Measuring the effect of enhanced cleaning in a UK hospital : a prospective cross-over study

Increasing hospital-acquired infections have generated much attention over the last decade. There is evidence that hygienic cleaning has a role in the control of hospital-acquired infections. This study aimed to evaluate the potential impact of one additional cleaner by using microbiological standards based on aerobic colony counts and the presence of Staphylococcus aureus including meticillin-resistant S. aureus. We introduced an additional cleaner into two matched wards from Monday to Friday, with each ward receiving enhanced cleaning for six months in a cross-over design. Ten hand-touch sites on both wards were screened weekly using standardised methods and patients were monitored for meticillin-resistant S. aureus infection throughout the year-long study. Patient and environmental meticillin-resistant S. aureus isolates were characterised using molecular methods in order to investigate temporal and clonal relationships. Enhanced cleaning was associated with a 32.5% reduction in levels of microbial contamination at handtouch sites when wards received enhanced cleaning (P < 0.0001: 95% CI 20.2%, 42.9%). Near-patient sites (lockers, overbed tables and beds) were more frequently contaminated with meticillin-resistant S. aureus/S. aureus than sites further from the patient (P = 0.065). Genotyping identified indistinguishable strains from both handtouch sites and patients. There was a 26.6% reduction in new meticillin-resistant S. aureus infections on the wards receiving extra cleaning, despite higher meticillin-resistant S. aureus patient-days and bed occupancy rates during enhanced cleaning periods (P = 0.032: 95% CI 7.7%, 92.3%). Adjusting for meticillin-resistant S. aureus patient-days and based upon nine new meticillin-resistant S. aureus infections seen during routine cleaning, we expected 13 new infections during enhanced cleaning periods rather than the four that actually occurred. Clusters of new meticillin-resistant S. aureus infections were identified 2 to 4 weeks after the cleaner left both wards. Enhanced cleaning saved the hospital £30,000 to £70,000.Introducing one extra cleaner produced a measurable effect on the clinical environment, with apparent benefit to patients regarding meticillin-resistant S. aureus infection. Molecular epidemiological methods supported the possibility that patients acquired meticillin-resistant S. aureus from environmental sources. These findings suggest that additional research is warranted to further clarify the environmental, clinical and economic impact of enhanced hygienic cleaning as a component in the control of hospital-acquired infection

Dasatinib inhibits CXCR4 signaling in chronic lymphocytic leukaemia cells and impairs migration towards CXCL12

Chemokines and their ligands play a critical role in enabling chronic lymphocytic leukaemia (CLL) cells access to protective microenvironmental niches within tissues, ultimately resulting in chemoresistance and relapse: disruption of these signaling pathways has become a novel therapeutic approach in CLL. The tyrosine kinase inhibitor dasatinib inhibits migration of several cell lines from solid-organ tumours, but effects on CLL cells have not been reported. We studied the effect of clinically achievable concentrations of dasatinib on signaling induced by the chemokine CXCL12 through its' receptor CXCR4, which is highly expressed on CLL cells. Dasatinib pre-treatment inhibited Akt and ERK phosphorylation in CLL cells upon stimulation with CXCL12. Dasatinib also significantly diminished the rapid increase in actin polymerisation observed in CLL cells following CXCL12 stimulation. Moreover, the drug significantly inhibited chemotaxis in a transwell assay, and reduced the percentage of cells able to migrate beneath a CXCL12-expressing murine stromal cell line. Dasatinib also abrogated the anti-apoptotic effect of prolonged CXCL12 stimulation on cultured CLL cells. These data suggest that dasatinib, akin to other small molecule kinase inhibitors targeting the B-cell receptor signaling pathway, may redistribute CLL cells from protective tissue niches to the peripheral blood, and support the investigation of dasatinib in combination strategies

Implications of sperm banking for health-related quality of life up to 1 year after cancer diagnosis.

Sperm banking is recommended for all men diagnosed with cancer where treatment is associated with risk of long-term gonadatoxicity, to offer the opportunity of fatherhood and improved quality of life. However, uptake of sperm banking is lower than expected and little is known about why men refuse. Our aims were to determine: (i) demographic and medical variables associated with decisions about banking and (ii) differences in quality of life between bankers and non-bankers at diagnosis (Time 1 (T1)) and 1 year later (Time 2 (T2))

Exercise therapy for chronic low back pain:protocol for an individual participant data meta-analysis

<p>Abstract</p> <p>Background</p> <p>Low back pain (LBP) is one of the leading causes of disability and has a major socioeconomic impact. Despite a large amount of research in the field, there remains uncertainty about the best treatment approach for chronic LBP, and identification of relevant patient subgroups is an important goal. Exercise therapy is a commonly used strategy to treat chronic low back pain and is one of several interventions that evidence suggests is moderately effective.</p> <p>In parallel with an update of the 2005 Cochrane review, we will undertake an individual participant data (IPD) meta-analysis, which will allow us to standardize analyses across studies and directly derive results, and to examine differential treatment effects across individuals to estimate how patients’ characteristics modify treatment benefit.</p> <p>Methods/design</p> <p>We will use standard systematic review methods advocated by the Cochrane Collaboration to identify relevant trials. We will include trials evaluating exercise therapy compared to any or no other interventions in adult non-specific chronic LBP. Our primary outcomes of interest include pain, functional status, and return-to-work/absenteeism. We will assess potential risk of bias for each study meeting selection criteria, using criteria and methods recommended by the Cochrane BRG.</p> <p>The original individual participant data will be requested from the authors of selected trials having moderate to low risk of bias. We will test original data and compile a master dataset with information about each trial mapped on a pre-specified framework, including reported characteristics of the study sample, exercise therapy characteristics, individual patient characteristics at baseline and all follow-up periods, subgroup and treatment effect modifiers investigated. Our analyses will include descriptive, study-level meta-analysis and meta-regression analyses of the overall treatment effect, and individual-level IPD meta-analyses of treatment effect modification. IPD meta-analyses will be conducted using a one-step approach where the IPD from all studies are modeled simultaneously while accounting for the clustering of participants with studies.</p> <p>Discussion</p> <p>We will analyze IPD across a large number of LBP trials. The resulting larger sample size and consistent presentation of data will allow additional analyses to explore patient-level heterogeneity in treatment outcomes and prognosis of chronic LBP.</p

Prognostic implications of the Quebec Task Force classification of back-related leg pain: An analysis of longitudinal routine clinical data

Background: Low back pain (LBP) patients with related leg pain have a more severe profile than those with local LBP and a worse prognosis. Pain location above or below the knee and the presence of neurological signs differentiate patients with different profiles, but knowledge about the prognostic value of these subgroups is sparse. The objectives of this study were (1) to investigate whether subgroups consisting of patients with Local LBP only, LBP + leg pain above the knee, LBP + leg pain below the knee, and LBP + leg pain and neurological signs had different prognoses, and (2) to determine if this was explained by measured baseline factors. Methods. Routine clinical data were collected during the first visit to an outpatient department and follow-ups were performed after 3 and 12 months. Patients were divided into the four subgroups and associations between subgroups and the outcomes of activity limitation, global perceived effect (GPE) after 3 months, and sick leave after 3 months were tested by means of generalised estimating equations. Models were univariate (I), adjusted for duration (II), and adjusted for all baseline differences (III). Results: A total of 1,752 patients were included, with a 76% 3-month and 70% 12-month follow-up. Subgroups were associated with activity limitation in all models (p &lt; 0.001). Local LBP had the least and LBP + neurological signs the most severe limitations at all time-points, although patients with neurological signs improved the most. Associations with GPE after 3 months were only significant in Model I. Subgroups were associated with sick leave after 3 months in model I and II, with sick leave being most frequent in the subgroup with neurological signs. No significant differences were found in any pairwise comparisons of patients with leg pain above or below the knee. Conclusions: Subgrouping LBP patients, based on pain location and neurological signs, was associated with activity limitation and sick leave, but not with GPE. The presence of neurological signs and pain in the leg both have prognostic implications but whether that leg pain without neurological signs is above or below the knee does not

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

Effect of a Simple Information Booklet on Pain Persistence after an Acute Episode of Low Back Pain: A Non-Randomized Trial in a Primary Care Setting

Mass-media campaigns have been known to modify the outcome of low back pain (LBP). We assessed the impact on outcome of standardized written information on LBP given to patients with acute LBP.A 3-month pragmatic, multicenter controlled trial with geographic stratification.Primary care practice in France.2752 patients with acute LBP.An advice book on LBP (the "back book").The main outcome measure was persistence of LBP three months after baseline evaluation.2337 (85%) patients were assessed at follow-up and 12.4% of participants reported persistent LBP. The absolute risk reduction of reporting persistent back pain in the intervention group was 3.6% lower than in the control group (10.5% vs. 14.1%; 95% confidence interval [-6.3% ; -1.0%]; p value adjusted for cluster effect = 0.01). Patients in the intervention group were more satisfied than those in the control group with the information they received about physical activities, when to consult their physician, and how to prevent a new episode of LBP. However, the number of patients who had taken sick leave was similar, as was the mean sick-leave duration, in both arms, and, among patients with persistent pain at follow-up, the intervention and control groups did not differ in disability or fear-avoidance beliefs.The level of improvement of an information booklet is modest, but the cost and complexity of the intervention is minimal. Therefore, the implications and generalizability of this intervention are substantial.ClinicalTrials.gov NCT00343057

Huntington's disease

Huntington’s disease is devastating to patients and their families — with autosomal dominant inheritance, onset typically in the prime of adult life, progressive course and combination of motor, cognitive and behavioural features. The disease is caused by an expanded CAG trinucleotide repeat (of variable length) in HTT, the gene which encodes the protein huntingtin. In mutation carriers, huntingtin is produced with abnormally long polyglutamine sequences that confers toxic gains of function and predispose the protein to fragmentation, resulting in neuronal dysfunction and death. In this Primer, we review the epidemiology of Huntington’s disease, noting that prevalence is higher than previously thought, geographically variable and increasing. We describe the relationship between CAG repeat length and clinical phenotype and the concept of genetic modifiers of the disease. We discuss normal huntingtin protein function, evidence for differential toxicity of mutant huntingtin variants, theories of huntingtin aggregation and the many different mechanisms of Huntington’s disease pathogenesis. We describe the genetic and clinical diagnosis of the condition, its clinical assessment and the multidisciplinary management of symptoms, given the absence of effective disease-modifying therapies. We review past and present clinical trials and therapeutic strategies under investigation, including impending trials of targeted huntingtin-lowering drugs and the progress in development of biomarkers that will support the next generation of trials

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