Objective Clear understanding of the long-term consequences of critical care survivorship is essential. We investigated the care process and individual factors associated with long-term mortality among ICU survivors and explored hospital use in this group. Design Population based data linkage study using the Secure Anonymised Information Linkage (SAIL) databank. Setting All ICUs between 2006-2013 in Wales, UK. Patients We identified 40,631 patients discharged alive from Welsh adult ICUs. Intervention none. Measurements and Main results Primary outcome was 365-day survival. The secondary outcomes were 30 and 90-day survival and hospital utilisation in the 365 days following ICU discharge. Kaplan-Meier curves were plotted to compare survival rates. Cox proportional hazards regression models were used to determine risk factors of mortality. 7,883 (19.4%) patients died during the 1-year follow-up period. In the multivariable Cox regression analysis, advanced age and comorbidities were significant determinants of long-term mortality. Expedited discharge due to ICU bed shortage was associated with higher risk. The rate of hospitalisation in the year prior to the critical care admission was 28 hospitalised days/1000 days, post critical care was 88 hospitalised days/1000 days for those who were still alive; and 57 hospitalised days/1000 days and 412 hospitalised days/1000 days for those who died by the end of the study, respectively. Conclusions One in five ICU survivors die within one year, with advanced age and comorbidity being significant predictors of outcome, leading to high resource use. Care process factors indicating high system stress were associated with increased risk. More detailed understanding is needed on the effects of the potentially modifiable factors to optimise service delivery and improve long-term outcomes of the critically ill.
IntroductionThis study will evaluate the effectiveness of home adaptations, both in preventing hospital admissions due to falls for older people, and improving timely discharge. Results will provide evidence for services at the interface between health and social care, informing policies seeking to promote healthy ageing through prudent healthcare and fall prevention.Methods and analysisAll individuals living in Wales, UK, aged 60 years and over, will be included in the study using anonymised linked data from the Secure Anonymised Information Linkage Databank. We will use a national database of home modifications implemented by the charity organisation Care & Repair Cymru (C&R) from 2009 to 2017 to define an intervention cohort. We will use the electronic Frailty Index to assign individual levels of frailty (fit, mild, moderate or severe) and use these to create a comparator group (non-C&R) of people who have not received a C&R intervention. Coprimary outcomes will be quarterly numbers of emergency hospital admissions attributed to falls at home, and the associated length of stay. Secondary outcomes include the time in moving to a care home following a fall, and the indicative financial costs of care for individuals who had a fall. We will use appropriate multilevel generalised linear models to analyse the number of hospital admissions related to falls. We will use Cox proportional hazard models to compare the length of stay for fall-related hospital admissions and the time in moving to a care home between the C&R and non-C&R cohorts. We will assess the impact per frailty group, correct for population migration and adjust for confounding variables. Indicative costs will be calculated using financial codes for individual-level hospital stays. Results will provide evidence for services at the interface between health and social care, informing policies seeking to promote healthy ageing through prudent healthcare and prevention.Ethics and disseminationInformation governance requirements for the use of record-linked data have been approved and only anonymised data will be used in our analysis. Our results will be submitted for publication in peer-reviewed journals. We will also work with lay members and the knowledge transfer team at Swansea University to create communication and dissemination materials on key findings.
Purpose: Duodenal polyposis and cancer are important causes of morbidity and mortality in familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). This study aimed to comprehensively characterize somatic genetic changes in FAP and MAP duodenal adenomas to better understand duodenal tumorigenesis in these disorders.Experimental Design: Sixty-nine adenomas were biopsied during endoscopy in 16 FAP and 10 MAP patients with duodenal polyposis. Ten FAP and 10 MAP adenomas and matched blood DNA samples were exome sequenced, 42 further adenomas underwent targeted sequencing, and 47 were studied by array comparative genomic hybridization. Findings in FAP and MAP duodenal adenomas were compared with each other and to the reported mutational landscape in FAP and MAP colorectal adenomas.Results: MAP duodenal adenomas had significantly more protein-changing somatic mutations (P ¼ 0.018), truncating mutations (P ¼ 0.006), and copy number variants (P ¼ 0.005) than FAP duodenal adenomas, even though MAP patients had lower Spigelman stage duodenal polyposis. Fifteen genes were significantly recurrently mutated. Targeted sequencing of APC, KRAS, PTCHD2, and PLCL1 identified further mutations in each of these genes in additional duodenal adenomas. In contrast to MAP and FAP colorectal adenomas, neither exome nor targeted sequencing identified WTX mutations (P ¼ 0.0017).Conclusions: The mutational landscapes in FAP and MAP duodenal adenomas overlapped with, but had significant differences to those reported in colorectal adenomas. The significantly higher burden of somatic mutations in MAP than FAP duodenal adenomas despite lower Spigelman stage disease could increase cancer risk in the context of apparently less severe benign disease.
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