ObjectivesFor eligible patient groups, hospital-at-home (HaH) programmes have been shown to deliver equivalent patient outcomes with cost reduction compared with standard care. This study aims to ...establish a benchmark of inpatient admissions that could potentially be substituted by HaH services.DesignDescriptive retrospective cohort study.SettingAcademic tertiary hospital in Singapore.Participants124 253 medical admissions over 20 months (January 2016 to August 2017).Primary and secondary outcome measuresThe primary measure was the proportion of hospitalised patients who may be eligible for HaH, based on eligibility criteria adapted for the Singapore context. The secondary measures were the utilisation patterns and outcomes of these patients.ResultsApplying generalised eligibility criteria to the retrospective dataset showed that 53.0% of 124 253 medical admissions fitted the eligibility criteria for HaH based on administrative data. 46.8% of such patients had a length of stay <48 hours (‘short-stay’) and 53.1% had a length of stay ≥48 hours (‘medium-stay’). The mortality rate and the 30-day readmission rate were lower in the ‘short-stay’ cohort (0.6%, 12.8%) compared with the ‘medium-stay’ cohort (0.7%, 20.3%). The key services used by both groups were: parenteral drug administration, blood investigations, imaging procedures and consultations with allied health professionals.ConclusionsUp to 53.0% of medical admissions receive care elements that HaH programmes could provide. Applying estimates of functional limitations and patient preferences, we propose a target of ~18% of inpatient medical admissions to be substituted by HaH services. The methodology adopted in this paper is a reproducible approach to characterise potential patients and service utilisation requirements when developing such programmes.
G-quadruplex DNAs form four-stranded helical structures and are proposed to play key roles in different cellular processes. Targeting G-quadruplex DNAs for cancer treatment is a very promising ...prospect. Here, we show that CX-5461 is a G-quadruplex stabilizer, with specific toxicity against BRCA deficiencies in cancer cells and polyclonal patient-derived xenograft models, including tumours resistant to PARP inhibition. Exposure to CX-5461, and its related drug CX-3543, blocks replication forks and induces ssDNA gaps or breaks. The BRCA and NHEJ pathways are required for the repair of CX-5461 and CX-3543-induced DNA damage and failure to do so leads to lethality. These data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. CX-5461 is now in advanced phase I clinical trial for patients with BRCA1/2 deficient tumours (Canadian trial, NCT02719977, opened May 2016).
ObjectivesThis study aimed to examine the prevalence of frailty coding within the Dr Foster Global Comparators (GC) international database. We then aimed to develop and validate a risk prediction ...model, based on frailty syndromes, for key outcomes using the GC data set.DesignA retrospective cohort analysis of data from patients over 75 years of age from the GC international administrative data. A risk prediction model was developed from the initial analysis based on seven frailty syndrome groups and their relationship to outcome metrics. A weighting was then created for each syndrome group and summated to create the Dr Foster Global Frailty Score. Performance of the score for predictive capacity was compared with an established prognostic comorbidity model (Elixhauser) and tested on another administrative database Hospital Episode Statistics (2011-2015), for external validation.Setting34 hospitals from nine countries across Europe, Australia, the UK and USA.ResultsOf 6.7 million patient records in the GC database, 1.4 million (20%) were from patients aged 75 years or more. There was marked variation in coding of frailty syndromes between countries and hospitals. Frailty syndromes were coded in 2% to 24% of patient spells. Falls and fractures was the most common syndrome coded (24%). The Dr Foster Global Frailty Score was significantly associated with in-hospital mortality, 30-day non-elective readmission and long length of hospital stay. The score had significant predictive capacity beyond that of other known predictors of poor outcome in older persons, such as comorbidity and chronological age. The score’s predictive capacity was higher in the elective group compared with non-elective, and may reflect improved performance in lower acuity states.ConclusionsFrailty syndromes can be coded in international secondary care administrative data sets. The Dr Foster Global Frailty Score significantly predicts key outcomes. This methodology may be feasibly utilised for case-mix adjustment for older persons internationally.
ObjectiveWe seek to address gaps in knowledge and agreement around optimal frailty assessment in the acute medical care setting. Frailty is a common term describing older persons who are at increased ...risk of developing multimorbidity, disability, institutionalisation and death. Consensus has not been reached on the practical implementation of this concept to assess clinically and manage older persons in the acute care setting.DesignModified Delphi, via electronic questionnaire. Questions included ranking items that best recognise frailty, optimal timing, location and contextual elements of a successful tool. Intraclass correlation coefficients for overall levels of agreement, with consensus and stability tested by 2-way ANOVA with absolute agreement and Fisher's exact test.ParticipantsA panel of national experts (academics, front-line clinicians and specialist charities) were invited to electronic correspondence.ResultsVariables reflecting accumulated deficit and high resource usage were perceived by participants as the most useful indicators of frailty in the acute care setting. The Acute Medical Unit and Care of the older Persons Ward were perceived as optimum settings for frailty assessment. ‘Clinically meaningful and relevant’, ‘simple (easy to use)’ and ‘accessible by multidisciplinary team’ were perceived as characteristics of a successful frailty assessment tool in the acute care setting. No agreement was reached on optimal timing, number of variables and organisational structures.ConclusionsThis study is a first step in developing consensus for a clinically relevant frailty assessment model for the acute care setting, providing content validation and illuminating contextual requirements. Testing on clinical data sets is a research priority.
ObjectivesChallenges with manual methodologies to identify frailty, have led to enthusiasm for utilising large-scale administrative data, particularly standardised diagnostic codes. However, concerns ...have been raised regarding coding reliability and variability. We aimed to quantify variation in coding frailty syndromes within standardised diagnostic code fields of an international dataset.SettingPooled data from 37 hospitals in 10 countries from 2010 to 2014.ParticipantsPatients ≥75 years with admission of >24 hours (N=1 404 671 patient episodes).Primary and secondary outcome measuresFrailty syndrome groups were coded in all standardised diagnostic fields by creation of a binary flag if the relevant diagnosis was present in the 12 months leading to index admission. Volume and percentages of coded frailty syndrome groups by age, gender, year and country were tabulated, and trend analysis provided in line charts. Descriptive statistics including mean, range, and coefficient of variation (CV) were calculated. Relationship to in-hospital mortality, hospital readmission and length of stay were visualised as bar charts.ResultsThe top four contributors were UK, US, Norway and Australia, which accounted for 75.4% of the volume of admissions. There were 553 595 (39.4%) patient episodes with at least one frailty syndrome group coded. The two most frequently coded frailty syndrome groups were ‘Falls and Fractures’ (N=3 36 087; 23.9%) and ‘Delirium and Dementia’ (N=221 072; 15.7%), with the lowest CV. Trend analysis revealed some coding instability over the frailty syndrome groups from 2010 to 2014. The four countries with the lowest CV for coded frailty syndrome groups were Belgium, Australia, USA and UK. There was up to twofold, fourfold and twofold variation difference for outcomes of length of stay, 30-day readmission and inpatient mortality, respectively, across the countries.ConclusionsVariation in coding frequency for frailty syndromes in standardised diagnostic fields are quantified and described. Recommendations are made to account for this variation when producing risk prediction models.
Background Chronic diseases are increasingly prevalent in Western countries. Once hospitalised, the chance for another hospitalisation increases sharply with large impact on well-being of patients ...and costs. The pattern of readmissions is very complex, but poorly understood for multiple chronic diseases. Methods This cohort study of administrative discharge data between 2009-2014 from 21 tertiary hospitals (eight USA, five UK, four Australia, four continental Europe) investigated rates and reasons of readmissions to the same hospital within 30 days after unplanned admission with one of the following chronic conditions; heart failure; atrial fibrillation; myocardial infarction; hypertension; stroke; chronic obstructive pulmonary disease (COPD); bacterial pneumonia; diabetes mellitus; chronic renal disease; anaemia; arthritis and other cardiovascular disease. Proportions of readmissions with similar versus different diseases were analysed. Results Of 4,901,584 admissions, 866,502 (17.7%) were due to the 12 chronic conditions. In-hospital, 43,573 (5.0%) patients died, leaving 822,929 for readmission analysis. Of those, 87,452 (10.6%) had an emergency 30-day readmission, rates ranged from 2.8% for arthritis to 18.4% for COPD. One third were readmitted with the same condition, ranging from 53% for anaemia to 11% for arthritis. Reasons for readmission were due to another chronic condition in 10% to 35% of the cases, leaving 30% to 70% due to reasons other than the original 12 conditions (most commonly, treatment related complications and infections). The chance of being readmitted with the same cause was lower in the USA, for female patients, with increasing age, more co-morbidities, during study period and with longer initial length of stay. Conclusion Readmission in chronic conditions is very common and often caused by diseases other than the index hospitalisation. Interventions to reduce readmissions should therefore focus not only on the primary condition but on a holistic consideration of all the patient's comorbidities.
Acquired resistance to PARP inhibitors (PARPi) is a major challenge for the clinical management of high grade serous ovarian cancer (HGSOC). Here, we demonstrate CX-5461, the first-in-class inhibitor ...of RNA polymerase I transcription of ribosomal RNA genes (rDNA), induces replication stress and activates the DNA damage response. CX-5461 co-operates with PARPi in exacerbating replication stress and enhances therapeutic efficacy against homologous recombination (HR) DNA repair-deficient HGSOC-patient-derived xenograft (PDX) in vivo. We demonstrate CX-5461 has a different sensitivity spectrum to PARPi involving MRE11-dependent degradation of replication forks. Importantly, CX-5461 exhibits in vivo single agent efficacy in a HGSOC-PDX with reduced sensitivity to PARPi by overcoming replication fork protection. Further, we identify CX-5461-sensitivity gene expression signatures in primary and relapsed HGSOC. We propose CX-5461 is a promising therapy in combination with PARPi in HR-deficient HGSOC and also as a single agent for the treatment of relapsed disease.
Because of fundamental differences in healthcare systems, US readmission data cannot be extrapolated to the European setting: To investigate the opinions of readmitted patients, their carers, nurses ...and physicians on predictability and preventability of readmissions and using majority consensus to determine contributing factors that could potentially foresee (preventable) readmissions.
Prospective observational study. Readmitted patients, their carers, and treating professionals were surveyed during readmission to assess the discharge process and the predictability and preventability of the readmission. Cohen's Kappa measured pairwise agreement of considering readmission as predictable/preventable by patients, carers and professionals. Subsequently, multivariable logistic regressionidentified factors associated with predictability/preventability.
15 hospitals in four European countries PARTICIPANTS: 1398 medical patients readmitted unscheduled within 30 days MAIN OUTCOMES AND MEASURES: (1) Agreement between the interviewed groups on considering readmissions likely predictable or preventable;(2) Factors distinguishing predictable from non-predictable and preventable from non-preventable readmissions.
The majority deemed 27.8% readmissions potentially predictable and 14.4% potentially preventable. The consensus on predictability and preventability was poor, especially between patients and professionals (kappas ranged from 0.105 to 0.173). The interviewed selected different factors as potentially associated with predictability and preventability. When a patient reported that he was ready for discharge during index admission, the readmission was deemed less likely by the majority (predictability: OR 0.55; 95% CI 0.40 to 0.75; preventability: OR 0.35; 95% CI 0.24 to 0.49).
There is no consensus between readmitted patients, their carers and treating professionals about predictability and preventability of readmissions, nor associated risk factors. A readmitted patient reporting not feeling ready for discharge at index admission was strongly associated with preventability/predictability. Therefore, healthcare workers should question patients' readiness to go home timely before discharge.
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