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.

Association Between the Clinical, Biochemical, and Endoscopic Activity of Inflammatory Bowel Diseases and Severity and Long-term Outcomes of Coronavirus Disease 2019-A Population-based Study.

This brief report investigated the impact of clinical, biochemical, and endoscopic activity of IBD on the severity and long-term outcomes of COVID-19 in a prospective population-based cohort. The study did not identify any association between IBD activity and COVID-19 outcomes.

Outcomes and Long-Term Effects of COVID-19 in Patients with Inflammatory Bowel Diseases - A Danish Prospective Population-Based Cohort Study with Individual-Level Data.

BACKGROUND AND AIMS: The health consequences of coronavirus disease 2019 [COVID-19] among patients with ulcerative colitis [UC] and Crohn's disease [CD] remain largely unknown. We aimed to investigate the outcomes and long-term effects of COVID-19 in patients with UC or CD. METHODS: We conducted a prospective, population-based study covering all Danish patients with CD or UC and confirmed COVID-19 between January 28, 2020 and April 1, 2021, through medical records and questionnaires. RESULTS: All 319 patients with UC and 197 patients with CD who developed COVID-19 in Denmark were included in this study and compared with the Danish background population with COVID-19 [N = 230 087]. A significantly higher risk of COVID-19-related hospitalization was observed among patients with UC (N = 46 [14.4%], relative risk [RR] = 2.49 [95% confidence interval, CI, 1.91-3.26]) and CD (N = 24 [12.2%], RR = 2.11 [95% CI 1.45-3.07]) as compared with the background population (N = 13 306 [5.8%]). A similar pattern was observed for admission to intensive care (UC: N = 8 [2.51%], RR = 27.88 [95% CI 13.88-56.00]; CD: N = 3 [1.52%], RR = 16.92 [95% CI 5.46-52.46]). After a median of 5.1 months (interquartile range [IQR] 4.5-7.9), 58 [42.3%] and 39 [45.9%] patients with UC and CD, respectively, reported persisting symptoms which were independently associated with discontinuation of immunosuppressive therapies during COVID-19 (odds ratio [OR] = 1.50 [95% CI 1.07-10.22], p = 0.01) and severe COVID-19 (OR = 2.76 [95% CI 1.05-3.90], p = 0.04), but not with age or presence of comorbidities. CONCLUSION: In this population-based study of 516 patients with IBD and COVID-19, 13.6% needed hospitalization and 2.1% required intensive care. Furthermore, sequelae were frequent, affecting 43.7% of COVID-19-infected patients. These findings might have implications for planning the healthcare of patients in the post-COVID-19 era.

Medical treatment and COVID-19 related worries in patients with inflammatory bowel disease.

INTRODUCTION: The aim of this study was to explore changes in medical therapy and document the level of COVID-19-specific worries in patients with inflammatory bowel disease (IBD) during the COVID-19 epidemic in Denmark. METHODS: A cross-sectional survey including 619 IBD patients was conducted. Patients answered questionnaires regarding IBD, IBD medicine, sociodemographic information, mental health, and COVID-19-specific worries (response rate = 64.6%). RESULTS: In total, 14.3% of patients using IBD medication had paused or stopped their IBD treatment during the initial phase of the COVID-19 epidemic, the majority (61.4%) either due to remission or because of side-effects. Only five patients stated that COVID-19 contributed to their decision. The majority of patients (70.5%) expressed worries about an increased risk of infection with coronavirus-2 and worries that their IBD and/or IBD treatment might result in severe COVID-19. Women, patients taking immunomodulators and patients who considered their IBD to be severe were significantly more worried than the remaining population. Age, type of IBD, co-morbidity, level of education, work capacity and mental health were not associated with an increased level of COVID-19-specific worries. CONCLUSIONS: In this selected IBD population, medical IBD treatment was rarely stopped or paused during the initial phase of the COVID-19 epidemic even though 70% of the respondents expressed COVID-19-specific worries. These worries should, nevertheless, be addressed and the characteristics of the population who expressed concerns may be used in future targeted information to secure compliance. FUNDING: none. TRIAL REGISTRATION: not relevant.

Prevalence and Outcomes of COVID-19 Among Patients With Inflammatory Bowel Disease-A Danish Prospective Population-based Cohort Study.

BACKGROUND AND AIMS: As no population-based study has investigated the susceptibility and disease course of COVID-19 among patients with inflammatory bowel diseases [IBD], we aimed to investigate this topic in a population-based setting. METHODS: Two cohorts were investigated. First, a nationwide cohort of all IBD patients diagnosed with COVID-19 was prospectively followed to investigate the disease courses of both diseases. Second, within a population-based cohort of 2.6 million Danish citizens, we identified all individuals tested for SARS-CoV-2 to determine the occurrence of COVID-19 among patients with and without IBD and other immune-mediated inflammatory diseases [IMIDs]. RESULTS: Between January 28, 2020 and June 2, 2020, a total of 76 IBD patients with COVID-19 were identified in the national cohort and prospectively followed for 35 days (interquartile range [IQR]: 25-51). A large proportion [n = 19: 25%] required a COVID-19-related hospitalisation for 7 days [IQR: 2-8.5] which was associated with being 65 years or older (odds ratio [OR] = 23].80, 95% confidence interval [CI] 6.32-89.63, p <0.01) and presence of any non-IMID comorbidity [OR = 8.12, 95% CI 2.55-25.87, p <0.01], but not use of immunomodulators [p = 0.52] or biologic therapies [p = 0.14]. In the population-based study, 8476 of 231 601 [3.7%] residents tested positive for SARS-CoV-2; however, the occurrence was significantly lower among patients with IBD [62 of the 2486 patients = 2.5%, p <0.01] and other IMIDs [531 of 16 492 patients = 3.2%, p <0.01] as compared with patients without IMIDs. CONCLUSIONS: Patients with IMIDs, including IBD, had a significantly lower susceptibility to COVID-19 than patients without IMIDs, and neither immunosuppressive therapies nor IBD activity were associated with the disease course of COVID-19.

Use of proton pump inhibitors among Danish children: A 16-year register-based nationwide study.

OBJECTIVES: Proton pump inhibitors (PPI) are among the most frequently used drugs in the developed countries. In recent years, their use among children and adolescents has been on the increase. Guidelines recommend use for a period no longer than 4-8 weeks. The aim of this study was to describe time trends in prescribing patterns of PPI use among children, with emphasis on persistence to therapy. METHODS: We used the Danish nationwide healthcare registries and identified all Danish children (0-17 years old) who were provided with a filled in PPI prescription between 2000 and 2015. Based on descriptive analyses, we reported trends over time in annual use, prevalent and incident users. Moreover, we evaluated persistence to treatment and doses used over time. Analyses were stratified by age groups (0-4, 5-11 and 12-17 years). RESULTS: We identified 212 056 filled in PPI prescriptions prescribed to 78 489 children. The total annual use of PPIs among children increased eight times from 2000 to 2015. Omeprazole was most frequently used (60% of all use). The proportion of prevalent users increased from 0.1 in 2000 to 3.1 per 1000 children in 2015, while the rate of new users increased from 1.2 to 8.0 per 1000 child years. In general, persistence to PPIs was low: in the youngest age groups (14%), slightly more children were covered by treatment 12 months after the first prescription compared with the oldest age groups (5%). CONCLUSION: The use of PPIs among Danish children has increased substantially during the last 15 years. In general, treatment with PPIs among children was of short duration. Attention should be paid to indications and rationality behind initiation of therapy.

Use of proton-pump inhibitors among adults: a Danish nationwide drug utilization study.

BACKGROUND: The use of proton-pump inhibitors (PPIs) has increased over the last decade. The objective of this study was to provide detailed utilization data on PPI use over time, with special emphasis on duration of PPI use and concomitant use of ulcerogenic drugs. METHODS: Using the nationwide Danish Prescription Registry, we identified all Danish adults filling a PPI between 2002 and 2014. Using descriptive statistics, we reported (i) the distribution of use between single PPI entities, (ii) the development in incidence and prevalence of use over time, (iii) measures of duration and intensity of treatment, and (iv) the prevalence of use of ulcerogenic drugs among users of PPIs. RESULTS: We identified 1,617,614 adults using PPIs during the study period. The prevalence of PPI use increased fourfold during the study period to 7.4% of all Danish adults in 2014. PPI use showed strong age dependency, reaching more than 20% among those aged at least 80 years. The proportion of users maintaining treatment over time increased with increasing age, with less than10% of those aged 18-39 years using PPIs 2 years after their first prescription, compared with about 40% among those aged at least 80 years. The overall use of ulcerogenic drugs among PPI users increased moderately, from 35% of users of PPI in 2002 to 45% in 2014. CONCLUSIONS: The use of PPIs is extensive and increasing rapidly, especially among the elderly.

Use of antacids, alginates and proton pump inhibitors: a survey of the general Danish population using an internet panel.

OBJECTIVE: Both over-the-counter medicine, such as antacids or alginates, and proton pump inhibitors (PPI) are used for treating acid-related disorders. We sought to describe what characterizes users of these different medicines, including long-term PPI users within the general population. METHOD: A cross-sectional survey was conducted in an internet panel representative of the Danish adult population in 2012. Data queried included antacid/alginate and PPI use, reason for therapy, co-medication, and presence of upper gastrointestinal symptoms. Long-term PPI use was defined as using PPI ≥1/3 of the last year (∼120 days). Risk of long-term PPI use was estimated by logistic regression. RESULTS: A total of 18,223 people received the questionnaire, of which 52% (9390) responded. Antacid/alginate use was reported by 23%; 16% reported use of only antacid/alginate. PPI use was reported by 13.6%; 6.2% were defined as long-term PPI users. Antacid/alginate users were younger, used less co-medication, had most often started on therapy because of reflux symptoms, and had less often ongoing symptoms. Risk of long-term PPI use appeared to be increased in male gender, by renewing PPI prescription by phone/e-mail, using co-medication, and having started on PPI for several reasons. Combination of antacid/alginate and PPI was reported by approximately 50% of those on therapy with weekly or daily symptoms. CONCLUSION: 23% of Danish adults were using antacids or alginates and 14% were using PPI, of which one-half were on long-term therapy. Prescription renewal by phone or e-mail and use of other prescription medication were associated with long-term PPI use, indicating a behavioral pattern, in which unnecessary PPI therapy may be maintained.

Use of proton pump inhibitors after antireflux surgery: a nationwide register-based follow-up study.

OBJECTIVE: Antireflux surgery (ARS) has been suggested as an alternative to lifelong use of proton pump inhibitors (PPI) in reflux disease. Data from clinical trials on PPI use after ARS have been conflicting. We investigated PPI use after ARS in the general Danish population using nationwide healthcare registries. DESIGN: A nationwide retrospective follow-up study of all patients aged ≥18 and undergoing first-time ARS in Denmark during 1996-2010. Two outcome measures were used: redemption of first PPI prescription after ARS (index prescription) and a marker of long-term use, defined by an average PPI use of ≥180 defined daily doses (DDDs) per year. Kaplan-Meier curves and Cox proportional hazards model were used for statistics. RESULTS: 3465 patients entered the analysis. 12.7% used no PPI in the year before surgery, while 14.2%, 13.4% and 59.7% used 1-89 DDD, 90-179 DDD and ≥180 DDD, respectively. Five-, 10- and 15-year risks of redeeming index PPI prescription were 57.5%, 72.4% and 82.6%, respectively. Similarly, 5-, 10- and 15-year risks of taking up long-term PPI use were 29.4%, 41.1% and 56.6%. Female gender, high age, ARS performed in most recent years, previous use of PPI and use of nonsteroidal anti-inflammatory drugs or antiplatelet therapy significantly increased the risk of PPI use. CONCLUSIONS: Risk of PPI use after ARS was higher than previously reported, and more than 50% of patients became long-term PPI users 10-15 years postsurgery. Patients should be made aware that long-term PPI therapy is often necessary after ARS.

Systematic review: symptoms of rebound acid hypersecretion following proton pump inhibitor treatment.

INTRODUCTION: While the physiological existence of rebound acid hypersecretion (RAHS) after withdrawal of proton pump inhibitors (PPI) therapy is established, the clinical implications are less certain. It has been speculated that a clinical relevant rebound phenomenon may be responsible for difficulties in getting off acid-suppressive medication and partly explain the increase in long-term use of PPI. A number of studies addressing this issue have been published recently. The authors aimed to systematically review the existing evidence of clinically relevant symptoms caused by acid rebound following PPI treatment. MATERIAL AND METHODS: PubMed was searched using the terms "rebound acid hypersecretion" and generic names of PPIs. RESULTS: Five studies were included. Two studies on asymptomatic volunteers found that 44% experienced acid-related symptoms up to 4 weeks after treatment was withdrawn. Symptoms were generally mild to moderate and mainly heartburn and regurgitation. Three studies, using patients with reflux disease, found no signs of symptoms caused by acid rebound. CONCLUSION: Gastric acid rebound hypersecretion following PPI therapy induces reflux-like symptoms post-treatment in asymptomatic volunteers, but the significance of this in patient populations is not clear. The studies in patients with reflux disease found no evidence of symptomatic RAHS, but these studies were hampered by severe methodological weaknesses.

Advantages and controversies in the era of intrarenal volumetry.

BACKGROUND/AIMS: Ultrasound is the preferred imaging modality in nephrology. In many kidney diseases, however, more accurate methods are needed to distinguish between relevant intrarenal structures. MRI could be a solution, although the use of MRI contrast has caused severe complications in some cases, and invasive kidney biopsies may follow, even though such small specimens traditionally provide inaccurate quantitative data. We evaluated the usefulness of MRI volumetry and quantitative kidney biopsies to assess glomerular number and volume as well as cortical volume. METHODS: We specifically highlight an experimental study in which different MRI scans were performed in healthy pigs as well as pigs with unilateral ureteral obstruction to assess intrarenal volume. Single-kidney glomerular filtration rate (GFR) was measured using ureteral cannulation and (51)Cr-EDTA. Kidney biopsies were taken and evaluated employing stereological techniques to measure number and volume of glomeruli. Pigs were sacrificed and kidneys were removed for stereological analysis. Non-contrast-based MRI intrarenal volumes were - without significant difference to intrarenal volumes - obtained using contrast-enhanced MRI and ex vivo techniques. RESULTS: Kidney biopsies gave valid estimates regarding quantitative parameters, such as mean number and volume of glomeruli in the cortex. Different structural parameters correlated with kidney GFR with high, although varying, correlation coefficients. CONCLUSION: Non-contrast MRI is suitable for estimating intrarenal volumes in healthy and diseased kidneys. We advocate further research in diagnostic modalities combining MRI and biopsies. Major challenges are the cortical architecture and heterogeneous distribution of glomeruli within the kidney.

[Intestinal tuberculosis as a differential diagnosis of inflammatory bowel disease]. / Intestinal tuberkulose som differentialdiagnose til inflammatorisk tarmsygdom.

Intestinal tuberculosis (ITB) is a rare differential diagnosis of inflammatory bowel disease (IBD) in Denmark. In the presented case, a 44-year-old native Danish man was examined for IBD symptoms. Colonoscopy and microscopy of colonic biopsies suggested IBD. The patient was started on steroid therapy, but without effect so tumour necrosis factor alpha therapy was planned. Routine interferon-gamma release assay was normal, but chest X-ray revealed an apical infiltration. New tests on the colonic biopsies using polymerase chain reaction were positive for Mycobacterium tuberculosis and the patient was treated for ITB and pulmonary tuberculosis.

The association between renal function and structural parameters: a pig study.

BACKGROUND: The objective was to investigate the association between renal structural parameters and renal function. The structural parameters were renal cortical volume, total renal volume, number of glomeruli, and total glomerular volume, and renal function was expressed by the single kidney GFR (skGFR). Investigations were performed using both healthy and chronically diseased kidneys. We investigated which of the structural parameters showed the best correlation to renal function and evaluated the possibility of predicting the renal function from structural parameters. METHODS: Twenty-four pigs, twelve with healthy kidneys and twelve with diseased kidneys, underwent skGFR measurements. Nephrectomies were performed and structural parameters were estimated using stereological procedures. The correlation between the structural parameters and skGFR was analysed by Pearson's correlation test. The prediction of skGFR from structural parameters was analysed by a linear regression test. RESULTS: In general, we demonstrated a good correlation between structural parameters and skGFR. When all kidneys were evaluated together Pearson's correlation coefficient between skGFR and any stereological parameter was above 0.60 and highly significant (p < 0.001), and with r-values ranging from 0.62 regarding number of glomeruli, to 0.78 regarding cortical volume. The best correlation was found between cortical volume and skGFR. Prediction of single kidney GFR from any structural parameter showed to be quite imprecise. CONCLUSION: The observed correlations between structural parameters and renal function suggest that these parameters may potentially be useful as surrogate markers of the renal function. At present, however, precise prediction of renal function based on a single structural parameter seems hard to obtain.

Kidney biopsies can be used for estimations of glomerular number and volume: a pig study.

In this study, we wanted to evaluate the use of kidney biopsies for estimation of N(glom) and V(glom) in both healthy and chronically diseased kidneys. Danish Landrace pigs with mean weight of 29 kg (range: 25-35 kg) were either subjected to unilateral ureteral obstruction (UUO) or non-obstruction (healthy). N(glom) and V(glom) was estimated by design-based methods using biopsies, N(glom)(biopsy) and V(glom)(biopsy). From each kidney, six biopsies were withdrawn at six topographically different sites. All estimates were done following stereological principles and reference methods estimated number with the physical fractionator, N(glom)(PF), and volume with test point system, V(glom)(TPS). N(glom)(PF) was 1.30 +/- 0.28 x 10(6) for UUO kidneys and 1.59 +/- 0.28 x 10(6) for healthy kidneys. N(glom)(biopsy) was 1.18 +/- 0.28 x 10(6) (p > 0.05) for UUO and 1.33 +/- 0.24 x 10(6) (p = 0.04) for healthy kidneys. When UUO and healthy kidneys were grouped, N(glom)(PF) was 1.46 +/- 0.31 x 10(6), and N(glom)(biopsy) was 1.28 +/- 0.25 x 10(6) (p > 0.05). V(glom)(TPS) was 1,079 +/- 126 mm(3) for UUO and 1,707 +/- 263 mm(3) for healthy kidneys. V(glom)(biopsy) was 1,048 +/- 291 mm(3) for UUO (p > 0.05) and 1,373 +/- 393 mm(3) for healthy kidneys (p > 0.05). When UUO and healthy kidneys were grouped, V(glom)(TPS) was 1,180 +/- 229 mm(3) and V(glom)(biopsy) 1,129 +/- 334 mm(3) (p > 0.05). Biopsy sites were tested for any systematic differences between site- and mean values, and no significant difference was found (p > 0.05). This study showed that biopsies can be used for estimating N(glom) and V(glom) by design-based methods, but more precise determination of biopsy volume is needed.

Different strategies for MRI measurements of renal cortical volume.

PURPOSE: First, to measure renal cortical volume (Vc) using different MRI methods combined with a semiautomatic segmentation method. Second, to compare MRI measurements of Vc using the semiautomatic segmentation method with a manual segmentation method. Third, to evaluate the reproducibility of Vc measurements. MATERIALS AND METHODS: A total of 22 pigs, 13 with healthy kidneys and nine with diseased kidneys, underwent MRI with two non-contrast-agent methods (MRI 100 x 900 and MRI 300 x 1100) and one contrast-agent method (MRI Gd). For each of these methods, Vc was estimated using semiautomatic (Vc(100 x 900), Vc(300 x 1100), and Vc(Gd)), as well as manual (Vc MANUAL) segmentation. Reference volumes were estimated by stereological means (Vc STEREOLOGY). MRI-derived volumes were compared with reference volumes using a two-tailed paired t-test, and variances between methods were visualized with Bland Altman plots. Reproducibilities were analyzed using covariance analysis. RESULTS: Neither measurements of Vc 100 x 900, Vc 300 x 1100, nor Vc Gd differed markedly from Vc STEREOLOGY using semiautomatic segmentation. Vc was comparable when semiautomatic and manual segmentations were performed at the same scan. Reproducibility of MRI estimated Vc values offered intra- and interindividual differences <5%. CONCLUSION: Vc can in both healthy and diseased kidneys be measured accurately with MRI using both semiautomatic and manual segmentation, and measurements can be obtained with a high reproducibility. Measurements of Vc 100 x 900 may in the future become suitable in patients with chronic renal failure.