More than meets the eye: visual attention biases in individuals reporting chronic pain

The present study used eye-tracking technology to assess whether individuals who report chronic pain direct more attention to sensory pain-related words than do pain-free individuals. A total of 113 participants (51 with chronic pain, 62 pain-free) were recruited. Participants completed a dot-probe task, viewing neutral and sensory pain-related words while their reaction time and eye movements were recorded. Eye-tracking data were analyzed by mixed-design analysis of variance with group (chronic pain versus pain-free) as the between-subjects factor, and word type (sensory pain versus neutral) as the within-subjects factor. Results showed a significant main effect for word type: all participants attended to pain-related words more than neutral words on several eye-tracking parameters. The group main effect was significant for number of fixations, which was greater in the chronic pain group. Finally, the group by word type interaction effect was significant for average visit duration, number of fixations, and total late-phase duration, all greater for sensory pain versus neutral words in the chronic pain group. As well, participants with chronic pain fixated significantly more frequently on pain words than did pain-free participants. In contrast, none of the effects for reaction time were significant. The results support the hypothesis that individuals with chronic pain display specific attentional biases toward pain-related stimuli and demonstrate the value of eye-tracking technology in measuring differences in visual attention variables.Samantha Fashler is supported by an Ontario Graduate Scholarship and a Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best CGS Master’s Award. Joel Katz is supported by a CIHR Canada Research Chair (CRC) in Health Psychology. Funds to support the project were obtained from Dr Katz’s CRC. We are grateful to Dr. Paul Ritvo for providing partial funding for the purchase of the Tobii eye-tracker through a Federal Development Grant. This article was derived, in part, from Samantha Fashler’s master’s thesis

Keeping an eye on pain: investigating visual attention biases in individuals with chronic pain using eye-tracking methodology

Attentional biases to painful stimuli are evident in individuals with chronic pain, although the directional tendency of these biases (ie, toward or away from threat-related stimuli) remains unclear. This study used eye-tracking technology, a measure of visual attention, to evaluate the attentional patterns of individuals with and without chronic pain during exposure to injury-related and neutral pictures. Individuals with (N=51) and without chronic pain (N=62) completed a dot-probe task using injury-related and neutral pictures while their eye movements were recorded. Mixed-design analysis of variance evaluated the interaction between group (chronic pain, pain-free) and picture type (injury-related, neutral). Reaction time results showed that regardless of chronic pain status, participants responded faster to trials with neutral stimuli in comparison to trials that included injury-related pictures. Eye-tracking measures showed within-group differences whereby injury-related pictures received more frequent fixations and visits, as well as longer average visit durations. Between-group differences showed that individuals with chronic pain had fewer fixations and shorter average visit durations for all stimuli. An examination of how biases change over the time-course of stimulus presentation showed that during the late phase of attention, individuals with chronic pain had longer average gaze durations on injury pictures relative to pain-free individuals. The results show the advantage of incorporating eye-tracking methodology when examining attentional biases, and suggest future avenues of research.We are grateful to Dr Paul Ritvo for his assistance. Samantha Fashler was supported by an Ontario Graduate Scholarship, a Canadian Institutes of Health Research (CIHR) CGS Master’s Award, and a CIHR Vanier Canada Graduate Scholarship. Joel Katz is supported by a CIHR Canada Research Chair (CRC) in Health Psychology. Funds to support the project were obtained from Dr Katz’s CRC and Dr Ritvo’s Federal Development Program. This article was derived, in part, from Samantha Fashler’s Master’s thesis. The research in this manuscript was presented as a poster presentation at the Canadian Pain Society in May 2014. An abstract of the poster was published in Pain Research & Management (vol 19, issue 3, e31–e102, 2014)

Substance use disorders and the risk of suicide mortality among men and women in the US Veterans Health Administration

Background and AimsLimited information is available regarding links between specific substance use disorders (SUDs) and suicide mortality; however, the preliminary evidence that is available suggests that suicide risk associated with SUDs may differ for men and women. This study aimed to estimate associations between SUDs and suicide for men and women receiving Veterans Health Administration (VHA) care.DesignA cohort study using national administrative health records.SettingNational VHA system, USA.ParticipantsAll VHA users in fiscal year (FY) 2005 who were alive at the beginning of FY 2006 (n = 4 863 086).MeasurementsThe primary outcome of suicide mortality was assessed via FY 2006–2011 National Death Index (NDI) records. Current SUD diagnoses were the primary predictors of interest, and were assessed via FY 2004–2005 VHA National Patient Care Database (NPCD) records.FindingsIn unadjusted analyses, a diagnosis of any current SUD and the specific current diagnoses of alcohol, cocaine, cannabis, opioid, amphetamine and sedative use disorders were all associated significantly with increased risk of suicide for both males and females [hazard ratios (HRs)] ranging from 1.35 for cocaine use disorder to 4.74 for sedative use disorder for men, and 3.89 for cannabis use disorder to 11.36 for sedative use disorder for women]. Further, the HR estimates for the relations between any SUD, alcohol, cocaine and opioid use disorders and suicide were significantly stronger for women than men (P < 0.05). After adjustment for other factors, most notably comorbid psychiatric diagnoses, associations linking SUDs with suicide were attenuated markedly and the greater suicide risk among females was observed for only any SUD and opioid use disorder (P < 0.05).ConclusionsCurrent substance use disorders (SUDs) signal increased suicide risk, especially among women, and may be important markers to consider including in suicide risk assessment strategies. None the less, other co‐occurring psychiatric disorders may partially explain associations between SUDs and suicide, as well as the observed excess suicide risk associated with SUDs among women.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137620/1/add13774.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137620/2/add13774_am.pd

Chronic pain, psychopathology, and DSM-5 somatic symptom disorder

Unlike acute pain that warns us of injury or disease, chronic or persistent pain serves no adaptive purpose. Though there is no agreed on definition of chronic pain, it is commonly referred to as pain that is without biological value, lasting longer than the typical healing time, not responsive to treatments based on specific remedies, and of a duration greater than 6 months. Chronic pain that is severe and intractable has detrimental consequences, including psychological distress, job loss, social isolation, and, not surprisingly, it is highly comorbid with depression and anxiety. Historically, pain without an apparent anatomical or neurophysiological origin was labelled as psychopathological. This approach is damaging to the patient and provider alike. It pollutes the therapeutic relationship by introducing an element of mutual distrust as well as implicit, if not explicit, blame. It is demoralizing to the patient who feels at fault, disbelieved, and alone. Moreover, many medically unexplained pains are now understood to involve an interplay between peripheral and central neurophysiological mechanisms that have gone awry. The new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, somatic symptom disorder overpsychologizes people with chronic pain; it has low sensitivity and specificity, and it contributes to misdiagnosis, as well as unnecessary stigma. Adjustment disorder remains the most appropriate, accurate, and acceptable diagnosis for people who are overly concerned about their pain.Preparation of this manuscript was facilitated by support from a Canadian Institutes of Health Research (CIHR) Canada Research Chair in Health Psychology awarded to Dr Katz and a CIHR Canada Graduate Master’s Award to Samantha Fashler

Systematic Review of Multidisciplinary Chronic Pain Treatment Facilities

This study reviewed the published literature evaluating multidisciplinary chronic pain treatment facilities to provide an overview of their availability, caseload, wait times, and facility characteristics. A systematic literature review was conducted using PRISMA guidelines following a search of MEDLINE, PsycINFO, and CINAHL databases. Inclusion criteria stipulated that studies be original research, survey more than one pain treatment facility directly, and describe a range of available treatments. Fourteen articles satisfied inclusion criteria. Results showed little consistency in the research design used to describe pain treatment facilities. Availability of pain treatment facilities was scarce and the reported caseloads and wait times were generally high. A wide range of medical, physical, and psychological pain treatments were available. Most studies reported findings on the percentage of practitioners in different health care professions employed. Future studies should consider using more comprehensive search strategies to survey facilities, improving clarity on what is considered to be a pain treatment facility, and reporting on a consistent set of variables to provide a clear summary of the status of pain treatment facilities. This review highlights important information for policymakers on the scope, demand, and accessibility of pain treatment facilities.Samantha Fashler is supported by an Ontario Graduate Scholarship and a Canadian Institutes of Health Research (CIHR) Vanier Canada Graduate Scholarship. Lindsay Burns is supported by a Frederick Banting and Charles Best CIHR Doctoral Scholarship. Joel Katz is supported by a CIHR Canada Research Chair in Health Psychology. This project was conducted in collaboration with the Canadian Pain Coalition (CPC) as a part of the Report Card on Pain

Heart rate variability is enhanced in controls but not maladaptive perfectionists during brief mindfulness meditation following stress-induction: A stratified-randomized trial

Heart rate variability (HRV) is a vagal nerve-mediated biomarker of cardiac function used to investigate chronic illness, psychopathology, stress and, more recently, attention-regulation processes such as meditation. This study investigated HRV in relation to maladaptive perfectionism, a stress-related personality factor, and mindfulness meditation, a stress coping practice expected to elevate HRV, and thereby promote relaxation. Maladaptive perfectionists (n=21) and Controls (n=39) were exposed to a lab-based assessment in which HRV was measured during (1) a 5-minute baseline resting phase, (2) a 5-minute cognitive stress-induction phase, and (3) a post-stress phase. In the post-stress phase, participants were randomly assigned to a 10-minute audio instructed mindfulness meditation condition or a 10-minute rest condition with audio-description of mindfulness meditation. Analyses revealed a significant elevation in HRV during meditation for Controls but not for Perfectionists. These results suggest that mindfulness meditation promotes relaxation following cognitive stress and that the perfectionist personality hinders relaxation possibly because of decreased cardiac vagal tone. The results are discussed in the context of developing psychophysiological models to advance therapeutic interventions for distressed populations.The authors have no conflicts of interest: they have no financial or personal relationships with other people or organizations that could inappropriately influence their work. The authors gratefully acknowledge the assistance of all persons and volunteers whose participation was essential in the successful completion of the study. The authors would also like to thank Professor John B. Allen for his advice on HRV analysis, and the Statistical Consulting Service offered by the Institute for Social Research at York University. Joel Katz is supported by a Canadian Institutes of Health Research Canada Research Chair in Health Psychology

Haemophilus ducreyi Cutaneous Ulcer Strains Are Nearly Identical to Class I Genital Ulcer Strains

BACKGROUND: Although cutaneous ulcers (CU) in the tropics is frequently attributed to Treponema pallidum subspecies pertenue, the causative agent of yaws, Haemophilus ducreyi has emerged as a major cause of CU in yaws-endemic regions of the South Pacific islands and Africa. H. ducreyi is generally susceptible to macrolides, but CU strains persist after mass drug administration of azithromycin for yaws or trachoma. H. ducreyi also causes genital ulcers (GU) and was thought to be exclusively transmitted by microabrasions that occur during sex. In human volunteers, the GU strain 35000HP does not infect intact skin; wounds are required to initiate infection. These data led to several questions: Are CU strains a new variant of H. ducreyi or did they evolve from GU strains? Do CU strains contain additional genes that could allow them to infect intact skin? Are CU strains susceptible to azithromycin? METHODOLOGY/PRINCIPAL FINDINGS: To address these questions, we performed whole-genome sequencing and antibiotic susceptibility testing of 5 CU strains obtained from Samoa and Vanuatu and 9 archived class I and class II GU strains. Except for single nucleotide polymorphisms, the CU strains were genetically almost identical to the class I strain 35000HP and had no additional genetic content. Phylogenetic analysis showed that class I and class II strains formed two separate clusters and CU strains evolved from class I strains. Class I strains diverged from class II strains ~1.95 million years ago (mya) and CU strains diverged from the class I strain 35000HP ~0.18 mya. CU and GU strains evolved under similar selection pressures. Like 35000HP, the CU strains were highly susceptible to antibiotics, including azithromycin. CONCLUSIONS/SIGNIFICANCE: These data suggest that CU strains are derivatives of class I strains that were not recognized until recently. These findings require confirmation by analysis of CU strains from other regions

Genetic Basis of Inherited Retinal Disease in a Molecularly Characterized Cohort of More Than 3000 Families from the United Kingdom.

PURPOSE: In a large cohort of molecularly characterized inherited retinal disease (IRD) families, we investigated proportions with disease attributable to causative variants in each gene. DESIGN: Retrospective study of electronic patient records. PARTICIPANTS: Patients and relatives managed in the Genetics Service of Moorfields Eye Hospital in whom a molecular diagnosis had been identified. METHODS: Genetic screening used a combination of single-gene testing, gene panel testing, whole exome sequencing, and more recently, whole genome sequencing. For this study, genes listed in the Retinal Information Network online resource (https://sph.uth.edu/retnet/) were included. Transcript length was extracted for each gene (Ensembl, release 94). MAIN OUTCOME MEASURES: We calculated proportions of families with IRD attributable to variants in each gene in the entire cohort, a cohort younger than 18 years, and a current cohort (at least 1 patient encounter between January 1, 2017, and August 2, 2019). Additionally, we explored correlation between numbers of families and gene transcript length. RESULTS: We identified 3195 families with a molecular diagnosis (variants in 135 genes), including 4236 affected individuals. The pediatric cohort comprised 452 individuals from 411 families (66 genes). The current cohort comprised 2614 families (131 genes; 3130 affected individuals). The 20 most frequently implicated genes overall (with prevalence rates per families) were as follows: ABCA4 (20.8%), USH2A (9.1%), RPGR (5.1%), PRPH2 (4.6%), BEST1 (3.9%), RS1 (3.5%), RP1 (3.3%), RHO (3.3%), CHM (2.7%), CRB1 (2.1%), PRPF31 (1.8%), MY07A (1.7%), OPA1 (1.6%), CNGB3 (1.4%), RPE65 (1.2%), EYS (1.2%), GUCY2D (1.2%), PROM1 (1.2%), CNGA3 (1.1%), and RDH12 (1.1%). These accounted for 71.8% of all molecularly diagnosed families. Spearman coefficients for correlation between numbers of families and transcript length were 0.20 (P = 0.025) overall and 0.27 (P = 0.017), -0.17 (P = 0.46), and 0.71 (P = 0.047) for genes in which variants exclusively cause recessive, dominant, or X-linked disease, respectively. CONCLUSIONS: Our findings help to quantify the burden of IRD attributable to each gene. More than 70% of families showed pathogenic variants in 1 of 20 genes. Transcript length (relevant to gene delivery strategies) correlated significantly with numbers of affected families (but not for dominant disease)

Study protocol: developing a decision system for inclusive housing: applying a systematic, mixed-method quasi-experimental design

Background Identifying the housing preferences of people with complex disabilities is a much needed, but under-developed area of practice and scholarship. Despite the recognition that housing is a social determinant of health and quality of life, there is an absence of empirical methodologies that can practically and systematically involve consumers in this complex service delivery and housing design market. A rigorous process for making effective and consistent development decisions is needed to ensure resources are used effectively and the needs of consumers with complex disability are properly met. Methods/Design This 3-year project aims to identify how the public and private housing market in Australia can better respond to the needs of people with complex disabilities whilst simultaneously achieving key corporate objectives. First, using the Customer Relationship Management framework, qualitative (Nominal Group Technique) and quantitative (Discrete Choice Experiment) methods will be used to quantify the housing preferences of consumers and their carers. A systematic mixed-method, quasi-experimental design will then be used to quantify the development priorities of other key stakeholders (e.g., architects, developers, Government housing services etc.) in relation to inclusive housing for people with complex disabilities. Stakeholders randomly assigned to Group 1 (experimental group) will participate in a series of focus groups employing Analytical Hierarchical Process (AHP) methodology. Stakeholders randomly assigned to Group 2 (control group) will participate in focus groups employing existing decision making processes to inclusive housing development (e.g., Risk, Opportunity, Cost, Benefit considerations). Using comparative stakeholder analysis, this research design will enable the AHP methodology (a proposed tool to guide inclusive housing development decisions) to be tested. Discussion It is anticipated that the findings of this study will enable stakeholders to incorporate consumer housing preferences into commercial decisions. Housing designers and developers will benefit from the creation of a parsimonious set of consumer-led housing preferences by which to make informed investments in future housing and contribute to future housing policy. The research design has not been applied in the Australian research context or elsewhere, and will provide a much needed blueprint for market investment to develop viable, consumer directed inclusive housing options for people with complex disability

Chemoinformatic-Guided Engineering of Polyketide Synthases.

Polyketide synthase (PKS) engineering is an attractive method to generate new molecules such as commodity, fine and specialty chemicals. A significant challenge is re-engineering a partially reductive PKS&nbsp;module to produce a saturated β-carbon through a reductive loop (RL) exchange. In this work, we sought to establish that chemoinformatics, a field traditionally used in drug discovery, offers a viable strategy for RL exchanges. We first introduced a set of donor RLs of diverse genetic origin and chemical substrates&nbsp; into the first extension module of the lipomycin PKS (LipPKS1). Product titers of these engineered unimodular PKSs correlated with chemical structure&nbsp;similarity between the substrate of the donor RLs and recipient LipPKS1, reaching a titer of 165 mg/L of short-chain fatty acids produced by&nbsp;the host&nbsp;Streptomyces albus J1074. Expanding this method to larger intermediates that require bimodular communication, we introduced RLs of divergent chemosimilarity into LipPKS2 and determined triketide lactone production. Collectively, we observed a statistically significant correlation between atom pair chemosimilarity and production, establishing a new chemoinformatic method that may aid in the engineering of PKSs to produce desired, unnatural products