BioMed Central Page 1 of 11 (page number not for citation purposes) Health and Quality of Life Outcomes Open Access Research Testing a model of association between patient identified problems and responses to global measures of health in low back pain patients: a prospective study Ricky Mullis*, Martyn Lewis and Elaine M Hay Address: Arthritis Research Campaign National Primary Care Centre, Keele University, Keele, UK Email: Ricky Mullis* - r.mullis@cphc.keele.ac.uk; Martyn Lewis - a.m.lewis@cphc.keele.ac.uk; Elaine M Hay - e.m.hay@cphc.keele.ac.uk * Corresponding author Abstract Background: Self-rated health status has been shown to be related to physical function. Therefore, changes in functional ability should be associated with changes in general health. However, functional needs may vary greatly between individuals. The purpose of this study was to propose and test a model of association between patient identified functional problems and responses to global measures of health in low back pain patients. Methods: Participants in a low back pain clinical trial were followed up for 12 months. A series of analyses were undertaken using the Jonckheere-Terpstra test and chi-square for trends to determine the associations between two individualised items related to function, and measures of "overall improvement in condition", "general health status" and performance of "usual activities". Results: Significant associations between responses to the five items were found. Performance of usual activities is significantly associated with ratings of general health status (p < 0.001) and overall condition of the back (p < 0.001). The extent to which the patient identified problems influence an individual's perception on multi-task performance is dependent upon the degree of difficulty and level of importance attached to these problems. Conclusion: The relationship between patient identified problems and responses to global measures of health is complex. The explanatory model proposed here may improve our understanding of these interactions. Trial Registration: ISRCTN 32765488 Background Theory underpinning possible associations between responses Measuring the success of an intervention to change a patient's health is central to both research and clinical practice. Self-rated health status has been shown to be related to a number of distinct constructs including phys- ical function, medication use and mental well-being [1-3]. Wilson and Cleary [4] described a five level classification scheme for different measures of health outcome, ranging from biological and physical factors, symptoms, function- ing, general health perceptions, through to overall quality of life (QoL). Further, they proposed a causal link between the levels, with each becoming "increasingly Published: 5 August 2009 Health and Quality of Life Outcomes 2009, 7:74 doi:10.1186/1477-7525-7-74 Received: 19 February 2009 Accepted: 5 August 2009 This article is available from: http://www.hqlo.com/content/7/1/74 © 2009 Distinguish between problems and predicaments Distinguish between problems and predicaments Bởi: Joe Tye “Dreaming is one thing, staying on the path is another Sustaining the vision is the most difficult part Along the way we can be so easily distracted by other, easier paths, or disheartened by the relentless effort required to forge ahead Only those capable of climbing through adversity see the vision realized.” Paul Stoltz: Adversity Quotient: Turning Obstacles Into Opportunities Dissatisfaction can be a powerful source of personal motivation if, and only if, it is effectively channeled To complain about anything and everything, though, is to fritter away that motivational power Pay attention to the things you complain about (even if you’re just complaining silently, not saying the words aloud) Are you complaining about problems or predicaments? Here’s the difference: a problem has a solution, a predicament does not (a problem is an alcoholic neighbor, a predicament is an alcoholic mother-in-law; you can deal with a problem but you have to live with a predicament) When you are clear about whether whatever it is that’s bothering you is a problem or a predicament, then you can cease wasting your emotional energy on either If it’s a problem, start working on a solution If it’s a predicament, grin and bear it And remember the famous Serenity Prayer by Reinhold Niehbur: “Grant me serenity to accept the things I cannot change (predicaments), courage to change the things I can (problems), and wisdom to know the difference (and the strength to not whine and complain about either!).” 1/1 BioMed Central Page 1 of 11 (page number not for citation purposes) Health and Quality of Life Outcomes Open Access Research Testing a model of association between patient identified problems and responses to global measures of health in low back pain patients: a prospective study Ricky Mullis*, Martyn Lewis and Elaine M Hay Address: Arthritis Research Campaign National Primary Care Centre, Keele University, Keele, UK Email: Ricky Mullis* - r.mullis@cphc.keele.ac.uk; Martyn Lewis - a.m.lewis@cphc.keele.ac.uk; Elaine M Hay - e.m.hay@cphc.keele.ac.uk * Corresponding author Abstract Background: Self-rated health status has been shown to be related to physical function. Therefore, changes in functional ability should be associated with changes in general health. However, functional needs may vary greatly between individuals. The purpose of this study was to propose and test a model of association between patient identified functional problems and responses to global measures of health in low back pain patients. Methods: Participants in a low back pain clinical trial were followed up for 12 months. A series of analyses were undertaken using the Jonckheere-Terpstra test and chi-square for trends to determine the associations between two individualised items related to function, and measures of "overall improvement in condition", "general health status" and performance of "usual activities". Results: Significant associations between responses to the five items were found. Performance of usual activities is significantly associated with ratings of general health status (p < 0.001) and overall condition of the back (p < 0.001). The extent to which the patient identified problems influence an individual's perception on multi-task performance is dependent upon the degree of difficulty and level of importance attached to these problems. Conclusion: The relationship between patient identified problems and responses to global measures of health is complex. The explanatory model proposed here may improve our understanding of these interactions. Trial Registration: ISRCTN 32765488 Background Theory underpinning possible associations between responses Measuring the success of an intervention to change a patient's health is central to both research and clinical practice. Self-rated health status has been shown to be related to a number of distinct constructs including phys- ical function, medication use and mental well-being [1-3]. Wilson and Cleary [4] described a five level classification scheme for different measures of health outcome, ranging from biological and physical factors, symptoms, function- ing, general health perceptions, through to overall quality of life (QoL). Further, they proposed a causal link between the levels, with each becoming "increasingly Published: 5 August 2009 Health and Quality of Life Outcomes 2009, 7:74 doi:10.1186/1477-7525-7-74 Received: 19 February 2009 Accepted: 5 August 2009 This article is available from: http://www.hqlo.com/content/7/1/74 © 2009 BioMed Central Page 1 of 10 (page number not for citation purposes) Journal of Inflammation Open Access Research The glucocorticoid RU24858 does not distinguish between transrepression and transactivation in primary human eosinophils Mirkka Janka-Junttila 1 , Eeva Moilanen 1 , Hannele Hasala 1 , Xianzhi Zhang 1,3 , Ian Adcock 2 and Hannu Kankaanranta* 1,4 Address: 1 The Immunopharmacology Research Group, Medical School, FIN-33014 University of Tampere and Research Unit, Tampere University Hospital, Tampere, Finland, 2 Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK, 3 The Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China and 4 Department of Pulmonary Medicine Tampere University Hospital, Tampere, Finland Email: Mirkka Janka-Junttila - mirkka.janka@uta.fi; Eeva Moilanen - eeva.moilanen@uta.fi; Hannele Hasala - hannele.hasala@uta.fi; Xianzhi Zhang - Xianzhi.Zhang@uta.fi; Ian Adcock - ian.adcock@imperial.ac.uk; Hannu Kankaanranta* - hannu.kankaanranta@uta.fi * Corresponding author Abstract Background: Glucocorticoids are used to treat chronic inflammatory diseases such as asthma. Induction of eosinophil apoptosis is considered to be one of the main mechanisms behind the anti-asthmatic effect of glucocorticoids. Glucocorticoid binding to its receptor (GR) can have a dual effect on gene transcription. Activated GR can activate transcription (transactivation), or by interacting with other transcription factors such as NF-κB suppress transcription (transrepression). RU24858 has been reported to transrepress but to have little or no transactivation capability in other cell types. The dissociated properties of RU24858 have not been previously studied in non-malignant human cells. As the eosinophils have a very short lifetime and many of the modern molecular biological methods cannot be used, a "dissociated steroid" would be a valuable tool to evaluate the mechanism of action of glucocorticoids in human eosinophils. The aim of this study was to elucidate the ability of RU24858 to activate and repress gene expression in human eosinophils in order to see whether it is a dissociated steroid in human eosinophils. Methods: Human peripheral blood eosinophils were isolated under sterile conditions and cultured in the presence and/or absence RU24858. For comparison, dexamethasone and mometasone were used. We measured chemokine receptor-4 (CXCR4) and Annexin 1 expression by flow cytometry and cytokine production by ELISA. Apoptosis was measured by DNA fragmentation and confirmed by morphological analysis. Results: RU24858 (1 μM) increased CXCR4 and Annexin 1 expression on eosinophils to a similar extent as mometasone (1 μM) and dexamethasone (1 μM). Like dexamethasone and mometasone, RU24858 did suppress IL-8 and MCP-1 production in eosinophils. RU24858 also increased spontaneous eosinophil apoptosis to a similar degree as dexamethasone and mometasone, but unlike dexamethasone and mometasone it did not reverse IL-5- or GM-CSF-induced eosinophil survival. Conclusion: Our results suggest that in human eosinophils RU24858 acts as transactivator and transrepressor like classical glucocorticoids. Thus, RU24858 seems not to be a "dissociated steroid" in primary human eosinophils in contrast to that reported in animal cells. In addition, functionally RU24858 seems to be a less potent glucocorticoid as it did not reverse IL-5- and GM-CSF-afforded eosinophil survival similarly to dexamethasone and mometasone. Published: 12 July 2006 Journal of Inflammation 2006, 3:10 doi:10.1186/1476-9255-3-10 Received: 04 January 2006 Accepted: 12 July 2006 This article is available from: http://www.journal-inflammation.com/content/3/1/10 © 2006 Janka-Junttila et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2 Prostate cancer Prostate cancer constitutes a major health burden, being the most common non-cutaneous malignancy among men in developed countries. In 2007, almost 800,000 new cases of prostate cancer and 250,000 deaths from this disease were estimated to have occurred worldwide [1]. e highest incidence of prostate cancer is observed in the USA, with 192,280 new cases and 27,360 deaths expected in 2009, thereby being the second most common cause of cancer-related death [2]. Prostate cancer is a heterogeneous disease and its natural history is not completely understood. Early autopsy studies have shown a high prevalence of clinically undetected prostate cancer at time of death. In the USA, more than one in three men over 50 years of age had histologic evidence of prostate cancer at autopsy and this prevalence was observed to increase with age, with more than 67% of men aged over 80 years having prostate cancer at time of death [3]. ese findings indicate that a high proportion of prostate tumors are clinically insignificant and will never lead to a lethal outcome. Furthermore, the introduction and widespread application of prostate-specific antigen (PSA) testing has led to increased detection of early-stage, low- volume, non-palpable tumors. is has in turn raised concerns of increased overdiagnosis and unnecessary treatment of indolent disease [4,5]. To this end, new strategies to help clinicians distinguish between lethal and indolent prostate cancer are urgently needed. Prostate cancer is one of the most heritable cancers in men and recent studies have revealed numerous genetic variants associated with this disease. is review will give an overview of the current knowledge of prostate cancer genetics, with a special focus on the ability of genetic variants to predict more aggressive forms. Prostate cancer susceptibility variants A family history of prostate cancer is one of the strongest risk factors, and twin studies suggest that as much as 42% of the disease risk is explained by heritable factors [6]. Attempts to decipher the heritable component of prostate cancer based on candidate gene association studies and genome-wide linkage studies in multiple case families have suggested numerous prostate cancer sus- cep tibility genes and loci. However, an inability to repli- cate reported linkage and association findings suggest that prostate cancer is genetically complex with multiple common low-penetrance genes involved in prostate cancer predisposition [7]. Recently, genome-wide asso- cia tion studies (GWAS) have emerged as a powerful method to identify genomic low-risk susceptibility regions for complex diseases, including cancer [8]. rough genotyping platforms that explore hundreds of thousands of single nucleotide polymorphisms (SNPs) simultaneously, it is possible to screen the complete genome for common genetic variation associated with the disease of interest. In 2006 the first prostate cancer susceptibility region was identified at chromosome 8q24. Abstract Prostate cancer is one of the most heritable cancers in men, and recent genome-wide association studies have revealed numerous genetic variants associated with disease. The risk variants identied using case- control designs that compared unaected individuals with all types of patients with prostate cancer show little or no ability to discriminate between indolent and fatal forms of this disease. This suggests dierent genetic components are involved in the initiation as compared with the prognosis of prostate cancer. Future studies contrasting patients with more and less aggressive disease, and exploring association with disease progression and prognosis, should be more eective in detecting genetic risk factors for prostate cancer outcome. © 2010 BioMed Central Ltd Prostate cancer genomics: can we distinguish between indolent and fatal disease using genetic markers? Fredrik Wiklund* R E VI E W Brink P, Wright JC, Schumacher J: An investigation of the ability of the glu- taraldehyde test to distinguish between acute and chronic inflammatory disease in horses. Acta vet. scand. 2005, 46, 69-78. – The glutaraldehyde test (GT), a rapid and inexpensive test, has been utilized empirically for many years in bovine practice for di- agnosing inflammatory diseases. GT is used primarily to demonstrate increased serum concentrations of fibrinogen and globulin. Glutaraldehyde binds with free amino groups in fibrinogen and immunoglobulin to create a clot in a first degree chemical reaction. The clotting time of the GT estimates the content of proteins produced in response to in- flammation. The applicability of GT for diagnosing inflammation in the horse has never been investigated. The objective of this study was to determine the ability of GT to dis- tinguish between acute and chronic inflammatory disease in horses. Thirty-seven horses with suspected inflammatory diseases were evaluated using the GT, history, complete clinical examination and routine blood analysis. GT-times, laboratory results and clini- cal outcome were compared statistically. Horses that were determined to be acutely af- fected (based on history, clinical examination and routine blood analysis) tended to have a negative GT (75%). Results of the GT did not correlate with blood fibrinogen con- centration. Positive GT also predicted a fatal outcome in 69% of the clinical cases. The results of this trial indicate that GT can be a useful screening test to distinguish between acute and chronic inflammatory disease in horses. Glutaraldehyde test, inflammation, horse diseases, equine, diagnostic techniques, prognosis, immunoglobulin, globulin, blood clot, infectious diseases, hypergamma- globulinemia, serum biochemistries. Acta vet. scand. 2005, 46, 69-78. Acta vet. scand. vol. 46 no. 1-2, 2005 An Investigation of the Ability of the Glutaraldehyde Test to Distinguish between Acute and Chronic Inflammatory Disease in Horses By P. Brink 1 , J.C. Wright 2 , and J. Schumacher 3 1 ATG Equine Clinic, Jägersro, 21237 Malmö, Sweden, 2 Department of Pathobiology and 3 Department of Clin- ical Sciences, Auburn University, Auburn, AL 36849-5522, USA. Introduction The glutaraldehyde reagent in the glutaralde- hyde test (GT) creates a clot with either fibrino- gen or gammaglobulin in EDTA-stabilized blood by chemical reaction between the alde- hyde groups in glutaraldehyde and free amino groups in fibrinogen and immunoglobulins (Sandholm 1974a, Sandholm 1974b, Martin et al. 1985). The process is believed to run as a first degree chemical reaction, where the reac- tion time is directly proportional to the concen- tration of fibrinogen and immunoglobulins (Sandholm 1974a, Sandholm 1974b, Eriksen 1984). The rapid and inexpensive GT has been used with success empirically in Europe for many years for diagnosing inflammatory diseases in cattle (Sandholm 1974a, Sandholm 1974b, Liberg et al. 1975a, Liberg et al. 1975b, Nielsen 1975, Martens 1977, Liberg 1978, Tennant et al. 1979, Liberg 1981, Liberg 1982, Eriksen 1984, Keulen et al. 1984, Doll et al. 1985, Lars- son 1985, Mahlin et al. 1985, Chadli & Mahin 1986, Kovac 1988, Katholm & Jorgensen 1992, Kantor et al. 1993, Tyler et al. 1996, Sen et al. 2000, Ramprabhu et al. 2002), pigs (Liberg 1979, Hansen 1985, Kovac et al. 1993), goats (Satpathy et al. 1996, Vihan 1989), mink (Sand- holm & Kangas 1973), dogs (Sandholm & Kivisto 1975, Wolff 1986), and zoo animals (O'-Rourke & Satterfield 1981, Carstairs-Grant et al. 1988, Juyal & Uppal 1995). In these species, the test was used to indicate whether an inflammatory disease was acute or chronic (Doll et al. 1985, Chadli & Mahin 1986). The GT, because of its simplicity, is very useful in bovine practice for rapidly diagnosing in- flammation under circumstances where it is not practical or economically possible to have blood analyzed at a professional clinical labora- tory