Real-world Effectiveness of Fecal Microbiota Transplantation for First or Second Clostridioides difficile Infection.

BACKGROUND & AIMS: Clostridioides difficile infection (CDI) is associated with high mortality. Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI, but its use for first or second CDI remains experimental. We aimed to investigate the effectiveness of FMT for first or second CDI in a real-world clinical setting. METHODS: This multi-site Danish cohort study included patients with first or second CDI treated with FMT from June 2019 to February 2023. The primary outcome was cure of C. difficile-associated diarrhea (CDAD) 8 weeks after the last FMT treatment. Secondary outcomes included CDAD cure 1 and 8 weeks after the first FMT treatment and 90-day mortality following positive C. difficile test. RESULTS: We included 467 patients, with 187 (40%) having their first CDI. The median patient age was 73 years (interquartile range [IQR], 58-82 years). Notably, 167 (36%) had antibiotic-refractory CDI, 262 (56%) had severe CDI, and 89 (19%) suffered from fulminant CDI. Following the first FMT treatment, cure of CDAD was achieved in 353 patients (76%; 95% confidence interval [CI], 71%-79%) at week 1. At week 8, 255 patients (55%; 95% CI, 50%-59%) maintained sustained effect. In patients without initial effect, repeated FMT treatments led to an overall cure of CDAD in 367 patients (79%; 95% CI, 75%-82%). The 90-day mortality was 10% (95% CI, 8%-14%). CONCLUSION: Repeated FMT treatments demonstrate high effectiveness in managing patients with first or second CDI. Forwarding FMT in CDI treatment guidelines could improve patient survival. CLINICALTRIALS: gov, Number: NCT03712722.

Beyond diagnosis: investigating hospital referral impact on biological treatment initiation, hospital admission, and surgery patterns in inflammatory bowel disease - a Danish population based study.

OBJECTIVES: Early biological treatment in patients with inflammatory bowel disease (IBD) is important in disease control. Previous studies have suggested that patients with IBD from Non-Academic Hospitals were less likely to receive biologics. The aims of this study were (1) to use the granular data in the clinical database, GASTROBIO, to study detailed differences in time from IBD diagnosis to first administration of biologics, hospital admission, and surgery in patients referred to Academic Hospitals versus to Non-Academic Hospitals, and (2) to explore differences in disease extent, behavior, and indication for biological treatment. MATERIAL AND METHODS: This was a retrospective cross-sectional descriptive population-based quality study of patients with IBD initiating biologics in the North Denmark Region between 2016 and 2018. Data from GASTROBIO were extracted, namely demographic data, time of diagnosis, biological treatments with indications, hospital admission, and surgery. RESULTS: Of the 146 patients included, 84 were from the Academic and 62 from the Non-Academic Hospitals. No significant differences in median time from diagnosis to (1) treatment, (2) hospital admission or (3) IBD surgery between the groups were observed. A higher percentage of patients with luminal Crohn's disease were treated with biologics at the Academic Hospital (78% and 66%). CONCLUSIONS: Based on the findings of this population-based study, we found no evidence that the referral area had a significant impact on the duration from diagnosis to the initiation of biological treatment, hospital admissions, or surgery. However, the data suggested that fewer patients with luminal Crohn's disease were referred to biologics from Non-Academic Hospitals.

A retrospective cohort study on oesophageal food bolus obstruction in the North Denmark region in 2021-two thirds were never diagnosed with a cause.

BACKGROUND: Food bolus obstruction (FBO) leading to hospital treatment is often associated with eosinophilic oesophagitis (EoE), stenosis, or oesophageal cancer (1). Danish national guidelines recommend that patients with FBO undergo a diagnostic upper endoscopy within two weeks of presentation to exclude possible malignancy, and histological evaluation of eight biopsies (2, 3). AIMS: The aims of this study were to (1) report the incidence and describe the causes and treatment of FBO in the North Denmark Region (NDR), (2) determine the proportion of patients who underwent upper endoscopy and biopsy according to regional and national guidelines, and (3) identify International Classification of Diseases 10th Revision (ICD-10) diagnosis and procedure codes applied to the hospital visits due to FBO in the NDR. METHODS: Among all acute hospital visits in the NDR in 2021, all visits with ICD-10 codes possibly reflecting FBO, as well as a random sample of 14,400 visits with unspecific ICD-10 codes (R and Z codes), were screened manually for possible FBO. Diagnosis, follow-up, and treatment of all patients with FBO were recorded. RESULTS: The median patient age was 66.0 (Q1-Q3: 49.8-81.0) years, and half of the patients had experienced FBO before. Two thirds of patients (66.0%) were never diagnosed with a cause of FBO, followed by 17.3% with EoE. 30% of patients did not undergo upper endoscopy within two weeks of the hospital visit, and 50.7% were never biopsied in the oesophagus. Of 1886 hospital visits with registry ICD-10 codes that possibly reflected FBO, 8.4% were due to FBO, while FBO was present in 0.028% of the random sample of unspecific ICD-10 codes. CONCLUSIONS: Most hospitalized FBO patients in the NDR in 2021 were never diagnosed with a cause. In these patients there is a high risk of overlooked EoE or upper gastrointestinal cancers. The area needs immediate focus and changed routines to improve treatment and prevent new FBO.

Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry.

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed.  A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70-145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient's age, and patients' origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders. What is Known: • Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness. What is New: • Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy. • PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.

Convergent and discriminant validity of the Minimal Eating Observation Form - version II: a cross-sectional study.

BACKGROUND: The Minimal Eating Observation Form - Version II (MEOF-II) is a brief and easy to use screening tool for eating difficulties, that is psychometrically robust. The aim of this study was to explore convergent (measuring similar constructs) and discriminant (measuring somewhat different constructs) validity of the MEOF-II to other validated dysphagia specific, activity and participation related instruments. METHODS: In this cross-sectional study, participants (n = 100, mean age 72, n = 42 women), diagnosed with either chronic pulmonary disease, Parkinson´s disease, Multiple Sclerosis, or stroke were recruited from rehabilitation centres. Patient-reported outcomes and clinical-rated assessments, capturing eating ability in general and swallowing in specific, included: The Dysphagia Handicap Index (DHI), the 4-question test (4QT), the Minimal Eating Observation Form - II, the Volume - Viscosity Swallow Test (V-VST), Flexible Endoscopic Evaluation of Swallowing (FEES) documented according to the Penetration-Aspiration Scale (PAS). Type of oral intake was documented using the Functional Oral Intake Scale (FOIS). Activities in daily living was assessed with Barthel index (BI). Spearman's correlation coefficient was used to analyze associations. The MEOF-II total score was hypothesised to have moderate correlations (r ≥ 0.3) with the other assessments, besides with PAS and FOIS (weak correlations, r < 0.3). RESULTS: In total 78 participants had any type of eating difficulties (MEOF-II), 69 reported dysphagia (4QT), 62 had dysphagia according to V-VST, 29 showed evidence of penetration/aspiration (PAS), and 31 participants had decreased oral intake ability (FOIS). The MEOF-II total score had moderate correlations with DHI, BI, 4QT, V-VST volume, and weak correlations with V-VST dysphagia and viscosity, PAS, and FOIS. Comparing a prior hypothesised correlation strengths against empirical findings showed that 83% of the hypothesised correlations were correct. CONCLUSIONS: The MEOF-II is a holistic and objective screening tool that can indicate the need for further assessment and corresponds well with the persons' subjective experiences. MEOF-II does not specifically assess the risk for penetration/aspiration.

There is a long way from current clinical practice in Denmark compared to recent published English guideline on management of children with eosinophilic oesophagitis.

BACKGROUND: A low incidence of eosinophilic esophagitis (EoE) in children in the North Denmark Region (NDR) were measured in 2007-2017. Few of the children diagnosed before 2017 were treated to remission suggesting a lack of awareness. While there currently are no guidelines for treating EoE in Denmark, a new English guideline was published in 2022 renewing focus on the disease. OBJECTIVE: The aim of this study was to measure the difference of current Danish clinical practice for treatment and follow-up of EoE children in the NDR with the new English guideline from the British Society of Gastroenterology (BSG) and the British Society of Pediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN). METHODS: This retrospective, register-based DanEoE cohort study included 31 children diagnosed with EoE between 2007 and 2021 in NDR. Medical records were reviewed and information about treatment and follow-up were collected. RESULTS: In 32% of the children with EoE in the NDR, first-line treatment corresponded with the new English guideline. One in 6 children were never started on any treatment even though treatment always is recommended. Histologic evaluation within 12 weeks as recommended was performed in 13% of the children. CONCLUSIONS: In Denmark focus on improving EoE treatment and follow-up for children is needed, as there is a significant difference between current clinical practice and the recommendations in the new English guideline.

Deaths Among Ambulance Patients Released from the Emergency Department Within the First 24 Hours With Nonspecific Diagnoses - Expected or Not?

BACKGROUND: Emergency patients are frequently assigned nonspecific diagnoses. Nonspecific diagnoses describe observations or symptoms and are found in chapters R and Z of the International Classification of Diseases, 10th edition (ICD-10). Patients with such diagnoses have relatively low mortality, but due to patient volume, the absolute number of deaths is substantial. However, information on cause of short-term mortality is limited. OBJECTIVES: To investigate whether death could be expected for ambulance patients brought to the emergency department (ED) after a 1-1-2 call, released with a nonspecific ICD-10 diagnosis within 24 h, and who subsequently died within 30 days. METHODS: Retrospective medical record review of adult 1-1-2 emergency ambulance patients brought to an ED in the North Denmark Region during 2017-2021. Patients were divided into three categories: unexpected death, expected death (terminal illness), and miscellaneous. Charlson Comorbidity Index (CCI) was assessed. RESULTS: We included 492 patients. Mortality was distributed as follows: Unexpected death 59.2% (n = 291), expected death (terminal illness) 25.8% (n = 127), and miscellaneous 15.0% (n = 74). Patients who died unexpectedly were old (median age of 82 years) and had CCI 1-2 (58.1%); 43.0% used at least five daily prescription drugs, and they were severely acutely ill upon arrival (24.7% with red triage, 60.1% died within 24 h). CONCLUSIONS: More than half of ambulance patients released within 24 h from the ED with nonspecific diagnoses, and who subsequently died within 30 days, died unexpectedly. One-fourth died from a pre-existing terminal illness. Patients dying unexpectedly were old, treated with polypharmacy, and often life-threateningly sick at arrival.

Defining dysphagia - a modified multi-professional Danish Delphi study.

OBJECTIVE: To establish a generally accepted Danish definition of dysphagia to enhance collaboration across sectors and professions. METHODS: The study was initiated by a multi-professional group of experienced researchers and board members of the Danish Society for Dysphagia. We used a modified Delphi methodology to achieve consensus among experienced health care professionals from different professions and contexts. The initial stage consisted of a literature search leading to the draft of different definitions followed by two Delphi rounds between professionals and a stakeholder consultation round. RESULTS: We conducted two Delphi rounds until one definition was clearly preferred. A total of 194 participants responded in round one, and 279 in round two. Both rounds had a broad representation of sectors and geography and most participants had worked with dysphagia for more than four years. CONCLUSION: The preferred definition was 'Dysphagia is a functional impairment that either prevents or limits the intake of food and fluids, and which makes swallowing unsafe, inefficient, uncomfortable or affects quality of life'. The definition was widely accepted among different health professional groups, patients and across sectors.

Less prevalent use of biologics for inflammatory bowel disease in patients from Non-Academic hospitals - a Danish register-based study of a region with 580,000 citizens.

INTRODUCTION: Biologic therapy is widely used for inflammatory bowel disease (IBD) and may decrease surgery rates. However, it remains uncertain if there is unwarranted geographic variation in access to biologic therapy. The aim of the study was to explore if all patients had equal access to biologic therapy in the North Denmark Region. METHODS: A cross-sectional register-based study of use of biologics, hospital contacts and surgery among all IBD patients having a hospital contact in the geographically well-defined North Denmark Region during 2016-2018. ICD-10 diagnosis codes, hospital contacts and procedure codes were retrieved from the region's hospital registry. The population is served by an Academic Hospital and two Non-Academic Hospitals constituting three referral areas (according to postal codes). RESULTS: In total, 2371 patients with ulcerative colitis (UC) and 1383 patients with Crohn's disease (CD) had a hospital contact in the region during 2016-2018. Compared to patients from the Academic Hospital, patients from the Non-Academic Hospitals experienced a lower incidence of biologic therapy for UC IRR 0.786 (0.621: 0.994), as well as for CD IRR 0.912 (0.781: 1.065). The incidence of bowel related hospital contacts were higher in patients from Non-Academic hospitals for both UC IRR 1.318 (1.207: 1.438) and CD IRR 1.165 (0.915: 1.483). CONCLUSIONS: Patients with IBD living in a referral area to a Non-Academic Hospital in the North Denmark Region are less likely to receive biologics. This was associated with an increased prevalence of IBD related surgical procedures.

The incidence of eosinophilic oesophagitis in 2007-2017 among children in North Denmark Region is lower than expected.

BACKGROUND: In North Denmark Region (NDR), the incidence of Eosinophilic Oesophagitis (EoE) among adults has increased following a new biopsy protocol in 2011, whereas data on the incidence of EoE among children is lacking. AIMS: To describe the incidence of EoE in children aged 0-17 in NDR as well as diagnostic delay, clinical manifestations, treatment and complications. METHODS: This retrospective, register-based DanEoE cohort study included 18 children diagnosed with EoE between 2007-2017 in NDR. Medical files were reviewed with attention to symptoms, reason for referral, disease progress, treatment, symptomatic and histological remission as well as diagnostic delay. RESULTS: The median incidence per year (2007-2017) was 0.86/100,000 children in NDR aged 0-17 years. The median diagnostic delay among children was four years and six months. Sixty percent presented with food impaction at first hospital visit. After initial treatment, only one of 18 children achieved symptomatic and histologic remission and had a long-term treatment plan. CONCLUSIONS: The calculated incidence among children was lower compared to similar studies. Combined with poor remission rates and lack of follow-up, it is likely that EoE is an underdiagnosed and insufficiently treated disease among children in NDR. Our findings suggest that more knowledge concerning EoE in children could lead to a higher incidence, shorter diagnostic delay and more effective treatment.

Implementation of a biopsy protocol to improve detection of esophageal eosinophilia: a Danish registry-based study.

BACKGROUND : In the North Denmark Region (580 272 inhabitants), only 0-4 cases of possible eosinophilic esophagitis (EoE) were identified annually in 1999-2010, suggesting underdiagnosis. This study aimed to increase the diagnosis of EoE by introducing a regional biopsy protocol for patients with dysphagia. METHODS : In 2011, leaders of regional endoscopy units attended a consensus meeting where a biopsy protocol was proposed. The national pathology registry was used to identify patients with esophageal eosinophilic inflammation during 2007-2017. RESULTS : Discussion resulted in consensus on a protocol to take eight biopsy samples in dysphagia patients (four biopsies from 4 cm and 14 cm above the esophagogastric junction-"4-14-4 rule") regardless of the macroscopic appearance, and to code eosinophilia systematically in the pathology registry. A pictogram showing the 4-14-4 rule was sent to all endoscopy units. The number of patients with esophageal eosinophilia detected per year increased 50-fold after the protocol was implemented in 2011 (median of 1 [interquartile range 0-3] vs. 52 [47-56]; P < 0.001), and the number of biopsy samples per patient doubled (median 4 [4-5] vs. 8 [6-9]; P < 0.04). Of 309 patients diagnosed with esophageal eosinophilia in 2007-2017, 24 % had erosive esophagitis or Barrett's esophagus, and 74 % had EoE. CONCLUSIONS : A consensus-based biopsy protocol and improved coding of eosinophilia in the pathology registry resulted in a 50-fold increase in patients diagnosed with esophageal eosinophilia/year. These patients can now receive treatment. The effort to establish the protocol and change the culture of endoscopists and pathologists was minimal.

Normal values and regional differences in oesophageal impedance-pH metrics: a consensus analysis of impedance-pH studies from around the world.

OBJECTIVE: Limitations of existing impedance-pH thresholds include small sample size of normative studies, inclusion of artefactual pH drops and incorrect identification of impedance reflux events. We aimed to obtain new impedance-pH thresholds from expert consensus analysis of tracings from a large number of healthy subjects. DESIGN: Of 541 studies performed worldwide using two different systems (Diversatek, USA, and Laborie, Netherlands), 150 tracings with oesophageal diagnoses, behavioural disorders and study-related artefacts were excluded. The remainder studies were subject to two reviewer consensus analysis, in-person or through video conference, consisting of editing meals and pH drops, identification of impedance reflux and postreflux swallow-induced peristaltic wave (PSPW) using strict pre-established criteria and measurement of distal mean nocturnal baseline impedance (MNBI). RESULTS: Consensus analysis was performed in 391 tracings (age 32.7 years, range 18-71, 54.2% female). Normative thresholds were significantly different between Diversatek and Laborie (total acid exposure time: 2.8% and 5%; reflux episodes: 55 and 78; MNBI at 3 cm: 1400 and 1500 ohms, at 5 cm: 1400 and 1800 ohms). Males had higher acid exposure, more reflux episodes and lower MNBI. Significant regional differences were identified, including higher PSPW scores in Western countries, and higher MNBI in Asia using Diversatek, and higher acid exposure in the Netherlands, higher MNBI in Asia and South Africa, and lower MNBI in Turkey using Laborie. CONCLUSION: Normal impedance-pH monitoring thresholds have regional and system-related differences. Clinical interpretation needs to use normal thresholds valid for the system used and world region, following careful editing of the tracings.

Can a mass media campaign raise awareness of alcohol as a risk factor for cancer and public support for alcohol related policies?

Alcohol consumption increases the risk of several cancers, but public awareness of alcohol as a risk factor for cancer is low. Research indicates that public opinion about alcohol related policies can be influenced by mass media campaigns and awareness of alcohol as a carcinogen. The objective of this study was to test whether a mass media campaign intended to raise awareness of the relation between alcohol and cancer is associated with higher public awareness of alcohol as a risk factor for cancer, and higher levels of support for alcohol related policies. Cross-sectional surveys of a nationally representative sample of N = 6000 Danish adults were conducted pre- (n = 3000) and post campaign (n = 3000) in 2017-2018. Awareness of alcohol as a cancer risk factor significantly increased between the pre and post campaign survey (approximately 5 percentage points). The proportion of respondents who supported minimum unit pricing, a ban on alcohol advertising, and mandatory nutrition labelling was significantly higher post campaign than pre campaign, while support for limited number of retail outlets and limited sale hours were unchanged. For males, but not females, higher support for an 18 year age limit for purchasing alcohol, age limits for buying alcohol at secondary education school parties, and increased enforcement of age limits was found after the campaign than prior to it. Conclusively, the results show that a mass media campaign was associated with an increase in awareness of alcohol as a risk factor for cancer as well as alcohol policy support at a population level.

The Short Health Scale: A Simple, Valid, Reliable, and Responsive Way of Measuring Subjective Health in Patients With Irritable Bowel Syndrome.

GOALS: To evaluate validity, reliability, and responsiveness of the Short Health Scale (SHS) in irritable bowel syndrome (IBS) patients. BACKGROUND: Subjective health assessment is central when treating patients with IBS. The "Short Health Scale" is a quick 4-item questionnaire covering most aspects of subjective health that has been validated for inflammatory bowel disease. STUDY: To test validity, 451 patients with IBS (mean age, 38 y; 81% females) completed the SHS and questionnaires assessing IBS symptom severity (IBS-SSS), gastrointestinal (GI)-specific anxiety (VSI), and quality of life (IBSQOL). To evaluate reliability and responsiveness to changes, the questionnaires were repeated after 2 weeks in 18 patients, and after 12 weeks in 212 patients who had completed a patient-education program. RESULTS: Validity was documented with (1) gradually increasing mean scores for all 4 SHS items with increasing IBS-SSS (P<0.0001), and (2) correlations between the 4 SHS items and the corresponding items from the other subjective health assessment tools [item 1 (symptom burden): ρ=0.67, item 2 (daily function): ρ=-0.44 to -0.46, item 3 (disease-related worry): ρ=-0.51 to 0.57, item 4 (general well-being): ρ=-0.34 to -0.46, P<0.0001]. Reliability was confirmed (Spearman ρ>0.7 and intraclass correlations >0.7). Responsiveness was good with responders to the patient-education program (IBS-SSS reduction ≥50 points) having significant reductions in 3 of the SHS items (P<0.05), and borderline change for the fourth SHS item (P=0.06). CONCLUSIONS: SHS is a health measure that shows promising evidence of validity, reliability, and responsiveness in IBS patients. It is quickly completed and evaluated, which supports its usefulness in the busy clinical practice.

Quantitative differences between primary and secondary peristaltic contractions of the esophagus.

BACKGROUND AND AIMS: Differences in contraction characteristics between primary and secondary peristalsis have only been scarcely studied. Recently new measures of contractile activity in the human esophagus were developed. The study aims were to use combined manometry and impedance planimetry [pressure-cross-sectional area (P-CSA)] recordings from healthy volunteers to examine esophageal peristalsis, and, furthermore, to investigate the effect of the motility enhancing drug erythromycin to study differential effects on the two types of contractions. METHODS: Sixteen healthy volunteers participated in the study [mean age 23 (range, 19-34) years, 6 females]. An esophageal probe with a bag for CSA measurement was positioned 10 cm above the lower esophageal sphincter. Bag volume was increased stepwise from 5 to 25 ml before and after intravenous infusion of 250 mg erythromycin. Swallow-evoked primary and distension-evoked secondary esophageal peristalsis were compared with regard to (1) pressure amplitude, (2) CSA amplitude, (3) preload tension (wall tension before an evoked contraction), (4) contractile tension, and (5) work outputs. RESULTS: Primary peristalsis induced more efficient contractions as the contraction amplitudes, work output and contractile tension were higher compared to secondary peristalsis (P < 0.001). Erythromycin induced change in CSA during distension-evoked secondary peristalsis (CSA before 212.9 ± 26.8 vs. after 180.5 ± 23.3, P < 0.05). The sensitivity to esophageal distension increased with the distending volume both before and during erythromycin. The sensitivity was not changed by erythromycin (P = 0.6). CONCLUSIONS: Esophageal primary peristaltic contractions were more forceful with longer duration, and higher work output compared to secondary peristalsis contractions. Erythromycin affected peristalsis only to a minor degree.

Patients with eosinophilic oesophagitis in Denmark have higher use of psychotropic drugs: A Danish nationwide study of psychotropic drug use in 3367 patients and 16,835 matched comparators.

BACKGROUND: Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated disease of the oesophagus. Eosinophilic oesophagitis is associated with a substantial disease burden affecting the quality of life and affecting mental health. There are limited data describing the incidence of psychiatric disorders and the use of psychotropic drugs (PDs) in EoE patients. OBJECTIVES: The aim was to investigate whether EoE patients in Denmark have higher use of PDs, contacts with the department of psychiatry, and attempts of suicide or intentional self-harm compared with the general population after being diagnosed with EoE. METHODS: This study was a nationwide, population-based register study including 3367 EoE patients and 16,835 age- and sex-matched comparators. A register-based EoE definition was used to identify cases. Incident PD use was extracted from the prescription register and information regarding psychiatric contacts was retrieved from the Danish Psychiatric Central Research Register. RESULTS: The 5-year incidence of PD use in EoE patients was 13.8% compared to 7.1% of the matched comparators (Hazard ratio 1.83; confidence interval 1.6-2.0; p ≤ 0.001). Antidepressants were the most frequently prescribed PD, whereas antipsychotics were the least prescribed PD. Increasing age, lower educational level, and comorbidity (Charlson Comorbidity Index score ≥1) were associated with the prescription of PDs. The risk of PD use was lower in men than in women with EoE. CONCLUSION: Treatment with PDs were more common in EoE patients after they were diagnosed than in the general Danish population, indicating that EoE patients have an increased risk of psychiatric disorders.

Swallowed topical corticosteroids for eosinophilic esophagitis: Utilization and real-world efficacy from the EoE CONNECT registry.

BACKGROUND: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses. OBJECTIVE: To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice. METHODS: Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations. RESULTS: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness. CONCLUSION: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness.

Randomized clinical trial: inhibition of the TRPV1 system in patients with nonerosive gastroesophageal reflux disease and a partial response to PPI treatment is not associated with analgesia to esophageal experimental pain.

OBJECTIVE: Many patients with nonerosive reflux disease (NERD) have insufficient relief on proton pump inhibitors (PPIs). Some patients have a hypersensitive esophagus and may respond to transient receptor potential vanilloid 1 (TRPV1) antagonists. Aim. To investigate the effect of the TRPV1 antagonist AZD1386 on experimental esophageal pain in NERD patients. MATERIAL AND METHODS: Enrolled patients had NERD and a partial PPI response (moderate-to-severe heartburn or regurgitation ≥3 days/week before enrolment despite ≥6 weeks' PPI therapy). Fourteen patients (21-69 years, 9 women) were block-randomized into this placebo-controlled, double-blinded, crossover study examining efficacy of a single dose (95 mg) of AZD1386. On treatment days, each participant's esophagus was stimulated with heat, distension, and electrical current at teaching hospitals in Denmark and Sweden. Heat and pressure pain served as somatic control stimuli. Per protocol results were analyzed. RESULTS: Of 14 randomized patients, 12 were treated with AZD1386. In the esophagus AZD1386 did not significantly change the moderate pain threshold for heat [-3%, 95% confidence interval (CI), -22;20%], distension (-11%, 95% CI, -28;10%), or electrical current (6%, 95% CI, -10;25%). Mean cutaneous heat tolerance increased by 4.9°C (95% CI, 3.7;6.2°C). AZD1386 increased the maximum body temperature by a mean of 0.59°C (95% CI, 0.40-0.79°C), normalizing within 4 h. CONCLUSIONS: AZD1386 had no analgesic effect on experimental esophageal pain in patients with NERD and a partial PPI response, whereas it increased cutaneous heat tolerance. TRPV1 does not play a major role in heat-, mechanically and electrically evoked esophageal pain in these patients. ClinicalTrials.gov identifier: D9127C00002.

Are patients with eosinophilic esophagitis treated at an academic hospital comparable to a patient from a population-based cohort? Not in Denmark.

Background and Aim: Little are known about differences in eosinophilic esophagitis (EoE) patients in the general population compared with patients treated at academic hospitals. This might affect the generalizability of study results. The aims of the study were to compare clinical features, and complications of EoE between patients from a population-based cohort (DanEoE) and patients from an academic hospital cohort in Copenhagen (EoE-Cph). Methods: The DanEoE cohort is a population- and register-based cohort including all 236 adult EoE patients diagnosed in the North Denmark Region in 2007-2017 previously described in detail. The new EoE-Cph cohort consists of 245 consecutively referred adult patients to a dedicated EoE center in an Academic Hospital in the Danish capital in 2013-2020. Data were collected from medical registries and medical files. Results: Patients in the academic cohort were at symptom debut 12 (SD 16) years younger (P = 0.001). At the time of diagnosis they were 5.4 (SD 15) years younger (P < 0.001). Where Gastro-esophageal reflux disease (GORD) was present in one-third of the population-based cohort, this was only observed in 14% of the EoE-Cph group (P < 0.05). Food bolus obstruction before diagnosis was 24% less common in the EoE-Cph patients (P < 0.001). Conclusion: Results indicated that EoE patients referred to a Danish EoE center is a selected subgroup with disease debut at a younger age, less comorbid GORD, and rarely food bolus obstruction before diagnosis. This suggests that study results from academic hospitals might not have generalizability to the average EoE patient in a population.

The phenotype of adults with complicated eosinophilic esophagitis is dominated by a 5-year longer diagnostic delay: A population-based study of the DanEoE cohort.

Background and Aim: The DanEoE is a previously described population- and register-based cohort of 236 adult patients with eosinophilic esophagitis (EoE) in a well-defined Danish region with a population of 580 000 and free medical treatment. The aim of the study was to compare the phenotype and treatment response between EoE patients with complications to patients without complications at diagnosis. Methods: A retrospective cross-sectional study of the DanEoE cohort's 236 adult EoE patients diagnosed between 2007 and 2017 in the North Denmark Region. Patients were divided into a group who had had complications (dilated or food bolus obstruction [FBO]) before or at the diagnosis, and a group without. Results: At the diagnostic endoscopy, 61% had never had a complication, and 39% had either had FBO (n = 77) or been dilated (n = 15). The complicated group had the same mean age at symptom debut (37 [SD = 16] vs 37 [SD = 17] years, P = 1.0), but were diagnosed significantly later with a resulting longer diagnostic delay (13 [SD = 13] vs 7.9 [SD = 11] years, P = 0.01). Almost half of all patients were never treated to symptomatic remission (uncomplicated 40%, complicated 49%). The histological remission was not secured in the majority (uncomplicated 68%, complicated 70%). Despite this, <15% of patients with previous FBO experienced this after the diagnosis. Conclusion: In the population-based DanEoE cohort, results indicated that the complicated EoE phenotype was a patient with a 5-year longer diagnostic delay. In the current study, the complication status did not predict the treatment response.