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Nocebo effects are thought to influence the rate of reported adverse events (AEs) and subject withdrawal in both the treatment and placebo groups of randomized clinical trials (RCTs). Neuromodulators are commonly prescribed to treat disorders of gut-brain interaction (DGBIs), but adherence to these medications is often limited by side effects such as headache, dry mouth, fatigue, and altered bowel habits. We performed a systematic review and meta-analysis to assess the proportion and risk difference of patients who experienced side effects leading to withdrawal in the placebo arm versus the treatment arm of RCTs of neuromodulators for DGBIs. We also sought to estimate the risk of developing any AE in the placebo arm of these studies as well as the rate of specific individual adverse events.We searched MEDLINE, Embase, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials Searches to identify RCTs that included terms for DGBIs and for commonly prescribed neuromodulators. We calculated pooled proportions of patients experiencing an AE leading to withdrawal in the active treatment group versus the placebo group with 95% confidence intervals (CI), the pooled proportions of patients experiencing any adverse event, the pooled proportions of patients experiencing specific adverse events such as dizziness and headache, the pooled proportions of patients experiencing severe adverse events and corresponding pooled risk differences with 95% CIs.There were 30 RCTs included representing 2284 DGBI patients. 27 RCTs reported data on AEs leading to withdrawal. The pooled proportion of total patients with AEs leading to withdrawal in the placebo group was 4% (95% CI 0.02 - 0.04). The pooled proportion of patients with AEs leading to withdrawal who received neuromodulators was 9% (95% CI 0.06-0.13). In the 12 studies reporting data on patients experiencing at least one AE, the pooled proportion of patients experiencing any adverse event in the placebo group was 18% (95% CI 0.08 - 0.30), compared to 43% (95% CI 0.24 - 0.63) in the neuromodulator group. Thus, approximately 44% of the rate of withdrawal (0.04/0.09) and 42% of the rate reporting any side effects (0.18/0.43) in the neuromodulator group may be attributed to nocebo effects in the right context. Subgroup analysis by sex, medication class, risk of bias, and specific DGBIs revealed differing withdrawal rates. There was no statistically significant difference in patients experiencing individual AEs of dizziness, headache or diarrhea. Rates of dry mouth, fatigue and constipation were higher in treatment groups compared to placebo groups.Patients with DGBIs in RCTs randomized to placebo groups frequently experience AEs and AEs that lead to withdrawal consistent with a strong nocebo effect. Non-specific AEs such as dizziness, headaches and diarrhea occurred similarly in patients receiving placebo compared to those receiving neuromodulators.

Opioids-induced esophageal dysfunction has been described with characteristic manometric patterns, but the population burden of dysphagia attributable to opioid use remains unclear.National Ambulatory Medical Care Survey (NAMCS) from 2008-2018 was used to assess the relationship between opioid use and outpatient visits for dysphagia.After controlling for potential confounders there were no significant difference in ambulatory visits for dysphagia between opioid users and non-users (adjusted odds ratio=0.98, confidence interval: 0.59-1.65).No correlation between opioid use and ambulatory visits for dysphagia was found in a nationwide sample. Opioid-related manometric changes may be clinically relevant only in a small proportion of patients.

Academic gastroenterology (GI) hospitalists are increasing, however the impacts on fellowship training and clinical care are unclear. Motivations for implementation of the GI hospitalist model are uninvestigated.We aimed to determine the prevalence of GI hospitalists, explore motivations for and against adoption of a GIH model, and investigate the model's effects on fellowship training.Leadership at current general GI fellowships were surveyed about current staffing models, as well as effects and perceptions of the hospitalist model.There was a total of 52 (26%) respondents and 12 (23%) reported having a GI hospitalist at their institution. A majority of respondents stated burnout and reduced time on service for other faculty was a primary reason for hiring a GI hospitalist.The largest perceived benefit of a hospitalist is reduced burnout and time on service for outpatient GI faculty. Many respondents also believed a GIH would improve fellowship education and quality of inpatient care.

OBJECTIVES:Although the endogenous cannabinoid system modulates bowel function, our understanding of the impact of recreational marijuana (MJ) use on bowel motility is limited. This study examines the effect of MJ on self-reported bowel function among a large cohort of US adults.METHODS:We identifie

Goals We sought to determine the incidence of jackhammer esophagus (JE) after lung transplantation (LT) and identify potential risk factors for the development of JE after LT. Background JE is a rare esophageal motility disorder, and its pathophysiology remains unclear. Lung transplantation has been implicated as a potential risk factor for JE, but the incidence of JE after LT is unknown. Study A retrospective cohort of adult patients who underwent LT at 2 tertiary care centers over 7.5 years was reviewed. Analysis was performed on patients who underwent a high-resolution esophageal manometry (EM) study before and after LT. JE was defined according to the latest Chicago classification, version 3.0. Results A total of 57 patients without JE identified on pre-LT EM also underwent an EM study after LT. Fifteen (25.4%) were found to have new JE after LT. Patients with newly diagnosed JE after LT were older (61.3±5.3 y vs. 51.6±15.6 y; P=0.02) and more often had chronic obstructive pulmonary disease (COPD; 47.6% vs. 16.6%; P=0.03) compared with those without COPD. There was a trend toward increased risk for JE among female individuals (60% vs. 33.3%; P=0.07) and those with shorter surgical anastomosis times (75.8±12.2 min vs. 84.4±14.3; P=0.06). There was no significant difference between body mass index, opioid use, pretransplant EM findings, surgical ischemic time, occurrence of gastroparesis, or measured post-LT outcomes between the 2 groups. Conclusions JE occurs not uncommonly in patients after LT. Older age and COPD pre-LT may be significant risk factors.

Examining the prevalence of irritable bowel syndrome (IBS) across regions has been challenging given significant methodological heterogeneity. We aimed to perform a uniform assessment of the global burden of IBS using data from Google Trends, a novel, online tool. Google Trends measures popularity of a search term in a given week compared to popularity of all search terms in that week, calculated as relative search volume (RSV). We compiled data on the popularity of IBS and its treatments across 173 countries between 2014 and 2018. We compared Google Trends popularity for IBS with prior epidemiological prevalence data, while controlling for gross domestic product (GDP) per capita and physician density. Of the 173 countries with Google Trends data, 137 countries also had data for GDP per capita and physician density. Worldwide popularity of IBS as a search topic increased from 79 to 89 (13% increase by RSV) over the 5-year period between 2014 and 2018. Country-specific change in IBS RSV ranged from − 35% (Nigeria) to + 64% (Pakistan). There was poor correlation between the Google Trends data and prior epidemiological data (0.08, Pearson correlation, p = 0.64). Popularity of the low-FODMAP diet increased the most among 8 common therapies (RSV 41 to 89, 117% increase). Google Trends is a novel tool that can complement traditional epidemiological methods in gastrointestinal disease. Future research is needed to assess its utility and accuracy as a measure of disease burden across different gastrointestinal diseases.

When evaluating the internal validity of clinical trials, physicians and medical researchers place substantial importance on factors such as blinding and randomization. For a particular randomized-controlled trial (RCT), causal inference and explanation require additional contextual considerations, to which we assign the term "epistemological weight." We argue that one component of epistemological weight, epistemological function, depends on a trial's results. We further note that discordant RCTs often lead to hypothesis generation, an epistemological function that is rare among concordant studies. As an example of methodologically sound but discordant studies, we explore the issue of hormone-replacement therapy and cardiovascular outcomes.

Background: Prenatal detection of transposition of the great arteries (TGA) varies by region, center type, and local practice pattern. One major practice pattern variation impacting detection rate is whether or not fetal cardiac outflow tracts are included in second trimester anatomic survey ultrasounds. Outflow tract assessment has been shown to improve detection of TGA and conotruncal anomalies compared to a four-chamber image alone. Despite the inclusion of the outflow tract views being currently recommended from the American Institute of Ultrasound Medicine (AIUM) and the International Society of Ultrasound in …

Background Aims Individuals with eating disorders (EDs) frequently have constipation-related symptoms, although the mechanisms of this relationship are not clear. We examined the frequency of and relation between EDs and constipation in patients with chronic constipation referred for anorectal manometry. Methods We analyzed data from 279 patients with chronic constipation (79.2% female) seen at a tertiary center from June 2017 through September 2018. Participants completed a standardized psychometric assessment (patient assessment of constipation symptoms questionnaire and hospital anxiety and depression scale and visceral sensitivity index analyses) and anorectal manometry. A subset of patients completed colonic transit testing. Participants with clinically significant ED pathology were identified based on scores of 20 or more on the eating attitudes test-26. We performed logistic regression analysis to examine factors associated with likelihood of having ED pathology. Odds ratios (ORs) were calculated based on continuous variables. We examined the contribution of anxiety to the relationship between severity of ED pathology and symptoms of constipation (such as abdominal pain) using a regression-based bootstrapping approach. Results Of the study participants, 53 (19.0%) had clinically significant ED pathology. The presence of ED pathology was associated with greater general anxiety scores, based on the hospital anxiety and depression scale (OR, 1.20; 95% CI, 1.05–1.38), and greater gastrointestinal-specific anxiety scores, based on the visceral sensitivity index (OR, 1.06; 95% CI, 1.03–1.09). Gastrointestinal-specific anxiety fully mediated the relationship between the severity of ED pathology and constipation (standardized β, 0.11–0.16; P=.026–.024). We found no differences in anorectal manometry or colonic transit between patients with vs without ED pathology. Conclusions In an analysis of patients with chronic constipation, we found that 19% had clinically significant ED pathology. Our preliminary finding indicate that ED pathology might contribute to constipation via gastrointestinal-specific anxiety. Clinicians should consider screening patients with chronic constipation for EDs—especially patients who report symptoms such as bloating and abdominal pain.

Plain film abdominal x-ray (AXR) is frequently used in the evaluation of constipation, but studies assessing the association between stool burden on AXR and colonic transit have been limited. We sought to investigate the relationship between colonic stool burden and slow transit constipation, as determined by a radiopaque marker (ROM) transit study.A retrospective cohort population was assembled, consisting of adult patients with chronic constipation who underwent testing with both a ROM study and anorectal manometry at 2 tertiary care centers over 5 years. Stool burden was graded by 2 independent observers, with colonic transit being assessed by the Hinton method.Of 361 patients, 145 (40.3%) had slow transit constipation, and women were more likely than men to have slow transit constipation (42.3% vs 26.5%, P = 0.04). The mean stool burden scores by observer 1 and observer 2 for patients with slow transit constipation were significantly higher than the mean stool burden scores for patients with normal transit constipation (8.1 ± 1.6 vs 6.9 ± 1.9, P0.0001; 8.5 ± 1.5 vs 5.8 ± 1.6, P0.0001). The Pearson correlation coefficient for the stool burden score and number of remaining ROMs was 0.31 (moderate) for observer 1 (P0.0001) and 0.62 (strong) for observer 2 (P0.0001), whereas the Pearson correlation coefficient for interrater reliability of the stool burden score was 0.58 (P0.0001), indicating a strong correlation. The ideal score cutoff for both observers was 7, with moderate agreement by Cohen's kappa (0.43, P0.0001).Stool burden assessment on AXR may be a reliable alternative ROM study in the assessment of colonic transit.

Multiplex rapid viral tests and nasopharyngeal flocked swabs are increasingly used for viral testing in PICUs. This study aimed at evaluating how the sampling site and the type of diagnostic test influence test results in children with suspected severe viral infection.Prospective cohort study.PICUs at 21 tertiary pediatric referral centers in the United States.During the 2010-2011 and 2011-2012 influenza seasons, we enrolled children (6 mo to 17 yr old) who were suspected to have severe viral infection.We collected samples by using a standardized protocol for nasopharyngeal aspirate and nasopharyngeal flocked swabs in nonintubated patients and for endotracheal tube aspirate and nasopharyngeal flocked swabs in intubated patients.Viral testing included a single reverse transcription-polymerase chain reaction influenza test and the GenMark Respiratory Viral Panel (20 viruses). We enrolled 90 endotracheally intubated and 133 nonintubated children. We identified influenza in 45 patients with reverse transcription-polymerase chain reaction testing; the multiplex panel was falsely negative for influenza in two patients (4.4%). Six patients (13.3%) had not been diagnosed with influenza in the PICU. Non-influenza viruses were identified in 172 of 223 children (77.1%). In nonintubated children, the same virus was identified by nasopharyngeal flocked swabs and nasopharyngeal aspirate in 133 of 183 paired samples (72.7%), with +nasopharyngeal aspirate/-nasopharyngeal flocked swabs in 32 of 183 paired samples (17.4%). In intubated children, the same virus was identified by nasopharyngeal flocked swabs and endotracheal tube aspirate in 67 of 94 paired samples (71.3%), with +nasopharyngeal flocked swabs/- endotracheal tube aspirate in 22 of 94 paired samples (23.4%). Most discrepancies were either adenovirus or rhinovirus in both groups.Standardized specimen collection and sensitive diagnostic testing with a reverse transcription-polymerase chain reaction increased the identification of influenza in critically ill children. For most pathogenic viruses identified, results from nasopharyngeal flocked swabs agreed with those from nasopharyngeal or endotracheal aspirates.

Google Trends is an online tool that allows measurement of search term popularity on Google, spatially and temporally. While not an epidemiological tool for determining incidence, it can estimate the popularity of a certain disease by search volume over time.1,2 It has previously correlated well with infectious disease incidence and has demonstrated utility in disease forecasting, especially with influenza data.3 We utilized Google Trends to investigate whether search interest in common gastrointestinal (GI) symptoms would correlate with coronavirus disease 2019 (COVID-19) incidence data.

We explore a combinatorial framework which efficiently quantifies the asymmetries between minima and maxima in local fluctuations of time series. We first showcase its performance by applying it to a battery of synthetic cases. We find rigorous results on some canonical dynamical models (stochastic processes with and without correlations, chaotic processes) complemented by extensive numerical simulations for a range of processes which indicate that the methodology correctly distinguishes different complex dynamics and outperforms state of the art metrics in several cases. Subsequently, we apply this methodology to real-world problems emerging across several disciplines including cases in neurobiology, finance and climate science. We conclude that differences between the statistics of local maxima and local minima in time series are highly informative of the complex underlying dynamics and a graph-theoretic extraction procedure allows to use these features for statistical learning purposes. Fil: Hasson, Uri. University of Chicago; Estados Unidos. University of Trento; Italia Fil: Iacovacci, Jacopo. The Francis Crick Institute; Reino Unido. Imperial College London; Reino Unido Fil: Davis, Ben. University of Trento; Italia Fil: Flanagan, Ryan. Queen Mary University of London; Reino Unido Fil: Tagliazucchi, Enzo Rodolfo. Netherlands Institute for Neuroscience; Países Bajos Fil: Laufs, Helmut. Goethe Universitat Frankfurt; Alemania. University Hospital Kiel; Alemania Fil: Lacasa, Lucas. Queen Mary University of London; Reino Unido

Schizophrenia, a mental disorder that is characterized by abnormal social behaviour and failure to distinguish one’s own thoughts and ideas from reality, has been associated with structural abnormalities in the architecture of functional brain networks. In this article, we (1) investigate whether mesoscale network properties give relevant information to distinguish groups of patients from controls in different scenarios and (2) use this lens to examine network effects of different antipsychotic treatments. Using various methods of network analysis, we examine the effect of two classical therapeutic antipsychotics—Aripiprazole and Sulpiride—on the architecture of functional brain networks of both controls (i.e., a set of people who were deemed to be healthy) and patients (who were diagnosed with schizophrenia). We compare community structures of functional brain networks of different individuals using mesoscopic response functions, which measure how community structure changes across different scales of a network. Our approach does a reasonably good job of distinguishing patients from controls, and the distinction is sharper for patients and controls who have been treated with Aripiprazole. Unexpectedly, we find that this increased separation between patients and controls is associated with a change in the control group, as the functional brain networks of the patient group appear to be predominantly unaffected by this drug. This suggests that Aripiprazole has a significant and measurable effect on community structure in healthy individuals but not in individuals who are diagnosed with schizophrenia, something that conflicts with the naive assumption that the drug alters the mesoscale network properties of the patients (rather than the controls). By contrast, we are less successful at separating the networks of patients from those of controls when the subjects have been given the drug Sulpiride. Taken together, in our results, we observe differences in the effects of the drugs (and a placebo) on community structure in patients and controls and also that this effect differs across groups. From a network-science perspective, we thereby demonstrate that different types of antipsychotic drugs selectively affect mesoscale properties of brain networks, providing support that structures such as communities are meaningful functional units in the brain.

Over the course of 20th and 21st centuries, the diagnosis and treatment of achalasia have evolved significantly. While a variety of techniques are employed, the decision of which intervention to use for any given patient remains highly individualized. While surgical and endoscopic myotomy are important cornerstones in the management of achalasia, pneumatic dilation (PD) remains an effective way to address failed lower esophageal sphincter (LES) relaxation and it deserves to be discussed as an option especially for those patients hesitant regarding myotomy. Factors favoring successful PD include older age (greater than 45 years), female gender, narrow esophagus, and type 2 pattern of achalasia. It generally is not routinely considered in pediatric patients. Its role is not only in the primary management of achalasia but also as rescue therapy when other interventions have failed. Traditionally, a concern for the use of PD has centered on the risk of perforation and of subsequent emergent surgery and myotomy. In a subset of centers with sufficient expertise and volume, it is a relatively well tolerated and effective procedure. Should perforation occur, it can often be managed conservatively without surgical intervention. At our institution, systematic use of graded guide-wire directed dilation and fluoroscopy enhances the safety profile of the procedure, as well as obtaining a post-procedure esophagram. In the coming years we look forward to rigorous comparisons of the two principal endoscopic approaches [PD vs . per-oral endoscopic myotomy (POEM)] to determine efficacy and durability. While it is known that routine, non-pneumatic balloon and bougie dilation is insufficient to manage achalasia, counseling on the use of novel variations of dilation such as dilation guided by planimetry in the form of EsoFLIP technology is limited by the relative lack of comparative data. In short, while POEM has been an exciting newer technique increasingly employed over the past decade and Heller myotomy remains a mainstay of surgical management, PD continues to have an important role in the present-day management of achalasia.

EMB, the gold standard for diagnosis of ACR, poses unique risks in children. Limited cross-sectional data have associated LV MPI with ACR. We hypothesize that a relative change in MPI from baseline without ACR to the time of ACR will better detect ACR than an absolute threshold LV MPI value. We identified 40 children with ACR ≥60 days post-transplant matching them by age and time from transplantation to 40 children without ACR. There was a significant increase in LV MPI at time of ACR vs. baseline (0.59 ± 0.17 vs. 0.41 ± 0.11; p

The majority of sudden, nontraumatic deaths in young, otherwise healthy individuals result from an unknown underlying cardiac abnormality. The low sensitivity of the traditional history and physical exam in detecting these anomalies has led to a debate regarding the use of routine screening electrocardiograms (ECGs) in young adults. The present study screened 1,099 ROTC cadets applying for aviator status during the summers of 2005 and 2006. Seven candidates (0.6%) were disqualified because of ECG abnormalities, including two with Wolf Parkinson White syndrome. None of the individuals were identified by history and physical exam. ECG was an effective screening tool for detecting silent abnormalities with potential for arrhythmia in our population of healthy young adults. Other ECG findings indicative of anatomic abnormalities were not found. ECG screening can be a valuable tool and should be used in evaluating certain subsets of the population.

Visibility algorithms are a family of methods to map time series into networks, with the aim of describing the structure of time series and their underlying dynamical properties in graph-theoretical terms. Here we explore some properties of both natural and horizontal visibility graphs associated to several nonstationary processes, and we pay particular attention to their capacity to assess time irreversibility. Nonstationary signals are (infinitely) irreversible by definition (independently of whether the process is Markovian or producing entropy at a positive rate), and thus the link between entropy production and time series irreversibility has only been explored in nonequilibrium stationary states. Here we show that the visibility formalism naturally induces a new working definition of time irreversibility, which allows us to quantify several degrees of irreversibility for stationary and nonstationary series, yielding finite values that can be used to efficiently assess the presence of memory and off-equilibrium dynamics in nonstationary processes without the need to differentiate or detrend them. We provide rigorous results complemented by extensive numerical simulations on several classes of stochastic processes.

Pharmacologic manipulation of afterload or systemic vascular resistance (SVR) has become increasingly important in the management of pediatric cardiac patients, just as it has for adult cardiac patients.

Congenital cytomegalovirus (CMV) infection can cause significant morbidity and mortality in the newborn period. Postnatally acquired CMV infection has been thought to carry much less morbidity. We report 5 cases of severe morbidity and mortality in very low birth weight infants with postnatally acquired, breast milk associated CMV infection.

A 6-month-old boy presents with a temperature of 38.9°C and barking cough of 3 days’ duration as well as a rash over his body for 1 day. On physical examination, his temperature is 37.5°C, respiratory rate is 28 breaths/min, and blood pressure is 87/52 mm Hg. He appears nontoxic and has a barking cough, injected conjunctiva with whitish discharge, dry lips, mild inspiratory stridor, a blanching erythematous maculopapular rash on his trunk and extremities, and small cervical lymph nodes. The rest of his physical findings are normal. His Hgb is 12.8 g/dL (128 g/L), WBC count is 11.7×103/mcL (11.7×109/L) with 75% neutrophils and 23% lymphocytes, and platelet count is 515×103/mcL (515×109/L). His stridor is considered to be due to viral croup, and he is treated with intramuscular (IM) dexamethasone and nebulized racemic epinephrine. A lateral neck radiograph reveals widening of the retropharyngeal space (Fig. 1), and he is started on clindamycin. CT scan of the neck reveals a right retropharyngeal abscess (Fig. 2). He continues to have high spiking fevers and experiences stridor at rest. He is started on IM dexamethasone every 6 hours, and his fever subsides the following day. Figure 1. Lateral neck radiograph showing widening of the retropharyngeal space. Figure 2. CT scan of the neck showing a right retropharyngeal abscess (arrow). On hospital day 6, the corticosteroids are stopped, but the fever returns the following day. Two days later, an erythematous maculopapular rash reappears, and the child’s lips are dry and cracked. On day 10, repeat CT scan shows that the retropharyngeal abscess has resolved. An additional imaging study reveals the cause of his symptoms. A 3-month-old previously healthy girl presents to the ED with a 1-day history of a blistering rash. Her parents noted an erythematous area on her occiput after …

Here we describe a case of viral sepsis beyond the neonatal period caused by human parechovirus subtype 3 (HPeV-3), which manifested as cardio-respiratory failure, hepatitis, and necrotizing enterocolitis (NEC). HPeV-1 and 2 were originally classified as enteroviruses but the advent of sequence analysis led to them being recognized as a new genus in the picornavirus family. Subsequently, nine additional HPeV strains have been reported including HPeV-3 in 1999. 1 The spectrum of disease that these viruses may cause is still unknown, and they are rarely screened for in clinical practice.