Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; 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/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Spatial point analysis based on dengue surveys at household level in central Brazil

<p>Abstract</p> <p>Background</p> <p>Dengue virus (DENV) affects nonimunne human populations in tropical and subtropical regions. In the Americas, dengue has drastically increased in the last two decades and Brazil is considered one of the most affected countries. The high frequency of asymptomatic infection makes difficult to estimate prevalence of infection using registered cases and to locate high risk intra-urban area at population level. The goal of this spatial point analysis was to identify potential high-risk intra-urban areas of dengue, using data collected at household level from surveys.</p> <p>Methods</p> <p>Two household surveys took place in the city of Goiania (~1.1 million population), Central Brazil in the year 2001 and 2002. First survey screened 1,586 asymptomatic individuals older than 5 years of age. Second survey 2,906 asymptomatic volunteers, same age-groups, were selected by multistage sampling (census tracts; blocks; households) using available digital maps. Sera from participants were tested by dengue virus-specific IgM/IgG by EIA. A Generalized Additive Model (GAM) was used to detect the spatial varying risk over the region. Initially without any fixed covariates, to depict the overall risk map, followed by a model including the main covariates and the year, where the resulting maps show the risk associated with living place, controlled for the individual risk factors. This method has the advantage to generate smoothed risk factors maps, adjusted by socio-demographic covariates.</p> <p>Results</p> <p>The prevalence of antibody against dengue infection was 37.3% (95%CI [35.5–39.1]) in the year 2002; 7.8% increase in one-year interval. The spatial variation in risk of dengue infection significantly changed when comparing 2001 with 2002, (ORadjusted = 1.35; p < 0.001), while controlling for potential confounders using GAM model. Also increasing age and low education levels were associated with dengue infection.</p> <p>Conclusion</p> <p>This study showed spatial heterogeneity in the risk areas of dengue when using a spatial multivariate approach in a short time interval. Data from household surveys pointed out that low prevalence areas in 2001 surveys shifted to high-risk area in consecutive year. This mapping of dengue risks should give insights for control interventions in urban areas.</p

Executive function does not predict coping with symptoms in stable patients with a diagnosis of schizophrenia

<p>Abstract</p> <p>Background</p> <p>Associations between coping with and control over psychotic symptoms were examined using the Maastricht Assessment of Coping Strategies-24, testing the hypothesis that the cognitive domain of executive functioning predicted quality and quantity of coping.</p> <p>Methods</p> <p>MACS-24 was administered to 32 individuals with a diagnosis of schizophrenia. For each of 24 symptoms, experience of distress, type of coping and the resulting degree of perceived control were assessed. Coping types were reduced to two contrasting coping categories: symptomatic coping (SC) and non-symptomatic coping (NSC; combining active problem solving, passive illness behaviour, active problem avoiding, and passive problem avoiding). Cognitive functioning was assessed using the GIT (Groninger Intelligence Test), the Zoo map (BADS: Behavioural Assessment of Dysexecutive function), Stroop-test and Trail making.</p> <p>Results</p> <p>Cognitive function was not associated with frequency of coping, nor did cognitive function differentially predict SC or NSC. Cognitive function similarly was not associated with symptom distress or level of perceived control over the symptom.</p> <p>Conclusion</p> <p>There was no evidence that cognitive function predicts quantity or quality of coping with symptoms in people with a diagnosis of schizophrenia. Variation in the realm of emotion regulation and social cognition may be more predictive of coping with psychotic symptoms.</p

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Update on hypertrophic cardiomyopathy and a guide to the guidelines

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting 1 in 500 individuals worldwide. Existing epidemiological studies might have underestimated the prevalence of HCM, however, owing to limited inclusion of individuals with early, incomplete phenotypic expression. Clinical manifestations of HCM include diastolic dysfunction, left ventricular outflow tract obstruction, ischaemia, atrial fibrillation, abnormal vascular responses and, in 5% of patients, progression to a 'burnt-out' phase characterized by systolic impairment. Disease-related mortality is most often attributable to sudden cardiac death, heart failure, and embolic stroke. The majority of individuals with HCM, however, have normal or near-normal life expectancy, owing in part to contemporary management strategies including family screening, risk stratification, thromboembolic prophylaxis, and implantation of cardioverter-defibrillators. The clinical guidelines for HCM issued by the ACC Foundation/AHA and the ESC facilitate evaluation and management of the disease. In this Review, we aim to assist clinicians in navigating the guidelines by highlighting important updates, current gaps in knowledge, differences in the recommendations, and challenges in implementing them, including aids and pitfalls in clinical and pathological evaluation. We also discuss the advances in genetics, imaging, and molecular research that will underpin future developments in diagnosis and therapy for HCM

A user's guide to the Encyclopedia of DNA elements (ENCODE)

The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment