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Clin Biochem Rev [journal]
- Erratum. [PUBLISHED ERRATUM]
- Clin Biochem Rev 2013 Nov; 34(3):145.
[This corrects the article on p. 96 in vol. 34.].
- In Search of Mechanisms Associated with Mesenchymal Stem Cell-Based Therapies for Acute Kidney Injury. [REVIEW]
- Clin Biochem Rev 2013 Nov; 34(3):131-144.
Acute kidney injury (AKI) is classically described as a rapid loss of kidney function. AKI affects more than 15% of all hospital admissions and is associated with elevated mortality rates. Although many advances have occurred, intermittent or continuous renal replacement therapies are still considered the best options for reversing mild and severe AKI syndrome. For this reason, it is essential that innovative and effective therapies, without side effects and complications, be developed to treat AKI and the end-stages of renal disease. Mesenchymal stem cell (MSC) based therapies have numerous advantages in helping to repair inflamed and damaged tissues and are being considered as a new alternative for treating kidney injuries. Numerous experimental models have shown that MSCs can act via differentiation-independent mechanisms to help renal recovery. Essentially, MSCs can secrete a pool of cytokines, growth factors and chemokines, express enzymes, interact via cell-to-cell contacts and release bioagents such as microvesicles to orchestrate renal protection. In this review, we propose seven distinct properties of MSCs which explain how renoprotection may be conferred: 1) anti-inflammatory; 2) pro-angiogenic; 3) stimulation of endogenous progenitor cells; 4) anti-apoptotic; 5) anti-fibrotic; 6) anti-oxidant; and 7) promotion of cellular reprogramming. In this context, these mechanisms, either individually or synergically, could induce renal protection and functional recovery. This review summarises the most important effects and benefits associated with MSC-based therapies in experimental renal disease models and attempts to clarify the mechanisms behind the MSC-related renoprotection. MSCs may prove to be an effective, innovative and affordable treatment for moderate and severe AKI. However, more studies need to be performed to provide a more comprehensive global understanding of MSC-related therapies and to ensure their safety for future clinical applications.
- The De Ritis Ratio: The Test of Time. [REVIEW]
- Clin Biochem Rev 2013 Nov; 34(3):117-130.
De Ritis described the ratio between the serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) almost 50 years ago. While initially described as a characteristic of acute viral hepatitis where ALT was usually higher than AST, other authors have subsequently found it useful in alcoholic hepatitis, where AST is usually higher than ALT. These interpretations are far too simplistic however as acute viral hepatitis can have AST greater than ALT, and this can be a sign of fulminant disease, while alcoholic hepatitis can have ALT greater than AST when several days have elapsed since alcohol exposure. The ratio therefore represents the time course and aggressiveness of disease that would be predicted from the relatively short half-life of AST (18 h) compared to ALT (36 h). In chronic viral illnesses such as chronic viral hepatitis and chronic alcoholism as well as non-alcoholic fatty liver disease, an elevated AST/ALT ratio is predictive of long terms complications including fibrosis and cirrhosis. There are methodological issues, particularly whether or not pyridoxal phosphate is used in the transaminase assays, and although this can have specific effects when patient samples are deficient in this vitamin, these method differences generally have mild effects on the usefulness of the assays or the ratio. Ideally laboratories should be using pyridoxal phosphate supplemented assays in alcoholic, elderly and cancer patients who may be pyridoxine deplete. Ideally all laboratories reporting abnormal ALT should also report AST and calculate the De Ritis ratio because it provides useful diagnostic and prognostic information.
- Adrenal Diagnostics: An Endocrinologist's Perspective focused on Hyperaldosteronism. [REVIEW]
- Clin Biochem Rev 2013 Nov; 34(3):111-116.
The era of sophisticated high resolution imaging with the consequent identification of previously unrecognised adrenal masses (adrenal incidentalomas), has emphasised the need for an appropriate biochemical approach to define adrenal function. The focus of this testing is on catecholamines from the adrenal medulla (testing that has been rendered relatively straightforward by plasma metanephrine measurements) and the physiological corticosteroids, cortisol and aldosterone, synthesised by the adrenal cortex. The diagnosis of hypercortisolism remains a challenge and has been extensively reviewed. In the context of hypertension and an adrenal incidentaloma, the exclusion of hyperaldosteronism has an importance beyond simple blood pressure control. This review focuses on the recommended approaches to both the diagnosis of hyperaldosteronism and the characterisation of its aetiology. Monogenetic causes of mineralocorticoid hypertension are discussed as are recent developments with respect to both the molecular aetiology and the differential diagnosis of aldosterone-producing adenomas.
- On-the-Job Evidence-Based Medicine Training for Clinician-Scientists of the Next Generation. [REVIEW]
- Clin Biochem Rev 2013 Aug; 34(2):93-103.
Clinical scientists are at the unique interface between laboratory science and frontline clinical practice for supporting clinical partnerships for evidence-based practice. In an era of molecular diagnostics and personalised medicine, evidence-based laboratory practice (EBLP) is also crucial in aiding clinical scientists to keep up-to-date with this expanding knowledge base. However, there are recognised barriers to the implementation of EBLP and its training. The aim of this review is to provide a practical summary of potential strategies for training clinician-scientists of the next generation. Current evidence suggests that clinically integrated evidence-based medicine (EBM) training is effective. Tailored e-learning EBM packages and evidence-based journal clubs have been shown to improve knowledge and skills of EBM. Moreover, e-learning is no longer restricted to computer-assisted learning packages. For example, social media platforms such as Twitter have been used to complement existing journal clubs and provide additional post-publication appraisal information for journals. In addition, the delivery of an EBLP curriculum has influence on its success. Although e-learning of EBM skills is effective, having EBM trained teachers available locally promotes the implementation of EBM training. Training courses, such as Training the Trainers, are now available to help trainers identify and make use of EBM training opportunities in clinical practice. On the other hand, peer-assisted learning and trainee-led support networks can strengthen self-directed learning of EBM and research participation among clinical scientists in training. Finally, we emphasise the need to evaluate any EBLP training programme using validated assessment tools to help identify the most crucial ingredients of effective EBLP training. In summary, we recommend on-the-job training of EBM with additional focus on overcoming barriers to its implementation. In addition, future studies evaluating the effectiveness of EBM training should use validated outcome tools, endeavour to achieve adequate power and consider the effects of EBM training on learning environment and patient outcomes.
- Monitoring in Clinical Biochemistry. [REVIEW]
- Clin Biochem Rev 2013 Aug; 34(2):85-92.
Monitoring tests form an increasing proportion of the workload in clinical biochemistry and biochemists can help by providing clinicians with information about the variability and precision of tests, the time frame for pharmacodynamic stabilisation after a treatment change, and the frequency of testing. This paper outlines the phases of monitoring, and how to decide if monitoring is beneficial, which test to use for monitoring, when a change in the test result indicates a need for the change in treatment and the length of testing intervals. We conclude with some recommendations for biochemists for future areas of research and advice that can be given to clinicians.
- HbA1c as a Diagnostic Test for Diabetes Mellitus - Reviewing the Evidence. [REVIEW]
- Clin Biochem Rev 2013 Aug; 34(2):75-83.
The evidence base in support of HbA1c as a diagnostic test for diabetes mellitus is focused on predicting a clinical outcome, considered to be the pinnacle of the Stockholm Hierarchy applied to reference intervals and clinical decision limits. In the case of diabetes, the major outcome of interest is the long term microvascular complications for which a large body of data has been accumulated, leading to the endorsement of HbA1c for diagnosis in many countries worldwide, with some variations in cut-offs and testing strategies.
- Economic Evidence and Point-of-Care Testing. [REVIEW]
- Clin Biochem Rev 2013 Aug; 34(2):61-74.
Health economics has been an established feature of the research, policymaking, practice and management in the delivery of healthcare. However its role is increasing as the cost of healthcare begins to drive changes in most healthcare systems. Thus the output from cost effectiveness studies is now being taken into account when making reimbursement decisions, e.g. in Australia and the United Kingdom. Against this background it is also recognised that the health economic tools employed in healthcare, and particularly the output from the use of these tools however, are not always employed in the routine delivery of services. One of the notable consequences of this situation is the poor record of innovation in healthcare with respect to the adoption of new technologies, and the realisation of their benefits. The evidence base for the effectiveness of diagnostic services is well known to be limited, and one consequence of this has been a very limited literature on cost effectiveness. One reason for this situation is undoubtedly the reimbursement strategies employed in laboratory medicine for many years, simplistically based on the complexity of the test procedure, and the delivery as a cost-per-test service. This has proved a disincentive to generate the required evidence, and little effort to generate an integrated investment and disinvestment business case, associated with care pathway changes. Point-of-care testing creates a particularly challenging scenario because, on the one hand, the unit cost-per-test is larger through the loss of the economy of scale offered by automation, whilst it offers the potential of substantial savings through enabling rapid delivery of results, and reduction of facility costs. This is important when many health systems are planning for complete system redesign. We review the literature on economic assessment of point-of-care testing in the context of these developments.
- From Evidence to Best Practice in Laboratory Medicine. [REVIEW]
- Clin Biochem Rev 2013 Aug; 34(2):47-60.
Laboratory tests offer value if they provide benefit to patients at acceptable costs. Laboratory testing is one of the most widely used diagnostic interventions supporting medical decisions, yet evidence demonstrating its value and impact on health outcomes is limited. This contributes to wide variations in test utilisation including underdiagnosis, overdiagnosis and misdiagnosis, which may impact the quality and the clinical- and cost-effectiveness of care and patient safety. Therefore implementing evidence into the care of patients is a moral and social imperative to laboratory professionals and all health care staff. This review investigates the reasons research does not get into practice, or only does with a very long delay. Apart from reviewing the common barriers to implementation, it also discusses the drivers of inappropriate test utilisation. By reviewing the theoretical and practical aspects of implementation science, recommendations are made for approaches that are thought to be most effective and that can be adopted to close the gap between evidence and practice, and to facilitate evidence-based laboratory medicine. Passive dissemination of the evidence and educational interventions are insufficient and do not offer sustainable solutions. A multifaceted and individualised implementation strategy, including individually tailored academic detailing, reminder systems, clinical decision support systems, feedback on performance, and participation of doctors and laboratory professionals in quality improvement activities addressing test selection and interpretation and in clinical audits, has greater potential for success. Examples of these initiatives at the laboratory and clinical interface are provided with links to valuable resources.
- Evidence-based laboratory medicine. [Journal Article]
- Clin Biochem Rev 2013 Aug; 34(2):43-6.