The applicability of commonly used predictive scoring systems in Indigenous Australians with sepsis: An observational study

Background Indigenous Australians suffer a disproportionate burden of sepsis, however, the performance of scoring systems that predict mortality in Indigenous patients with critical illness is incompletely defined. Materials and methods The study was performed at an Australian tertiary-referral hospital between January 2014 and June 2017, and enrolled consecutive Indigenous and non-Indigenous adults admitted to ICU with sepsis. The ability of the ANZROD, APACHE-II, APACHE-III, SAPS-II, SOFA and qSOFA scores to predict death before ICU discharge in the two populations was compared. Results There were 442 individuals enrolled in the study, 145 (33%) identified as Indigenous. Indigenous patients were younger than non-Indigenous patients (median (interquartile range (IQR) 53 (43-60) versus 65 (52-73) years, p = 0.0001) and comorbidity was more common (118/145 (81%) versus 204/297 (69%), p = 0.005). Comorbidities that were more common in the Indigenous patients included diabetes mellitus (84/145 (58%) versus 67/297 (23%), p<0.0001), renal disease (56/145 (39%) versus 29/297 (10%), p<0.0001) and cardiovascular disease (58/145 (40%) versus 83/297 (28%), p = 0.01). The use of supportive care (including vasopressors, mechanical ventilation and renal replacement therapy) was similar in Indigenous and non-Indigenous patients, and the two populations had an overall case-fatality rate that was comparable (17/145 (12%) and 38/297 (13%) (p = 0.75)), although Indigenous patients died at a younger age (median (IQR): 54 (50-60) versus 70 (61-76) years, p = 0.0001). There was no significant difference in the ability of any the scores to predict mortality in the two populations. Conclusions Although the crude case-fatality rates of Indigenous and non-Indigenous Australians admitted to ICU with sepsis is comparable, Indigenous patients die at a much younger age. Despite this, the ability of commonly used scoring systems to predict outcome in Indigenous Australians is similar to that of non-Indigenous Australians, supporting their use in ICUs with a significant Indigenous patient population and in clinical trials that enrol Indigenous Australians

Exploring the role of nurses in after-hours telephone services in regional areas; A scoping review

Introduction The management of patients who need chronic and complex care is a focus of attention internationally, brought about by an increase in chronic conditions, requiring significantly more care over longer periods of time. The increase in chronic conditions has placed pressure on health services, financially and physically, bringing about changes in the way care is delivered, with hospital avoidance and home-based care encouraged. In this environment, nurses play an important role in co-ordinating care across services. This review formed one part of a funded project that explored the nurse navigator role within a proposed 24-hour telephone-call service in one regional area that has a diverse population in terms of cultural identity and geographical location in relation to service access. Aim The review reports on the extant literature on the nurse’s role in the provision of afterhours telephone services for patients with chronic and complex conditions. The specific aim was to explore the effectiveness of services for patients in geographically isolated locations. Methods The methodological approach to the review followed the Preferred Reporting System for Meta-Analyses (PRISMA) guidelines. A thematic analysis was used to identify themes with chronic care models underpinning analysis. Results Three themes were identified; nurse-led decision making; consumer profile; and program outcomes. Each theme was divided into two sub-themes. The two sub-themes for decision making were: the experience of the staff who provided the service and the tool or protocol used. The two sub-themes for consumers profile were; the geographic/demographic identity of the consumers, and consumer satisfaction. The final theme of outcomes describes how the effectiveness of the service is measured, broken into two sub-themes: the economic/workforce outcomes and the consumer outcomes. Discussion The provision of an after-hours telephone service, in whatever model used should align with a Chronic Care Model. In this way, after-hours telephone services provided by experienced nurses, supported by ongoing professional development and relevant protocols, form part of the ongoing improvement for chronic and complex care management as a health priority

The use of telephone communication between nurse navigators and their patients

Background: Hospitals and other health care providers frequently experience difficulties contacting patients and their carers who live remotely from the town where the health service is located. In 2016 Nurse Navigator positions were introduced into the health services by Queensland Health, to support and navigate the care of people with chronic and complex conditions. One hospital in Far North Queensland initiated an additional free telephone service to provide another means of communication for patients and carers with the NNs and for off-campus health professionals to obtain details about a patient utilising the service. Calls made between 7am and 10pm, seven days per week are answered by a nurse navigator. Aim: To report utilisation of the service by navigated clients and remotely located clinicians compared to use of navigators' individual work numbers and direct health service numbers. We report the reason for calls to the free number and examine features of these calls. Methods: Statistical analysis examined the call reason, duration of calls, setting from where calls originated and stream of calls. Interactions between the reasons for calls and the features of calls, such as contact method, were examined. Results: The major reason for calls was clinical issues and the source of calls was primarily patients and carers. Clinical calls were longer in duration. Shorter calls were mainly non-clinical, made by a health professional. Setting for calls was not related to the reason. The most frequent number used was the individual mobile number of the NN, followed by the hospital landline. Although the free number was utilised by patients and carers, it was not the preferred option. Conclusion: As patients and carers preferred to access their NN directly than via the 1800 number, further research should explore options best suited to this group of patients outside normal business hours

Ожирение – фактор риска развития неуточненной инфекции подкожно-жировой клетчатки

Представлено результати дослідження С-пептиду, інсуліну та лептину, а також розраховано індекс маси тіла у хворих з неуточненою інфекцією підшкірної клітковини. У 47,62 % хворих ожиріння I-III ступеня, що збільшує ліпогенез, який провокує гіпертрофію адипоцитів.The results of C-peptide, insulin and leptin exploration are presented; also the body weight index among the ill with the subcutaneous cellular tissue unspecified infection has been calculated. 47,62 % of the ill has adiposity of levels I-III, which increases lipogenesis provoking the adepocites hypertrophy

Improved pregnancy outcomes in women with type 1 and type 2 diabetes but substantial clinic-to-clinic variations: a prospective nationwide study

Aims/hypothesis: The aim of this prospective nationwide study was to examine antenatal pregnancy care and pregnancy outcomes in women with type 1 and type 2 diabetes, and to describe changes since 2002/2003. Methods: This national population-based cohort included 3036 pregnant women with diabetes from 155 maternity clinics in England and Wales who delivered during 2015. The main outcome measures were maternal glycaemic control, preterm delivery (before 37 weeks), infant large for gestational age (LGA), and rates of congenital anomaly, stillbirth and neonatal death. Results: Of 3036 women, 1563 (51%) had type 1, 1386 (46%) had type 2 and 87 (3%) had other types of diabetes. The percentage of women achieving HbA1c < 6.5% (48 mmol/mol) in early pregnancy varied greatly between clinics (median [interquartile range] 14.3% [7.7–22.2] for type 1, 37.0% [27.3–46.2] for type 2). The number of infants born preterm (21.7% vs 39.7%) and LGA (23.9% vs 46.4%) were lower for women with type 2 compared with type 1 diabetes (both p < 0.001). The prevalence rates for congenital anomaly (46.2/1000 births for type 1, 34.6/1000 births for type 2) and neonatal death (8.1/1000 births for type 1, 11.4/1000 births for type 2) were unchanged since 2002/2003. Stillbirth rates are almost 2.5 times lower than in 2002/2003 (10.7 vs 25.8/1000 births for type 1, p = 0.0012; 10.5 vs 29.2/1000 births for type 2, p = 0.0091). Conclusions/interpretation: Stillbirth rates among women with type 1 and type 2 diabetes have decreased since 2002/2003. Rates of preterm delivery and LGA infants are lower in women with type 2 compared with type 1 diabetes. In women with type 1 diabetes, suboptimal glucose control and high rates of perinatal morbidity persist with substantial variations between clinics

Integrative Genomics Identifies the Molecular Basis of Resistance to Azacitidine Therapy in Myelodysplastic Syndromes

© 2017 The Author(s) Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis and progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only ∼50% of patients respond. A response only manifests after many months of treatment and is transient. The reasons underlying AZA resistance are unknown, and few alternatives exist for non-responders. Here, we show that AZA responders have more hematopoietic progenitor cells (HPCs) in the cell cycle. Non-responder HPC quiescence is mediated by integrin α5 (ITGA5) signaling and their hematopoietic potential improved by combining AZA with an ITGA5 inhibitor. AZA response is associated with the induction of an inflammatory response in HPCs in vivo. By molecular bar coding and tracking individual clones, we found that, although AZA alters the sub-clonal contribution to different lineages, founder clones are not eliminated and continue to drive hematopoiesis even in complete responders

HNF4alpha Dysfunction as a Molecular Rational for Cyclosporine Induced Hypertension

Induction of tolerance against grafted organs is achieved by the immunosuppressive agent cyclosporine, a prominent member of the calcineurin inhibitors. Unfortunately, its lifetime use is associated with hypertension and nephrotoxicity. Several mechanism for cyclosporine induced hypertension have been proposed, i.e. activation of the sympathetic nervous system, endothelin-mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in prostaglandin and nitric oxide, altered cytosolic calcium translocation, and activation of the renin-angiotensin system (RAS). In this regard the molecular basis for undue RAS activation and an increased signaling of the vasoactive oligopeptide angiotensin II (AngII) remain elusive. Notably, angiotensinogen (AGT) is the precursor of AngII and transcriptional regulation of AGT is controlled by the hepatic nuclear factor HNF4alpha. To better understand the molecular events associated with cyclosporine induced hypertension, we investigated the effect of cyclosporine on HNF4alpha expression and activity and searched for novel HNF4alpha target genes among members of the RAS cascade. Using bioinformatic algorithm and EMSA bandshift assays we identified angiotensin II receptor type 1 (AGTR1), angiotensin I converting enzyme (ACE), and angiotensin I converting enzyme 2 (ACE2) as genes targeted by HNF4alpha. Notably, cyclosporine represses HNF4alpha gene and protein expression and its DNA-binding activity at consensus sequences to AGT, AGTR1, ACE, and ACE2. Consequently, the gene expression of AGT, AGTR1, and ACE2 was significantly reduced as evidenced by quantitative real-time RT-PCR. While RAS is composed of a sophisticated interplay between multiple factors we propose a decrease of ACE2 to enforce AngII signaling via AGTR1 to ultimately result in vasoconstriction and hypertension. Taken collectively we demonstrate cyclosporine to repress HNF4alpha activity through calcineurin inhibitor mediated inhibition of nuclear factor of activation of T-cells (NFAT) which in turn represses HNF4alpha that leads to a disturbed balance of RAS

A Systems Biology Approach Identifies Molecular Networks Defining Skeletal Muscle Abnormalities in Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients

A Folding Pathway-Dependent Score to Recognize Membrane Proteins

While various approaches exist to study protein localization, it is still a challenge to predict where proteins localize. Here, we consider a mechanistic viewpoint for membrane localization. Taking into account the steps for the folding pathway of α-helical membrane proteins and relating biophysical parameters to each of these steps, we create a score capable of predicting the propensity for membrane localization and call it FP3mem. This score is driven from the principal component analysis (PCA) of the biophysical parameters related to membrane localization. FP3mem allows us to rationalize the colocalization of a number of channel proteins with the Cav1.2 channel by their fewer propensities for membrane localization

Genetic polymorphisms of the RAS-cytokine pathway and chronic kidney disease

Chronic kidney disease (CKD) in children is irreversible. It is associated with renal failure progression and atherosclerotic cardiovascular (CV) abnormalities. Nearly 60% of children with CKD are affected since birth with congenital or inherited kidney disorders. Preliminary evidence primarily from adult CKD studies indicates common genetic risk factors for CKD and atherosclerotic CV disease. Although multiple physiologic pathways share common genes for CKD and CV disease, substantial evidence supports our attention to the renin angiotensin system (RAS) and the interlinked inflammatory cascade because they modulate the progressions of renal and CV disease. Gene polymorphisms in the RAS-cytokine pathway, through altered gene expression of inflammatory cytokines, are potential factors that modulate the rate of CKD progression and CV abnormalities in patients with CKD. For studying such hypotheses, the cooperative efforts among scientific groups and the availability of robust and affordable technologies to genotype thousands of single nucleotide polymorphisms (SNPs) across the genome make genome-wide association studies an attractive paradigm for studying polygenic diseases such as CKD. Although attractive, such studies should be interpreted carefully, with a fundamental understanding of their potential weaknesses. Nevertheless, whole-genome association studies for diabetic nephropathy and future studies pertaining to other types of CKD will offer further insight for the development of targeted interventions to treat CKD and associated atherosclerotic CV abnormalities in the pediatric CKD population