Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study).

BACKGROUND AND PURPOSE: The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study. MATERIALS AND METHODS: This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients. RESULTS: Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs. INTERPRETATION: S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules.

Targeting KRAS mutations in pancreatic cancer: opportunities for future strategies.

Targeting the RAS pathway remains the holy grail of precision oncology. In the case of pancreatic ductal adenocarcinomas (PDAC), 90-92% harbor mutations in the oncogene KRAS, triggering canonical MAPK signaling. The smooth structure of the altered KRAS protein without a binding pocket and its affinity for GTP have, in the past, hampered drug development. The emergence of KRASG12C covalent inhibitors has provided renewed enthusiasm for targeting KRAS. The numerous pathways implicated in RAS activation do, however, lead to the development of early resistance. In addition, the dense stromal niche and immunosuppressive microenvironment dictated by oncogenic KRAS can influence treatment responses, highlighting the need for a combination-based approach. Given that mutations in KRAS occur early in PDAC tumorigenesis, an understanding of its pleiotropic effects is key to progress in this disease. Herein, we review current perspectives on targeting KRAS with a focus on PDAC.

Total neoadjuvant therapy versus standard neoadjuvant treatment strategies for the management of locally advanced rectal cancer: network meta-analysis of randomized clinical trials.

BACKGROUND: This study compared the advantages and disadvantages of total neoadjuvant therapy (TNT) strategies for patients with locally advanced rectal cancer, compared with the more traditional multimodal neoadjuvant management strategies of long-course chemoradiotherapy (LCRT) or short-course radiotherapy (SCRT). METHODS: A systematic review and network meta-analysis of exclusively RCTs was undertaken, comparing survival, recurrence, pathological, radiological, and oncological outcomes. The last date of the search was 14 December 2022. RESULTS: In total, 15 RCTs involving 4602 patients with locally advanced rectal cancer, conducted between 2004 and 2022, were included. TNT improved overall survival compared with LCRT (HR 0.73, 95 per cent credible interval 0.60 to 0.92) and SCRT (HR 0.67, 0.47 to 0.95). TNT also improved rates of distant metastasis compared with LCRT (HR 0.81, 0.69 to 0.97). Reduced overall recurrence was observed for TNT compared with LCRT (HR 0.87, 0.76 to 0.99). TNT showed an improved pCR compared with both LCRT (risk ratio (RR) 1.60, 1.36 to 1.90) and SCRT (RR 11.32, 5.00 to 30.73). TNT also showed an improvement in cCR compared with LCRT (RR 1.68, 1.08 to 2.64). There was no difference between treatments in disease-free survival, local recurrence, R0 resection, treatment toxicity or treatment compliance. CONCLUSION: This study provides further evidence that TNT has improved survival and recurrence benefits compared with current standards of care, and may increase the number of patients suitable for organ preservation, without negatively influencing treatment toxicity or compliance.

Reference compounds for characterizing cellular injury in high-content cellular morphology assays.

Robust, generalizable approaches to identify compounds efficiently with undesirable mechanisms of action in complex cellular assays remain elusive. Such a process would be useful for hit triage during high-throughput screening and, ultimately, predictive toxicology during drug development. Here we generate cell painting and cellular health profiles for 218 prototypical cytotoxic and nuisance compounds in U-2 OS cells in a concentration-response format. A diversity of compounds that cause cellular damage produces bioactive cell painting morphologies, including cytoskeletal poisons, genotoxins, nonspecific electrophiles, and redox-active compounds. Further, we show that lower quality lysine acetyltransferase inhibitors and nonspecific electrophiles can be distinguished from more selective counterparts. We propose that the purposeful inclusion of cytotoxic and nuisance reference compounds such as those profiled in this resource will help with assay optimization and compound prioritization in complex cellular assays like cell painting.

Optimisation of AAV-NDI1 Significantly Enhances Its Therapeutic Value for Correcting Retinal Mitochondrial Dysfunction.

AAV gene therapy for ocular disease has become a reality with the market authorisation of LuxturnaTM for RPE65-linked inherited retinal degenerations and many AAV gene therapies currently undergoing phase III clinical trials. Many ocular disorders have a mitochondrial involvement from primary mitochondrial disorders such as Leber hereditary optic neuropathy (LHON), predominantly due to mutations in genes encoding subunits of complex I, to Mendelian and multifactorial ocular conditions such as dominant optic atrophy, glaucoma and age-related macular degeneration. In this study, we have optimised the nuclear yeast gene, NADH-quinone oxidoreductase (NDI1), which encodes a single subunit complex I equivalent, creating a candidate gene therapy to improve mitochondrial function, independent of the genetic mutation driving disease. Optimisation of NDI1 (ophNdi1) substantially increased expression in vivo, protected RGCs and increased visual function, as assessed by optokinetic and photonegative response, in a rotenone-induced murine model. In addition, ophNdi1 increased cellular oxidative phosphorylation and ATP production and protected cells from rotenone insult to a significantly greater extent than wild type NDI1. Significantly, ophNdi1 treatment of complex I deficient patient-derived fibroblasts increased oxygen consumption and ATP production rates, demonstrating the potential of ophNdi1 as a candidate therapy for ocular disorders where mitochondrial deficits comprise an important feature.

Oncotherapeutic Strategies in Early Onset Colorectal Cancer.

Early onset colorectal cancer (EOCRC), defined as colorectal cancers in patients aged less than 50 years, is becoming an increasingly common issue, globally. Since 1994, the incidence of this condition has been rising by 2% annually. Approximately one in five patients under 50 years of age diagnosed with colorectal cancer have an underlying genetic predisposition syndrome. The detection of cancer among the other 80% of patients poses a considerable task, as there is no family history to advocate for commencing early screening in this group. Patients with EOCRC have distinct social, spiritual, fertility, and financial needs from their older counterparts that need to be addressed. This review discusses the risk factors associated with the development of EOCRC and current best practice for the management of this disease.

The People's Trial: supporting the public's understanding of randomised trials.

BACKGROUND: Randomised trials are considered the gold standard in providing robust evidence on the effectiveness of interventions. However, there are relatively few initiatives to help increase public understanding of what randomised trials are and why they are important. This limits the overall acceptance of and public participation in clinical trials. The People's Trial aims to help the public learn about randomised trials, to understand why they matter, and to be better equipped to think critically about health claims by actively involving them in all aspects of trial design. This was done by involving the public in the design, conduct, and dissemination of a randomised trial. METHODS: Using a reflexive approach, we describe the processes of development, conduct, and dissemination of The People's Trial. RESULTS: Over 3000 members of the public, from 72 countries, participated in The People's Trial. Through a series of online surveys, the public designed a trial called The Reading Trial. They chose the question the trial would try to answer and decided the components of the trial question. In December 2019, 991 participants were recruited to a trial to answer the question identified and prioritised by the public, i.e. 'Does reading a book in bed make a difference to sleep in comparison with not reading a book in bed?' We report the processes of The People's Trial in seven phases, paralleling the steps of a randomised trial, i.e. question identification and prioritisation, recruitment, randomisation, trial conduct, data analysis, and sharing of findings. We describe the decisions we made, the processes we used, the challenges we encountered, and the lessons we learned. CONCLUSION: The People's Trial involved the public successfully in the design, conduct, and dissemination of a randomised trial demonstrating the potential for such initiatives to help the public learn about randomised trials, to understand why they matter, and to be better equipped to think critically about health claims. TRIAL REGISTRATION: ClinicalTrials.gov NCT04185818 . Registered on 4 December 2019.

Design and user experience testing of a polygenic score report: a qualitative study of prospective users.

BACKGROUND: Polygenic scores-which quantify inherited risk by integrating information from many common sites of DNA variation-may enable a tailored approach to clinical medicine. However, alongside considerable enthusiasm, we and others have highlighted a lack of standardized approaches for score disclosure. Here, we review the landscape of polygenic score reporting and describe a generalizable approach for development of a polygenic score disclosure tool for coronary artery disease. METHODS: We assembled a working group of clinicians, geneticists, data visualization specialists, and software developers. The group reviewed existing polygenic score reports and then designed a two-page mock report for coronary artery disease. We then conducted a qualitative user-experience study with this report using an interview guide focused on comprehension, experience, and attitudes. Interviews were transcribed and analyzed for themes identification to inform report revision. RESULTS: Review of nine existing polygenic score reports from commercial and academic groups demonstrated significant heterogeneity, reinforcing the need for additional efforts to study and standardize score disclosure. Using a newly developed mock score report, we conducted interviews with ten adult individuals (50% females, 70% without prior genetic testing experience, age range 20-70 years) recruited via an online platform. We identified three themes from interviews: (1) visual elements, such as color and simple graphics, enable participants to interpret, relate to, and contextualize their polygenic score, (2) word-based descriptions of risk and polygenic scores presented as percentiles were the best recognized and understood, (3) participants had varying levels of interest in understanding complex genomic information and therefore would benefit from additional resources that can adapt to their individual needs in real time. In response to user feedback, colors used for communicating risk were modified to minimize unintended color associations and odds ratios were removed. All 10 participants expressed interest in receiving a polygenic score report based on their personal genomic information. CONCLUSIONS: Our findings describe a generalizable approach to develop a polygenic score report understandable by potential patients. Although additional studies are needed across a wider spectrum of patient populations, these results are likely to inform ongoing efforts related to polygenic score disclosure within clinical practice.

Synchronous Melanoma and Pancreas Malignancies Leading to a Discovery of a CDKN2A Mutation in a Patient with No Known Family History.

We report a case of a 60-year-old male with metachronous primary malignancies, pancreatic cancer and malignant melanoma which recurred simultaneously. Both cancers were challenging to diagnose and throughout the case at different times, the presence of two active malignancies obscured the clinical picture. A bleeding gastric lesion found in the stomach 6 months after a distal pancreatectomy for pancreatic adenocarcinoma revealed metastatic melanoma, presumed secondary from a melanoma excised from the patient's back 2 years previously. During surgery intended to resect the gastric lesion, peritoneal nodularity was identified, with histology confirming metastatic pancreas cancer. This case highlights two main points of interest. Firstly it emphasises the role for consideration of a genetic predisposition in young patients with more than one primary malignancy. The man in this case was not informed of his family history as he was adopted. If he had knowledge of previous family history, he may have been able to provide information to expedite arrival at the diagnosis of a CDKN2A mutation (melanoma-pancreatic carcinoma syndrome). In addition, this case also raises the issue of the challenges we face when treating synchronous primary malignancies. The two malignancies here behaved equally aggressively and posed obstacles for treatment as there is no mutual method of carcinogenesis that could be targeted with treatment; therefore, treatment modalities had to be chosen to treat each malignancy separately. To date, studies evaluating the role for targeted therapy in the setting of CDKN2A mutations have not conclusively provided meaningful benefits to patients.

Does reading a book in bed make a difference to sleep in comparison to not reading a book in bed? The People's Trial-an online, pragmatic, randomised trial.

BACKGROUND: The best way of comparing healthcare treatments is through a randomised trial. In a randomised trial, we compare something (a treatment or intervention) to something else, often another treatment. Who gets what is decided at random, meaning everyone has an equal chance of getting any of the treatments. This means any differences found can be put down to the treatment received rather than other things, such as where people live, or health conditions they might have. The People's Trial aimed to help the public better understand randomised trials by inviting them to design and carry out a trial. The question chosen by the public for The People's Trial was: 'Does reading a book in bed make a difference to sleep, in comparison to not reading a book in bed?' This paper describes that trial, called 'The Reading Trial'. METHODS: The Reading Trial was an online, randomised trial. Members of the public were invited to take part through social media campaigns. People were asked to either read a book in bed before going to sleep (intervention group) or not read a book in bed before going to sleep (control group). We asked everyone to do this for 7 days, after which they measured their sleep quality. RESULTS: During December 2019, a total of 991 people took part in The Reading Trial, half (496 (50%)) in the intervention group and half (495 (50%)) in the control group. Not everyone finished the trial: 127 (25.6%) people in the intervention group and 90 (18.18%) people in the control group. Of those providing data, 156/369 (42%) people in the intervention group felt their sleep improved, compared to 112/405 (28%) of those in the control group, a difference of 14%. When we consider how certain we are of this finding, we estimate that, in The Reading Trial, sleep improved for between 8 and 22% more people in the intervention group compared to the control group. CONCLUSIONS: Reading a book in bed before going to sleep improved sleep quality, compared to not reading a book in bed. TRIAL REGISTRATION: ClinicalTrials.gov NCT04185818. Registered on 4 December 2019.

Gastrointestinal side effects of cancer treatments.

Cancer survival rates have significantly improved over the last number of years due to advancements in cancer therapies. Unfortunately this has come at a cost. Therapeutic side effects are feared complications of therapy that may result in decreased quality of life and early cessation of the therapy, which can have knock-on effects on outcomes. This article outlines the main gastrointestinal side effects seen with radiation therapy, chemotherapy and immunotherapy, and discusses appropriate investigation and management.

The challenge of primary gastric melanoma: a systematic review.

AIM: Primary gastric melanoma is a rare clinical presentation. The purpose of this review was to compare the 1-year survival in patients who underwent surgery with patients who did not receive treatment. PATIENTS & METHODS: A systematic search of databases for case reports and case series of primary gastric melanoma was conducted. RESULTS: The mean survival of patients was 22 months. One-year survival was 56.5% with surgery, rising to 66% with adjuvant therapy. Mean survival of the surgical group was 21.05 months (±20.2) versus 4.5 months (±3.61) in the nonsurgical group. CONCLUSION: Primary gastric melanoma has a poor prognosis but early surgical intervention can have a significant impact on patient outcome. We reviewed the biology and clinical diagnosis of gastrointestinal melanoma and the current management options available.

Measuring antimicrobial prescribing quality in outpatient parenteral antimicrobial therapy (OPAT) services: development and evaluation of a dedicated national antimicrobial prescribing survey.

BACKGROUND: Antimicrobial stewardship programmes are important in driving safety and quality of antimicrobial prescribing. The National Antimicrobial Prescribing Survey (NAPS) is a point-prevalence audit of inpatient antimicrobial prescribing in Australian hospitals. OBJECTIVES: To design and adapt the NAPS tool for use in the outpatient parenteral antimicrobial therapy (OPAT) and hospital-in-the-home (HITH) setting. METHODS: An inter-disciplinary working group with expertise in OPAT and HITH services was established to adapt the NAPS template for use in the OPAT setting-called HITH-NAPS. This was initially trialled in 5 HITH services, subsequently adapted following participant feedback, then offered nationally to 50 services in 2017. RESULTS: There were 1154 prescriptions for 715 patients audited via the HITH-NAPS. The most common antimicrobials prescribed were cefazolin (22%), flucloxacillin (12%), piperacillin/tazobactam (10%) and ceftriaxone (10%). The most common infections treated were cellulitis (30%) and respiratory tract infections (14%). Eighty-seven percent of prescriptions were assessed as appropriate, 11% inappropriate and 2% not assessable. Prolonged durations of antimicrobials and unnecessarily broad-spectrum antibiotics were used in 9% of prescriptions. CONCLUSIONS: The HITH-NAPS pilot project revealed that auditing of this type is feasible in HITH. It showed that antibiotic use in these HITH services was generally appropriate, but there are some areas for improvement. A national OPAT/HITH-NAPS can facilitate benchmarking between services, identify potentially inappropriate prescribing and help guide quality improvement.

Identifying and prioritising midwifery care process metrics and indicators: a Delphi survey and stakeholder consensus process.

BACKGROUND: Measuring care processes is an important component of any effort to improve care quality, however knowing the appropriate metrics to measure is a challenge both in Ireland and other countries. Quality of midwifery care depends on the expert knowledge of the midwife and her/his contribution to women and their babies' safety in the healthcare environment. Therefore midwives need to be able to clearly articulate and measure what it is that they do, the dimensions of their professional practice frequently referred to as midwifery care processes. The objective of this paper is to report on the development and prioritisation of a national suite of Quality Care Metrics (QCM), and their associated indicators, for midwifery care processes in Ireland. METHODS: The study involved four discrete, yet complimentary, phases; i) a systematic literature review to identify midwifery care process metrics and their associated measurement indicators; ii) a two-round, online Delphi survey of midwives to develop consensus on the set of midwifery care process metrics to be measured; iii) a two-round online Delphi survey of midwives to develop consensus on the indicators that will be used to measure prioritised metrics; and iv) a face-to-face consensus meeting with midwives to review the findings and achieve consensus on the final suite of metrics and indicators. RESULTS: Following the consensus meeting, 18 metrics and 93 indicators were prioritised for inclusion in the suite of QCM Midwifery Metrics. These metrics span the pregnancy, birth and postpartum periods. CONCLUSION: The development of this suite of process metrics and indicators for midwifery care provides an opportunity for measuring the safety and quality of midwifery care in Ireland and for adapting internationally. This initial work should be followed by a rigorous evaluation of the impact of the new suite of metrics on midwifery care processes.

Attitudes and beliefs of Australian emergency department clinicians on antimicrobial stewardship in the emergency department: A qualitative study.

OBJECTIVE: To explore the attitudes and beliefs of Australian ED clinicians towards antimicrobial stewardship in the ED. METHODS: Semi-structured one-to-one interviews were conducted with ED clinicians between March and October 2015. Participants were identified via purposive and snowball sampling. Questionnaires were developed using the literature. Interviews were audio-recorded, transcribed and analysed using thematic analysis via the framework approach. Two researchers coded independently, with one using QSR International's NVivo 10 software and the other manually. Emergent themes were identified and classified. RESULTS: Twenty-two clinicians (eight doctors, eight nurses and six pharmacists) from seven institutions participated. Participants were aware and concerned about antimicrobial resistance. Clinicians were divided based on their opinion on whether antimicrobials are prescribed appropriately and judiciously in the ED, with many perceiving prescribing to be inappropriate. Prior knowledge of the term 'Antimicrobial Stewardship' was demonstrated by doctors and pharmacists, with a relative lack of awareness by nurses. Four main themes were identified as both barriers and facilitators to antimicrobial stewardship in the ED: individual healthcare provider, resource, organisational and cultural. Uncertainty of diagnosis, time and resource pressures, reliance on previous experience and lack of access to expert opinion were perceived barriers. To facilitate appropriate prescribing, clinicians emphasised the need for routine education and feedback, adequate staffing, robust guidelines, senior medical clinician advocacy and multidisciplinary support. CONCLUSIONS: Australian ED clinicians were aware of antimicrobial resistance. Many perceive injudicious antimicrobial use as problematic. Consideration of ED clinicians' perceived barriers and facilitators might enhance implementation of antimicrobial stewardship programmes in EDs.

Factors associated with unplanned readmissions in a major Australian health service.

Objective The aim of the present study was to gain an understanding of the factors associated with unplanned hospital readmission within 28 days of acute care discharge from a major Australian health service. Methods A retrospective study of 20575 acute care discharges from 1 August to 31 December 2015 was conducted using administrative databases. Patient, index admission and readmission characteristics were evaluated for their association with unplanned readmission in ≤28 days. Results The unplanned readmission rate was 7.4% (n=1528) and 11.1% of readmitted patients were returned within 1 day. The factors associated with increased risk of unplanned readmission in ≤28 days for all patients were age ≥65 years (odds ratio (OR) 1.3), emergency index admission (OR 1.6), Charlson comorbidity index >1 (OR 1.1-1.9), the presence of chronic disease (OR 1.4) or complications (OR 1.8) during the index admission, index admission length of stay (LOS) >2 days (OR 1.4-1.8), hospital admission(s) (OR 1.7-10.86) or emergency department (ED) attendance(s) (OR 1.8-5.2) in the 6 months preceding the index admission and health service site (OR 1.2-1.6). However, the factors associated with increased risk of unplanned readmission ≤28 days changed with each patient group (adult medical, adult surgical, obstetric and paediatric). Conclusions There were specific patient and index admission characteristics associated with increased risk of unplanned readmission in ≤28 days; however, these characteristics varied between patient groups, highlighting the need for tailored interventions. What is known about the topic? Unplanned hospital readmissions within 28 days of hospital discharge are considered an indicator of quality and safety of health care. What does this paper add? The factors associated with increased risk of unplanned readmission in ≤28 days varied between patient groups, so a 'one size fits all approach' to reducing unplanned readmissions may not be effective. Older adult medical patients had the highest rate of unplanned readmissions and those with Charlson comorbidity index ≥4, an index admission LOS >2 days, left against advice and hospital admission(s) or ED attendance(s) in the 6 months preceding index admission and discharge from larger sites within the health service were at highest risk of unplanned readmission. What are the implications for practitioners? One in seven discharges resulted in an unplanned readmission in ≤28 days and one in 10 unplanned readmissions occurred within 1 day of discharge. Although some patient and hospital characteristics were associated with increased risk of unplanned readmission in ≤28 days, statistical modelling shows there are other factors affecting the risk of readmission that remain unknown and need further investigation. Future work related to preventing unplanned readmissions in ≤28 days should consider inclusion of health professional, system and social factors in risk assessments.

A model of access combining triage with initial management reduced waiting time for community outpatient services: a stepped wedge cluster randomised controlled trial.

BACKGROUND: Long waiting times are associated with public community outpatient health services. This trial aimed to determine if a new model of care based on evidence-based strategies that improved patient flow in two small pilot trials could be used to reduce waiting time across a variety of services. The key principle of the Specific Timely Appointments for Triage (STAT) model is that patients are booked directly into protected assessment appointments and triage is combined with initial management as an alternative to a waiting list and triage system. METHODS: A stepped wedge cluster randomised controlled trial was conducted between October 2015 and March 2017, involving 3116 patients at eight sites across a major Australian metropolitan health network. RESULTS: The intervention reduced waiting time to first appointment by 33.8% (IRR = 0.663, 95% CI 0.516 to 0.852, P = 0.001). Median waiting time decreased from a median of 42 days (IQR 19 to 86) in the control period to a median of 24 days (IQR 13 to 48) in the intervention period. A substantial reduction in variability was also noted. The model did not impact on most secondary outcomes, including time to second appointment, likelihood of discharge by 12 weeks and number of appointments provided, but was associated with a small increase in the rate of missed appointments. CONCLUSIONS: Broad-scale implementation of a model of access and triage that combined triage with initial management and actively managed the relationship between supply and demand achieved substantial reductions in waiting time without adversely impacting on other aspects of care. The reductions in waiting time are likely to have been driven, primarily, by substantial reductions for those patients previously considered low priority. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615001016527 registration date: 29/09/2015.

Factors associated with unplanned readmissions within 1 day of acute care discharge: a retrospective cohort study.

BACKGROUND: Unplanned hospital readmissions are a quality and safety indicator. In Australian, 8% to 11.1% of unplanned readmissions occur ≤1 day of acute care discharge. The aim of this study was to explore the reasons for unplanned hospital readmissions ≤1 day of acute care discharge, and determine what proportion of such unplanned hospital readmissions were potentially preventable. METHODS: A retrospective exploratory cohort design was used to conduct this two phase study. In Phase 1, organisational data from 170 readmissions ≤1 day and 1358 readmissions between 2 and 28 days were compared using the Cochran-Mantel-Haenszel test. Binary logistic regression was used to examine factors associated with unplanned readmission ≤1 day. In Phase 2, a medical record audit of 162 Phase 1 readmissions ≤1 day was conducted and descriptive statistics used to summarise the study data. Index discharges occurred between 1 August and 31 December 2015. RESULTS: In Phase 1, unplanned readmissions ≤1 day were more likely in paediatric patients (< 0.001); index discharges on weekends (p = 0.006), from short stay unit (SSU) (p < 0.001) or against health professional advice (p = 0.010); or when the readmission was for a Diagnosis Related Group (p < 0.001). The significant predictors of unplanned readmission ≤1 day were index discharge against advice or from SSU, and 1-5 hospital admissions in the 6 months preceding index admission. In Phase 2, 88.3% readmissions were unpreventable and 11.7% were preventable. The median patient age was 57 years and comorbidities were uncommon (3.1%). Most patients (94.4%) lived at home and with others (78.9%). Friday was the most common day of index discharge (17.3%) and Saturday was the most common day of unplanned readmission (19.1%). The majority (94.4%) of readmissions were via the emergency department: 58.5% were for a like diagnosis and pain was the most common reason for readmission. CONCLUSIONS: Advanced age, significant comorbidities and social isolation did not feature in patients with an unplanned readmission ≤1 day. One quarter of patients were discharged on a Friday or weekend, one quarter of readmissions occurred on a weekend, and pain was the most common reason for readmission raising issues about access to services and weekend discharge planning.