Research methods for subgrouping low back pain

<p>Abstract</p> <p>Background</p> <p>There is considerable clinician and researcher interest in whether the outcomes for patients with low back pain, and the efficiency of the health systems that treat them, can be improved by 'subgrouping research'. Subgrouping research seeks to identify subgroups of people who have clinically important distinctions in their treatment needs or prognoses. Due to a proliferation of research methods and variability in how subgrouping results are interpreted, it is timely to open discussion regarding a conceptual framework for the research designs and statistical methods available for subgrouping studies (a method framework). The aims of this debate article are: (1) to present a method framework to inform the design and evaluation of subgrouping research in low back pain, (2) to describe method options when investigating prognostic effects or subgroup treatment effects, and (3) to discuss the strengths and limitations of research methods suitable for the hypothesis-setting phase of subgroup studies.</p> <p>Discussion</p> <p>The proposed method framework proposes six phases for studies of subgroups: studies of assessment methods, hypothesis-setting studies, hypothesis-testing studies, narrow validation studies, broad validation studies, and impact analysis studies. This framework extends and relabels a classification system previously proposed by McGinn et al (2000) as suitable for studies of clinical prediction rules. This extended classification, and its descriptive terms, explicitly anchor research findings to the type of evidence each provides. The inclusive nature of the framework invites appropriate consideration of the results of diverse research designs. Method pathways are described for studies designed to test and quantify prognostic effects or subgroup treatment effects, and examples are discussed. The proposed method framework is presented as a roadmap for conversation amongst researchers and clinicians who plan, stage and perform subgrouping research.</p> <p>Summary</p> <p>This article proposes a research method framework for studies of subgroups in low back pain. Research designs and statistical methods appropriate for sequential phases in this research are discussed, with an emphasis on those suitable for hypothesis-setting studies of subgroups of people seeking care.</p

Isolation of human monoclonal autoantibodies derived from pancreatic lymph node and peripheral blood B cells of islet autoantibody-positive patients

Aims/hypothesis Autoantibodies against pancreatic islets and infections by enteroviruses are associated with type 1 diabetes, but the specificity of immune responses within the type 1 diabetic pancreas is poorly characterised. We investigated whether pancreatic lymph nodes could provide a source of antigen-specific B cells for analysis of immune responses within the (pre)diabetic pancreas. Methods Human IgG antibodies were cloned from single B lymphocytes sorted from pancreatic lymph node cells of three organ donors positive for islet autoantibodies, and from the peripheral blood of a patient with type 1 diabetes. Antibodies to insulinoma-associated antigen 2 (IA-2), GAD65, zinc trans- porter 8 (ZnT8) and Coxsackie B virus proteins were assayed by immunoprecipitation and by immunofluorescence on pan- creatic sections. Results Human IgG antibodies (863) were successfully cloned and produced from 4,092 single B cells from lymph nodes and peripheral blood. Reactivity to the protein tyrosine phosphatase domain of the IA-2 autoantigen was detected in two cloned antibodies: one derived from a pancreatic lymph node and one from peripheral blood. Epitopes for these two antibodies were similar to each other and to those for circulat- ing antibodies in type 1 diabetes. The remaining 861 antibod- ies were negative for reactivity to IA-2, GAD65 or ZnT8 by both assays tested. Reactivity to a Coxsackie viral protein 2 was detected in one antibody derived from a peripheral blood B cell, but not from lymph nodes. Conclusions/interpretation We show evidence for the infre- quent presence of autoantigen-specific IgG+ B lymphocytes in the pancreatic-draining lymph nodes of islet autoantibody- positive individuals

Livelihood responses to Lantana camara invasion and biodiversity change in southern India: application of an asset function framework

Natural resources play key roles as assets in the livelihoods of rural communities. However, the benefits of these assets in livelihoods are frequently conceived narrowly as income generating or vulnerability reducing. We contend that they have other important roles to play in poverty reduction and livelihood change. In this paper we use a case study of two ethnic communities in a village in southern India to investigate livelihood responses to change in forest biodiversity through an examination of changes in attributes of natural assets resulting from the invasion of Lantana camara and wider socio-economic change. The invasion of forest by Lantana has contributed to changes in the attributes and functions of four key natural assets: forest grazing, bamboo for basketry, Phoenix loureie for brooms, and wild yams. We observe that differences in households’ and individuals’ ability to substitute important functions of lost or declining assets affect their ability to adapt to changes in resource availability and attributes. Analysing changes in asset attributes for different user groups allows the social effects of environmental change to be disaggregated

Estimated Comparative Integration Hotspots Identify Different Behaviors of Retroviral Gene Transfer Vectors

Integration of retroviral vectors in the human genome follows non random patterns that favor insertional deregulation of gene expression and may cause risks of insertional mutagenesis when used in clinical gene therapy. Understanding how viral vectors integrate into the human genome is a key issue in predicting these risks. We provide a new statistical method to compare retroviral integration patterns. We identified the positions where vectors derived from the Human Immunodeficiency Virus (HIV) and the Moloney Murine Leukemia Virus (MLV) show different integration behaviors in human hematopoietic progenitor cells. Non-parametric density estimation was used to identify candidate comparative hotspots, which were then tested and ranked. We found 100 significative comparative hotspots, distributed throughout the chromosomes. HIV hotspots were wider and contained more genes than MLV ones. A Gene Ontology analysis of HIV targets showed enrichment of genes involved in antigen processing and presentation, reflecting the high HIV integration frequency observed at the MHC locus on chromosome 6. Four histone modifications/variants had a different mean density in comparative hotspots (H2AZ, H3K4me1, H3K4me3, H3K9me1), while gene expression within the comparative hotspots did not differ from background. These findings suggest the existence of epigenetic or nuclear three-dimensional topology contexts guiding retroviral integration to specific chromosome areas

Does targeting manual therapy and/or exercise improve patient outcomes in nonspecific low back pain? A systematic review

<p>Abstract</p> <p>Background</p> <p>A central element in the current debate about best practice management of non-specific low back pain (NSLBP) is the efficacy of targeted versus generic (non-targeted) treatment. Many clinicians and researchers believe that tailoring treatment to NSLBP subgroups positively impacts on patient outcomes. Despite this, there are no systematic reviews comparing the efficacy of targeted versus non-targeted manual therapy and/or exercise. This systematic review was undertaken in order to determine the efficacy of such targeted treatment in adults with NSLBP.</p> <p>Method</p> <p>MEDLINE, EMBASE, Current Contents, AMED and the Cochrane Central Register of Controlled Trials were electronically searched, reference lists were examined and citation tracking performed. Inclusion criteria were randomized controlled trials of targeted manual therapy and/or exercise for NSLPB that used trial designs capable of providing robust information on targeted treatment (treatment effect modification) for the outcomes of activity limitation and pain. Included trials needed to be hypothesis-testing studies published in English, Danish or Norwegian. Method quality was assessed using the criteria recommended by the Cochrane Back Review Group.</p> <p>Results</p> <p>Four high-quality randomized controlled trials of targeted manual therapy and/or exercise for NSLBP met the inclusion criteria. One study showed statistically significant effects for short-term outcomes using McKenzie directional preference-based exercise. Research into subgroups requires much larger sample sizes than traditional two-group trials and other included studies showed effects that might be clinically important in size but were not statistically significant with their samples sizes.</p> <p>Conclusions</p> <p>The clinical implications of these results are that they provide very cautious evidence supporting the notion that treatment targeted to subgroups of patients with NSLBP may improve patient outcomes. The results of the studies included in this review are too patchy, inconsistent and the samples investigated are too small for any recommendation of any treatment in routine clinical practice to be based on these findings. The research shows that adequately powered controlled trials using designs capable of providing robust information on treatment effect modification are uncommon. Considering how central the notion of targeted treatment is to manual therapy principles, further studies using this research method should be a priority for the clinical and research communities.</p

An outbreak of post-acupuncture cutaneous infection due to Mycobacterium abscessus

BACKGROUND: Despite the increasing popularity of acupuncture, the importance of infection control is not adequately emphasized in Oriental medicine. In December 2001, an Oriental medical doctor in Seoul, South Korea, encountered several patients with persistent, culture-negative skin lesions on the trunk and extremities at the sites of prior acupuncture treatment. We identified and investigated an outbreak of Mycobacterium abscessus cutaneous infection among the patients who attended this Oriental medicine clinic. METHODS: Patients were defined as clinic patients with persistent cutaneous infections at the acupuncture sites. Medical records for the previous 7 months were reviewed. Clinical specimens were obtained from the patients and an environmental investigation was performed. M. abscessus isolates, cultured from patients, were compared by pulsed-field gel electrophoresis (PFGE). RESULTS: Forty patients who attended the Oriental medicine clinic and experienced persistent cutaneous wound infections were identified. Cultures from five of these patients proved positive, and all other diagnoses were based on clinical and histopathologic examinations. All environmental objects tested were negative for M. abscessus, however, most were contaminated by various nosocomial pathogens. Molecular analysis using PFGE found all wound isolates to be identical. CONCLUSION: We have identified a large outbreak of rapidly growing mycobacterial infection among patients who received acupuncture at a single Oriental medicine clinic. Physicians should suspect mycobacterial infections in patients with persistent cutaneous infections following acupuncture, and infection control education including hygienic practice, should be emphasized for Oriental medical doctors practicing acupuncture

Dihydrolipoic acid reduces cytochrome b561 proteins.

Cytochrome b561 (Cyt-b561) proteins constitute a family of trans-membrane proteins that are present in a wide variety of organisms. Two of their characteristic properties are the reducibility by ascorbate (ASC) and the presence of two distinct b-type hemes localized on two opposite sides of the membrane. Here we show that the tonoplast-localized and the putative tumor suppressor Cyt-b561 proteins can be reduced by other reductants than ASC and dithionite. A detailed spectral analysis of the ASC-dependent and dihydrolipoic acid (DHLA)-dependent reduction of these two Cyt-b561 proteins is also presented. Our results are discussed in relation to the known antioxidant capability of DHLA as well as its role in the regeneration of other antioxidant compounds of cells. These results allow us to speculate on new biological functions for the trans-membrane Cyt-b561 proteins