Strengths and weaknesses of the acute care systems in the United Kingdom and the Netherlands: what can we learn from each other?

Background The demand on Emergency Departments and acute medical services is increasing internationally, creating pressure on health systems and negatively influencing the quality of delivered care. Visible consequences of the increased demand on acute services is crowding and queuing. This manifests as delays in the Emergency Departments, adverse clinical outcomes and poor patient experience. Overview Despite the similarities in the UK’s and Dutch health care systems, such as universal health coverage, there are differences in the number of patients presenting at the Emergency Departments and the burden of crowding between these countries. Given the similarities in funding, this paper explores the similarities and differences in the organisational structure of acute care in the UK and the Netherlands. In the Netherlands, less patients are seen at the ED than in England and the admission rate is higher. GPs and so-called GP-posts serve 24/7 as gatekeepers in acute care, but EDs are heterogeneously organised. In the UK, the acute care system has a number of different access points and the accessibility of GPs seems to be suboptimal. Acute ambulatory care may relieve the pressure from EDs and Acute Medical Units. In both countries the ageing population leads to a changing case mix at the ED with an increased amount of multimorbid patients with polypharmacy, requiring generalistic and multidisciplinary care. Conclusion The acute and emergency care in the Netherlands and the UK face similar challenges. We believe that each system has strengths that the other can learn from. The Netherlands may benefit from an acute ambulatory care system and the UK by optimizing the accessibility of GPs 24/7 and improving signposting for urgent care services. In both countries the changing case mix at the ED needs doctors who are superspecialists instead of subspecialists. Finally, to improve the organisation of health care, doctors need to be visible medical leaders and participate in the organisation of care

What facilitates the delivery of dignified care to older people? A survey of health care professionals Geriatrics

Background: Whilst the past decade has seen a growing emphasis placed upon ensuring dignity in the care of older people this policy objective is not being consistently achieved and there appears a gap between policy and practice. We need to understand how dignified care for older people is understood and delivered by the health and social care workforce and how organisational structures and policies can promote and facilitate, or hinder, the delivery of such care. Methods: To achieve our objective of understanding the facilitators and to the delivery of dignified care we undertook a survey with health and social care professionals across four NHS Trusts in England. Participants were asked provide free text answers identifying any facilitators/barriers to the provision of dignified care. Survey data was entered into SPSSv15 and analysed using descriptive statistics. These data provided the overall context describing staff attitudes and beliefs about dignity and the provision of dignified care. Qualitative data from the survey were transcribed verbatim and categorised into themes using thematic analysis. Results: 192 respondents were included in the analysis. 79 % of respondents identified factors within their working environment that helped them provide dignified care and 68 % identified barriers to achieving this policy objective. Facilitators and barriers to delivering dignified care were categorised into three domains: 'organisational level'; 'ward level' and 'individual level'. Within the these levels, respondents reported factors that both supported and hindered dignity in care including 'time', 'staffing levels', training',' 'ward environment', 'staff attitudes', 'support', 'involving family/carers', and 'reflection'. Conclusion: Facilitators and barriers to the delivery of dignity as perceived by health and social care professionals are multi-faceted and range from practical issues to interpersonal and training needs. Thus interventions to support health and social care professionals in delivering dignified care, need to take a range of issues into account to ensure that older people receive a high standard of care in NHS Trusts.Professor David Oliver, Professor Andree le May, Dr. Sally Richards, Dr Wendy Marti

Assessment of the role of transcript for GATA-4 as a marker of unfavorable outcome in human adrenocortical neoplasms

BACKGROUND: Malignant neoplasia of the adrenal cortex is usually associated with very poor prognosis. When adrenocortical neoplasms are diagnosed in the early stages, distinction between carcinoma and adenoma can be very difficult to accomplish, since there is yet no reliable marker to predict tumor recurrence or dissemination. GATA transcription factors play an essential role in the developmental control of cell fate, cell proliferation and differentiation, organ morphogenesis, and tissue-specific gene expression. Normal mouse adrenal cortex expresses GATA-6 while its malignant counterpart only expresses GATA-4. The goal of the present study was to assess whether this reciprocal change in the expression of GATA factors might be relevant for predicting the prognosis of human adrenocortical neoplasms. Since human adrenal cortices express luteinizing hormone (LH/hCG) receptor and the gonadotropins are known to up-regulate GATA-4 in gonadal tumor cell lines, we also studied the expression of LH/hCG receptor. METHODS: We conducted a study on 13 non-metastasizing (NM) and 10 metastasizing/recurrent (MR) tumors obtained from a group of twenty-two adult and pediatric patients. The expression of GATA-4, GATA-6, and LH/hCG receptor (LHR) in normal and tumoral human adrenal cortices was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR) complemented by dot blot hybridization. RESULTS: Messenger RNA for GATA-6 was detected in normal adrenal tissue, as well as in the totality of NM and MR tumors. GATA-4, by its turn, was detected in normal adrenal tissue, in 11 out of 13 NM tumors, and in 9 of the 10 MR tumors, with larger amounts of mRNA found among those presenting aggressive clinical behavior. Transcripts for LH receptor were observed both in normal tissue and neoplasms. A more intense LHR transcript accumulation was observed on those tumors with better clinical outcome. CONCLUSION: Our data suggest that the expression of GATA-6 in human adrenal cortex is not affected by tumorigenesis. GATA-4 expression is more abundant in MR tumors, while NM tumors express more intensely LHR. Further studies with larger cohorts are needed to test whether relative expression levels of LHR or GATA-4 might be used as prognosis predictors

Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study

BACKGROUND: Adjuvant treatment with mitotane is commonly used after resection of adrenocortical carcinoma; however, treatment remains controversial, particularly if risk of recurrence is not high. We aimed to assess the efficacy and safety of adjuvant mitotane compared with surveillance alone following complete tumour resection in patients with adrenocortical carcinoma considered to be at low to intermediate risk of recurrence. METHODS: ADIUVO was a multicentre, open-label, parallel, randomised, phase 3 trial done in 23 centres across seven countries. Patients aged 18 years or older with adrenocortical carcinoma and low to intermediate risk of recurrence (R0, stage I-III, and Ki67 ≤10%) were randomly assigned to adjuvant oral mitotane two or three times daily (the dose was adjusted by the local investigator with the target of reaching and maintaining plasma mitotane concentrations of 14-20 mg/L) for 2 years or surveillance alone. All consecutive patients at 14 study centres fulfilling the eligibility criteria of the ADIUVO trial who refused randomisation and agreed on data collection via the European Network for the Study of Adrenal Tumors adrenocortical carcinoma registry were included prospectively in the ADIUVO Observational study. The primary endpoint was recurrence-free survival, defined as the time from randomisation to the first radiological evidence of recurrence or death from any cause (whichever occurred first), assessed in all randomly assigned patients by intention to treat. Overall survival, defined as time from the date of randomisation to the date of death from any cause, was a secondary endpoint analysed by intention to treat in all randomly assigned patients. Safety was assessed in all patients who adhered to the assigned regimen, which was defined by taking at least one tablet of mitotane in the mitotane group and no mitotane at all in the surveillance group. The ADIUVO trial is registered with ClinicalTrials.gov, NCT00777244, and is now complete. FINDINGS: Between Oct 23, 2008, and Dec 27, 2018, 45 patients were randomly assigned to mitotane and 46 to surveillance alone. Because the study was discontinued prematurely, 5-year recurrence-free and overall survival are reported instead of recurrence-free and overall survival as defined in the protocol. 5-year recurrence-free survival was 79% (95% CI 67-94) in the mitotane group and 75% (63-90) in the surveillance group (hazard ratio 0·74 [95% CI 0·30-1·85]). Two people in the mitotane group and five people in the surveillance group died, and 5-year overall survival was not significantly different (95% [95% CI 89-100] in the mitotane group and 86% [74-100] in the surveillance group). All 42 patients who received mitotane had adverse events, and eight (19%) discontinued treatment. There were no grade 4 adverse events or treatment-related deaths. INTERPRETATION: Adjuvant mitotane might not be indicated in patients with low-grade, localised adrenocortical carcinoma considering the relatively good prognosis of these patients, and no significant improvement in recurrence-free survival and treatment-associated toxicity in the mitotane group. However, the study was discontinued prematurely due to slow recruitment and cannot rule out an efficacy of treatment. FUNDING: AIFA, ENSAT Cancer Health F2-2010-259735 programme, Deutsche Forschungsgemeinschaft, Cancer Research UK, and the French Ministry of Health

Genome-wide RNA-Sequencing analysis reveals a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery

Fibrosis-related events play a part in most blinding diseases worldwide. However, little is known about the mechanisms driving this complex multifactorial disease. Here we have carried out the first genome-wide RNA-Sequencing study in human conjunctival fibrosis. We isolated 10 primary fibrotic and 7 non-fibrotic conjunctival fibroblast cell lines from patients with and without previous glaucoma surgery, respectively. The patients were matched for ethnicity and age. We identified 246 genes that were differentially expressed by over two-fold and p < 0.05, of which 46 genes were upregulated and 200 genes were downregulated in the fibrotic cell lines compared to the non-fibrotic cell lines. We also carried out detailed gene ontology, KEGG, disease association, pathway commons, WikiPathways and protein network analyses, and identified distinct pathways linked to smooth muscle contraction, inflammatory cytokines, immune mediators, extracellular matrix proteins and oncogene expression. We further validated 11 genes that were highly upregulated or downregulated using real-time quantitative PCR and found a strong correlation between the RNA-Seq and qPCR results. Our study demonstrates that there is a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery and provides new insights into the mechanistic pathways driving the complex fibrotic process in the eye and other tissues