Routine Review Research Articles

P-239. Leveraging Preliminary Blood Culture Reports at an Academic Medical Center: A Real-time Central Line-Associated Bloodstream Infection (CLABSI) Reduction Strategy

Abstract Background CLABSIs have been shown to result in adverse outcomes including increased morbidity and mortality, length of hospital stays, and healthcare costs. The National Healthcare Safety Network (NHSN) surveillance criteria are meant to be applied in a standardized manner, but this can result in discordance between clinical diagnoses and the surveillance definitions of secondary bloodstream infections (2° BSI). We hypothesized that routine review of preliminary positive blood cultures (B/Cs) in patients with central lines would result in the identification of possible CLABSI events in real-time and promote dissemination of feedback, thus reducing CLABSI cases and increasing 2° BSI attribution.Figure 1:CLABSI Case DeterminationClassification of cases identified by review of a preliminary blood culture report for patients with a central line eligible for CLABSI surveillance Methods An automated electronic medical record (EMR) report was developed to capture preliminary B/C results for patients with a central line eligible for CLABSI surveillance. Daily EMR review was performed to identify opportunities contributing to the event or evidence of a clinical 2° BSI without corresponding elements needed to meet NHSN definitions. Possible B/C contamination, gaps in care and, if clinically appropriate, necessary elements required to meet NHSN 2° BSI definitions were communicated to the care team. Secondary BSI Attribution Categorization of cases with a final determination of secondary BSI attribution Results Confirmed CLABSI cases with no intervention indicated were 35.5% of cases reviewed; 38.1% were determined to meet CLABSI exclusion criteria. Evidence of 2° BSI was identified in 26.5% of cases, which prompted queries to the care team to consider additional imaging, cultures, or documentation needed to clarify the clinical assessment. Feedback related to possible B/C contamination was given in 17.5% of cases. (Fig. 1-3) CLABSI Standardized Infection Ratio (SIR) Standardized infection ratio (SIR) trend: Tactic was adopted in May 2023 Conclusion CLABSI reduction requires a comprehensive approach that addresses various aspects of care including appropriate line selection, safe insertion practices, care bundles, and prompt line removal. The EMR can be used to hard-wire best practices, facilitate real-time communication, and identify CLABSI cases in a timely manner. We have shown that prompt review of positive B/Cs of patients with eligible central lines facilitates opportunities to align the clinical impression with the surveillance definitions for 2° BSI while bolstering quality improvement efforts and staff education. Disclosures All Authors: No reported disclosures

Neonatal indicator data in Tanzania District Health Information System: evaluation of availability and quality of selected newborn indicators, 2015-2022

BackgroundThe Every Newborn Action Plan (ENAP) indicators are essential in monitoring neonatal healthcare coverage and quality. The District Health Information System (DHIS2), an open-source platform in over 80 countries, supports health data collection and analysis, enabling progress tracking at national and subnational levels. This study evaluates the availability and quality of maternal and newborn health indicators, explicitly focusing on ENAP indicators within Tanzania’s DHIS2.MethodsUsing the EN-MINI tool, we assessed data availability for 20 ENAP indicators by analysing their numerators and denominators in Tanzania’s DHIS2 (2015–2022) across all healthcare levels. World Health Organization’s (WHO) data quality framework was adapted to examine four dimensions: (a) availability of indicators, (b) completeness of indicator reporting, (c) internal consistency of related indicators, and (d) indicator plausibility by comparing DHIS2 data with population-based Demographic and Health Survey (DHS) data.ResultsOf the 20 ENAP indicators, 14 were available in Tanzania’s DHIS2, with definitions, numerators and denominators aligned with WHO standards. Between 2015 and 2022, the number of facilities reporting at least one delivery annually increased by 19% from 5,898 to 7,016. During this period, 75% to 97% of facilities consistently reported data on skilled attendance at birth and early breastfeeding initiation. In contrast, 4% to 54% of facilities reported on maternal and newborn outcomes, including complications such as stillbirths and maternal mortality. Internal consistency was high (> 94%). However, neonatal mortality rates reported in DHIS2 were lower than those reported in Tanzania DHS for similar periods, even after a 20% adjustment to account for home births.ConclusionTanzania’s DHIS2 captures many ENAP indicators; however, notable variability in data quality persists, with substantial data gaps related to maternal and newborn outcomes and complications. To address these challenges, it is crucial to strengthen routine data review, implement robust quality checks, enhance validation processes, provide targeted training, deliver constructive feedback, and conduct supportive supervision. Placing greater emphasis on using DHIS2 data to monitor progress will help identify gaps and drive improvements in data quality, ultimately supporting better maternal and newborn health outcomes.

Delirium prevention in hospices: Opportunities and limitations - A focused ethnography.

Delirium is common and distressing for hospice in-patients. Hospital-based research shows delirium may be prevented by targeting its risk factors. Many preventative strategies address patients' fundamental care needs. However, there is little research regarding how interventions need to be tailored to the in-patient hospice setting. To explore the behaviours of hospice in-patient staff in relation to delirium prevention, and the influences that shape these behaviours. Focused ethnography supported by behaviour change theory. Observation, semi-structured interviews and document review were conducted. A total of 89 participants (multidisciplinary staff, volunteers, patients and relatives) at two UK in-patient hospice units. Hospice clinicians engaged in many behaviours associated with prevention of delirium as part of person-centred fundamental care, without delirium prevention as an explicit aim. Carrying out essential care tasks was highly valued and supported by adequate staffing levels, multidisciplinary team engagement and role clarity. Patients' reduced physical capability limited some delirium prevention behaviours, as did clinicians' behavioural norms related to prioritising patient comfort. Delirium prevention was not embedded into routine assessment and care decision-making, despite its potential to reduce patient distress. The value placed on fundamental care in hospices supports delirium prevention behaviours but these require adaptation as patients become closer to death. There is a need to increase clinicians' understanding of the potential for delirium prevention to reduce patient distress during illness progression; to support inclusion of delirium prevention in making decisions about care; and to embed routine review of delirium risk factors in practice.

Subjective and objectives measures of frailty among adults with advanced chronic kidney disease: a cross-sectional analysis of clinician misclassification.

Frailty is a recognisable clinical measure of impaired physiological reserve and vulnerability to adverse outcomes that is validated among patients with kidney disease. Practice patterns reveal inconsistent use of objective frailty measures by nephrologists, with clinicians prioritising subjective clinical impressions, possibly risking misclassification and discrimination. The aim of this study was to examine correlations between subjective and objective measures of frailty in a cohort of patients attending routine nephrologist review. Eighty-nine participants attending scheduled review with their primary treating nephrologist (n = 6) were included in cross-sectional analysis. Measured frailty based on Fried phenotype and subjective clinician impression were assessed for congruence using Pearson's correlation analysis and ĸ statistic. Ordinal logistic regression examined patient demographics associated with perceived frailty. Misclassification was explored using descriptive statistics and contingency table analysis. Frailty and prefrailty were prevalent by both objective and subjective means of assessment with minimal correlation between clinician impression and measured Fried phenotype (r = 0.50, P = 0.00, ĸ = 0.25, P = 0.00). Subjective clinician impression misclassified half of participants, influenced by surrogate frailty measures including female sex, comorbidity and reliance on a walking aid. Clinicians were equally likely to over-classify prefrailty as to under-recognise established frailty, with no evidence of systemic misclassification bias. Subjective clinican impression of frailty had a positive predictive value of 19.1% and a negative predictive value of 56.2%. Nephrologists' reliance on subjective clinical impressions that overlook or misclassify prefrailty offers incomplete prognostic assessment and potentially misses opportunities for early intervention.

Latent Tuberculosis Infection Amongst Allogeneic Hematopoietic Stem Cell Transplant Recipients: The Impact of Routine Pretransplant Review by a Transplant Infectious Diseases Physician.

Identifying patients with latent tuberculosis infection (LTBI) is challenging. This is particularly true amongst immunocompromised hosts, in whom the diagnostic accuracy of available tests is limited. The authors evaluated the impact of routine pretransplant review by a transplant infectious diseases (TID) physician on LTBI screening in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. Adult patients who received an alloHSCT between January 2018 and December 2022 were eligible for inclusion. Data were retrospectively extracted from patient records. Participants were dichotomized into those that had a routine pretransplant review with a TID physician and who that did not. Of the 116 participants included, 61.2% had a documented TID review. This intervention was associated with more frequent initiation of LTBI treatment (8.5% vs. 0.0%) and a tendency for LTBI treatment to be initiated in the absence of immunodiagnostic criteria (7.1%vs. 0.0%). A case of LTBI reactivation occurred in each group. Routine pretransplant review by TID physicians improved the recognition of risk factors for LTBI and increased the initiation of LTBI treatment in patients with a high pretest probability of LTBI. Further research is needed to evaluate the utility of routine pretransplant TID review and to determine the optimal strategy for preventing LTBI reactivation amongst alloHSCT recipients in low-endemic settings.

Role of surveillance data in detecting malaria outbreaks in an epidemic-prone region in Kenya: findings from an investigation of a suspected outbreak in Nandi County

BackgroundApproximately 70% of the Kenyan population is at risk for malaria, including 19 million people in highland epidemic-prone and seasonal transmission areas. Surveillance data showed a 288% increase in malaria cases and an incidence rate of 10.5 per 1000 population between January and May 2021 in Nandi County. We investigated the increased incidence of malaria in Nandi County.MethodsWe abstracted demographic and clinical data from the laboratory register in health facilities with high malaria burden. Key informant interviews using a structured questionnaire collected healthcare worker perceptions on malaria interventions and personnel capacity. We calculated means and medians for continuous variables and frequency and proportions for categorical variables. Data quality assessment (DQA) was conducted to evaluate timeliness and completeness, data accuracy, and overall system assessment.ResultsWe reviewed 19,526 records from 12 health facilities. Females contributed 61% cases (11,862). A majority of cases, 21% (4111), were between the age group 15–24 years. Of the 19,498 tested, 2662 tested positive (test positivity rate, TPR = 13.7%). Microscopy accounted for 39% (1041) and RDT for 61% (1620) of tests conducted, with some patients being double tested using both tests. Kapsabet County Referral contributed 26% (5051) suspected cases, TPR 3.2%, and Chemase Health Centre TPR was 33.2%. Facilities experienced major RDTs stock-outs in the preceding 3 months while three (30%) of the 10 facilities assessed conducted laboratory Internal Quality Control (IQC) programmes. Of the 12 facilities assessed, four (33%) facilities had an over-reporting of suspected cases in the monthly summary, while three (25%) facilities were over-reported in the online tool. On reporting confirmed malaria cases, over-reporting was noted in three (25%) facilities in both the monthly summaries and the online tool. Data completeness was 77% and timeliness 93%.ConclusionThe increase in malaria cases in Nandi County displayed a seasonal pattern that coincided with either the long or short rainy seasons, the investigation did not reveal an active outbreak at the time of the inquiry. Sub-county hospitals in Tinderet and Aldai sub-counties had malaria cases exceeding both the alert and action thresholds at specific times during the year under review, suggesting a potential occurrence of unidentified outbreaks, while several other facilities had an increase of cases reaching alert thresholds, indicating upsurges. In healthcare settings, we noted there were problems with data quality. We advised routine data review, analysis, and feedback; mentorships for data analysis and on the job and support supervision; mentorships for malaria diagnosis; and installation of laboratory quality assurance.

Before closing a program, ensure compliance, assess legal, reputational risks

Whether arising out of routine program review or unanticipated enrollment and economic challenges, institutions of higher education occasionally find a need to close a program.

Broken Drill Bits During Surgical Procedures: A Review of 156 Patient Safety Events

Background Broken surgical drill bits pose a risk to patient safety. A routine review of event reports submitted to the Pennsylvania Patient Safety Reporting System (PA-PSRS) uncovered an increase in the number of event reports related to broken drill bits, prompting an exploration to better understand patterns of drill bit breakage in Pennsylvania. Methods We queried the PA-PSRS database to identify event reports describing a broken drill bit during surgery submitted between January 1, 2021, and December 31, 2023. Event reports were manually coded to identify the procedure, anatomic location of breakage in the patient’s body, timing of discovery, and fragment fate. Results A total of 156 relevant event reports were identified. The procedure being performed was determined in 64 of 156 event reports. Fracture repair procedures were most commonly reported to encounter a broken drill bit (27 of 64; 42.2%). We were able to determine the anatomic location in the patient’s body where the drill bit breakage occurred in 108 of 156 event reports. The most commonly reported anatomic location was the femur (27 of 108; 25.0%). We were able to determine the fate of the broken drill bit in 141 of 156 event reports, and most drill bits were retained in the patient (99 of 141; 70.2%). Conclusion This data analysis provides insight into broken drill bits in Pennsylvania facilities. Because drill bits are commonly broken pieces of equipment and the fragments from these broken pieces are frequently retained, it is important to prevent drill bit breakage to improve patient safety. Table 2 (251188) outlines prevention strategies established by equipment manufacturers and previous research. Implementing these strategies can address breakage across multiple procedures and patients. Plain Language Summary While a rare occurrence, surgical instruments may break during a procedure. In the case of drill bits, which are one of the most frequently broken surgical instruments, pieces that are left inside of a patient could cause harm, and may migrate to other parts of the body. When Patient Safety Authority researchers noted an increased number of events involving broken and retained drill bits during surgery, they analyzed data from the Pennsylvania Patient Safety Reporting System (PA-PSRS) to help decrease the risk of broken drill bits in surgery. In studying cases involving a drill bit breaking during surgery, researchers learned that most of these events occurred during fracture repair procedures and joint replacement surgery, and drill bits most frequently broke in the femur (thigh bone). In most event reports, the broken drill bit was discovered during the procedure, but in 2.6% of event reports (4 out of 156 reports) it was discovered after the operation. Removing drill bit fragments is recommended; however, surgeons may decide to leave them in place if removal risks damage to the surrounding area, and in many event reports broken drill bits were retained following the surgery with no further intervention. Hospitals and surgical facilities should look to existing literature and device manufacturers’ guidelines for prevention strategies, such as recommended surgical techniques; drill bit sterilization, reprocessing, and storage; and general safety measures, some of which are summarized in the article.

The nature, sequence and duration of professional activities of Emergency Medical Service providers: An observational study to evaluate quality of care using the steps in the EMS care process as described by the SPART model.

The quality of care given by EMS staff is in part monitored by routine review of deployment reports that the providers must complete after each deployment. The assessment consists of determining whether a deployment was performed in a medically correct manner and thus whether the clinical reasoning process was appropriate. The time used during the deployment is also measured, as there are often time limits for performing different parts of the deployment and these must be adhered to. One might question whether measuring the time spent really gives insight into the quality of care, and if it might not be more useful to see how that time was spent. We therefore conceived a study to map the EMS care process and evaluate this process in relation to the time used. We used a focused ethnographic study design. Video recordings of EMS deployments in combination with semi-structured interviews of the EMS providers involved, were thematically analysed. This led to insights into the EMS care process and the embedded clinical reasoning. By categorising the professional activities we identified we were able to define a model that describes in general the EMS care process. We reported the first part of this study in which we developed this so called SPART model in a separate paper. In this second part of the study we determined the execution time within a deployment and measured the frequency of occurrence and the duration of the identified activities. We interpreted the operational content and the time variables both qualitatively and quantitatively. We also determined the distribution of activities over the three deployment operational periods (response, on-scene and transport period). Using the SPART model, we gained insight into the different activities' nature, order, and duration. We could qualitatively judge the effectiveness of the clinical reasoning process, i.e., the quality of care delivered. Generally, the studied cases were followable, and the clinical reasoning process was medically logical. The diagnostic process sometimes continued after the clinical decision, which was not medically logical. Remarkably, this never changed the clinical decision. Although this could negatively affect the quality of care, we found no clinical evidence that this was the case. Our findings demonstrated that the quality of care in EMS can be measured by using the SPART model to evaluate EMS deployments. We concluded that qualitative judgment was more important than quantitative evaluation. Interpreting the order of different activities led to the clearest understanding of the clinical reasoning process. It was concluded that knowledge of the exact time used per activity and, in total, had the least impact on understanding the clinical reasoning process.

Routine review of patient-reported outcome data influences radiotherapy care: IMPROVE study results.

Radiation oncologists closely monitor patients during weekly on-treatment visits (OTVs). This study examines whether routine patient-reported outcome measures (PROMs) during OTVs change physicians' perceptions of treatment-toxicity and inform symptom-management. IMPROVE is a single-arm prospective multicenter trial, conducted from 2020 to 2023. Patients with locally-advanced or oligometastatic thoracic or gastrointestinal cancers receiving definitive-intent radiation, with or without chemotherapy, and their physicians enrolled. Patients completed a 14-question disease-specific PROM in-clinic prior to OTVs. Physicians rated their patient's global toxicity-burden based on clinical data/assessments, then re-rated their patient's toxicity-burden and reported management-changes after PROM review. At radiotherapy end, physicians completed a Feedback Form. PROMs and outcome-data collection used electronic or paper forms. We report any change in physician-assessed burden-score and symptom-management due to PROMs. The 100 patients enrolled (49 academic, 51 community-based) were 70 years old (median), 51 % female, 81 % Caucasian, 95 % ECOG 0-1, and 94 % received concurrent chemotherapy. The median radiation dose was 60 Gy, delivered over 6 weeks. PROMs were available for review for 607/629 (97 %) OTVs: full 433/629 (69 %), partial 174/629 (28 %). For 75/100 patients (75 %; 95 % CI:65 %-83 %), PROM review resulted in any change in physician-reported burden-score, and for 50/100 patients (50 %; 95 % CI:40 %-60 %) any change in patients' on-treatment management. Rates of burden-score and management-changes were similar between academic and community-based practices (78 % vs. 73 %; 53 % vs. 47 %, respectively). For 78/100 patients with Feedback Forms, physicians agreed/strongly agreed that PROMs improved patients' quality-of-care (91 %). PROM review changes radiation oncologists' on-treatment toxicity assessment in 75 % and care delivery in 50 % of their patients.

An anesthesiology-led perioperative outreach service: experience from a Canadian centre and a focused narrative literature review.

Approximately 320 million surgeries occur annually worldwide, increasingly performed on an ageing, comorbid population in whom postoperative complications contribute significantly to mortality. While anesthesiologists have led advances in perioperative care, the optimal structure of the provision of postoperative care has lacked discourse. In this article, we describe the implementation, structure, role, and benefits of an Anesthesiology Perioperative Outreach Service (APOS) at a Canadian tertiary hospital, providing proactive daily review and management of high-risk surgical patients. The APOS involves routine reviews and care on surgical wards, emphasizing collaboration among anesthesiology, internal medicine, surgery, and geriatric medicine teams, with a specific screening pathway to identify patients experiencing myocardial injury after noncardiac surgery. We discuss case vignettes to illustrate common examples of how the APOS enabled early detection and treatment escalation for deteriorating patients and provide a focused narrative literature review. The anesthesiology-led perioperative outreach model described herein could provide an implementable framework for institutions seeking to enhance their quality of postoperative care-particularly among complex, comorbid patients at risk of postoperative morbidity.

Quality improvement project provides unexpected insights into hospitalized pain management

Patient education and multidisciplinary treatment plans are key best practices for pain management in hospitalized patients. In a routine compliance review, stakeholders at Baylor Scott & White Medical Center – Temple identified pain management patient education as an area needing improvement. A dual-sided medication explanation card was developed, including functional expectations and a QR code linking a companion website with additional pain management educational materials. This short communication details the results from a small quality improvement pilot study using QR code technology to deliver pain management education materials to hospitalized patients. Patients were surveyed the morning after admission and survey results are reported using standard descriptive statistics. Of 46 patients who received the education card, 44 reported well-controlled or moderately-controlled pain and 36 asked for as-needed pain medications. Fourteen patients said that the card was straightforward or made the medication options easy to understand. Per analytics, the companion website had at least 37 unique visitors during the survey period, with at least 8 visitors clicking additional links from the homepage. Though 30 % of patients reported that the education card was helpful and/or straightforward regarding medication options (as intended), five patients with moderately controlled pain who asked for as-needed medications reported they were delayed or ineffective, which revealed that timely administration and adjustments to regimens per patient feedback is also essential. Website analytics suggested that patients utilize and engage with available resources at differing rates. Limitations of this pilot study include small patient population, no pre-intervention comparator group, and disruption in analytics data gathering capabilities during the pilot. Despite limited qualitative data, the quality improvement objectively demonstrated regulatory compliance with pain management education standards and it was adopted throughout all the hospitals of the Baylor Scott & White Healthcare system.

Delivery of Supported Self-Management in Primary Care Asthma Reviews: Insights From the IMP2ART Programme.

Supported self-management (SSM) for asthma reduces the risk of asthma attacks and improves asthma control and quality of life. SSM optimally includes patient-centred communication and behaviour change support, however, the extent to which this occurs in routine primary care is unclear. This project was nested within the IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) programme; a UK-wide trial evaluating an implementation strategy (including healthcare professional (HCP) training on behaviour change strategies and patient-centred care) to improve support for asthma self-management. To provide an understanding of how healthcare professionals deliver SSM in UK clinical practice; through assessing time spent on SSM strategies, how and to what extent patient-centred care and behaviour change discussions are delivered, and to explore whether factors such as mode of review or implementation support influence delivery. We conducted an observational study using video-recordings of 12 HCPs delivering routine face-to-face and telephone asthma reviews (n = 64) in a sample of general practices participating in the IMP2ART trial (implementation n = 4; control n = 6). Analytical methods included: ALFA Toolkit Multi-Channel Video Observation (to code and quantify tasks undertaken); the Patient-Centred Observation Form; and The Behaviour Change Counselling Index (to assess patient-centeredness and behaviour change counselling used by HCPs). HCPs mostly spent time during routine asthma reviews discussing: an individual's asthma condition and management (average of 27.8% of consultation time); collaboratively reviewing and completing a personalised asthma action plan (6.3%) and training for practical self-management activities (5.4%). Areas of patient-centred care delivery and behavioural discussions included: creating and maintaining relationships, discussing asthma action plans and medication reconciliation. Professionals in IMP2ART implementation group practices delivered more SSM strategies. Comparison of face-to-face and remote consultations found no significant differences in HCP delivery of SSM. HCPs in UK primary care spent half the time in both face-to-face and remote asthma reviews delivering components of SSM suggesting that either mode of delivery may be acceptable. Reviews carried out in IMP2ART implementation group practices demonstrated more behaviour change and collaborative SSM strategies compared to those in the control group. Asthma UK Centre for Applied Research (AUKCAR) PPI members were involved throughout, including project conception, providing feedback on participant-facing documents, and discussing implications of study findings.

Impact of rapid blood culture identification PCR panel on optimal antibiotic use in methicillin-susceptible Staphylococcus aureus bacteremia.

In this retrospective study of 200 patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, the implementation of the BioFire® blood culture identification polymerase chain reaction (PCR) panel was associated with a decreased time to optimal MSSA antibiotic therapy and shorter durations of empiric anti-MRSA antibiotic therapy and bacteremia. The findings demonstrate the significant role of rapid PCR testing and routine stewardship review in optimizing antimicrobial therapy and management of MSSA bacteremia.

Evaluation of an oral small-molecule glucagon-like peptide-1 receptor agonist, lotiglipron, for type 2 diabetes and obesity: A dose-ranging, phase 2, randomized, placebo-controlled study.

The aim was to investigate the effects of lotiglipron, a once-daily, oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist, in participants with type 2 diabetes (T2D) or obesity. A phase 2, randomized, double-blind, placebo-controlled, dose-ranging study investigated the efficacy and safety of lotiglipron. The study was terminated early for safety reasons after routine data and monitoring review. The planned analyses for the end points were modified prior to unblinding the study. In total, 901 participants were treated with at least one dose of the study drug (T2D cohort: n = 512, obesity cohort: n = 389). Although the majority of participants who were randomly assigned to higher doses did not reach their target maintenance dose, statistically significant changes in HbA1c and body weight were observed. In the T2D cohort, reductions in HbA1c were observed across all lotiglipron doses at week 16 (p < 0.0001), with least squares mean decreases up to -1.44% (90% confidence interval [CI]: -1.63, -1.26) (lotiglipron 80 mg), versus placebo, -0.07% (90% CI: -0.25, 0.11). In the obesity cohort, decreases in body weight were observed across all lotiglipron doses at week 20 (p < 0.01), up to -7.47% (90% CI: -8.50, -6.43) (lotiglipron 200 mg, five-step titration), versus placebo, -1.84% (90% CI: -2.85, -0.83). Across cohorts, the most frequently reported treatment-emergent adverse events were gastrointestinal related (most mild to moderate severity), with nausea being the most common (ranging from 4% [placebo] to 28.8% [80 mg] in the T2D cohort and 12.5% [placebo] to 60.6% [200 mg, four-step titration] in the obesity cohort). Transaminase elevations were observed in a subset of participants (6.6% and 6.0% of participants on lotiglipron in the T2D and obesity cohorts, respectively, compared with 1.6% on placebo in the obesity cohort). The efficacy (HbA1c and/or body weight) of a range of lotiglipron doses was demonstrated in T2D and obesity cohorts. The safety profile was largely consistent with what has been previously known about the mechanism of action. Our results are unique in reporting elevations in liver transaminases in a subset of participants treated with lotiglipron, with attempts to identify the at-risk population unsuccessful and therefore clinical development of lotiglipron terminated. GOV: NCT05579977.

Unrecognised actionability for breast cancer risk variants identified in a national-level review of Australian familial cancer centres

Breast cancer remains a significant global health challenge. In Australia, the adoption of publicly-funded multigene panel testing for eligible cancer patients has increased accessibility to personalised care, yet has also highlighted the increasing prevalence of variants of uncertain significance (VUS), complicating clinical decision-making. This project aimed to explore the spectrum and actionability of breast cancer VUS in Australian familial cancer centers (FCCs). Leveraging data from 11 FCCs participating in the Inherited Cancer Connect database, we retrieved VUS results from 1472 patients. Through ClinVar crosschecks and application of gene-specific ACMG/AMP guidelines, we showed the potential for reclassification of 4% of unique VUS as pathogenic or likely pathogenic, and 80% as benign or likely benign. Surveys conducted with FCCs and diagnostic laboratories described current practices and challenges in variant reclassifications, highlighting resource constraints preventing periodic VUS review and notifications from the laboratories to the FCCs. Our study suggests there are benefits to routine VUS review and reclassification, particularly in publicly-funded healthcare systems. Future research should focus on assessing the clinical impact and cost-effectiveness of implementing routine variant review practices, alongside efforts to enhance communication between FCCs and laboratories.

Irregular breakfast eating in type 2 diabetes mellitus is associated with greater social jetlag and poorer metabolic health.

Circadian disruption, arising from conflict between internal circadian time and behavioural sleep-wake and fasting-feeding rhythms, may contribute to the prevalence of type 2 diabetes mellitus and disease severity. Previous studies have demonstrated a link between irregular breakfast eating and poorer metabolic health. We aimed to further explore the relationships between breakfast habits, circadian misalignment (social jetlag), and metabolic parameters in a cohort of adult participants with type 2 diabetes mellitus. A total of 330 adult participants with type 2 diabetes mellitus attending for routine clinical review completed structured questionnaires to assess habitual sleep timing, chronotype, and social jetlag. Statistical analysis was via inferential groupwise approaches and path analysis to establish interdependencies of effects of social jetlag, chronotype, and breakfast eating regularity on HbA1c. 22.7% of the participants reported eating breakfast five times or fewer a week, and were categorised as irregular breakfast eaters. Compared with those who ate breakfast six or seven times a week, irregular breakfast eaters had significantly higher HbA1c and diastolic blood pressure, were younger and had greater social jetlag. In the path analysis, irregular breakfast eating exerted a direct effect on HbA1c, whilst social jetlag exerted only an indirect effect on HbA1c through breakfast eating regularity. Chronotype did not exert any effect on HbA1c, but did exert an indirect effect on breakfast eating regularity via social jetlag. Our results showed that adult participants with type 2 diabetes mellitus, who ate breakfast irregularly had poorer metabolic health and greater social jetlag. The relationship between social jetlag and glycaemic control appears to be mediated through breakfast eating habits.

Clinical value of smear review of flagged samples analyzed with the Sysmex XN hematology analyzer.

A smear review is typically made in flagged differential counts performed with hematology analyzers although the clinical value of such reviews is uncertain. Therefore, we evaluated the differences in differential counts between Sysmex XN-9000 and a smear review in flagged samples. Furthermore, the clinical value of blasts identified was investigated. Data on all differential counts performed in a two-year period were identified at two laboratories. In patients with blasts, the electronic health record was reviewed. Agreement between automated and manual differential counts was evaluated by Bland-Altman plots. Concordance between the two methods categorized according to reference intervals was evaluated and adjusted for irrelevant non-concordance caused by random analytical error. In total, 5,500 flagged differential counts were identified from 4,092 patients. A good agreement between the automated and manual differential count was found for all cell types (-0.480×109/L to 0.297×109/L). The concordance between the two methods was excellent for all cell types, except for monocytes (82 %) where the automated estimates were higher than the manual in 19 % of samples. Blasts were identified in 241 (1 %) of smear reviews. Acute leukemia was diagnosed in 13 (5 %) patients, and only in one patient contributed the detection of blasts to the suspicion of acute leukemia. Our findings indicate that routine smear review of all flagged samples do not contribute with additional, significant information. After local validation and dialogue with clinical departments, such reviews may potentially be omitted to increase cost-effectiveness and reduce turn-around-time.

Oxygen uptake efficiency slope at anaerobic threshold can predict peak VO2 in adult congenital heart disease

IntroductionAssessment of exercise capacity by cardiopulmonary exercise testing (CPET) in adults with congenital heart disease (CHD) is important for prognostication and preoperative assessment. Peak oxygen uptake (PVO2) is used commonly, but can be challenging due to the difficulties of undertaking maximal CPET testing in this population. We explored whether oxygen uptake efficiency slope (OUES) at ventilatory anaerobic threshold (VAT), the point during CPET at which OUES becomes strongly correlated with PVO2, and is more reliably available from submaximal CPET, can predict PVO2 in adults with CHD. MethodsWe assessed consecutive individuals who completed maximal CPET at our cardiorespiratory centre, as part of routine service review, between March 2019 and August 2021, recording data such as PVO2, VAT and OUES at various proportions of a maximal test (75 %, 90 %, 100 %, and VAT). We employed linear regression modelling to analyse the association between PVO2 and OUES at VAT, and subsequently create an equation to predict PVO2 from OUES at VAT. Parametric data are presented using Pearson's correlation coefficient and non-parametric data using Spearman's rho. ResultsWe analysed 391 individuals (177 female, age 32 ± 11 years). Mean ± SD PVO2 was 23.3 ± 6.86 ml/min/kg or 1724 ± 540 ml/min, peak VE 86.7 ± 25.4 l/min. The point of VAT as a percentage of PVO2 achieved was 66.5 ± 9.4 %, and VAT as a percentage of predicted PVO2 46.9 ± 11.4 %. PVO2 was correlated with OUES at 100 % (R = 0.91, P < .001), 90 % (R = 0.91, P < .001), 75 % (R = 0.89, P < .001) of maximum, and VAT (R = 0.83, P < .001). PVO2(ml/min) could be predicted by: (OUES at VAT)∗685.245 + (BMI [kg/m2])∗5.045 + (FEV1[l])∗223.620 – 153.205. ConclusionsOUES at VAT can be used to calculate PVO2. To our knowledge, this is the first equation using OUES at VAT to predict PVO2 in adults with CHD. In a population who may find maximal CPET difficult, this may be a useful submaximal measurement of cardiovascular fitness, and to calculate PVO2, which is commonly used in guideline-based decision making in CHD.

Two thirds of patients may not need routine 12-month specialist review in an epilepsy clinic: A cross-sectional study of clinic appointments

ObjectivesTimely access to specialist outpatient clinics can be difficult to achieve as outpatient services are often oversubscribed leading to unacceptable wait times. New patients, or those with emergent issues may wait for appointments whilst existing patients are booked in for routine reviews “just in case” there is a problem, using considerable clinic resources. We investigated routine 12-month review appointments to assess whether these appointments changed patient management. MethodsThe medical records of 100 randomly selected adult patients attending annual review appointments over 12 months at a publicly-funded specialist outpatient epilepsy clinic in Melbourne, Australia were audited. Demographic and clinical data as well as information about the content of each appointment were analysed to determine whether the appointment resulted in changes to epilepsy management (eg medication change), administrative actions (eg drivers license approval) or the provision of information or education. Logistic regression was performed to assess what clinical factors were associated with changes in patient care arising from the 12-month review appointment. ResultsAlmost half (47%) of appointments resulted in no change to patient care and 37% had only administrative outcomes, such as the completion of a regulatory driving report. Only 16% of appointments resulted in a change in medical management. The only factor that independently predicted a change in medical management was the occurrence of a seizure in the previous year. The only factor independently associated with not having any change in medical management or administrative action was having an unknown seizure type. Conclusions/ significanceOnly a small number of patients experience a change in medical management when attending a 12-month epilepsy clinic appointment, with a need for management change associated with the presence of ongoing seizure. Outpatient services should limit the use of routine annual follow up to those patients most likely to need intervention or support, creating “just in time” capacity for timely access to review as issues arise.