Do acute elevations of serum creatinine in primary care engender an increased mortality risk?

Background: The significant impact Acute Kidney Injury (AKI) has on patient morbidity and mortality emphasizes the need for early recognition and effective treatment. AKI presenting to or occurring during hospitalisation has been widely studied but little is known about the incidence and outcomes of patients experiencing acute elevations in serum creatinine in the primary care setting where people are not subsequently admitted to hospital. The aim of this study was to define this incidence and explore its impact on mortality. Methods: The study cohort was identified by using hospital data bases over a six month period. Inclusion criteria: People with a serum creatinine request during the study period, 18 or over and not on renal replacement therapy. The patients were stratified by a rise in serum creatinine corresponding to the Acute Kidney Injury Network (AKIN) criteria for comparison purposes. Descriptive and survival data were then analysed. Ethical approval was granted from National Research Ethics Service (NRES) Committee South East Coast and from the National Information Governance Board. Results: The total study population was 61,432. 57,300 subjects with ‘no AKI’, mean age 64.The number (mean age) of acute serum creatinine rises overall were, ‘AKI 1’ 3,798 (72), ‘AKI 2’ 232 (73), and ‘AKI 3’ 102 (68) which equates to an overall incidence of 14,192 pmp/year (adult). Unadjusted 30 day survival was 99.9% in subjects with ‘no AKI’, compared to 98.6%, 90.1% and 82.3% in those with ‘AKI 1’, ‘AKI 2’ and ‘AKI 3’ respectively. After multivariable analysis adjusting for age, gender, baseline kidney function and co-morbidity the odds ratio of 30 day mortality was 5.3 (95% CI 3.6, 7.7), 36.8 (95% CI 21.6, 62.7) and 123 (95% CI 64.8, 235) respectively, compared to those without acute serum creatinine rises as defined. Conclusions: People who develop acute elevations of serum creatinine in primary care without being admitted to hospital have significantly worse outcomes than those with stable kidney function

What is the real impact of acute kidney injury?

Background: Acute kidney injury (AKI) is a common clinical problem. Studies have documented the incidence of AKI in a variety of populations but to date we do not believe the real incidence of AKI has been accurately documented in a district general hospital setting. The aim here was to describe the detected incidence of AKI in a typical general hospital setting in an unselected population, and describe associated short and long-term outcomes. Methods: A retrospective observational database study from secondary care in East Kent (adult catchment population of 582,300). All adult patients (18 years or over) admitted between 1st February 2009 and 31st July 2009, were included. Patients receiving chronic renal replacement therapy (RRT), maternity and day case admissions were excluded. AKI was defined by the acute kidney injury network (AKIN) criteria. A time dependent risk analysis with logistic regression and Cox regression was used for the analysis of in-hospital mortality and survival. Results: The incidence of AKI in the 6 month period was 15,325 pmp/yr (adults) (69% AKIN1, 18% AKIN2 and 13% AKIN3). In-hospital mortality, length of stay and ITU utilisation all increased with severity of AKI. Patients with AKI had an increase in care on discharge and an increase in hospital readmission within 30 days. Conclusions: This data comes closer to the real incidence and outcomes of AKI managed in-hospital than any study published in the literature to date. Fifteen percent of all admissions sustained an episode of AKI with increased subsequent short and long term morbidity and mortality, even in those with AKIN1. This confers an increased burden and cost to the healthcare economy, which can now be quantified. These results will furnish a baseline for quality improvement projects aimed at early identification, improved management, and where possible prevention, of AKI

Testing foundations of quantum mechanics with photons

The foundational ideas of quantum mechanics continue to give rise to counterintuitive theories and physical effects that are in conflict with a classical description of Nature. Experiments with light at the single photon level have historically been at the forefront of tests of fundamental quantum theory and new developments in photonics engineering continue to enable new experiments. Here we review recent photonic experiments to test two foundational themes in quantum mechanics: wave-particle duality, central to recent complementarity and delayed-choice experiments; and Bell nonlocality where recent theoretical and technological advances have allowed all controversial loopholes to be separately addressed in different photonics experiments.Comment: 10 pages, 5 figures, published as a Nature Physics Insight review articl

Bench-to-bedside review : targeting antioxidants to mitochondria in sepsis

Peer reviewedPublisher PD

Is the pharmacy profession innovative enough?: meeting the needs of Australian residents with chronic conditions and their carers using the nominal group technique

Background Community pharmacies are ideally located as a source of support for people with chronic conditions. Yet, we have limited insight into what innovative pharmacy services would support this consumer group to manage their condition/s. The aim of this study was to identify what innovations people with chronic conditions and their carers want from their ideal community pharmacy, and compare with what pharmacists and pharmacy support staff think consumers want. Methods We elicited ideas using the nominal group technique. Participants included people with chronic conditions, unpaid carers, pharmacists and pharmacy support staff, in four regions of Australia. Themes were identified via thematic analysis using the constant comparison method. Results Fifteen consumer/carer, four pharmacist and two pharmacy support staff groups were conducted. Two overarching themes were identified: extended scope of practice for the pharmacist and new or improved pharmacy services. The most innovative role for Australian pharmacists was medication continuance, within a limited time-frame. Consumers and carers wanted improved access to pharmacists, but this did not necessarily align with a faster or automated dispensing service. Other ideas included streamlined access to prescriptions via medication reminders, electronic prescriptions and a chronic illness card. Conclusions This study provides further support for extending the pharmacist’s role in medication continuance, particularly as it represents the consumer’s voice. How this is done, or the methods used, needs to optimise patient safety. A range of innovative strategies were proposed and Australian community pharmacies should advocate for and implement innovative approaches to improve access and ensure continuity of care

Einstein-Gauss-Bonnet black strings

We construct uniform black-string solutions in Einstein-Gauss-Bonnet gravity for all dimensions $d$ between five and ten and discuss their basic properties. Closed form solutions are found by taking the Gauss-Bonnet term as a perturbation from pure Einstein gravity. Nonperturbative solutions are constructed by solving numerically the equations of the model. The Gregory-Laflamme instability of the black strings is explored via linearized perturbation theory. Our results indicate that new qualitative features occur for $d=6$, in which case stable configurations exist for large enough values of the Gauss-Bonnet coupling constant. For other dimensions, the black strings are dynamically unstable and have also a negative specific heat. We argue that this provides an explicit realization of the Gubser-Mitra conjecture, which links local dynamical and thermodynamic stability. Nonuniform black strings in Einstein-Gauss-Bonnet theory are also constructed in six spacetime dimensions.Comment: 33 pages, 11 figure

From affect programs to dynamical discrete emotions

According to Discrete Emotion Theory, a number of emotions are distinguishable on the basis of neural, physiological, behavioral and expressive features. Critics of this view emphasize the variability and context-sensitivity of emotions. This paper discusses some of these criticisms, and argues that they do not undermine the claim that emotions are discrete. This paper also presents some works in dynamical affective science, and argues that to conceive of discrete emotions as self-organizing and softly assembled patterns of various processes accounts more naturally than traditional Discrete Emotion Theory for the variability and context-sensitivity of emotions

The ideal healthcare: priorities of people with chronic conditions and their carers

Background It is well established that health consumer opinions should be considered in the design, delivery, and evaluation of health services. However, the opinions of people with chronic conditions and their carers and what they actually consider as ideal healthcare is limited. The aim of this study is to investigate the healthcare priorities of consumers with chronic conditions and their carers, if there are differences between these two groups, and if priorities differ depending on geographical location. Methods The nominal group technique was used as a method to identify what is currently important to, or valued by, participants. This method was also particularly suited to learning about healthcare problems and generating important solutions, thereby helping to bridge the gap between research and policy. Recruitment was carried out via purposive sampling, with the assistance of community pharmacies, general practices, various health agencies, government and non-government organisations. A total of 11 nominal groups were conducted; five groups consisted predominantly of consumers (n = 33 participants), two groups consisted predominantly of carers (n = 12 participants) and four were mixed groups, i.e. consumers, carers, and both (n = 26 participants). Results The findings suggested that to create a model of ideal healthcare for people with chronic conditions and their carers, appropriate and timely healthcare access was of paramount importance. Continuity and coordinated care, patient-centred care and affordability were equally the second most important healthcare priorities for all groups. When compared with other groups, access was discussed more frequently among participants residing in the rural area of Mount Isa. Compared to consumers, carers also discussed priorities that were more reminiscent with their caring roles, such as increased access and continuity and coordinated care. Conclusions Access to healthcare is the most important priority for people with chronic conditions and their carers. In the event of inappropriate access for certain groups, all other efforts to increase the quality of healthcare delivery, e.g. patient-centred care, may be pointless. However, health professionals alone may be limited in their ability to address the concerns related to healthcare access; structural changes by health policy makers may be needed

Holographic and Wilsonian Renormalization Groups

We develop parallels between the holographic renormalization group in the bulk and the Wilsonian renormalization group in the dual field theory. Our philosophy differs from most previous work on the holographic RG; the most notable feature is the key role of multi-trace operators. We work out the forms of various single- and double-trace flows. The key question, `what cutoff on the field theory corresponds to a radial cutoff in the bulk?' is left unanswered, but by sharpening the analogy between the two sides we identify possible directions.Comment: 31 pages, 3 figures. v2: Minor clarifications. Added reference

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future