Paediatric triage practice and emergency severity index in the Maltese Islands

BACKGROUND: In the paediatric emergency department (PED) triage is a keystone service designed specifically for the recognition of severely ill patients. In this study, the local paediatric triage practice was assessed.METHODS: Data was collected retrospectively for children under 16 years of age presenting to the PED during the first seven days of August 2018, September 2018, January 2019 and February 2019. A triage priority category was assigned according to the Emergency Severity Index (ESI) algorithm (version 4) and compared to that assigned by the triage nurse.RESULTS: The kappa coefficient for inter-rater reliability (triage nurse vs investigator) was 0.360 (95% CI 0.329, 0.390). Weighted kappa was calculated to be 0.424 (95% CI 0.395, 0.454). Concordance between nurse triage and investigator triage was present for 51.32% of cases, whilst Chi-squared test showed significant differences between raters for the categories ESI-2, ESI-3, and ESI-5.CONCLUSION: This study has highlighted some concerns with our local paediatric triage practices, with fair to moderate agreement for inter-rater reliability, and the possibility of significant over-triage. The main recommendation is that paediatric triage is carried out by healthcare professionals who are experienced in dealing with sick children.peer-reviewe

National analyses on survival in Maltese adult patients on renal replacement therapy started during 2009–2012

Chronic kidney disease patients on maintenance dialysis (CKD 5D) experience major morbidity and mortality. No data on survival in Maltese dialysis patients exist; therefore, the aim of this study was to rigorously examine survival statistics in a complete cohort of Maltese CKD 5D patients. The study population was comprised of all incident chronic patients (N=328) starting dialysis at the renal unit, Mater Dei hospital, Msida, Malta, for 4 consecutive years (2009–2012). Each yearly cohort was analysed in detail up to 31st December 2017, providing up to 8 years follow-up. Demographics (male 65%; female 35%), aetiology of renal failure (diabetic kidney disease: n=191; 58.2%), comorbidities, transplant status, and death were documented. Data collection and follow up were completed and statistical analysis was performed on the aggregated cohorts with SPSS version 23 with censoring up to 31st December 2017. The cumulative adjusted 5-year overall survival in Maltese CKD 5D patients was 0.36 and 0.25 at 8 years. No statistical difference was observed according to the year of starting dialysis. Cox regression analysis showed that age and transplant status influenced survival. The unadjusted hazard of death increased by 3% for every 1-year increase in age and was increased by 7% if the patient did not receive a transplant, and overall 22% (n=72) of the entire cohort eventually received transplants. This study reports an approximate 65% mortality at 5 years in Maltese haemodialysis patients, a poor prognosis that, despite optimal medical management, is consistent with worldwide reports.peer-reviewe

Person-centredness - The ‘state’ of the art

Background: Person-centred practice is now firmly embedded in the nursing and healthcare discourse. While there is a growing body of development and research activity in the field, there is increased recognition of the need for further advances in the body of existing knowledge. This is reflected in the different approaches to person-centredness being adopted by healthcare systems internationally. Aims: To provide an overview of person-centredness and ways in which person-centred practice has been adopted in healthcare systems internationally. Methods: A summary review of the evidence underpinning the concepts and theory of person-centredness, incorporating an overview of national strategic frameworks that influence the development of person-centred practice in different countries. Findings: While there have been considerable advances in the development of person-centredness, there is a lot of work to be done in the adoption of more consistent approaches to its development and evaluation. In particular, a shared discourse and measurement tools are needed. Internationally, person-centredness is gaining momentum and many countries have strategic frameworks in place to direct its development and implementation

RIP3, a kinase promoting necroptotic cell death, mediates adverse remodelling after myocardial infarction

Aims Programmed necrosis (necroptosis) represents a newly identified mechanism of cell death combining features of both apoptosis and necrosis. Like apoptosis, necroptosis is tightly regulated by distinct signalling pathways. A key regulatory role in programmed necrosis has been attributed to interactions of the receptor-interacting protein kinases, RIP1 and RIP3. However, the specific functional role of RIP3-dependent signalling and necroptosis in the heart is unknown. The aims of this study were thus to assess the significance of necroptosis and RIP3 in the context of myocardial ischaemia. Methods and results Immunoblots revealed strong expression of RIP3 in murine hearts, indicating potential functional significance of this protein in the myocardium. Consistent with a role in promoting necroptosis, adenoviral overexpression of RIP3 in neonatal rat cardiomyocytes and stimulation with TNF-α induced the formation of a complex of RIP1 and RIP3. Moreover, RIP3 overexpression was sufficient to induce necroptosis of cardiomyocytes. In vivo, cardiac expression of RIP3 was up-regulated upon myocardial infarction (MI). Conversely, mice deficient for RIP3 (RIP3−/−) showed a significantly better ejection fraction (45 ± 3.6 vs. 32 ± 4.4%, P < 0.05) and less hypertrophy in magnetic resonance imaging studies 30 days after experimental infarction due to left anterior descending coronary artery ligation. This was accompanied by a diminished inflammatory response of infarcted hearts and decreased generation of reactive oxygen species. Conclusion Here, we show that RIP3-dependent necroptosis modulates post-ischaemic adverse remodelling in a mouse model of MI. This novel signalling pathway may thus be an attractive target for future therapies that aim to limit the adverse consequences of myocardial ischaemi

АСР температуры и расхода гелеобразного топлива в системе топливоподачи испытательного стенда

Объектом автоматизации является система топливоподачи испытательного стенда. Цель работы – проектирование автоматической системы регулирования температуры и расхода гелеобразного топлива в системе топливоподачи испытательного стенда. В процессе выполнения работы проводились экспериментальные исследования, анализ объекта автоматизации, составление структурной схемы автоматической системы регулирования температуры и расхода гелеобразного топлива в системе топливоподачи испытательного стенда, проектирование функциональной схемы, монтажной и принципиальной электрической схем, а также разработка чертежа общего вида щита автоматизации, выбор технических средств и приборов автоматизации с последующим составлением заказной спецификации, разработка мнемосхемы проекта.The object of automation is the fuel supply system of the test stand. The purpose of the work is to design an automatic system for controlling the temperature and the flow rate of gel-like fuel in the fuel dispensing system of the test bench. In the course of the work carried out, experimental studies, analysis of the automation facility, drafting structural diagram of the automatic temperature and flow gel-like fuel management system in the test bench system were carried out, Design of the functional circuit, mounting diagram and principle electrical circuits, as well as drawing of the general kind of automation shield, selection of technical means and automation devices with subsequent elaboration of the custom specification, development of the design mnemonic diagram

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Resident Cardiac Immune Cells and Expression of the Ectonucleotidase Enzymes CD39 and CD73 after Ischemic Injury

BACKGROUND: The ectoenzymes CD39 and CD73 are expressed by a broad range of immune cells and promote the extracellular degradation of nucleotides to anti-inflammatory adenosine. This study explored the abundance of CD73 and CD39 on circulating and resident cardiac leukocytes and coronary endothelial cells under control conditions and in response to inflammation following myocardial ischemia and reperfusion (I/R). METHODS AND RESULTS: A method was elaborated to permit FACS analysis of non-myocardial cells (resident leukocytes, coronary endothelium and CD31(-) CD45(-) cells) of the unstressed heart. Under control conditions the murine heart contained 2.3 × 10(3) resident leukocytes/mg tissue, the most prominent fraction being antigen-presenting mononuclear cells (CD11b(+) CD11c(+) F4/80(+) MHCII(+)) followed by B-cells, monocytes and T-cells. CD73 was highly expressed on circulating and resident cardiac lymphoid cells with little expression on myeloid cells, while the opposite was true for CD39. Cardiomyocytes and erythrocytes do not measurably express CD39/CD73 and CD39 dominates on coronary endothelium. Three days after I/R, CD73 was significantly upregulated on invading granulocytes (2.8-fold) and T-cells (1.5-fold). Compared with coronary endothelial cells, CD73 associated with leukocytes comprised 2/3 of the total cardiac CD73. CONCLUSION: Our study suggests that extracellular ATP formed during I/R is preferentially degraded by CD39 present on myeloid cells, while the formation of immunosuppressive adenosine is mainly catalysed by CD73 present on granulocytes and lymphoid cells. Upregulated CD73 on granulocytes and T-cells infiltrating the injured heart is consistent with the existence of an autocrine adenosinergic loop which may promote the healing process

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Peer reviewedPublisher PD

The Spectrum of FANCM Protein Truncating Variants in European Breast Cancer Cases

Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2–4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with FANCM PTVs ascertained in 20 centers from 13 European countries. We identified 27 different FANCM PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique FANCM PTVs, 15 have not been previously reported. We provide here the initial spectrum of FANCM PTVs in European breast cancer cases