care. Additional evaluation is needed to understand the barriers and facilitators and to measure the impact of navigation on patient outcomes. Since nearly all patients met high-risk criteria, future programs will eliminate risk stratification and target all patients with hospital-diagnosed ALC. Clinical trial information: NCT05722847 . [Table: see text]

Feasibility and utilization of electronic patient-reported outcome measures for lung cancer in routine clinical care.

11107 Background: Prior studies have shown the value of Patient-Reported Outcomes (PRO) in cost burden, quality of life (QoL), and survival in cancer care. To facilitate focus on patient-centricity and value-based care, the International Consortium for Health Outcomes Measurements (ICHOM) and European Health Outcomes Observatory (H2O) developed a Core Outcomes Set (COS) in lung cancer. We explored the feasibility of deploying standardized PRO measures among patients with lung cancer in US clinical practice. Methods: A retrospective database study was conducted, with IRB waiver, using Carevive PROmPT, an electronic PRO (ePRO) remote symptom monitoring platform with weekly surveys comparable in scope to ICHOM/H2O COS, of symptomatic adverse events (PRO-CTCAE), physical function (PROMIS 4A Physical Function), and QoL items (EORTC QLQ-C30 items #29,30). Severe PRO-CTCAE symptom scores triggered care team alerts. From 9/2020 to 5/2023, 207 patients enrolled across 9 US cancer centers. Patients were ≥18 years, with lung cancer, and in current treatment. Patient engagement was measured by survey compliance, follow-up time, and completeness; clinician engagement was measured by platform utilization time, time to alert response, and clinical action taken. Results: Participants were 50% female, 86% White, 12% African American, median age 68, 81% NSCLC, and 26% with metastatic disease. Median survey persistence: 8 weeks, with 85% compliance over that time. Of domains assessed, 37 (58%) from Carevive data overlapped with ICHOM/H2O COS, with 19 measured over time. Overlapping domains included 15 clinical outcomes with 60% median completion rate and 22 PRO domains with 98% median completion. Of 19 domains assessed longitudinally, median compliance was 76%. Of patients triggering ≥1 ePRO symptom alert, 87% were within 4 weeks, with 46% requesting call-backs. Median clinician follow-up to alerts was 20 hours, with 69.3% addressed within 48 hours. Clinicians accessed the platform 2-3 times weekly, for median 2 minutes (range: 1-14 minutes) per login for nurses and Advanced Practitioners (AP). 89% of alerts were addressed by nurses and AP. Of alert responses, 66% indicated continuation of treatment, 12% were escalated to the clinical team, and 1% were escalated to hospitalization or ER visit. Conclusions: Results support the feasibility of integrating a standard set of multi-domain ePRO measures, comparable to the ICHOM/H2O COS, into routine cancer care, across multiple sites, with consistent patient engagement and provider utilization. One limitation is that clinical and financial impact were not directly assessed. Future research should explore direct clinician feedback, systematic implementation of PRO measures, and impacts on patient outcomes, resource utilization, and health systems.

Sustained transmission over two decades of a previously unrecognised MPT64 negative Mycobacterium tuberculosis strain in Queensland, Australia: a whole genome sequencing study

MPT64 is a key protein used for Mycobacterium tuberculosis (MTB) complex strain identification. We describe protracted transmission of an MPT64 negative MTB strain in Queensland, Australia, and explore genomic factors related to its successful spread. All MPT64 negative strains identified between 2002 and 2022 by the Queensland Mycobacteria Reference Laboratory, and an additional 2 isolates from New South Wales (NSW), were whole genome sequenced. Bayesian modelling and phylogeographical analyses were used to assess their evolutionary history and transmission dynamics. Protein structural modelling to understand the putative functional effects of the mutated gene coding for MPT64 protein was performed. Forty-three MPT64 negative isolates were sequenced, belonging to a single MTB cluster of Lineage 4.1.1.1 strains. Combined with a UK dataset of the same lineage, molecular dating estimated 1990 (95% HPD 1987-1993) as the likely time of strain introduction into Australia. Although the strain has spread over a wide geographic area and new cases linked to the cluster continue to arise, phylodynamic analysis suggest the outbreak peaked around 2003. All MPT64 negative strains had a frame shift mutation (delAT, p.Val216fs) within the MPT64 gene, which confers two major structural rearrangements at the C-terminus of the protein. This study uncovered the origins of an MPT64 negative MTB outbreak in Australia, providing a richer understanding of its biology and transmission dynamics, as well as guidance for clinical diagnosis and public health action. The potential spread of MPT64 negative strains undermines the diagnostic utility of the MPT64 immunochromatographic test. This study was funded from an operational budget provided to the Queensland Mycobacterium Reference Laboratory by Pathology Queensland, Queensland Department of Health.

Semaglutide and obesity: beyond the nutritional and lifestyle intervention?

Semaglutide is the second marketed glucagon-like peptide 1 receptor agonist that can be used safely and efficiently in non-diabetic people with excess weight, providing a new milestone in the pharmacological treatment of obesity. This narrative review aims to describe the clinical actions of this new drug in weight management in non-diabetic patients along with possible side-effects and dropout reasons. To accomplish this, the PubMed database was searched to retrieve the most relevant clinical studies published to date on this topic, using the following keywords "semaglutide and obesity". Currently, semaglutide is on the market in two formulations, the once-weekly subcutaneous (s.c.) semaglutide and once-daily oral semaglutide. Data in the literature on the anti-obesity action of semaglutide are available for both routes of administration of the drug, with a prevalence of studies using the s.c. one. However, given its dosage, oral semaglutide may provide greater attractiveness and better treatment adherence, but further research is needed in this field.

Ketamine and fluoxetine exert similar actions on prelimbic and infralimbic responsivity to lateral septal nucleus stimulation in Wistar rats

Ketamine is a dissociative anesthetic that has been proposed to be a useful alternative in cases of a poor response to other treatments in patients with depression. Remarkably, beneficial clinical actions of ketamine are detected once its psychotropic actions disappear. Therefore, clinical actions may occur independently of dose. Most current studies focus on actions of ketamine on neurotrophic factors, but few studies have investigated actions of ketamine on neural structures for which actions of antidepressants have been previously explored. Lateral septal nucleus (LSN) stimulation reduces neural activity in the prelimbic cortex (PL) and infralimbic cortex (IL) subregions of the medial prefrontal cortex (mPFC). Fluoxetine increases inhibitory responsivity of the LSN-IL connection. In the present study, actions of an anesthetic dose of ketamine were compared with a high dose of fluoxetine on behavior and neural responsivity 24 h after drug administration. Fluoxetine reduced immobility in the forced swim test without changing locomotor activity in the open field test. Ketamine strongly decreased locomotor activity and did not produce changes in immobility. In another set of Wistar rats that received similar drug treatment regimens, the results indicated that LSN stimulation in saline-treated animals produced a long-lasting inhibitory afterdischarge in these mPFC subregions. Actions of ketamine on the LSN-mPFC connection reproduced actions of fluoxetine, consisting of accentuated inhibition of the LSN action on the mPFC. These findings suggest that independent of different actions on neurotransmission, the common final pathway of antidepressants lies in their actions on forebrain structures that are related to emotional regulation.

#2103 Accuracy of a continuous glucose monitor in people with diabetes on peritoneal dialysis

Abstract Background and Aims Globally 40% of people receiving peritoneal dialysis (PD) have a diagnosis of diabetes. Good glycaemic control can by complicated by the obligate glucose load associated with PD. Monitoring and treatment of people with diabetes (PwD) on PD has been limited by reduced reliability of traditional markers of glycaemia such as HbA1c in end-stage kidney disease. Continuous glucose monitors (CGMs) have been increasingly used in the care of PwD over the last 20 years. Monitors worn on the upper arm or abdomen measure glucose in interstitial fluid at regular intervals over the 24 hour period. CGMs are currently unlicensed in PD populations as they have not been tested in large scale studies. Concerns remain around accuracy in the presence of potentially interfering substances generated by the breakdown of osmotic agents used in PD fluid (e.g. Icodextrin). We aimed to assess the analytical and clinical accuracy of the FreeStyle Libre(FSL) CGM system in PwD on maintenance PD. Method We conducted a single centre observational study of 10 PwD who had been on PD for at least 3 months. For the 10 day study period participants wore a blinded research model FSL monitor which measured interstitial glucose levels every 15 minutes. Results from the FSL were compared with; Analytical accuracy was assessed using three methods; Clinical accuracy was assessed using the Parkes consensus error grid to assign each pair of readings to one of five risk zones and quantify the clinical implications of any difference between the two measurements. The International Organisation for Standardisation guidelines stipulates 99% of pairs should be in zones A and B, denoting little or no effect on clinical actions. Results Of 11 recruited participants, 10 completed the 10 day study period resulting in 76 paired CGM-YSI measurements and 375 paired CGM-CBG measurements. 7 participants were on APD and 3 on CAPD. All participants were prescribed a PD regime that included one daily dwell with Icodextrin. The aggregate MARD was 9.4% (95% CI 7.9, 10.4) for CGM-YSI matched pairs and 17.6% (95% CI 17, 19.3) for CGM-CBG matched pairs. Spearman's r was 0.94 (p &amp;lt; 0.0001) for CGM-YSI and 0.89 (p &amp;lt; 0.0001) for CGM-CBG. From Bland-Altman analysis, the systematic error of the CGM compared with YSI and CBG was −0.81 mmol/l (SD 0.81) and −1.6 mmol/l (SD 1.9) respectively. Parkes consensus error grid analysis showed that compared with YSI and CBG respectively, 100% and 99.9% of sensor values were in the clinically acceptable zones A and B (Fig. 1). Conclusion We have demonstrated satisfactory performance of the FSL monitoring system by both analytical and clinical metrics in this cohort of PD patients using treatment regimens including Icodextrin based fluids. CGMs provide much more information for the PwD and their clinical care team compared with random CBGs (which in themselves have been shown to exhibit significant between user variability) and time averaged markers such as HbA1c. They allow detection of asymptomatic hypoglycaemia and direct monitoring of the systemic effects of any change to the PD prescription resulting in a larger or smaller glucose load. These results should be reassuring for clinicians wishing to utilise the greater depth of information provided by CGMs to improve clinical care for their patients with diabetes on PD.

Circadian serum progesterone variations on the day of frozen embryo transfer in a modified natural cycle protocol.

Is there a circadian variation of serum progesterone (P) on the day of frozen embryo transfer (FET) in a modified natural cycle (mNC)? There is a statistically significant diurnal variation of serum P on the day of a FET in an mNC protocol. In recent years, the proportion of FET cycles has increased dramatically. To further optimize pregnancy outcomes after FET, recent studies have focused on serum luteal P levels in both natural and artificially prepared FET cycles. Despite the different cut-off values proposed to define low serum P in the NC, it is generally accepted that lower serum P values (<10 ng/ml) around the day of FET are associated with negative reproductive outcomes. However, a single serum P measurement is not reliable given that P levels are prone to diurnal fluctuations and are impacted by patients' characteristics. A prospective cohort study was conducted in a single university-affiliated fertility center, including 22 patients performing a single blastocyst mNC-FET from August 2022 to August 2023. Serum P levels were measured on the day of transfer at 08:00h, 12:00h, 16:00h, and 20:00h. Differences between P levels were compared using the Wilcoxon signed-rank test. The sample size was calculated to detect a difference of 15% between the first and last P measurements with a 5% false-positive rate and a 95% CI. Patients with a normal BMI, between 18 and 40 years old, without uterine diseases were eligible. Patients utilizing donated oocytes were excluded. The mNC-FET protocol involved monitoring the normal ovarian cycle and triggering ovulation with an injection of 250 μg of choriogonadotropin alfa when a pre-ovulatory follicle (16-20 mm diameter) was visualized. The blastocyst was transferred seven days later. The patients were not supplemented with exogenous P at any time before the day of the FET. The mean age and BMI of the study population were 33.6 ± 3.8 years and 22.7 ± 1.8 kg/m2, respectively. Mean P values at 08:00h, 12:00h, 16:00h, and 20:00h were 14.6 ± 4.5, 14.7 ± 4.1, 12.9 ± 3.5, and 14.6 ± 4.3 ng/ml, respectively. The mean P levels at 16:00h were significantly lower compared to all other time points (P < 0.05: P = 0.007 between P at 8:00h and 16:00h; P = 0.003 between P at 12:00h and 16:00h; P = 0.007 between P at 16:00h and 20:00h). No statistically significant difference was observed between P values at the other time points (P > 0.05: P = 0.88 between P at 8:00h and 12:00h; P = 0.96 between P at 8:00h and 20:00h; P = 0.83 between P at 12:00h and 20:00h). The study's limitations include the small sample size that may cause a bias when the results are extrapolated to a larger subfertile population undergoing mNC-FET. Ideally, larger prospective trials including a more heterogeneous patient population would be necessary to validate our findings. The current study demonstrates the existence of a diurnal fluctuation of serum P on the day of mNC-FET highlighting the importance of a standardized time point for its measurement. This is especially important for considering clinical actions, such as additional exogenous P supplementation, when encountering P values lower than 10 ng/ml on the day of FET. No funding was obtained for the study. The authors have no conflicts of interest to declare regarding the content of the study. NCT05511272.

Barriers and facilitators in self-care and management of chronic kidney disease in dialysis patients: A systematic review of qualitative studies.

To identify and synthesise qualitative studies on barriers and facilitators perceived by dialysis patients in relation to self-care and disease management. Systematic review of qualitative studies. Qualitative study articles were extracted from PUBMED, MEDLINE, COCHRANE, WEB OF SCIENCE (WOS), CINAHL PsycINFO and EMBASE and electronic journals of the Spanish Society of Nephrology and Spanish Society of Nephrological Nursing until May 2022. Studies on barriers and/or facilitators affecting self-care and disease management expressed by people undergoing haemodialysis or peritoneal dialysis were included. The SPICE (Setting, Perspective, Intervention, Comparison and Evaluation) strategy was used to develop issues and subissues through the thematic synthesis of the qualitative findings. GRADE-CERQual was used to evaluate the articles. From 172 articles, 15 qualitative articles about barriers and facilitators perceived by patients concerning self-care and disease management were finally included. Identified eight facilitators and four barriers. Patients perceived a significant number of barriers and facilitators. It is possible to identify which aspects facilitate self-management of their disease and to understand that the processes are individualised. This is why therapeutic strategies should be designed to foster the participation and empowerment of the person in the management of the disease. Identifying the barriers and facilitators concerning the management of chronic kidney disease furnishes us with knowledge for individualised clinical practice and improved care processes. This review is the first to synthesise barriers and facilitators in haemodialysis patients about the management of their disease and treatment. The results enable the proposal of improvements in the training of healthcare personnel, clinical practice guidelines and action protocols to improve the daily life and management of the disease by patients. No patient or public contribution due to this is a systematic review.

Association of a device-based remote management heart failure pathway with outcomes: TriageHF Plus real-world evaluation.

Clinical pathways have been shown to improve outcomes in patients with heart failure (HF). Although patients with HF often have a cardiac implantable electronic device, few studies have reported the utility of device-derived risk scores to augment and organize care. TriageHF Plus is a device-based HF clinical pathway (DHFP) that uses remote monitoring alerts to trigger structured telephone assessment for HF stability and optimization. We aimed to evaluate the impact of TriageHF Plus on hospitalizations and describe the associated workforce burden. TriageHF Plus was a multi-site, prospective study that compared outcomes for patients recruited between April 2019 and February 2021. All alert-triggered assessments were analysed to determine the appropriateness of the alert and the workload burden. A negative-binomial regression with inverse probability treatment weighting using a time-matched usual care cohort was applied to estimate the effect of TriageHF Plus on non-elective hospitalizations. A post hoc pre-COVID-19 sensitivity analysis was also performed. The TriageHF Plus cohort (n=443) had a mean age of 68.8±11.2years, 77% male (usual care cohort: n=315, mean age of 66.2±14.5years, 65% male). In the TriageHF Plus cohort, an acute medical issue was identified following an alert in 79/182 (43%) cases. Fifty assessments indicated acute HF, requiring clinical action in 44 cases. At 30day follow-up, 39/66 (59%) of initially symptomatic patients reported improvement, and 20 (19%) initially asymptomatic patients had developed new symptoms. On average, each assessment took 10min. The TriageHF Plus group had a 58% lower rate of hospitalizations across full follow-up [incidence relative ratio: 0.42, 95% confidence interval (CI): 0.23-0.76, P=0.004]. Across the pre-COVID-19 window, hospitalizations were 31% lower (0.69, 95% CI: 0.46-1.04, P=0.077). These data represent the largest real-world evaluation of a DHFP based on multi-parametric risk stratification. The TriageHF Plus clinical pathway was associated with an improvement in HF symptoms and reduced all-cause hospitalizations.