Anders Lødrup

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

Abstract 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studies on asymptomatic volunteers found that 44% experienced acid-related symptoms up to 4 weeks after treatment was withdrawn.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.

Randomised clinical trial: alginate (Gaviscon Advance) vs. placebo as add‐on therapy in reflux patients with inadequate response to a once daily proton pump inhibitor

Many reflux patients remain symptomatic on a standard dose of proton pump inhibitor (PPI). Alginates decrease the number of reflux events by forming a raft on top of the stomach content and thus offer a supplemental mechanism of action to acid suppression.

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.

Different strategies for MRI measurements of renal cortical volume

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.

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 10–15u2005years postsurgery. Patients should be made aware that long-term PPI therapy is often necessary after ARS.

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

Abstract 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.

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 51Cr-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.

Use of acid-suppressive therapy before anti-reflux surgery in 2922 patients: a nationwide register-based study in Denmark

Guidelines recommend that patients with gastro‐oesophageal reflux disease are adequately treated with acid‐suppressive therapy before undergoing anti‐reflux surgery. Little is known of the use of acid‐suppressive drugs before anti‐reflux surgery.

Editorial: anti-secretory therapy prior to anti-reflux surgery. Does dose matter? Authors' reply.

*Department of Medicine, Køge University Hospital, Køge, Denmark. Diagnostic Center, Silkeborg Hospital, Silkeborg, Denmark. Clinical Pharmacology, Department of Public Health, University of Southern Denmark, Odense, Denmark. Department of Clinical Chemistry & Pharmacology, Odense University Hospital, Odense, Denmark. Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark. E-mail: loedrup.ab@gmail.com