Risk factors for low back pain outcome: Does it matter when they are measured?

Background: The early identification of factors that increase risk of poor recovery from acute low back pain (LBP) is critical to prevent the transition to chronicity. Although most studies of risk factors for poor outcome in LBP tend to investigate the condition once it is already persistent, there is evidence to suggest that this differs from risk factors measured during the early-acute stage. This study aimed to identify early risk factors for poor outcome in the short- and long-term in individuals with acute LBP, and to compare this with factors identified at 3 months in the same cohort. Methods: One hundred and thirty-three individuals were recruited within 2 weeks of an acute LBP episode and completed questionnaires related to their sociodemographic, psychological, clinical and history/treatment status at baseline and 3 months later, and their pain-level fortnightly for 12 months. Results: Of the 133 participants recruited, follow-up data were provided by 120 at 3 months, 97 at 6 months, 85 at 9 months and 94 at 12 months. Linear regression identified various factors at baseline (acute phase) and 3 months later that predicted short- and long-term outcome (pain level, change in pain). Key findings were that: (1) depressive symptoms at baseline most consistently predicted worse outcome; (2) psychological factors in general at 3 months were more predictive of outcome than when measured at baseline; (3) early health care utilization predicted better outcome, whereas use of pain medication later (3 months) predicted worse outcome; and (4) sex and BMI predicted outcome inconsistently over 12-months. Conclusions: The results highlight the multidimensional nature of risk factors for poor outcome in LBP and the need to consider time variation in these factors

Effect of a consumer-focused website for low back pain on health literacy, treatment choices, and clinical outcomes: randomized controlled trial

BACKGROUND: The internet is used for information related to health conditions, including low back pain (LBP), but most LBP websites provide inaccurate information. Few studies have investigated the effectiveness of internet resources in changing health literacy or treatment choices. OBJECTIVE: This study aims to evaluate the effectiveness of the MyBackPain website compared with unguided internet use on health literacy, choice of treatments, and clinical outcomes in people with LBP. METHODS: This was a pragmatic, web-based, participant- and assessor-blinded randomized trial of individuals with LBP stratified by duration. Participants were randomly allocated to have access to the evidence-based MyBackPain website, which was designed with input from consumers and expert consensus or unguided internet use. The coprimary outcomes were two dimensions of the Health Literacy Questionnaire (dimension 2: “having sufficient information to manage my health;” dimension 3: “actively managing my health;” converted to scores 1-100) at 3 months. Secondary outcomes included additional Health Literacy Questionnaire dimensions, quality of treatment choices, and clinical outcomes. RESULTS: A total of 453 participants were recruited, and 321 (70.9%) completed the primary outcomes. Access to MyBackPain was not superior to unguided internet use on primary outcomes (dimension 2: mean difference −0.87 units, 95% CI −3.56 to 1.82; dimension 3: mean difference −0.41 units, 95% CI −2.78 to 1.96). Between-group differences in other secondary outcomes had inconsistent directions and were unlikely to be clinically important, although a small improvement of unclear importance in the quality of stated treatment choices at 1 month was found (mean difference 0.93 units, 95% CI 0.03 to 1.84). CONCLUSIONS: MyBackPain was not superior to unguided internet use for health literacy, but data suggest some short-term improvement in treatment choices. Future research should investigate if greater interactivity and engagement with the website may enhance its impact. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001292369; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372926 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2018-02751

Imaging with ultrasound in physical therapy: What is the PT’s scope of practice? A competency-based educational model and training recommendations.

Physical therapists employ ultrasound (US) imaging technology for a broad range of clinical and research purposes. Despite this, few physical therapy regulatory bodies guide the use of US imaging, and there are limited continuing education opportunities for physical therapists to become proficient in using US within their professional scope of practice. Here, we (i) outline the current status of US use by physical therapists; (ii) define and describe four broad categories of physical therapy US applications (ie, rehabilitation, diagnostic, intervention and research US); (iii) discuss how US use relates to the scope of high value physical therapy practice and (iv) propose a broad framework for a competency-based education model for training physical therapists in US. This paper only discusses US imaging— not ’therapeutic’ US. Thus, ’imaging’ is implicit anywhere the term ’ultrasound’ is used.pre-print847 K

Deweyan tools for inquiry and the epistemological context of critical pedagogy

This article develops the notion of resistance as articulated in the literature of critical pedagogy as being both culturally sponsored and cognitively manifested. To do so, the authors draw upon John Dewey\u27s conception of tools for inquiry. Dewey provides a way to conceptualize student resistance not as a form of willful disputation, but instead as a function of socialization into cultural models of thought that actively truncate inquiry. In other words, resistance can be construed as the cognitive and emotive dimensions of the ongoing failure of institutions to provide ideas that help individuals both recognize social problems and imagine possible solutions. Focusing on Dewey\u27s epistemological framework, specifically tools for inquiry, provides a way to grasp this problem. It also affords some innovative solutions; for instance, it helps conceive of possible links between the regular curriculum and the study of specific social justice issues, a relationship that is often under-examined. The aims of critical pedagogy depend upon students developing dexterity with the conceptual tools they use to make meaning of the evidence they confront; these are background skills that the regular curriculum can be made to serve even outside social justice-focused curricula. Furthermore, the article concludes that because such inquiry involves the exploration and potential revision of students\u27 world-ordering beliefs, developing flexibility in how one thinks may be better achieved within academic subjects and topics that are not so intimately connected to students\u27 current social lives, especially where students may be directly implicated

TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions

Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease

Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. We established the international FTLD-TDP whole genome sequencing consortium to thoroughly characterize the known genetic causes of FTLD-TDP and identify novel genetic risk factors. Through the study of 1,131 unrelated Caucasian patients, we estimated that C9orf72 repeat expansions and GRN loss-of-function mutations account for 25.5% and 13.9% of FTLD-TDP patients, respectively. Mutations in TBK1 (1.5%) and other known FTLD genes (1.4%) were rare, and the disease in 57.7% of FTLD-TDP patients was unexplained by the known FTLD genes. To unravel the contribution of common genetic factors to the FTLD-TDP etiology in these patients, we conducted a two-stage association study comprising the analysis of whole-genome sequencing data from 517 FTLD-TDP patients and 838 controls, followed by targeted genotyping of the most associated genomic loci in 119 additional FTLD-TDP patients and 1653 controls. We identified three genome-wide significant FTLD-TDP risk loci: one new locus at chromosome 7q36 within the DPP6 gene led by rs118113626 (pvalue=4.82e-08, OR=2.12), and two known loci: UNC13A, led by rs1297319 (pvalue=1.27e-08, OR=1.50) and HLA-DQA2 led by rs17219281 (pvalue=3.22e-08, OR=1.98). While HLA represents a locus previously implicated in clinical FTLD and related neurodegenerative disorders, the association signal in our study is independent from previously reported associations. Through inspection of our whole genome sequence data for genes with an excess of rare loss-of-function variants in FTLD-TDP patients (n≥3) as compared to controls (n=0), we further discovered a possible role for genes functioning within the TBK1-related immune pathway (e.g. DHX58, TRIM21, IRF7) in the genetic etiology of FTLD-TDP. Together, our study based on the largest cohort of unrelated FTLD-TDP patients assembled to date provides a comprehensive view of the genetic landscape of FTLD-TDP, nominates novel FTLD-TDP risk loci, and strongly implicates the immune pathway in FTLD-TDP pathogenesis

Methamphetamine Preconditioning Alters Midbrain Transcriptional Responses to Methamphetamine-Induced Injury in the Rat Striatum

Methamphetamine (METH) is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge. Quantitative PCR confirmed METH-induced changes in genes of interest and identified additional genes that were differentially impacted by the toxic METH challenge in the presence of METH preconditioning. These genes include small heat shock 27 kD 27 protein 2 (HspB2), thyrotropin-releasing hormone (TRH), brain derived neurotrophic factor (BDNF), c-fos, and some encoding antioxidant proteins including CuZn superoxide dismutase (CuZnSOD), glutathione peroxidase (GPx)-1, and heme oxygenase-1 (Hmox-1). These observations are consistent, in part, with the transcriptional alterations reported in models of lethal ischemic injuries which are preceded by ischemic or pharmacological preconditioning. Our findings suggest that multiple molecular pathways might work in tandem to protect the nigrostriatal dopaminergic pathway against the deleterious effects of the toxic psychostimulant. Further analysis of the molecular and cellular pathways regulated by these genes should help to provide some insight into the neuroadaptive potentials of the brain when repeatedly exposed to drugs of abuse

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development