The impact of pain-related fear on neural pathways of pain modulation in chronic low back pain

Introduction Pain-related fear plays a substantial role in chronic low back pain (LBP) by amplifying the experienced disability. Related dysfunctional emotions and cognitions may also affect sensory aspects of pain through a modulatory pathway in which the periaqueductal gray (PAG) and the amygdala play key roles. Objectives We therefore hypothesized a differential amygdala-PAG functional connectivity (FC) in patients with chronic LBP that is modulated by the degree of pain-related fear. Methods We used data of a previously reported fMRI study where 20 chronic LBP patients (7 females, mean age = 39.35) and 20 healthy controls (12 females, mean age = 32.10) were asked to observe video clips showing potentially harmful and neutral activities for the back. Pain-related fear was assessed using the Tampa Scale of kinesiophobia (TSK) and Fear Avoidance Beliefs questionnaires (FABQ). Generalized psychophysiological interactions were used to reveal task-based FC. Results Compared to controls, patients exhibited a significant decrease in amygdala-PAG-FC (P = 0.022) during observation of harmful activities, but not of neutral activities. Furthermore, amygdala-PAG-FC correlated negatively with Tampa Scale of kinesiophobia scores in patients (R2 = 0.28, P = 0.01) but not with Fear Avoidance Beliefs questionnaires scores. Discussion Our findings might indicate a maladaptive psychobiological interaction in chronic LBP patients characterized by a disrupted amygdala-PAG-FC that is modulated by the degree of pain-related fear. These results shed new light on brain mechanisms underlying psychological factors that may have pronociceptive effects in chronic LBP

An observational study on trajectories and outcomes of chronic low back pain patients referred from a spine surgery division for chiropractic treatment

Background: A close collaboration between surgeons and non-surgical spine experts is crucial for optimal care of low back pain (LBP) patients. The affiliation of a chiropractic teaching clinic to a university hospital with a large spine division in Zurich, Switzerland, enables such collaboration. The aim of this study was to describe the trajectories and outcomes of patients with chronic LBP referred from the spine surgery division to the chiropractic teaching clinic. Methods: The patients filled in an 11-point numeric rating scale (NRS) for pain intensity and the Bournemouth Questionnaire (BQ) (bio-psycho-social measure) at baseline and after 1 week, 1, 3, 6 and 12 months. Additionally, the Patient’s Global Impression of Change (PGIC) scale was recorded at all time points apart from baseline. The courses of NRS and BQ were analyzed using linear mixed model analysis and repeated measures ANOVA. The proportion of patients reporting clinically relevant overall improvement (PGIC) was calculated and the underlying factors were determined using logistic regression analyses. Results: Between June 2014 and October 2016, 67 participants (31 male, mean age = 46.8 ± 17.6 years) were recruited, of whom 46 had suffered from LBP for > 1 year, the rest for > 3 months, but < 1 year. At baseline, mean NRS was 5.43 (SD 2.37) and mean BQ was 39.80 (SD 15.16) points. NRS significantly decreased [F(5, 106.77) = 3.15, p = 0.011] to 4.05 (SD 2.88) after 12 months. A significant reduction was not observed before 6 months after treatment start (p = 0.04). BQ significantly diminished [F(5, 106.47) = 6.55, p < 0.001] to 29.00 (SD 17.96) after 12 months and showed a significant reduction within the first month (p < 0.01). The proportion of patients reporting overall improvement significantly increased from 23% after 1 week to 47% after 1 month (p = 0.004), when it stabilized [56% after 3 and 6 months, 44% after 12 months]. Reduction in bio-psycho-social impairment (BQ) was of higher importance for overall improvement than pain reduction. Conclusions: Chiropractic treatment is a valuable conservative treatment modality associated with clinically relevant improvement in approximately half of patients with chronic LBP. These findings provide an example of the importance of interdisciplinary collaboration in the treatment of chronic back pain patients

Novel therapeutic approaches for pulmonary fibrosis

Pulmonary fibrosis represents the end stage of a number of heterogeneous conditions and is, to a greater or lesser degree, the hallmark of the interstitial lung diseases. It is characterized by the excessive deposition of extracellular matrix proteins within the pulmonary interstitium leading to the obliteration of functional alveolar units and in many cases, respiratory failure. While a small number of interstitial lung diseases have known aetiologies, most are idiopathic in nature, and of these, idiopathic pulmonary fibrosis is the most common and carries with it an appalling prognosis – median survival from the time of diagnosis is less than 3 years. This reflects the lack of any effective therapy to modify the course of the disease, which in turn is indicative of our incomplete understanding of the pathogenesis of this condition. Current prevailing hypotheses focus on dysregulated epithelial–mesenchymal interactions promoting a cycle of continued epithelial cell injury and fibroblast activation leading to progressive fibrosis. However, it is likely that multiple abnormalities in a myriad of biological pathways affecting inflammation and wound repair – including matrix regulation, epithelial reconstitution, the coagulation cascade, neovascularization and antioxidant pathways – modulate this defective crosstalk and promote fibrogenesis. This review aims to offer a pathogenetic rationale behind current therapies, briefly outlining previous and ongoing clinical trials, but will focus on recent and exciting advancements in our understanding of the pathogenesis of idiopathic pulmonary fibrosis, which may ultimately lead to the development of novel and effective therapeutic interventions for this devastating condition

The myofibroblast matrix: implications for tissue repair and fibrosis

Myofibroblasts, and the extracellular matrix ( ECM ) in which they reside, are critical components of wound healing and fibrosis. The ECM , traditionally viewed as the structural elements within which cells reside, is actually a functional tissue whose components possess not only scaffolding characteristics, but also growth factor, mitogenic, and other bioactive properties. Although it has been suggested that tissue fibrosis simply reflects an ‘exuberant’ wound‐healing response, examination of the ECM and the roles of myofibroblasts during fibrogenesis instead suggest that the organism may be attempting to recapitulate developmental programmes designed to regenerate functional tissue. Evidence of this is provided by the temporospatial re‐emergence of embryonic ECM proteins by fibroblasts and myofibroblasts that induce cellular programmatic responses intended to produce a functional tissue. In the setting of wound healing (or physiological fibrosis), this occurs in a highly regulated and exquisitely choreographed fashion which results in cessation of haemorrhage, restoration of barrier integrity, and re‐establishment of tissue function. However, pathological tissue fibrosis, which oftentimes causes organ dysfunction and significant morbidity or mortality, likely results from dysregulation of normal wound‐healing processes or abnormalities of the process itself. This review will focus on the myofibroblast ECM and its role in both physiological and pathological fibrosis, and will discuss the potential for therapeutically targeting ECM proteins for treatment of fibrotic disorders.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94657/1/path4104.pd

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

How do students learn or fail to learn in a traditional chiropractic curriculum?

The objective of this research was to identify and evaluate the most important factors affecting student learning in a traditional four year chiropractic curriculum. An open-ended interview survey identified that student learning was affected by the educational environment, personal and curricular motivations to learn, personal perceptions of the curriculum and individual approaches to learning and studying. Additionally, student cohorts were found to suffer from different learning problems depending upon their year of study on the course as a result of the organisation of the curriculum. The above factors were selected for study in greater detail.An open-ended, cross-sectional questionnaire survey of students' personal and curricular motivations to learn identified that students in the first two years were motivated to learn by exemplary teaching and interest in the pre-clinical content of the curriculum, while students in the final two clinical years were more motivated to learn by the clinical and chiropractic content of the course. However, most students preferred vocational, clinical and chiropractic content to motivate them to learn.The Short Inventory of Approaches to Learning (SIAS) questionnaire was shown in this study to be a reliable instrument for use in chiropractic educational research. In a longitudinal cohort survey, the SIAS questionnaire identified distinctive variations to learning approaches for the four student cohorts' within an academic year as a result of the curricular organisation of the course into pre-clinical and clinical years of study.A purpose-designed, cross-sectional problems questionnaire survey identified students greatest problems in the pre-clinical years were examination and assessment stress, information overload, study and time management problems, coursework load, and information recall. Relevance, integration and application of knowledge and skills in the clinical setting were the greatest problem for year three and four clinical students.</p

Outcomes of pregnant patients with low back pain undergoing chiropractic treatment: a prospective cohort study with short term, medium term and 1 year follow-up

BACKGROUND Low back pain in pregnancy is common and research evidence on the response to chiropractic treatment is limited. The purposes of this study are 1) to report outcomes in pregnant patients receiving chiropractic treatment; 2) to compare outcomes from subgroups; 3) to assess predictors of outcome. METHODS Pregnant patients with low back or pelvic pain, no contraindications to manipulative therapy and no manual therapy in the prior 3 months were recruited.Baseline numerical rating scale (NRS) and Oswestry questionnaire data were collected. Duration of complaint, number of previous LBP episodes, LBP during a previous pregnancy, and category of pain location were recorded.The patient's global impression of change (PGIC) (primary outcome), NRS, and Oswestry data (secondary outcomes) were collected at 1 week, 1 and 3 months after the first treatment. At 6 months and 1 year the PGIC and NRS scores were collected. PGIC responses of 'better' or 'much better' were categorized as 'improved'.The proportion of patients 'improved' at each time point was calculated. Chi-squared test compared subgroups with 'improvement'. Baseline and follow-up NRS and Oswestry scores were compared using the paired t-test. The unpaired t-test compared NRS and Oswestry scores in patients with and without a history of LBP and with and without LBP during a previous pregnancy. Anova compared baseline and follow-up NRS and Oswestry scores by pain location category and category of number of previous LBP episodes. Logistic regression analysis also was also performed. RESULTS 52% of 115 recruited patients 'improved' at 1 week, 70% at 1 month, 85% at 3 months, 90% at 6 months and 88% at 1 year. There were significant reductions in NRS and Oswestry scores (p < 0.0005). Category of previous LBP episodes number at one year (p = 0.02) was related to ,improvement' when analyzed alone, but was not strongly predictive in logistic regression. Patients with more prior LBP episodes had higher 1 year NRS scores (p = 0.013). CONCLUSIONS Most pregnant patients undergoing chiropractic treatment reported clinically relevant improvement at all time points. No single variable was strongly predictive of, improvement' in the logistic regression model