Publications

BACKGROUND: We examined whether the difficulties of patients with somatoform disorders (SFDs) in integrating medical reassurance can be altered by preventing patients from devaluing reassuring information through defensive cognitive strategies.

METHOD: Patients with SFD (n = 60), patients with major depression (n = 32), and healthy volunteers (n = 37) watched a videotaped doctor's report, which provided medical reassurance for gastroenterological complaints. Subsequently, participants were asked about their perception of the report. In the SFD sample, patients' appraisal of the reassuring was experimentally modulated: In one condition, doubts about the validity of the doctor's diagnostic assessment were triggered; in another condition, the devaluation of medical reassurance was blocked through underscoring the validity of the doctor's diagnostic assessment; and a control condition received no manipulation.

RESULTS: As evident on all outcome variables, patients with SFD had more difficulty integrating medical reassurance than depressed and healthy people. Within the SFD sample, participants from the experimental condition blocking the devaluation of medical reassurance rated the likelihood of an undetected serious disease to be significantly lower than the other two conditions. They also reported less emotional concern and a lower desire to seek the opinion of another doctor.

CONCLUSIONS: By comparing patients with SFD to both a healthy and a clinical control group, the current study suggests that the difficulty in processing reassuring medical information is a specific psychopathological feature of SFD. Furthermore, our results suggest that the integration of medical reassurance can be improved by preventing patients from devaluing reassuring information through dismissive cognitive strategies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

BACKGROUND: The estimated prevalence of bloating is 15 to 30% in the adult US population and is even higher in patients with disorders of gut-brain interaction (DGBIs). Despite this frequency, there is little research into patients who endorse bloating as a predominant symptom. The aim of this study was to better characterize these patients.

MATERIALS AND METHODS: New patients with DGBIs were asked to identify their 3 most predominant symptoms over the preceding 3 months; those who reported bloating were classified as "bloating predominant." Rome IV and symptom-specific questionnaires were administered to assess for the frequency of DGBIs and other predominant symptoms in this patient population. Using univariable and multivariable modeling, we analyzed the associations between bloating predominance, DGBI subtype, and clinical characteristics.

RESULTS: Of the 586 patients surveyed, 242 (41%) reported predominant bloating. Bloating-predominant patients were more likely to be female, younger, and meet the criteria for IBS-mixed (IBS-M), functional constipation, and functional dyspepsia compared with nonbloating-predominant patients. Bloating-predominant patients were also more likely to endorse concurrently predominant constipation, incomplete evacuation, abdominal pain, belching, and/or nausea. On multivariable logistic regression, constipation and abdominal pain severity were positively associated, although depression was negatively associated with predominant bloating.

CONCLUSIONS: Patients with predominant bloating are more likely to have constipation-related symptoms than diarrhea-related symptoms. They are also more likely to have more severe abdominal pain than patients without predominant bloating. These findings help characterize patients with bloating as a predominant symptom and suggest that diagnosing and treating constipation should be considered as first-line treatment.

INTRODUCTION: Exposure-outcome relationship data show that higher infliximab concentrations are associated with better outcomes in patients with Crohn's disease (CD). However, most of these data were derived from adult patients on maintenance therapy. We aimed to investigate the association of infliximab concentrations during and early after induction therapy of infliximab with short-term and long-term clinical outcomes in a pediatric CD population.

METHODS: We conducted a post hoc analysis of the REACH trial which included pediatric patients with moderate-to-severe CD treated with infliximab (n = 103). The investigated outcomes were early clinical remission (CR) defined as a pediatric CD activity index score of ≤ 10, assessed at week 10, and long-term clinical response (LTCR) defined as a decrease from baseline in the pediatric CD activity index score of at least 15 points, with a total score of ≤ 30 and no need for drug discontinuation, assessed at weeks 30 and 54.

RESULTS: Based on multivariable logistic regression analysis, higher week 10 infliximab concentrations were independently associated with CR at week 10 (odds ratio: 1.54; 95% confidence interval: 1.06-2.22; P = 0.022) and LTCR at week 30 (odds ratio: 1.62; 95% confidence interval: 1.12-2.36; P = 0.010). Receiver operating characteristic analysis identified week 10 infliximab concentration thresholds of ≥7.1 μg/mL and ≥6.5 μg/mL to be associated with CR at week 10 and LTCR at week 30, respectively.

DISCUSSION: Higher postinduction infliximab concentrations are associated with both short-term and long-term favorable clinical outcomes in pediatric patients with CD. Tailoring dosing during induction to achieve higher infliximab exposure may lead to better outcomes in pediatric patients with CD.

Psoriasis is a recurring, immune-mediated dermatological disorder. Many therapeutic agents are available for the treatment of psoriasis, including immunosuppressants and biologic treatments with immunosuppressant action. The employment of nanotechnology allows drug tailoring to achieve dermal targeting, improve efficacy and minimize undesirable effects. Here we discuss the use of the topical route in combination with nano-based drug delivery systems containing immunosuppressants for the management of psoriasis. This review is based on articles selected from 2011 to 2022, using the keywords "Psoriasis" AND "Immunosuppressants" AND "Nano*" in the main databases. Fifty-seven articles were retrieved, although only forty-two matched the inclusion criteria. Nanocarriers such as liposomes, ethosomes, niosomes, solid lipid nanoparticle, nanostructured lipid carriers and microspheres containing immunosuppressive drugs (methotrexate, cyclosporine, tacrolimus, and etanercept) were identified. The main findings of these studies are related to the improved in vitro/ex vivo permeation/penetration and therapeutic efficacy of nanoparticles in vitro and in vivo, compared to the drug in solution. Based on the studies discussed in this review, encapsulation in several types of nanocarriers decreases toxicity, dose, and dose frequency. Furthermore, it enables specific targeting of the active drug, pointing to the possibility of improving topical therapy for psoriasis. In conclusion, nanoformulations represent a novel and promising tool for psoriasis treatment.

INTRODUCTION: Nocebo effects are believed to influence the rate of reported adverse events (AE) and subject withdrawal in both the treatment and placebo groups of randomized clinical trials (RCT). Neuromodulators are commonly prescribed to treat disorders of gut-brain interaction (DGBI), 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 vs the treatment arm of RCT of neuromodulators for DGBI. We also sought to estimate the risk of developing any AE in the placebo arm of these studies and the rate of specific individual AEs.

METHODS: We searched MEDLINE, Embase, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials Searches to identify RCT that included terms for DGBI and for commonly prescribed neuromodulators. We calculated pooled proportions of patients experiencing an AE leading to withdrawal in the active treatment group vs the placebo group with 95% confidence intervals (CI), the pooled proportions of patients experiencing any AE, the pooled proportions of patients experiencing specific AE such as dizziness and headache, the pooled proportions of patients experiencing severe AE, and corresponding pooled risk differences with 95% CI.

RESULTS: There were 30 RCT included representing 2,284 patients with DGBI. Twenty-seven RCT reported data on AE leading to withdrawal. The pooled proportion of total patients with AE leading to withdrawal in the placebo group was 4% (95% CI 0.02-0.04). The pooled proportion of patients with AE 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 1 AE, the pooled proportion of patients experiencing any AE in the placebo group was 18% (95% CI 0.08-0.30), compared with 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 DGBI revealed differing withdrawal rates. There was no statistically significant difference in patients experiencing individual AE of dizziness, headache, or diarrhea. Rates of dry mouth, fatigue, and constipation were higher in treatment groups compared with those in placebo groups.

DISCUSSION: Patients with DGBI in RCT randomized to placebo groups frequently experience AE and AE that lead to withdrawal consistent with a strong nocebo effect. Nonspecific AE such as dizziness, headaches, and diarrhea occurred similarly in patients receiving placebo compared with those receiving neuromodulators.

Acute lower gastrointestinal bleeding (LGIB) is a common reason for hospitalization in the United States and is associated with significant utilization of hospital resources, as well as considerable morbidity and mortality. These revised guidelines implement the Grading of Recommendations, Assessment, Development, and Evaluation methodology to propose recommendations for the use of risk stratification tools, thresholds for red blood cell transfusion, reversal agents for patients on anticoagulants, diagnostic testing including colonoscopy and computed tomography angiography (CTA), endoscopic therapeutic options, and management of antithrombotic medications after hospital discharge. Important changes since the previous iteration of this guideline include recommendations for the use of risk stratification tools to identify patients with LGIB at low risk of a hospital-based intervention, the role for reversal agents in patients with life-threatening LGIB on vitamin K antagonists and direct oral anticoagulants, the increasing role for CTA in patients with severe LGIB, and the management of patients who have a positive CTA. We recommend that most patients requiring inpatient colonoscopy undergo a nonurgent colonoscopy because performing an urgent colonoscopy within 24 hours of presentation has not been shown to improve important clinical outcomes such as rebleeding. Finally, we provide updated recommendations regarding resumption of antiplatelet and anticoagulant medications after cessation of LGIB.

BACKGROUND AIMS: Preventative care plays an important role in maintaining health in patients with inflammatory bowel disease (IBD). We aimed to assess the overall quality, strength, and transparency of conflicts among guidelines on preventative care in IBD.

METHODS: A systematic literature search was performed in multiple databases to identify all guidelines pertaining to preventative care in IBD in April 2021. All guidelines were reviewed for the transparency of conflicts of interest and funding, recommendation quality and strength, external guideline review, patient voice inclusion, and plan for update-as per Institute of Medicine standards. In addition, recommendations and their quality were compared between societies.

RESULTS: Fifteen distinct societies and a total of 89 recommendations were included. Not all guidelines provided recommendations on the key aspects of preventative care in IBD-such as vaccinations, cancer prevention, stress reduction, and diet/exercise. Sixty-seven percent of guidelines reported on conflicts of interest, 20% underwent external review, and 27% included patient representation. In all, 6.7%, 21.3%, and 71.9% of recommendations were based on high, moderate, and low-quality evidence, respectively. Twenty-seven percent, 23.6%, and 49.4% of recommendations were strong, weak/conditional, and did not provide a strength, respectively. The proportion of high-quality evidence ( P =0.28) and strong recommendations ( P =0.41) did not significantly differ across societies.

CONCLUSIONS: Many guidelines do not provide recommendations on key aspects of preventative care in IBD. As over 70% of recommendations are based on low-quality evidence, further studies on preventative care in IBD are warranted to improve the overall quality of evidence.

Gut-directed hypnotherapy (GDH) is a highly effective brain-gut behavioral therapy which is recommended in international guidelines for the treatment of irritable bowel syndrome (IBS). There is increasing recognition of the value of GDH as part of integrated care alongside medical and dietary approaches. This has led to recent innovations to widen access to GDH to meet the increasing demand. Recent advances include streamlined courses of individualized GDH, group therapy, and remote delivery. In this issue of Neurogastroenterology and Motility, Peters et al. retrospectively report outcomes of smartphone app-delivered GDH in a population with self-reported IBS. While adherence was low, those that completed smart phone-delivered GDH-achieved symptom benefit. This mini-review summarizes the current evidence-base for available modalities of GDH and discusses the current and future utility and development of mobile health applications in the digital therapeutics' era.