Real-world effectiveness of fecal microbiota transplantation for first or second Clostridioides difficile infection.

BACKGROUND AND 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) eight weeks after the last FMT treatment. Secondary outcomes included CDAD cure one and eight 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 one. At week eight, 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.

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.

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.

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.

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.