Search

Introduction: The incidence of immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICI) is well described. However, the impact on emergency care services is not. This study investigated the incidence of irAEs out-of-hours, and the management used to mitigate symptoms and side effects. Methods: This retrospective cohort study reviewed all emergency presentations triaged by the acute oncology team between December 2021 and June 2022, between 5 pm and 9 am. Patients were identified from triage audit sheets and remaining data points were retrieved from electronic health records. Inclusion criteria included all adult patients admitted on an ICI at one tertiary centre. Results: In 7 months, 970 patients called the acute oncology helpline 11% (n = 109) of patients were on an ICI treatment. After clinical review, 78% (n = 70) resulted in hospital admissions, with length of stay cumulating to 496 bed days. 56% (n = 39) of patients delayed reporting symptoms, ranging between 12 hours and 10 days from symptom onset to seeking support. 49% (n = 34) patients received steroids to manage suspected irAEs. Dexamethasone was the most common steroid used in 71% (n = 24) of patients, and variation was found in prescribed doses. Conclusions: These results underline the urgent need to address patient and staff education on adverse effects related to ICI. Patients require a comprehensive understanding of the symptoms and importance of prompt reporting. Staff education on recognition and treatment management is needed to reduce variation in practice. Further research is needed to identify barriers in symptom reporting and focus on realtime reporting to reduce the out-of-hours burden on services. [ABSTRACT FROM AUTHOR]

Background: Re‐designing services and processes to meet growing demands in chemotherapy services is necessary with increasing treatments. There is little evidence guiding the timing and thresholds to be attained of pre‐chemotherapy blood assessments, namely neutrophils. Methods: A survey was developed and distributed to health professionals in the United Kingdom (UK) to examine current practice in timing and threshold values of neutrophils and platelets before treatment administration. This was followed by a retrospective cohort study, using data from electronic patient record systems; including patients initiating treatment between January 2013 and December 2018, to determine a safe timeframe for blood assessments; comparing neutrophil, platelet, creatinine and bilirubin levels at different time points. Results: The survey captured 25% of hospitals in the UK and variations were apparent in both the timing of assessments and thresholds needed, particularly for neutrophils. 616 (6.5%) of 4007 patients included had neutrophil levels measured twice within 7 days of treatment (with the first level taken beyond 3 days and the second test being within 3 days of treatment‐ the UK standard). Of the patients that attained an acceptable neutrophil level at their first test, five of the 616 (0.8%) became ineligible for administration from the test 2 level. 23% of patients improved their grade and became eligible for treatment. Little difference was observed for platelets. Conclusions: We have demonstrated that extending the timeframe for blood tests can be safe, however, this practice may cause unnecessary delays for patients if only an early test is relied on for eligibility. [ABSTRACT FROM AUTHOR]

Background: The development and rapid uptake of immune checkpoint inhibitors (CPI) has changed the outlook for patients with cancer. However, CPIs have different adverse event (AE) profiles to other systemic therapies, and prompt AE management is essential to assure optimal outcomes. In order to understand what and when adverse events are experienced, reported and managed during CPI treatment, a mixed methods study was conducted, including a case note review of patients who were receiving immunotherapy and semi-structured interviews with patients to understand their experience, management and reporting of AEs after receiving immune CPI treatment.Methods: This mixed methods study was conducted at a large cancer hospital in the United Kingdom. A case note review identified how and where patients reported AEs. Data relating to patients with lung, bladder, prostate and head & neck cancers who received CPI treatment between 01/04/2015 and 31/07/2018 were extracted from e-prescribing databases and clinical data were included for analysis at a single time point (31 July 2018). Semi-structured interviews were conducted with patients receiving CPI treatment, exploring experience of AEs and reasons for delays in AE reporting and management.Results: Sixty-two patients were included in the case note review, with 78 AEs being experienced by 36 patients (58%), including one patient experiencing 10 AEs. Serious AEs were experienced by 12 patients (19%) and ten AEs (17%) required oral steroids as treatment. The majority of AEs were reported to clinicians prior to further dosing, although milder AEs were often not addressed until subsequent clinic appointments. Interviews with 13 patients yielded major themes: variability, causality, decision making and impact.Conclusion: Most CPI-associated AEs are manageable if reported and treated promptly. Both the case note review and interviews found that reporting of non-serious AEs is often left until routine clinic visits, despite impacting patient experience, leaving the opportunity for AEs to be left unreported and implying a potential benefit for real time monitoring. Our study highlights a need to provide patients with reminders around AEs and their timely reporting even when apparently innocuous; patients must understand that AEs can occur at any cycle and even following treatment completion. [ABSTRACT FROM AUTHOR]

PURPOSE The growth in understanding of molecular biology and genomics has augmented the development of targeted cancer treatments; however, challenges exist in access to molecular testing, an essential precursor to treatment decision-making. We used data from a cross-sectional survey to evaluate the differences in uptake of molecular testing, METHODS Using the aggregated results of a questionnaire developed and distributed to clinicians by IQVIA, including treatment details and investigations undertaken for patients, we compared proportions of patients receiving molecular testing and targeted treatment by cancer type for the United Kingdom, France, Italy, Germany, Spain, South Korea, Japan, and China. We used multivariable logistic regression methods to understand the effect of country on the odds of receiving a molecular test. RESULTS There was a total of 61,491 cases. Across countries and cancer types, uptake rates for molecular testing ranged between 2% and 98%, with the greatest differences seen in gastric cancers (range, 23% to 70%), and significant variations were observed for both European and Asian countries. China consistently demonstrated a significantly reduced uptake for all molecular tests assessed; however; uptake of drug treatment in gastric cancers after testing positive for the human epidermal growth factor receptor 2 gene was higher than in some European countries (China, 85%; European range, 8% to 66%). The uptake of epidermal growth factor receptor gene testing was greater in some Asian countries relative to the United Kingdom, where incidence of lung cancer is higher (Japan: odds ratio, 3.1 [95% CI, 2.6 to 3.8]; South Korea: odds ratio, 2.7 [95% CI, 2 to 3.4]). CONCLUSION We have highlighted inequity in access to molecular testing and subsequent treatments across countries, which warrants improvements. [ABSTRACT FROM AUTHOR]

Background: On average 20% of patients require a systemic anti-cancer treatment (SACT) delay.1 The risk of toxicity-related dose delays, with SACT, should be included as part of pre-treatment education and be considered by clinicians upon prescribing chemotherapy. An objective measure of individual risk could influence clinical decisions, such as the escalation of standard supportive care and stratification of some patients, to receive proactive toxicity monitoring. The understanding of this risk may also support the advanced preparation of treatments for those that have a lower risk of delay. Data available within hospital systems can support the understanding of risk through the development of a risk score. In this study, we developed and validated a score to assess the risk of a SACT dose delay of 7 days (delay-7 score). Objectives: To develop and internally validate a risk score to predict the occurrence of a 7-day dose delay for patients receiving cycle 1 treatments for breast and colorectal cancers and diffuse large b-cell lymphomas. To assess the discrimination and calibration of the model. Methods: Four hospitals were included in our study, recruited through BOPA. Data were collected for patients aged 18 or over, identified through the chemotherapy prescribing systems at each hospital for the period of 1 January 2013 to 1 January 2018. The first chemotherapy treatment date was used as the index date for entry to the cohort during the study period. The study data was restricted to the following three tumour groups: breast, colorectal and diffuse large B-Cell lymphoma. Data included hospital treatment, age at the start of SACT, gender, ethnicity, body mass index, cancer diagnosis, chemotherapy regimen, colony-stimulating factor use, first cycle dose modifications and baseline blood values. Baseline blood values included neutrophils, platelets, haemoglobin, creatinine and bilirubin. A risk prediction model was developed using multivariable logistic regression and all analysis methods complied with the Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD).2 Shrinkage was used to adjust for over-optimism of predictor effects. For internal validation (of the full models in the development data) we computed the ability of the models to discriminate between those with and without poor outcomes (c-statistic), and the agreement between predicted and observed risk (calibration slope). Results: A total of 4604 patients were included in our study of which 628 (13.6%) incurred a 7-day delay to the second cycle of chemotherapy. Delay-7 showed good discrimination and calibration, with a c-statistic of 0.68 [95% confidence interval (CI) 0.66–0.7], following internal validation and calibration-in-the-large of −0.006. Conclusions: Delay-7 predicts a patient’s individualised risk of a treatment-related delay at cycle two of treatment. The score can be used to stratify interventions to reduce the occurrence of treatment-related toxicity. However, to be used in the clinical setting a prospective study should be conducted to ensure the reliability of the score. Nonetheless, we have identified that the score can be useful to support advance preparation in pharmacy aseptic units and a small validation in this setting is planned. [ABSTRACT FROM AUTHOR]

Background: In those receiving cytotoxic chemotherapy, renal and hepatic dysfunction can increase the risk of toxicity and should therefore be monitored. However, only a small proportion of patients will experience a change in these functions (measured through creatinine and bilirubin levels) following a second cycle of treatment [1]. We have previously found that less than 10% of patients will encounter changes to their renal and hepatic function. Furthermore, we found the occurrence of one-grade changes does not change the timing of next treatment or dosing. Variation exists in hospital policies. Some hospitals would require renal and hepatic function, taken within 7 days, to be assessed by pharmacists before clinical verification, whereas other hospitals would verify based on blood from prior cycles. To support, clinicians, pharmacists and nurses streamline pathways and reduce national variations in practice, we aimed to develop a machine learning model. The objective of the model was to identify those patients that need closer monitoring of their renal and hepatic function, enabling a safer and more efficient service. Methods: Weused retrospective data, from a large academic hospital, for patients treated with chemotherapy for breast cancer, colorectal cancer and Diffuse-large B-cell lymphoma. The outcome of interest was any grade change in creatinine or bilirubin among patients included, at any cycle following cycle two. We chose bilirubin as an outcome measure rather than ALT; rises in ALT are common with a number of chemotherapeutic agents and rarely cause clinical concern or reflect dysfunction of the liver. The predictors incorporated into the development model were baseline, cycle one and cycle two blood results, patient demographics and details of treatment. The data enabled us to train and validate a model to predict the outcomes: unacceptable rises in bilirubin or creatinine. To assess the performance of the model, validation was performed using patient data from an independent hospital, containing the same variables. Using this dataset, we evaluated the sensitivity and specificity of our models. Results: We identified 1214 patients in total. Of these, 684 were included in the training set and 530 patients in validation. The training set had almost perfect sensitivity and specificity of > 0.95. The area under the curve was 0.99 (95% CI 0.98–1.00) for creatinine and 0.97 (95% CI: 0.95–0.99) for bilirubin. The validation set had good sensitivity (creatinine: 0.60, 95% CI: 0.55–0.64, bilirubin: 0.54, 95% CI: 0.52–0.56), and specificity (creatinine 0.98, 95% CI: 0.96–0.99, bilirubin 0.90, 95% CI: 0.87–0.94) and area under the curve (creatinine: 0.76, 95% CI: 0.70, 0.82, bilirubin 0.72, 95% CI: 0.68–0.76). Conclusion: We have demonstrated that a multi-layer perceptron model can be used within electronic prescribing systems to reduce the number of blood tests required for some patients and improve safety for others. Our study needs further validation and we have been awarded innovative UK funding to both validate the work and develop software that can be used by all hospitals in the UK, to redesign their pathways. [ABSTRACT FROM AUTHOR]

Introduction: HDMTX (dose > 1 g/m²) is used commonly as a treatment for high-grade lymphomas, ALL and sarcomas. Glucarpidase is available for urgent treatment of MTX-induced renal dysfunction, in patients with toxic plasma MTX levels, at risk of life threatening complications. Pharmacist peer discussion nationally, highlighted a recent requirement for glucarpidase in overweight adult patients, prompting this study. Aims and objectives: Primary objective: To investigate associations between high BMI and requirement for glucarpidase, a proxy measure for severe toxicity. Secondary objective: to examine national variation in glucarpidase dosing in patients with raised BMI. Methodology: We developed two cohorts to achieve our objectives: Cohort 1. Retrospective review of UK adult patients receiving glucarpidase between 01 January 2019 and 01 July 2021, identified via UK sales. A data collection form was developed and piloted, and hospitals having placed orders were invited to participate. Patient baseline demographics, clinical characteristics, MTX regimen/ dose and interacting medicines were collated. The glucarpidase dose calculation method and toxicity outcome were recorded. Cohort 2: A control group from three participating centres of all patients that received HDMTX, not requiring glucarpidase, during the same period. BMI was categorised according to WHO definitions for overweight and obesity; we described the % of patients in each category and BMI distributions. BMIs across the two cohorts were compared using an unpaired t-test. Results: 23/24 Adult Treatment Centres completed data collection on 34 patients – 32 patients received glucarpidase, and two orders were not administered. In the control group (N = 209), 61% had BMI > 25 kg/m², and 23%hadBMI > 30 kg/m² compared to 85% and 59% in the glucarpidase group respectively (p = < 0.0001). The BMI average of the control group was 26.9 kg/m², compared to 31.6 kg/m² in the glucarpidase-treated group. 29/32 patients received glucarpidase dosed according to total body weight (TBW), and three patients according to adjusted body weight (ABW40). Discussion: Full weight-based chemotherapy dosing is recommended practice for treating obese patients with cancer, especially with curative intent.1 Only four out of 20 patients with BMI ≥ 30 in the glucarpidase cohort did not receive TBW dose methotrexate, when the reason for dose modification was stated as obesity. There is a known association between obesity and risk of haematological malignancy, particularly DLBCL,2 however this small case series suggests obese patients are overly represented in the HDMTX UK patient population experiencing the most severe toxicity, proposing a significant association but not causation. One study has shown an association between overweight patients and increased serum creatinine post-HDMTX,3 conversely another showed no association between obesity and delayed MTX clearance.4 Study limitations and areas of further investigation: Further work is required, using a larger dataset, to determine if obesity is an independent risk factor for MTX-induced renal dysfunction and delayed clearance. Study outcomes are complicated by the fact the precise indication for glucarpidase is ambiguous. In our study, all three patients receiving glucarpidase dosed according to ABW40 successfully cleared methotrexate, a renal function returning to baseline, supported by published literature on the use of lower doses5 – an approach which may reduce treatment costs. Larger patient numbers are required to further investigate the optimal dose. [ABSTRACT FROM AUTHOR]

Introduction: Systemic anti-cancer treatment (SACT) requires toxicity assessment prior to initiation to ensure adequate bone marrow, renal and liver function. The timing of these assessments is determined locally, with the results guiding clinicians to delay treatment or request for repeated blood tests if the desired range is not attained. The time to obtain these tests is ideal on the day chemotherapy commences, however, this is not practical within the NHS. Common practice is for patients to undergo these assessments prior to the treatment day with some policies1 recommended earlier at five or six days prior to initiations with potential impact on patient experience. This research aims to study the main policies relating to pre-chemotherapy assessment in three cancer groups: early breast cancer, colorectal cancer and DLBCL. Objectives: (1) Examine the policies on the time-periods used to perform toxicity assessment prior to chemotherapy at hospitals in the United Kingdom (UK). (2) Identify if there is variation reported within the same hospital sites. Methods: A cross-sectional online survey (Qualtrics) was sent out to members of the BOPA and ACP society between 1 July 2020 and 31 July 2020. The survey was validated by four experts in survey design and chemotherapy regimen. The sample size was calculated based on the total population of hospitals in the UK (n = 256). Based on a 95% CI, n = 131 was needed. Data was exported and analysed on STATA 15 and presented as counts and percentages. Ethics was obtained and findings have been recently published in objective 1 only. Results: • 91 participants completed the questionnaire in full. • 25 hospitals had more than one profession/participant responding. • 12 hospitals had complete responses for each question from each participant. • Two hospitals had participants responding within the same time frame. In both settings, the responses were from the same profession. • Hospital A: × 2 participants (pharmacists) • Hospital B: ×4 participants (medical oncologists) • 10 hospitals had different responses despite the profession with a difference in the time frame from 1 to 4 days between respondents. Discussion/conclusion: Toxicity assessments guide clinicians on dose delay and dose intensity of chemotherapy. Policies on when to conduct these assessments vary across the UK irrespective of the chemotherapy in all three cancer groups. Results demonstrate there is variation at the same hospital site despite professional background. As cancer patient numbers are growing and advanced preparation is vital, many hospitals are investigating extending the validity period of blood. Depending on the chemotherapy regimen, between 13 and 15 sites are currently practicing using between 4 and 7 days. However, the more this is extended there may be a need for duplicate blood where patients do not reach desired thresholds.1 Further evidence is required in this area and the need to reduce variation in pre-chemotherapy blood assessments at the same site and across sites within the UK. This study was limited by its method of dissemination, with the majority of respondents receiving a response from their membership societies, where members pay to join. [ABSTRACT FROM AUTHOR]

Objectives: Increasing operational pressures on emergency departments (ED) make it imperative to quickly and accurately identify patients requiring urgent clinical intervention. The widespread adoption of electronic health records (EHR) makes rich feature patient data sets more readily available. These large data stores lend themselves to use in modern machine learning (ML) models. This paper investigates the use of transformer-based models to identify critical deterioration in unplanned ED admissions, using free-text fields, such as triage notes, and tabular data, including early warning scores (EWS)., Design: A retrospective ML study., Setting: A large ED in a UK university teaching hospital., Methods: We extracted rich feature sets of routine clinical data from the EHR and systematically measured the performance of tree- and transformer-based models for predicting patient mortality or admission to critical care within 24 hours of presentation to ED. We compared our proposed models to the National EWS (NEWS)., Results: Models were trained on 174 393 admission records. We found that models including free-text triage notes outperform structured tabular data models, achieving an average precision of 0.92, compared with 0.75 for tree-based models and 0.12 for NEWS., Conclusions: Our findings suggests that machine learning models using free-text data have the potential to improve clinical decision-making in the ED; our techniques significantly reduce alert rate while detecting most high-risk patients missed by NEWS., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form and declare: MW, SBL, DG, MH and NAM report support from an HDR UK and NIHR Winter Pressures grant for this project. MW, PC and NAM also report support from an Innovate UK grant. PC reports research funding from Gilead and Pfizer that is unrelated to this research. MH reports three separate honoraria/payments from the Society for Acute Medicine, Welsh Acute Physicians Society and Doctors.NET for invited talks and/or educational packages on the National Early Warning Score. PC reports honoraria from GSK, unrelated to this research. PC reports support for attending educational meetings from Gilead, unrelated to this research. NAM is employed by Evergreen Life Ltd. All authors report no other financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Aims: We aim to evaluate change in the use of prognostic guideline-directed medical therapies (GDMTs) for heart failure (HF) before and after a cancer diagnosis as well as the matched non-cancer controls, including renin-angiotensin-system inhibitors (RASIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs)., Methods and Results: We conducted a longitudinal study in patients with HF in the UK Clinical Practice Research Datalink between 2005 and 2021. We selected patients with probable HF with reduced ejection fraction (HFrEF) based on diagnostic and prescription records. We described the longitudinal trends in the use and dosing of GDMTs before and after receiving an incident cancer diagnosis. HF patients with cancer were matched with a 1:1 ratio to HF patients without cancer to investigate the association between cancer diagnosis and treatment adherence, persistence, initiation, and dose titration as odds ratios (ORs) with 95% confidence intervals (CIs) using multivariable logistic regression models. Of 8504 eligible HFrEF patients with incident cancer, 4890 were matched to controls without cancer. The mean age was 75.7 (±8.4) years and 73.9% were male. In the 12 months following a cancer diagnosis, patients experienced reductions in the use and dosing of GDMT. Compared with the non-cancer controls, patients with cancer had higher risks for poor adherence for all three medication classes (RASIs: OR = 1.51, 95% CI = 1.35-1.68; beta-blockers: OR = 1.22, 95% CI = 1.08-1.37; MRAs: OR = 1.31, 95% CI = 1.08-1.59) and poor persistence (RASIs: OR = 2.04, 95% CI = 1.75-2.37; beta-blockers: OR = 1.35, 95% CI = 1.12-1.63; MRAs: OR = 1.49, 95% CI = 1.16-1.93), and higher risks for dose down-titration for RASIs (OR = 1.69, 95% CI = 1.40-2.04) and beta-blockers (OR = 1.31, 95% CI = 1.05-1.62). Cancer diagnosis was not associated with treatment initiation or dose up-titration. Event rates for HF hospitalization and mortality were higher in patients with poor adherence or persistence to GDMTs., Conclusions: Following a cancer diagnosis, patients with HFrEF were more likely to have reduced use of GDMTs for HF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)