Objective: Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease. Studies suggest that pro-inflammatory cytokines may be attenuated by the vagus nerve through the cholinergic ...anti-inflammatory pathway. We aimed to evaluate the anti-inflammatory effects of short-term transcutaneous non-invasive vagus nerve stimulation (n-VNS) applied to the cervical vagus nerve in patients with RA.
Method: We conducted a single-centre, open-label, preliminary proof-of-concept study of n-VNS in two cohorts of participants with RA: one with high disease activity (n = 16) and one with low disease activity (n = 20). Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP), cardiac vagal tone, and pro-inflammatory cytokines were measured at baseline and after 1 and 4 days of n-VNS.
Results: In the high disease activity group, n-VNS resulted in reductions in DAS28-CRP (4.1 to 3.8, p = 0.02), CRP (8.2 to 6 mg/mL, p = 0.01), and interferon-γ (29.8 to 22.5 pg/mL, p = 0.02). In the low disease activity group, there was no effect on DAS28-CRP, and n-VNS was associated with a decrease in cardiac vagal tone (p = 0.03) and a reduction in interleukin-10 (0.8 to 0.6 pg/mL, p = 0.02). Participants with high disease activity had lower baseline cardiac vagal tone than those with low disease activity (3.6 ± 2 vs 4.9 ± 3 linear vagal scale, p = 0.03). Cardiac vagal tone was negatively associated with DAS28-CRP (r = −0.37, p = 0.03). Overall, n-VNS was well tolerated.
Conclusion: This study provides preliminary support for an anti-inflammatory effect of n-VNS in patients with RA. These findings warrant further investigation in larger placebo-controlled trials.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Irritable bowel syndrome is a widespread disorder with a marked socioeconomic burden. Previous studies support the proposal that a subset of patients with features compatible with ...diarrhoea‐predominant IBS (IBS‐D) have bile acid malabsorption (BAM).
Aim
To perform a systematic review and meta‐analysis to assess the prevalence of BAM in patients meeting the accepted criteria for IBS‐D.
Methods
MEDLINE and EMBASE were searched up to March 2015. Studies recruiting adults with IBS‐D, defined by the Manning, Kruis, Rome I, II or III criteria and which used 23‐seleno‐25‐homotaurocholic acid (SeHCAT) testing for the assessment of BAM were included. BAM was defined as 7 day SeHCAT retention of <10%. We calculated the rate of BAM and 95% confidence intervals (CI) using a random effects model. The methodological quality of included studies was evaluated using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS‐2).
Results
The search strategy identified six relevant studies comprising 908 individuals. The rate of BAM ranged from 16.9% to 35.3%. The pooled rate was 28.1% (95% CI: 22.6–34%). There was significant heterogeneity in effect sizes (Q‐test χ2 = 17.9, P < 0.004; I2 = 72.1%). The type of diagnostic criteria used or study country did not significantly modify the effect.
Conclusions
These data provide evidence that in excess of one quarter of patients meeting accepted criteria for IBS‐D have bile acid malabsorption. This distinction has implications for the interpretation of previous studies, as well as contemporaneous clinical practice and future guideline development.
Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high population prevalence. The disorder can be debilitating in some patients, whereas others may have mild or moderate ...symptoms. The most important single risk factors are female sex, younger age and preceding gastrointestinal infections. Clinical symptoms of IBS include abdominal pain or discomfort, stool irregularities and bloating, as well as other somatic, visceral and psychiatric comorbidities. Currently, the diagnosis of IBS is based on symptoms and the exclusion of other organic diseases, and therapy includes drug treatment of the predominant symptoms, nutrition and psychotherapy. Although the underlying pathogenesis is far from understood, aetiological factors include increased epithelial hyperpermeability, dysbiosis, inflammation, visceral hypersensitivity, epigenetics and genetics, and altered brain-gut interactions. IBS considerably affects quality of life and imposes a profound burden on patients, physicians and the health-care system. The past decade has seen remarkable progress in our understanding of functional bowel disorders such as IBS that will be summarized in this Primer.
Background:
Anxiety and depression are common in patients with inflammatory bowel disease (IBD); however, the factors associated with mood disorders in patients with ulcerative colitis (UC) and ...Crohn's disease (CD) are poorly defined.
Methods:
In all, 103 patients with UC, 101 with CD, and 124 healthy controls completed the Hospital Anxiety and Depression Scale (HADS). Disease activity was defined both from symptom scores and in UC endoscopically, and in CD by fecal calprotectin and/or serum C‐reactive protein. Multivariate regression analyses were used to identify factors associated with anxiety and depression.
Results:
In both UC and CD, anxiety (HADS‐A) and depression (HADS‐D) scores were higher than in controls (HADS‐A: 8.5 ± 4.1 mean ± SD, 8.6 ± 3.9, 3.2 ± 1.8, P < 0.001; and HADS‐D: 4.1 ± 3.3, 4.7 ± 3.3, 1.7 ± 1.4, P < 0.001, respectively). There were no differences in the prevalence of mild, moderate, and severe anxiety and depression in UC and CD. In UC, anxiety scores were associated with perceived stress and a new diagnosis of IBD; depression was associated with stress, inpatient status, and active disease. In CD, anxiety was associated with perceived stress, abdominal pain, and lower socioeconomic status, and depression with perceived stress and increasing age.
Conclusions:
Anxiety and depression are common in IBD. Perceived stress is associated with mood disturbances in both UC and CD, but the other associated factors differ in the two diseases. Gastroenterologists should look for mood disorders in IBD and consider stress management and psychotherapy in affected patients. (Inflamm Bowel Dis 2012;)
Background Unexplained gastrointestinal (GI) symptoms and joint hypermobility (JHM) are common in the general population, the latter described as benign joint hypermobility syndrome (BJHS) when ...associated with musculo‐skeletal symptoms. Despite overlapping clinical features, the prevalence of JHM or BJHS in patients with functional gastrointestinal disorders has not been examined.
Methods The incidence of JHM was evaluated in 129 new unselected tertiary referrals (97 female, age range 16–78 years) to a neurogastroenterology clinic using a validated 5‐point questionnaire. A rheumatologist further evaluated 25 patients with JHM to determine the presence of BJHS. Groups with or without JHM were compared for presentation, symptoms and outcomes of relevant functional GI tests.
Key Results Sixty‐three (49%) patients had evidence of generalized JHM. An unknown aetiology for GI symptoms was significantly more frequent in patients with JHM than in those without (P < 0.0001). The rheumatologist confirmed the clinical impression of JHM in 23 of 25 patients, 17 (68%) of whom were diagnosed with BJHS. Patients with co‐existent BJHS and GI symptoms experienced abdominal pain (81%), bloating (57%), nausea (57%), reflux symptoms (48%), vomiting (43%), constipation (38%) and diarrhoea (14%). Twelve of 17 patients presenting with upper GI symptoms had delayed gastric emptying. One case is described in detail.
Conclusions & Inferences In a preliminary retrospective study, we have found a high incidence of JHM in patients referred to tertiary neurogastroenterology care with unexplained GI symptoms and in a proportion of these a diagnosis of BJHS is made. Symptoms and functional tests suggest GI dysmotility in a number of these patients. The possibility that a proportion of patients with unexplained GI symptoms and JHM may share a common pathophysiological disorder of connective tissue warrants further investigation.
Background
The parasympathetic nervous system, whose main neural substrate is the vagus nerve, exerts a fundamental antinociceptive role and influences gastrointestinal sensori‐motor function. Our ...research question was to whether combined electrical and physiological modulation of vagal tone, using transcutaneous electrical vagal nerve stimulation (t‐VNS) and deep slow breathing (DSB) respectively, could increase musculoskeletal pain thresholds and enhance gastroduodenal motility in healthy subjects.
Methods
Eighteen healthy subjects were randomized to a subject‐blinded, sham‐controlled, cross‐over study with an active protocol including stimulation of auricular branch of the vagus nerve, and breathing at full inspiratory capacity and forced full expiration. Recording of cardiac derived parameters including cardiac vagal tone, moderate pain thresholds to muscle, and bone pressure algometry, conditioned pain modulation using a cold pressor test and a liquid meal ultrasonographic gastroduodenal motility test were performed.
Key Results
Cardiac vagal tone increased during active treatment with t‐VNS and DSB compared to sham (p = 0.009). In comparison to sham, thresholds to bone pain increased (p = 0.001), frequency of antral contractions increased (p = 0.004) and gastroduodenal motility index increased (p = 0.016) with active treatment. However, no effect on muscle pain thresholds and conditioned pain modulation was seen.
Conclusions & Inferences
This experimental study suggests that this noninvasive approach with combined electrical and physiological modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity. These findings warrant further investigation in patients with disorders characterized with chronic pain and gastrointestinal dysmotility such as functional dyspepsia and irritable bowel syndrome.
The aim was to explore the effect of combined electrical and physiological modulation of vagal tone on musculoskeletal pain thresholds and gastroduodenal motility. Cardiac vagal tone, thresholds to bone pain, frequency of antral contractions, and gastroduodenal motility index all increased during active treatment compared to sham.
Objectives. The vagal nerve exerts an essential pathway in controlling the cholinergic anti-inflammatory reflex. Thus, the study is aimed at investigating the acute effect of a noninvasive ...transcutaneous vagus nerve stimulation on clinical disease activity and systemic levels of inflammation in patients with psoriatic arthritis or ankylosing spondylitis. Methods. Twenty patients with psoriatic arthritis (PsA) and 20 patients with ankylosing spondylitis (AS) were included and stimulated bilaterally with a handheld vagal nerve stimulator for 120 seconds 3 times a day for 5 consecutive days. All patients were in remission. Cardiac vagal tone, clinical scores, CRP, and cytokine levels were assessed. Results. In PsA and AS, decreased heart rate was observed, confirming compliance. Furthermore, in PsA, a clear reduction of clinical disease activity associated with a 20% reduction in CRP was shown. In AS, a reduction in interferon-γ, interleukin- (IL-) 8, and 10 was shown. No side effects were described. Conclusion. This open-label study provides support for an anti-inflammatory effect of transcutaneous vagus nerve stimulation in patients with psoriatic arthritis and ankylosing spondylitis. The modulated immune response and reduced disease activity and CRP-levels raise the fascinating possibility of using neuromodulation as an add-on to existing pharmacological treatments.
Raman amplification arising from the excitation of a density echelon in plasma could lead to amplifiers that significantly exceed current power limits of conventional laser media. Here we show that ...1-100 J pump pulses can amplify picojoule seed pulses to nearly joule level. The extremely high gain also leads to significant amplification of backscattered radiation from "noise", arising from stochastic plasma fluctuations that competes with externally injected seed pulses, which are amplified to similar levels at the highest pump energies. The pump energy is scattered into the seed at an oblique angle with 14 J sr
, and net gains of more than eight orders of magnitude. The maximum gain coefficient, of 180 cm
, exceeds high-power solid-state amplifying media by orders of magnitude. The observation of a minimum of 640 J sr
directly backscattered from noise, corresponding to ≈10% of the pump energy in the observation solid angle, implies potential overall efficiencies greater than 10%.
Summary
Background
Chronic idiopathic constipation is a common symptom‐based gastrointestinal disorder responsible for a substantial economic health service burden. Current guidelines recommend the ...use of fibre as a first‐line treatment.
Aim
To investigate the effect of fibre (including prebiotic) supplementation on global symptom response, stool output, gut microbiota composition and adverse events in adults with chronic idiopathic constipation.
Methods
Medline, EmBase, Web of Science, Scopus and the Cochrane central register of controlled trials were searched through to February 2016. Conference proceedings from 2003 to 2015 were hand‐searched. There were no language restrictions. Forest plots with 95% CIs were generated using a random‐effects model.
Results
The search strategy generated 1072 citations, of which seven individual randomised controlled trials were eligible. Overall, 113 of 147 (77%) patients assigned to fibre responded to therapy, compared with 61 of 140 (44%) allocated to placebo (RR of success to respond 1.71, 95% CI 1.20–2.42, P = 0.003). Fibre significantly increased stool frequency (SMD, standardised mean difference = 0.39; 95% CI 0.03–0.76; P = 0.03) and softened stool consistency (SMD = 0.35; 95% CI 0.04–0.65; P = 0.02) compared with placebo. Flatulence was significantly higher with fibre compared to placebo (SMD 0.56, 0.12–1.00, P = 0.01). Overall quality of evidence was low.
Conclusions
This meta‐analysis demonstrates that fibre is moderately effective, but also causes moderate gastrointestinal side effects. However, these findings need to be treated with caution due to a high risk of bias. Accordingly, further large, methodologically rigorous trials are required, before any definitive recommendation regarding its risk–benefit profile can be made.
PROSPERO registration number CRD42014007005.
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