Cystatin C--a paradigm of evidence based laboratory medicine

Cystatin C is a 13-kDa protein, of the cysteine proteinase inhibitor superfamily, produced by all nucleated cells. Its production rate is constant throughout the ages of 1 to 50 years. It is freely filtered at the glomerulus and then resorbed and fully catabolised by proximal renal tubules, making it an ideal marker of glomerular filtration rate (GFR). Serum creatinine, the most established marker of renal function, is affected by age, gender, muscle mass, nutritional status and analytical interference. The abbreviated Modifiation of Diet in Renal Diseases (MDRD) equation has recently been introduced in an attempt to overcome these shortcomings, but still has many limitations. Cystatin C is not affected by gender, muscle mass, malignancy, its production rate is usually constant and its plasma concentration therefore is dependent only on GFR. Cystatin C has been demonstrated to be more accurate than serum creatinine in the detection of early renal impairment and in specific populations may allow for early detection of renal disease. Cystatin C has also been found to be a strong predictor of long-term clinical outcomes in patients with cardiovascular diseases. Although cystatin C may have advantages in detection of early renal impairment there is a paucity of evidence that it significantly improves clinical decision making over creatinine. This coupled with assay cost may be the reason why cystatin C, although well recognised, has not been introduced into routine operational use, although that may eventuate with emerging evidence.     

General practitioner's perceptions of the route to evidence based medicine: a questionnaire survey.

OBJECTIVES: To determine the attitude of general practitioners towards evidence based medicine and their related educational needs. DESIGN: A questionnaire study of general practitioners. SETTING: General practice in the former Wessex region, England. SUBJECTS: Randomly selected sample of 25% of all general practitioners (452), of whom 302 replied. MAIN OUTCOME MEASURES: Respondents'' attitude towards evidence based medicine, ability to access and interpret evidence, perceived barriers to practising evidence based medicine, and best method of moving from opinion based to evidence based medicine. RESULTS: Respondents mainly welcomed evidence based medicine and agreed that its practice improves patient care. They had a low level of awareness of extracting journals, review publications, and databases (only 40% knew of the Cochrane Database of Systematic Reviews), and, even if aware, many did not use them. In their surgeries 20% had access to bibliographic databases and 17% to the world wide web. Most had some understanding of the technical terms used. The major perceived barrier to practising evidence based medicine was lack of personal time. Respondents thought the most appropriate way to move towards evidence based general practice was by using evidence based guidelines or proposals developed by colleagues. CONCLUSION: Promoting and improving access to summaries of evidence, rather than teaching all general practitioners literature searching and critical appraisal, would be the more appropriate method of encouraging evidence based general practice. General practitioners who are skilled in accessing and interpreting evidence should be encouraged to develop local evidence based guidelines and advice.     

Personalized medicine using DNA biomarkers: a review

Biomarkers are of increasing importance for personalized medicine, with applications including diagnosis, prognosis, and selection of targeted therapies. Their use is extremely diverse, ranging from pharmacodynamics to treatment monitoring. Following a concise review of terminology, we provide examples and current applications of three broad categories of biomarkers-DNA biomarkers, DNA tumor biomarkers, and other general biomarkers. We outline clinical trial phases for identifying and validating diagnostic and prognostic biomarkers. Predictive biomarkers, more generally termed companion diagnostic tests predict treatment response in terms of efficacy and/or safety. We consider suitability of clinical trial designs for predictive biomarkers, including a detailed discussion of validation study designs, with emphasis on interpretation of study results. We specifically discuss the interpretability of treatment effects if a large set of DNA biomarker profiles is available and the number of therapies is identical to the number of different profiles.     

Wellness programs: a review of the evidence

OBJECTIVE: To review studies that have examined an association between wellness programs and improvements in quality of life and to assess the strength of the scientific evidence. DATA SOURCES: A MEDLINE search was constructed with the following medical subject headings: "psychoneuroimmunology," "chronic disease" and "health promotion," "chronic disease" and "health behaviour," "relaxation techniques," "music therapy," "laughter," "anger," "mediation" and "behavioural medicine." Searches using the text words "wellness" and "wellness program" were also carried out. References from the primary articles identified in the search and contemporary writing on wellness were also considered. STUDY SELECTION: Selection was limited to randomized controlled trials or prospective studies published in English that involved human subjects and that took place between 1980 and 1996. All studies with an intervention aimed at promoting wellness and measuring outcomes were included, except studies of patients with cancer and HIV and studies of health promotion programs in the workplace. Of the 1082 references initially identified, 11 met the criteria for inclusion in the critical appraisal. DATA EXTRACTION: The following information was extracted from the 11 studies: characteristics of the study population, number of participants (and number followed to completion), length of follow-up, type of intervention, outcome measures and results. All 11 studies were assessed for the quality of their evidence. DATA SYNTHESIS: All studies reported some positive outcomes following the intervention in question, although many had limitations precluding applicability of the results to a wider population. CONCLUSIONS: Despite the suggested benefit associated with wellness programs, the evidence was inconclusive. Whether the composition of the target group or the type of intervention has a role in determining outcomes is unknown. Although trends suggest that wellness programs may be cost-effective, further research is needed for confirmation.     

Natural substances and Alzheimer's disease: from preclinical studies to evidence based medicine

Over the last 10 years, the potential therapeutic effects of nutraceuticals to prevent or delay Alzheimer's disease were proposed. Among dietary antioxidants curcumin, Ginkgo biloba and carnitines were extensively studied for their neuroprotective effects. The rationale for this alternative therapeutic approach was based on several preclinical studies which suggested the neuroprotective effects for curcumin, Ginkgo biloba and acetyl-l-carnitine due to either a free radical scavenging activity or the inhibition of pro-inflammatory pathways or the potentiation of the cell stress response. However, although these are interesting premises, clinical studies were not able to demonstrate significant beneficial effects of curcumin, Ginkgo biloba and acetyl-l-carnitine in improving cognitive functions in Alzheimer's disease patients. The aim of this review is to summarize the main pharmacologic features of curcumin, Ginkgo biloba and carnitines as well as to underlie the main outcomes reached by clinical studies designed to demonstrate the efficacy of these natural substances in Alzheimer's disease patients. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.     

Keratin based thermoplastic biocomposites: a review

Reviews in Environmental Science and Bio/Technology - Fibre reinforced composites have become important materials for manufacturing a diverse range of industrial products. Keratin-rich materials...     

Infant mortality in Bangladesh: a review of recent evidence

Estimates of child mortality are mainly based on reports by mothers on the survival status of their children. Infant mortality estimates from such data do not seem to have declined in recent years. The Bangladesh Bureau of Statistics sample registration infant mortality estimates appear to be suspiciously low.     

Direct experimental evidence for alternative stable states: a review

A large number of studies have presented empirical arguments for the existence of alternative stable states (ASS) in a wide range of ecological systems. However, most of these studies have used non-manipulative, indirect methods, which findings remain open for alternative explanations. Here, we review the direct evidence for ASS resulting from manipulation experiments. We distinguish four conclusive experimental approaches which test for predictions made by the hysteresis effect: (1) discontinuity in the response to an environmental driving parameter, (2) lack of recovery potential after a perturbation, (3) divergence due to different initial conditions and (4) random divergence. Based on an extensive literature search we found 35 corresponding experiments. We assessed the ecological stability of the reported contrasting states using the minimum turnover of individuals in terms of life span and classified the studies according to 4 categories: (1) experimental system, (2) habitat type, (3) involved organisms and (4) theoretical framework. 13 experiments have directly demonstrated the existence of alternative stable states while 8 showed the absence of ASS in other cases. 14 experiments did not fulfil the requirements of a conclusive test, mostly because they applied a too short time scale. We found a bias towards laboratory experiments compared to field experiments in demonstrating bistability. There was no clear pattern of the distribution of ASS over categories. The absence of ASS in 38% of the tested systems indicates that ASS are just one possibility of how ecological systems can behave. The relevance of the concept of ASS for natural systems is discussed, in particular under consideration of the observed laboratory bias, perturbation frequency and variable environments. It is argued, that even for a permanently transient system, alternative attractors may still be of relevance.