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Layer 5 pyramidal neurons of sensory cortices project “corticofugal” axons to myriad sub-cortical targets, thereby broadcasting high-level signals important for perception and learning. Recent studies suggest dendritic Ca2+ spikes as key biophysical mechanisms supporting corticofugal neuron function: these long-lasting events drive burst firing, thereby initiating uniquely powerful signals to modulate sub-cortical representations and trigger learning-related plasticity. However, the behavioral relevance of corticofugal dendritic spikes is poorly understood. We shed light on this issue using 2-photon Ca2+ imaging of auditory corticofugal dendrites as mice of either sex engage in a GO/NO-GO sound-discrimination task. Unexpectedly, only a minority of dendritic spikes were triggered by behaviorally relevant sounds under our conditions. Task related dendritic activity instead mostly followed sound cue termination and co-occurred with mice’s instrumental licking during the answer period of behavioral trials, irrespective of reward consumption. Temporally selective, optogenetic silencing of corticofugal neurons during the trial answer period impaired auditory discrimination learning. Thus, auditory corticofugal systems’ contribution to learning and plasticity may be partially nonsensory in nature. [ABSTRACT FROM AUTHOR]

Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting. This randomised, double-blind, placebo-controlled trial (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment [ATLANTIS]) was conducted at 55 general practices in England. Eligible participants were aged 18 years or older, with Rome IV IBS of any subtype, and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥75 points) despite dietary changes and first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomly assigned (1:1) to low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily), according to symptoms and tolerability. Participants, their general practitioners, investigators, and the analysis team were all masked to allocation throughout the trial. The primary outcome was the IBS-SSS score at 6 months. Effectiveness analyses were according to intention-to-treat; safety analyses were on all participants who took at least one dose of the trial medication. This trial is registered with the ISRCTN Registry (ISRCTN48075063) and is closed to new participants. Between Oct 18, 2019, and April 11, 2022, 463 participants (mean age 48·5 years [SD 16·1], 315 [68%] female to 148 [32%] male) were randomly allocated to receive low-dose amitriptyline (232) or placebo (231). Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (–27·0, 95% CI –46·9 to –7·10; p=0·0079). 46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months. There were five serious adverse reactions (two in the amitriptyline group and three in the placebo group), and five serious adverse events unrelated to trial medication. To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial. National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01). [ABSTRACT FROM AUTHOR]

The inferior colliculus (IC) is a midbrain hub critical for perceiving complex sounds, such as speech. In addition to processing ascending inputs from most auditory brainstem nuclei, the IC receives descending inputs from auditory cortex that control IC neuron feature selectivity, plasticity, and certain forms of perceptual learning. Although corticofugal synapses primarily release the excitatory transmitter glutamate, many physiology studies show that auditory cortical activity has a net inhibitory effect on IC neuron spiking. Perplexingly, anatomy studies imply that corticofugal axons primarily target glutamatergic IC neurons while only sparsely innervating IC GABA neurons. Corticofugal inhibition of the IC may thus occur largely independently of feedforward activation of local GABA neurons. We shed light on this paradox using in vitro electrophysiology in acute IC slices from fluorescent reporter mice of either sex. Using optogenetic stimulation of corticofugal axons, we find that excitation evoked with single light flashes is indeed stronger in presumptive glutamatergic neurons compared with GABAergic neurons. However, many IC GABA neurons fire tonically at rest, such that sparse and weak excitation suffices to significantly increase their spike rates. Furthermore, a subset of glutamatergic IC neurons fire spikes during repetitive corticofugal activity, leading to polysynaptic excitation in IC GABA neurons owing to a dense intracollicular connectivity. Consequently, recurrent excitation amplifies corticofugal activity, drives spikes in IC GABA neurons, and generates substantial local inhibition in the IC. Thus, descending signals engage intracollicular inhibitory circuits despite apparent constraints of monosynaptic connectivity between auditory cortex and IC GABA neurons. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a disorder of a gut-brain interaction characterised by abdominal pain and a change in stool form or frequency. Current symptom-based definitions and the classification of IBS promote heterogeneity amongst patients, meaning that there may be several different pathophysiological abnormalities leading to similar symptoms. Although our understanding of IBS is incomplete, there are several indicators that the microbiome may be involved in a subset of patients. Techniques including a faecal sample analysis, colonic biopsies, duodenal aspirates or surrogate markers, such as breath testing, have been used to examine the gut microbiota in individuals with IBS. Because of a lack of a clear definition of what constitutes a healthy gut microbiota, and the fact that alterations in gut microbiota have only been shown to be associated with IBS, a causal relationship is yet to be established. We discuss several hypotheses as to how dysbiosis may be responsible for IBS symptoms, as well as potential treatment strategies. We review the current evidence for the use of antibiotics and probiotics to alter the microbiome in an attempt to improve IBS symptoms. Rifaximin, a non-absorbable antibiotic, is the most studied antibiotic and has now been licensed for use in IBS with diarrhoea in the USA, but the drug remains unavailable in many countries for this indication. Current evidence also suggests that certain probiotics, including Lactobacillus plantarum DSM 9843 and Bifidobacterium bifidum MIMBb75, may be efficacious in some patients with IBS. Finally, we describe the future challenges facing us in our attempt to modulate the microbiome to treat IBS. [ABSTRACT FROM AUTHOR]

Summary: Background: Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown. Aim: To perform a systematic review with network meta‐analysis to resolve this uncertainty. Methods: We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities. Results: We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58‐0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36‐0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo. Conclusions: TCAs, histamine‐2 receptor antagonists, standard‐ and low‐dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome is a functional gastrointestinal disorder with symptoms including abdominal pain associated with a change in stool form or frequency. The condition affects between 5% and 10% of otherwise healthy individuals at any one point in time and, in most people, runs a relapsing and remitting course. The best described risk factor is acute enteric infection, but irritable bowel syndrome is also more common in people with psychological comorbidity and in young adult women than in the rest of the general population. The pathophysiology of irritable bowel syndrome is incompletely understood, but it is well established that there is disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and altered CNS processing. Other less reproducible mechanisms might include genetic associations, alterations in gastrointestinal microbiota, and disturbances in mucosal and immune function. In most people, diagnosis can be made on the basis of clinical history with limited and judicious use of investigations, unless alarm symptoms such as weight loss or rectal bleeding are present, or there is a family history of inflammatory bowel disease or coeliac disease. Once the diagnosis is made, an empathetic approach is key and can improve quality of life and symptoms, and reduce health-care expenditure. The mainstays of treatment include patient education about the condition, dietary changes, soluble fibre, and antispasmodic drugs. Other treatments tend to be reserved for people with severe symptoms and include central neuromodulators, intestinal secretagogues, drugs acting on opioid or 5-HT receptors, or minimally absorbed antibiotics (all of which are selected according to predominant bowel habit), as well as psychological therapies. Increased understanding of the pathophysiology of irritable bowel syndrome in the past 10 years has led to a healthy pipeline of novel drugs in development. [ABSTRACT FROM AUTHOR]

Dyspepsia is a complex of symptoms referable to the gastroduodenal region of the gastrointestinal tract and includes epigastric pain or burning, postprandial fullness, or early satiety. Approximately 80% of individuals with dyspepsia have no structural explanation for their symptoms and have functional dyspepsia. Functional dyspepsia affects up to 16% of otherwise healthy individuals in the general population. Risk factors include psychological comorbidity, acute gastroenteritis, female sex, smoking, use of non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. The pathophysiology remains incompletely understood, but it is probably related to disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and alterations in gastrointestinal microbiota, mucosal and immune function, and CNS processing. Although technically a normal endoscopy is required to diagnose functional dyspepsia, the utility of endoscopy in all patients with typical symptoms is minimal; its use should be restricted to people aged 55 years and older, or to those with concerning features, such as weight loss or vomiting. As a result of our incomplete understanding of its pathophysiology, functional dyspepsia is difficult to treat and, in most patients, the condition is chronic and the natural history is one of fluctuating symptoms. Eradication therapy should be offered to patients with functional dyspepsia who test positive for Helicobacter pylori. Other therapies with evidence of effectiveness include proton pump inhibitors, histamine-2 receptor antagonists, prokinetics, and central neuromodulators. The role of psychological therapies is uncertain. As our understanding of the pathophysiology of functional dyspepsia increases, it is probable that the next decade will see the emergence of truly disease-modifying therapies for the first time. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Gunn et al papers. To view these articles, visit https://doi.org/10.1111/apt.17426 and https://doi.org/10.1111/apt.17462 [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Although the incidence of GC is predicted to continue declining in a growing number of countries in the future, on a global scale the number of newly diagnosed GC cases will remain high, or increase even further, due to changes in population size and increasing risks observed in younger generations. In a retrospective cohort study, collecting data from the Veterans Health Administration, treatment of Helicobacter pylori infection decreased GC risk only if eradication was successful. In a German case‐control study, among GC patients with autoimmune gastritis, pernicious anemia was associated with earlier detection of GC, which translated into a significantly better 5‐year survival. In an updated meta‐analysis, H. pylori eradication therapy in healthy individuals significantly reduced both GC incidence and mortality from GC with a number needed to treat of 72 and 135, respectively. In Korea, successful H. pylori eradication substantially reduced GC incidence in first‐degree relatives of GC patients as well. A meta‐analysis of four trials including 1,556 patients with resectable GC reported that the patient subgroup tumors with high microsatellite instability undergoing surgery did not benefit from perioperative or adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder that is thought to be due to a disorder of brain–gut function. Drugs acting centrally, such as antidepressants, and psychological therapies may, therefore, be effective. METHODS: We updated a previous systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, PsychINFO, and the Cochrane Controlled Trials Register were searched (up to July 2017). Trials recruiting adults with IBS, which compared antidepressants versus placebo, or psychological therapies versus control therapy or "usual management" were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). RESULTS: The search strategy identified 5316 citations. Fifty-three RCTs, reported in 51 separate articles, were eligible for inclusion: 17 compared antidepressants with placebo, 35 compared psychological therapies with control therapy or "usual management", and one compared both psychological therapy and antidepressants with placebo. Four of the trials of psychological therapies, and one of the RCTs of antidepressants, were identified since our previous meta-analysis. The RR of IBS symptoms not improving with antidepressants versus placebo was 0.66 (95% CI 0.57–0.76), with similar treatment effects for both tricyclic antidepressants and SSRIs, although with heterogeneity between RCTs of the latter (I2 = 49%, P = 0.07). The RR of symptoms not improving with psychological therapies was 0.69 (95% CI 0.62–0.76). Cognitive behavioral therapy, relaxation therapy, multi-component psychological therapy, hypnotherapy, and dynamic psychotherapy were all beneficial when data from two or more RCTs were pooled. There was significant heterogeneity between studies (I2 = 69%, P < 0.001) and significant funnel plot asymmetry. There were also issues regarding trial design, including lack of blinding. CONCLUSIONS: Antidepressants are efficacious in reducing symptoms in IBS patients. Psychological therapies also appear to be effective treatments for IBS, although there are limitations in the quality of the evidence, and treatment effects may be overestimated as a result. [ABSTRACT FROM AUTHOR]

Summary: Background: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder. Disturbances in the gastrointestinal microbiome may be involved in its aetiology. Aim: To perform a systematic review and meta‐analysis to examine the efficacy of prebiotics, probiotics, synbiotics and antibiotics in IBS. Methods: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to July 2017). Randomised controlled trials (RCTs) recruiting adults with IBS, comparing prebiotics, probiotics, synbiotics or antibiotics with placebo or no therapy were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardised mean difference with a 95% CI. Results: The search identified 4017 citations. Data for prebiotics and synbiotics were sparse. Fifty‐three RCTs of probiotics, involving 5545 patients, were eligible. Particular combinations of probiotics, or specific species and strains, appeared to have beneficial effects on global IBS symptoms and abdominal pain, but it was not possible to draw definitive conclusions about their efficacy. There were five trials of similar design that used rifaximin in non‐constipated IBS patients, which was more effective than placebo (RR of symptoms persisting = 0.84; 95% CI 0.79‐0.90). Adverse events were no more common with probiotics or antibiotics. Conclusions: Which particular combination, species or strains of probiotics are effective for IBS remains, for the most part, unclear. Rifaximin has modest efficacy in improving symptoms in non‐constipated IBS. [ABSTRACT FROM AUTHOR]

Objective: Dietary triggers such as gluten and highly fermentable oligo-, di- and monosaccharides and polyols (FODMAP)-containing foods have been associated with worsening irritable bowel syndrome (IBS) symptoms. However, the true impact of dietary restriction on IBS symptoms has remained unclear. The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the efficacy of exclusion diets (we focused on low FODMAP and gluten-free diets (GFD)) in IBS.Methods: We conducted a search of the literature using the electronic databases MEDLINE (1946 to November 2017), EMBASE (1974 to November 2017), Cochrane Central Register of Controlled Trials (November 2017), and Cochrane Database of Systematic Reviews (2005 to November, 2017) for RCTs of exclusion diets in IBS. Two independent reviewers screened citations and a third reviewer resolved disagreement. Two independent reviewers performed eligibility assessment and data abstraction. For inclusion, RCTs that evaluated an exclusion diet versus an alternative or usual diet and assessed improvement in either global IBS symptoms or abdominal pain were required. Data were synthesized as relative risk of symptoms remaining using a random effects model. Quality of evidence was assessed using GRADE methodology.Results: A total of 1726 citations were identified. After full-text screening a total of nine studies were eligible for the systematic review. There were two RCTs of a GFD, involving 111 participants. Both selected patients who responded to a GFD and then randomized them to continue the diet or have the diet “spiked” with gluten. A GFD was associated with reduced global symptoms compared with a control diet (RR = 0.42; 95% CI 0.11 to 1.55; I2 = 88%), although this was not statistically significant. There were seven RCTs comparing a low FODMAP diet with various control interventions in 397 participants. A low FODMAP diet was associated with reduced global symptoms compared with control interventions (RR = 0.69; 95% CI 0.54 to 0.88; I2 = 25%). The three RCTS that compared low FODMAP diet with rigorous control diets had the least heterogeneity between studies, but also the least magnitude of effect. The overall quality of the data was “very low” according to GRADE criteria.Conclusions: There is insufficient evidence to recommend a GFD to reduce IBS symptoms. There is very low quality evidence that a low FODMAP diet is effective in reducing symptoms in IBS patients. [ABSTRACT FROM AUTHOR]

An electron-positron cascade in the magnetospheres of Kerr black holes (BHs) is a fundamental ingredient to fueling the relativistic γ -ray jets seen at the polar regions of galactic supermassive BHs (SMBHs). This leptonic cascade occurs in the spark gap region of a BH magnetosphere where the unscreened electric field parallel to the magnetic field is present; hence, it is affected by the magnetic field structure. A previous study explored the case of a thin accretion disk, representative of active galactic nuclei. Here we explore the case of a quasi-spherical gas distribution, as is expected to be present around the SMBH Sgr A* in the center of our Milky Way galaxy, for example. The properties and efficiency of the leptonic cascade are studied. The findings of our study and the implications for SMBH systems in various spectral and accretion states are discussed. The relationships and scalings derived from varying the mass of the BH and background photon spectra are further used to analyze the leptonic cascade process to power jets seen in astronomical observations. In particular, one finds the efficiency of the cascade in a quasi-spherical gas distribution peaks at the jet axis. Observationally, this should lead to a more prominent jet core, in contrast to the thin disk accretion case, where it peaks around the jet–disk interface. One also finds the spectrum of the background photons plays a key role. The cascade efficiency is maximum for a spectral index of 2, while harder and softer spectra lead to a less efficient cascade. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a disorder of the brain-gut axis; the pathophysiological mechanisms include altered colonic motility, bile acid metabolism, neurohormonal regulation, immune dysfunction, alterations in the epithelial barrier and secretory properties of the gut. This article reviews the mechanisms, efficacy, and safety of current pharmacotherapy, and medications that are in phase III trials for the treatment of IBS. There remains a significant unmet need for effective treatments—particularly for the pain component of IBS—although the introduction of drugs directed at secretion, motility and a non-absorbable antibiotic provide options for the bowel dysfunction in IBS. [ABSTRACT FROM AUTHOR]

We are grateful to Trindade et al. 1 for their interest in our paper, which examined the factor structure of the visceral sensitivity index (VSI) among 811 individuals with Rome IV irritable bowel syndrome (IBS) from the UK.2 The VSI is a measure of gastrointestinal symptom-specific anxiety that had not been validated in the UK population. The original validation study involved only 96 individuals who self-identified with IBS, of whom 85% met Rome II criteria.3 We also recruited individuals who self-identified with IBS, but our study cohort was much larger, and we only included those who met diagnostic criteria for IBS. Abbreviations IBS irritable bowel syndrome VSI visceral sensitivity index CONFLICT OF INTEREST CJB and ACF have none to declare. [Extracted from the article]

The article describes the chronic and functional disabling irritable bowel syndrome (IBS). The authors mention the emerging evidence that suggests the role of pathophysiological disturbances beyond the psychiatric somatosensory disorder. They recommend a precise IBS diagnosis to ensure effective treatment and cure to reduce the negative affects of IBS in the patients' quality of life and work productivity.

INTRODUCTION: These post hoc analyses provide clinically relevant data concerning time to response for individual irritable bowel syndrome with constipation (IBS-C) symptoms after linaclotide use. METHODS: Time-to-response data were pooled from 4 randomized controlled trials. Response time for abdominal symptoms (pain, discomfort, and bloating) and complete spontaneous bowel movements (CSBMs) were analyzed using the Kaplan-Meier method; patients were categorized as early responders (≤4 weeks), late responders (>4-12 weeks), or nonresponders. RESULTS: Among 2,350 patients (1,172 placebo and 1,178 linaclotide 290 mg), >50% of patients with IBS-C who initiated linaclotide treatment experienced a decrease of ≥30% in abdominal pain, discomfort, or bloating within 3-4 weeks (median). The median time to achieving ≥3 CSBMs was 4 weeks. Although not all linaclotide-treated patients responded within 12 weeks, a late response occurred between 4 and 12 weeks in 1 in 6 patients for abdominal pain and in approximately 1 in 10 patients for CSBM frequency. Comparisons of early responders, late responders, and nonresponders for both response definitions indicated that women, Whites, and patients with less severe baseline abdominal symptoms were more likely to respond early. DISCUSSION: Although treatment responses with linaclotide occurred in >50% of patients with IBS-C within 4 weeks of treatment initiation, benefits for individual abdominal symptoms and/or CSBM frequency can still occur between 4 and 12 weeks. A lack of improvement in one symptom does not negate the possibility of response for others, highlighting the importance of discussing all symptoms with patients and not assuming treatment futility at 4 weeks. [ABSTRACT FROM AUTHOR]

Antecedentes El cáncer gástrico es la tercera causa más frecuente de muerte por cáncer en todo el mundo. Los individuos con infección por Helicobacter pylori tienen una mayor probabilidad de desarrollar cáncer gástrico que los individuos que no están infectados. La erradicación del H. pylori en individuos asintomáticos sanos de la población general puede reducir la incidencia de cáncer gástrico, pero la magnitud de este efecto es incierta. [ABSTRACT FROM AUTHOR]

High-amplitude, chaotic or turbulent electromagnetic fluctuations are ubiquitous in high-energy-density laboratory and astrophysical plasmas, where they can be excited by various kinetic-streaming and/or anisotropydriven instabilities, such as the Weibel instability. These fields typically exist on "sub-Larmor scales"-scales smaller than the electron Larmor radius. Electrons moving through such magnetic fields undergo small-angle stochastic deflections of their pitch angles, thus establishing diffusive transport on long time scales. We show that this behavior, under certain conditions, is equivalent to Coulomb collisions in collisional plasmas. The magnetic pitch-angle diffusion coefficient, which acts as an effective "collision" frequency, may be substantial in these, otherwise, collisionless environments. We show that this effect, colloquially referred to as the plasma "quasicollisionality," may radically alter the expected radiative transport properties of candidate plasmas. We argue that the modified magneto-optic effects in these plasmas provide an attractive, radiative diagnostic tool for the exploration and characterization of small-scale magnetic turbulence, as well as affect inertial confinement fusion and other laser-plasma experiments. [ABSTRACT FROM AUTHOR]

The article focuses on dyspepsia and emphasizes the need for physicians to recognize functional dyspepsia, use investigations and diagnostic tests wisely, and recommend effective treatments to minimize the potential adverse social and economic effects of the condition. Topics discussed include diagnosis of functional dyspepsia, its classification, and its pathophysiological features. It also details treatment of and prognosis in functional dyspepsia.

Plasmas with electromagnetic fields turbulent at sub-Larmor scales are a feature of a wide variety of high-energy-density environments and are essential to the description of many astrophysical and laboratory plasma phenomena. Radiation from particles, whether they are relativistic or nonrelativistic, moving through small-scale magnetic turbulence has spectral characteristics distinct from both synchrotron and cyclotron radiation. The radiation, carrying information on the statistical properties of the magnetic turbulence, is also intimately related to the particle diffusive transport. We have investigated, both theoretically and numerically, the transport of nonrelativistic and trans-relativistic particles in plasmas with high-amplitude isotropic sub-Larmor-scale magnetic turbulence, and its relation to the spectra of radiation simultaneously produced by these particles. Consequently, the diffusive and radiative properties of plasmas turbulent on sub-Larmor scales may serve as a powerful tool to diagnosis laboratory and astrophysical plasmas. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Black et al and Simmons & Taft papers. To view these articles, visit https://doi.org/10.1111/apt.16322 and https://doi.org/10.1111/apt.16345 [ABSTRACT FROM AUTHOR]

AimTo examine beliefs about irritable bowel syndrome (IBS) management among primary care physicians.BackgroundThere have been considerable advances in evidence synthesis concerning management of IBS in the last five years, with guidelines for its management in primary care published by the National Institute for Health and Care Excellence (NICE).MethodsThis was a cross-sectional web-based questionnaire survey of 275 primary care physicians. We emailed a link to a SurveyMonkey questionnaire, containing 18 items, to all eligible primary care physicians registered with three clinical commissioning groups in Leeds, UK. Participants were given one month to respond, with a reminder sent out after two weeks.FindingsOne-hundred and two (37.1%) primary care physicians responded. Among responders, 70% believed IBS was a diagnosis of exclusion, and >80% checked coeliac serology often or always in suspected IBS. Between >50% and >70% believed soluble fibre, antispasmodics, peppermint oil, and psychological therapies were potentially efficacious therapies. The respondents were less convinced that antidepressants or probiotics were effective. Despite perceived efficacy of psychological therapies, 80% stated these were not easily available. Levels of use of soluble fibre, antispasmodics, and peppermint oil were in the range of 40% to >50%. Most primary care physicians obtained up-to-date evidence about IBS management from NICE guidelines. Most primary care physicians still believe IBS is a diagnosis of exclusion, and many are reluctant to use antidepressants or probiotics to treat IBS. More research studies addressing diagnosis and treatment of IBS based in primary are required. [ABSTRACT FROM AUTHOR]

Objectives Many cross-sectional surveys have reported the prevalence of uninvestigated dyspepsia, but there has been no recent systematic review of data from all studies to determine its global prevalence and risk factors. Design MEDLINE, EMBASE and EMBASE Classic were searched (until January 2014) to identify populationbased studies that reported the prevalence of uninvestigated dyspepsia in adults (=15 years old); dyspepsia was defined using symptom-based criteria or questionnaires. The prevalence of dyspepsia was extracted for all studies and according to the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, ORs and 95% CIs were calculated. Results Of the 306 citations evaluated, 103 reported the prevalence of uninvestigated dyspepsia in 100 separate study populations, containing 312 415 subjects. Overall pooled prevalence in all studies was 20.8% (95% CI 17.8% to 23.9%). The prevalence varied according to country (from 1.8% to 57.0%) and criteria used to define dyspepsia. The greatest prevalence values were found when a broad definition of dyspepsia (29.5%; 95% CI 25.3% to 33.8%) or upper abdominal or epigastric pain or discomfort (20.4%; 95% CI 16.3% to 24.8%) were used. The prevalence was higher in women (OR 1.24; 95% CI 1.13 to 1.36), smokers (OR 1.25; 95% CI 1.12 to 1.40), non-steroidal antiinflammatory drug (NSAID) users (OR 1.59; 95% CI 1.27 to 1.99) and Helicobacter pylori-positive individuals (OR 1.18; 95% CI 1.04 to 1.33). Conclusions The overall pooled prevalence of uninvestigated dyspepsia was 21%, but varied among countries and according to the criteria used to define its presence. Prevalence is significantly higher in women, smokers, NSAID users and H. pylori-positive individuals, although these associations were modest. [ABSTRACT FROM AUTHOR]

Objectives:Anxiety and depression occur frequently in patients with functional gastrointestinal disorders (FGIDs), but their precise prevalence is unknown. We addressed this issue in a large cohort of adult patients and determined the underlying factors.Methods:In total, 4,217 new outpatients attending 2 hospitals in Hamilton, Ontario, Canada completed questionnaires evaluating FGIDs and anxiety and depression (Hospital Anxiety and Depression scale). Chart review was performed in a random sample of 2,400 patients.Results:Seventy-six percent of patients fulfilled Rome III criteria for FGIDs, but only 57% were diagnosed with FGIDs after excluding organic diseases, and the latter group was considered for the analysis. Compared with patients not meeting the criteria, prevalence of anxiety (odds ratio (OR) 2.66, 95% confidence interval (CI): 1.62-4.37) or depression (OR 2.04, 95% CI: 1.03-4.02) was increased in patients with FGIDs. The risk was comparable to patients with organic disease (anxiety: OR 2.12, 95% CI: 1.24-3.61; depression: OR 2.48, 95% CI: 1.21-5.09). The lowest prevalence was observed in asymptomatic patients (OR 1.37; 95% CI 0.58-3.23 and 0.51; 95% CI 0.10-2.48; for both conditions, respectively). The prevalence of anxiety and depression increased in a stepwise manner with the number of co-existing FGIDs and frequency and/or severity of gastrointestinal (GI) symptoms. Psychiatric comorbidity was more common in females with FGIDs compared with males (anxiety OR 1.73; 95% CI 1.35-2.28; depression OR 1.52; 95% CI 1.04-2.21). Anxiety and depression were formally diagnosed by the consulting physician in only 22% and 9% of patients, respectively.Conclusions:Psychiatric comorbidity is common in patients referred to a secondary care center but is often unrecognized. The prevalence of both anxiety and depression is influenced by gender, presence of organic diseases, and FGIDs, and it increases with the number of coexistent FGIDs and frequency and severity of GI symptoms. [ABSTRACT FROM AUTHOR]

OBJECTIVES:There are few data concerning the utility of symptoms and signs at first presentation in predicting a diagnosis of ulcerative colitis (UC) or Crohn's disease (CD). We conducted a study to examine this issue in secondary care.METHODS:We collected complete symptom, colonoscopy, and histology data prospectively from 1,981 consecutive adult patients with lower gastrointestinal symptoms at two hospitals in Hamilton, Ontario. Assessors were blinded to symptom status. The reference standard used to define the presence of UC or CD was according to accepted histological criteria. Patients without UC or CD served as controls. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated for individual items from the clinical history, as well as combinations of these.RESULTS:In identifying 302 patients with inflammatory bowel diseases (IBD), positive LRs for individual items ranged from 1.18 (incomplete emptying) to 2.30 (passage of stools more than four times per day at least most of the time) and negative LRs from 0.70 (bloody stools) to 0.96 (incomplete emptying). Combinations of items had a high specificity, but at the expense of sensitivity. Items that were independent predictors of IBD after logistic regression analysis were family history of IBD, younger age, passage of stools more than four times per day ≥75% of the time, urgency most of the time, and anemia.CONCLUSIONS:Individual items from the clinical history are not helpful in predicting a diagnosis of UC or CD. However, this may be because some items lacked sufficient detail. Combinations of symptoms and computer models had a high specificity, but overall were only modestly useful diagnostically. Future studies should evaluate biological markers in combination with symptoms to improve accuracy. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC) are functional bowel disorders. Evidence suggests that disturbance in the gastrointestinal microbiota may be implicated in both conditions. We performed a systematic review and meta-analysis to examine the efficacy of prebiotics, probiotics, and synbiotics in IBS and CIC.METHODS:MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Randomized controlled trials (RCTs) recruiting adults with IBS or CIC, which compared prebiotics, probiotics, or synbiotics with placebo or no therapy, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized or weighted mean difference with a 95% CI.RESULTS:The search strategy identified 3,216 citations. Forty-three RCTs were eligible for inclusion. The RR of IBS symptoms persisting with probiotics vs. placebo was 0.79 (95% CI 0.70-0.89). Probiotics had beneficial effects on global IBS, abdominal pain, bloating, and flatulence scores. Data for prebiotics and synbiotics in IBS were sparse. Probiotics appeared to have beneficial effects in CIC (mean increase in number of stools per week=1.49; 95% CI=1.02-1.96), but there were only two RCTs. Synbiotics also appeared beneficial (RR of failure to respond to therapy=0.78; 95% CI 0.67-0.92). Again, trials for prebiotics were few in number, and no definite conclusions could be drawn.CONCLUSIONS:Probiotics are effective treatments for IBS, although which individual species and strains are the most beneficial remains unclear. Further evidence is required before the role of prebiotics or synbiotics in IBS is known. The efficacy of all three therapies in CIC is also uncertain. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence relating to the treatment of this condition with antidepressants and psychological therapies continues to accumulate.METHODS:We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Trials recruiting adults with IBS, which compared antidepressants with placebo, or psychological therapies with control therapy or 'usual management,' were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI).RESULTS:The search strategy identified 3,788 citations. Forty-eight RCTs were eligible for inclusion: thirty-one compared psychological therapies with control therapy or 'usual management,' sixteen compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Ten of the trials of psychological therapies, and four of the RCTs of antidepressants, had been published since our previous meta-analysis. The RR of IBS symptom not improving with antidepressants vs. placebo was 0.67 (95% CI=0.58-0.77), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms not improving with psychological therapies was 0.68 (95% CI=0.61-0.76). Cognitive behavioral therapy, hypnotherapy, multicomponent psychological therapy, and dynamic psychotherapy were all beneficial.CONCLUSIONS:Antidepressants and some psychological therapies are effective treatments for IBS. Despite the considerable number of studies published in the intervening 5 years since we last examined this issue, the overall summary estimates of treatment effect have remained remarkably stable. [ABSTRACT FROM AUTHOR]

The article discusses the symptoms, treatment, and diagnosis of irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC) (functional constipation). Emphasis is given to the efficacy of medical interventions such as diet and dietary manipulation, the modification of microbiota, and evaluation of the agonists and antagonists to serotonergic receptors.

In this article authors concluded that several thresholds were clinically useful for screening and for diagnosing bile acid diarrhea. Topics include considered that SeHCAT scanning is not available in several countries and provision is not uniform, and thresholds used to define BAD inconsistent; and examines that the discussion of the selection of study patients is essential and relevant.

The article presents the discussion on efficacy of bimodal release ondansetron in irritable bowel syndrome with diarrhea combining the symptoms recommended by the Food and Drug Administration.

OBJECTIVES:There has been no definitive synthesis of the evidence for any benefit of available pharmacological therapies in opioid-induced constipation (OIC). We conducted a systematic review and meta-analysis to address this deficit.METHODS:We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials through to December 2012 to identify placebo-controlled trials of μ-opioid receptor antagonists, prucalopride, lubiprostone, and linaclotide in the treatment of adults with OIC. No minimum duration of therapy was required. Trials had to report a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Effect of pharmacological therapies was reported as relative risk (RR) of failure to respond to therapy, with 95% confidence intervals (CIs).RESULTS:Fourteen eligible randomized controlled trials (RCTs) of μ-opioid receptor antagonists, containing 4,101 patients, were identified. These were superior to placebo for the treatment of OIC (RR of failure to respond to therapy=0.69; 95% CI 0.63-0.75). Methylnaltrexone (six RCTs, 1,610 patients, RR=0.66; 95% CI 0.54-0.84), naloxone (four trials, 798 patients, RR=0.64; 95% CI 0.56-0.72), and alvimopan (four RCTs, 1,693 patients, RR=0.71; 95% CI 0.65-0.78) were all superior to placebo. Total numbers of adverse events, diarrhea, and abdominal pain were significantly commoner when data from all RCTs were pooled. Reversal of analgesia did not occur more frequently with active therapy. Only one trial of prucalopride was identified, with a nonsignificant trend toward higher responder rates with active therapy. Two RCTs of lubiprostone were found, with significantly higher responder rates with lubiprostone in both, but reporting of data precluded meta-analysis.CONCLUSIONS:μ-Opioid receptor antagonists are safe and effective for the treatment of OIC. More data are required before the role of prucalopride or lubiprostone in the treatment of OIC are clear. [ABSTRACT FROM AUTHOR]

We searched Medline, Embase, the Cochrane Database of Systematic Reviews, and Clinical Evidence online using the search term "dyspepsia", as well as recent conference proceedings. We limited studies to those conducted in adults and focused on systematic reviews, meta-analyses, and high quality randomised controlled trials published during the past five years whenever possible. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Several anti-tumor necrosis factor-α (TNFα) antibodies have demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC). These drugs carry the theoretical risk of opportunistic infection, but no systematic review and meta-analysis has examined this issue specifically.METHODS:MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through to November 2012). Randomized controlled trials (RCTs) recruiting adults with active or quiescent CD or UC comparing anti-TNFα therapy with placebo were eligible. Dichotomous data were pooled to obtain a relative risk (RR) of opportunistic infection, with a 95% confidence interval (CI). The number needed to harm (NNH) was estimated from the reciprocal of the risk difference from the meta-analysis.RESULTS:The search strategy identified 20,563 citations, 21 of which were eligible, reporting 22 separate RCTs with between 2 and 56 weeks of follow-up. In total, there were 39 (0.9%) opportunistic infections among 4,135 patients allocated to anti-TNFα therapy, compared with 9 (0.3%) among 2,919 assigned to placebo. Among patients receiving active therapy these included eight cases of Mycobacterium tuberculosis, eight cases of herpes simplex infection, six cases of oral or esophageal candidiasis, six cases of herpes zoster infection, two cases of varicella-zoster virus infection, two cases of cytomegalovirus or Epstein-Barr virus infection, and one case of Nocardia infection. The RR of developing an opportunistic infection was significantly higher with anti-TNFα therapy (2.05; 95% CI 1.10-3.85, NNH=500; 95% CI 200-1,567). The RR of tuberculosis infection was 2.52 (95% CI 0.62-10.21).CONCLUSIONS:Anti-TNF therapy doubles the risk of opportunistic infections in inflammatory bowel disease patients. This underlines the importance of adherence to guidelines for their prevention and management. [ABSTRACT FROM AUTHOR]

Background: Previously, we used latent class analysis (LCA) to identify novel subgroups in people with irritable bowel syndrome (IBS). There are four other functional bowel disorders that, although characterized as discrete disorders, overlap considerably with, and fluctuate to, IBS. These might instead be conceptualized as a milder form of IBS. We explored this hypothesis using LCA in a cohort of people with non‐IBS functional bowel disorders. Methods: We collected demographic, symptom, and psychological health data from 1375 adults in the community who self‐identified as having IBS and identified individuals meeting Rome IV criteria for any non‐IBS functional bowel disorder. We performed LCA to identify specific subgroups (clusters). We followed participants up at 12 months to reassess gastrointestinal and psychological heath and also gather data about healthcare utilization and impact of symptoms. Key results: 811 people met Rome IV criteria for IBS and 558 Rome IV criteria for another functional bowel disorder (76 (5.5%) functional constipation; 198 (14.5%) functional diarrhea; 129 (9.5%) functional abdominal bloating or distension; and 155 (11.4%) unspecified functional bowel disorder). LCA in these 558 people identified five clusters defined by a combination of gastrointestinal symptoms and the extent of psychological co‐morbidity. However, correlation between these clusters and the Rome IV functional bowel disorder diagnoses was poor and 75% of people were classified as having mild IBS using our previous IBS‐derived model. By 12 months, one‐third of people had fluctuated and met criteria for IBS. Clusters with high psychological burden had a poorer prognosis, with higher rates of medical consultation, medication use, and greater impact of symptoms on daily life. Conclusions and inferences: The functional bowel disorders may be better characterized as a spectrum of IBS rather than separate disorders. Adopting this pragmatic stance may help to simply diagnosis, treatment, and recruitment of patients to research trials. [ABSTRACT FROM AUTHOR]

The article discusses ulcerative colitis that affects the colorectum and is more common in young adulthood and developed nations. It describes the causes, associated conditions and treatment options. It also discusses treatment of refractory disease, colorectal cancer screening and osteoporosis in ulcerative colitis. It also states that patients with the disease have serious implications for pregnancy. INSET: Discussing ulcerative colitis and its treatment with patients.

OBJECTIVES:Irritable bowel syndrome (IBS) and gastro-esophageal reflux-type symptoms (GERS) are highly prevalent in the general population, and the two appear to be related. We conducted a systematic review and meta-analysis to estimate the prevalence of GERS in individuals with IBS, and to quantify the overlap between the two disorders.METHODS:MEDLINE, EMBASE, and EMBASE Classic were searched (up to October 2011) to identify population-based studies reporting the prevalence of IBS and GERS in adults (≥15 years), defined using a specific symptom-based criteria or a questionnaire. The prevalence of IBS and GERS were extracted for all studies. Pooled prevalence, according to study location and criteria used to define IBS or GERS, as well as odds ratios (OR), with 95% confidence intervals (CIs) were calculated. The degree of overlap between the two was examined.RESULTS:Of 390 papers evaluated, 81 reported prevalence of IBS. Thirteen of these, containing 49,939 participants, reported the proportion of individuals with GERS. The prevalence of GERS in IBS was 42.0% (95% CI, 30.0-55.0). The pooled OR for GERS in individuals with IBS, compared with those without, was 4.17 (95% CI, 2.85-6.09). The OR for GERS in IBS remained significantly higher in all geographical regions studied, and for all diagnostic criteria used. The degree of overlap between the two conditions varied from 14.2, when the Rome II criteria for IBS were used, to 26.7% with the Manning criteria.CONCLUSIONS:The OR of GERS in individuals with IBS was four-fold that of individuals without IBS. Reasons for this remain speculative, but may include shared pathophysiological mechanisms or residual confounding. [ABSTRACT FROM AUTHOR]

The article discusses the use of laxatives as a form of relieving chronic constipation in adults. Some of the red flags that need to be kept in mind by physicians while diagnosing adults for chronic constipation include recent onset of constipation in older age over 50 years, obstructive symptoms, rectal bleeding, weight loss, family history of colon cancer, iron deficiency anemia, and Haem positive stool. The different types of laxatives along with their positive and negative effects are described. The precautions to be taken with regards to the use of laxatives are also included. Some tips for patients to follow regarding constipation and the use of laxatives are highlighted. INSET: TIPS FOR PATIENTS.

OBJECTIVES:Symptoms compatible with irritable bowel syndrome (IBS) may co-exist in patients with inflammatory bowel disease (IBD), presenting a clinical dilemma for physicians. We conducted a systematic review and meta-analysis to examine this issue.METHODS:MEDLINE, EMBASE, and EMBASE Classic were searched (through February 2012) to identify cross-sectional surveys or case-control studies reporting the prevalence of symptoms meeting diagnostic criteria for IBS in ≥50 unselected adult IBD patients. The number of individuals with symptoms meeting criteria for IBS was extracted for each study, and pooled prevalence and odds ratios (ORs), with 95% confidence intervals (CIs), were calculated.RESULTS:The search identified 3,045 articles. Thirteen studies, containing 1,703 patients, were eligible. The pooled prevalence for IBS in all IBD patients was 39% (95% CI 30-48%), with an OR compared with controls of 4.89 (95% CI 3.43-6.98). In IBD patients in remission, the OR was 4.39 (95% CI 2.24-8.61). For IBD patients with active disease, the pooled prevalence of IBS was 44%, compared with 35% in those felt to be in remission (OR 3.89; 95% CI 2.71-5.59). The prevalence in patients with Crohn's disease (CD) was higher than in those with ulcerative colitis (UC; 46 vs. 36%, OR 1.62; 95% CI 1.21-2.18).CONCLUSIONS:Symptoms compatible with IBS were significantly higher in patients with IBD compared with non-IBD controls, even among those felt to be in remission. IBS-type symptoms were also significantly more common in CD than in UC patients, and in those with active disease. Management strategies for IBD patients with symptoms suggestive of IBS are required. [ABSTRACT FROM AUTHOR]

The article discusses irritable bowel syndrome (IBS), one of the commonest gastrointestinal conditions encountered in primary or secondary care, more prevalent in younger people and women, and is not associated with increased mortality. The pathophysiology of IBS, as well as its symptoms and diagnostic techniques are described. Some of the different treatment methodologies for IBS including diet and lifestyle, antispasmodic drugs, antidepressants, agents acting on the 5-hydroxytryptamine (5-HT) receptor, antibiotics and probiotics, psychological and behavioral therapy, and alternative therapies are included. The main things that non-specialists need to keep in mind for IBS are highlighted.

OBJECTIVES:Irritable bowel syndrome (IBS) is thought to be commoner in women. However, no systematic review has confirmed whether this is the case, or assessed whether any proposed female preponderance remains stable according to geography and criteria used to define IBS. Nor has effect of gender on subtype of IBS been examined systematically.METHODS:MEDLINE, EMBASE, and EMBASE Classic were searched (up to October 2011) to identify population-based studies reporting prevalence of IBS in adults (≥15 years) according to gender, and defined using symptom-based criteria, or questionnaire. The prevalence of IBS in women and men was extracted for all studies, and according to study location and diagnostic criteria used, and compared using odds ratios (ORs) with 95% confidence intervals (CIs). Prevalence of each subtype of IBS, according to predominant stool pattern, was compared in women and men with IBS.RESULTS:Of the 390 papers evaluated, 56 studies containing 188,229 subjects were eligible. The OR for IBS in women, compared with men, in all studies was 1.67 (95% CI: 1.53-1.82). Prevalence of IBS was not significantly higher in women, compared with men, in South Asian, South American, or African studies. The OR was highest with the Rome I criteria (1.99; 95% CI: 1.76-2.25), and lowest with the Rome II criteria (1.40; 95% CI: 1.24-1.59). Women with IBS were more likely to exhibit the constipation-predominant subtype (OR: 2.38; 95% CI: 1.45-3.92), and less likely to meet criteria for the diarrhea-predominant subtype (OR: 0.45; 95% CI: 0.32-0.65) than men with IBS.CONCLUSIONS:Prevalence of IBS appeared modestly higher in women, and this remained relatively stable according to geography and criteria used to define its presence. However, among individuals with IBS, subtypes varied according to gender. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Most chronic and recurrent gastrointestinal (GI) symptoms in the community are caused by functional GI disorders, such as functional dyspepsia and irritable bowel syndrome (IBS). It is not known, however, whether these conditions affect mortality. We present the results of a large community-based prospective study that examines this issue.METHODS:This was a 10-year follow-up, conducted in 2004, of individuals recruited into a community-based screening program for Helicobacter pylori. Data on mortality and cause of death at 10 years were obtained from the Office for National Statistics. Baseline demographic data, lifestyle factors, GI symptoms, and quality of life were recorded at study entry. The effect of all these factors on 10-year mortality was examined using univariate analysis and multivariate Cox regression analysis. All results were expressed as hazard ratios (HRs) with 99% confidence intervals (CIs).RESULTS:Symptom data were available for 8,323 (99.0%) of 8,407 individuals originally enrolled, comprising over 84,000 years of follow-up: 3,169 (38.1%) subjects had dyspepsia, and 264 (3.2%) IBS. There were 137 (1.65%) individuals who had died at 10 years. After multivariate analysis, there was no significant difference in likelihood of death at 10 years in those with dyspepsia (HR: 0.94; 99% CI: 0.58-1.54) or IBS (HR: 1.35; 99% CI: 0.36-5.10), compared with those not meeting the criteria for either condition.CONCLUSIONS:Dyspepsia was not associated with an increased mortality in the community. Data for any effect of IBS on survival were less clear. Further studies are required to assess the impact of functional GI disorders on life expectancy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Infliximab is licenced for use in Crohn''s disease (CD). Trial data demonstrate that infliximab is effective for inducing remission of active CD, healing fistulising CD, and preventing relapse once in remission. However, long-term data regarding efficacy, safety, and predictors of response are still emerging. Aim: To examine these issues in a large cohort of patients who received infliximab for CD. Methods: A retrospective analysis of prospectively collected data was performed for 210 patients receiving infliximab for luminal or fistulising CD. Response to infliximab induction therapy, and sustained clinical benefit, were assessed by a decrease in Harvey–Bradshaw Index (HBI) of ≥2 points. Remission was defined as an HBI≤4. Physician''s global assessment was used where HBI could not be obtained. Demographic and disease factors that may predict response to therapy were analysed by Kaplan–Meier plots and univariate and multivariate analyses. Results: Overall, 173 (82.4%) patients responded to infliximab induction, with 114 (65.9%) achieving sustained clinical benefit. Almost 40% of the study cohort had an HBI≤4, indicating remission, at last point of follow-up (median 24months). Concomitant immunosuppression predicted sustained clinical benefit in the first 6months of therapy (P=0.03). An inflammatory disease phenotype (P=0.04 univariate analysis, P=0.03 Kaplan Meier analysis) and male gender (P=0.03) also predicted sustained clinical benefit. Episodic therapy was associated with an increased likelihood of secondary non-response. Adverse events, including malignancies, were few. Conclusion: In this single centre study, infliximab was efficacious and well-tolerated in CD. [Copyright &y& Elsevier]

OBJECTIVES:Efficacy of 5-aminosalicylic acids (5-ASAs) in ulcerative colitis (UC) has been studied previously in meta-analyses. However, no recent meta-analysis has studied the relative efficacies of differing routes of administration.METHODS:MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through May 2011). Eligible trials recruited adults with mildly to moderately active UC, or quiescent UC, and compared oral 5-ASAs with either topical 5-ASAs or a combination of oral and topical 5-ASAs. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active UC, and RR of relapse of disease activity in quiescent UC, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference.RESULTS:The search identified 3,061 citations, and 12 randomized controlled trials (RCTs) were eligible. Four compared topical with oral 5-ASAs in active UC remission, with an RR of no remission with topical 5-ASAs of 0.82 (95% CI=0.52-1.28). Four trials compared combined with oral 5-ASAs in active UC (RR of no remission=0.65; 95% CI=0.47-0.91; NNT=5). Three RCTs compared intermittent topical with oral 5-ASAs in preventing relapse of quiescent UC (RR=0.64; 95% CI=0.43-0.95; NNT=4), and two compared combined with oral 5-ASAs (RR of relapse=0.48; 95% CI=0.17-1.38).CONCLUSIONS:Combined 5-ASA therapy appeared superior to oral 5-ASAs for induction of remission of mildly to moderately active UC. Intermittent topical 5-ASAs appeared superior to oral 5-ASAs for preventing relapse of quiescent UC. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Maintenance therapy with 5-aminosalicylates (5-ASAs) is recommended in patients with quiescent ulcerative colitis (UC), but compliance rates are low. Once-daily dosing may improve adherence, but impact on the relapse of disease activity is unclear as no previous meta-analysis has studied this issue.METHODS:MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through April 2011). Eligible randomized controlled trials (RCTs) recruited adults with quiescent UC, and compared once-daily dosing of 5-ASAs with a more frequent dosing schedule of an identical total daily dose of the same 5-ASA drug. Minimum treatment duration was 6 months. Trials reported a dichotomous assessment of relapse of disease activity at last point of follow-up. Data concerning non-compliance and adverse events were extracted, where reported. Effect of once-daily vs. more frequent dosing schedule was reported as relative risk (RR) of relapse with a 95% confidence interval (CI).RESULTS:The search identified 3,061 citations, and seven RCTs containing 2,745 patients were eligible. All RCTs used mesalamine. Relapse rates were not significantly different between once-daily and conventional dosing schedules for mesalamine (RR of relapse=0.94; 95% CI: 0.82-1.08). Non-compliance (RR=0.87; 95% CI: 0.46-1.66) and adverse events were no more likely with once-daily dosing (RR=1.08; 95% CI: 0.97-1.20).CONCLUSIONS:Once-daily dosing with mesalamine is as effective as conventional dosing schedules for the prevention of relapse of quiescent UC, although there is no definitive evidence that compliance with once-daily dosing is better. Adverse events occur at a similar frequency. [ABSTRACT FROM AUTHOR]