Peter Haastrup

Strategies for discontinuation of proton pump inhibitors: a systematic review

PURPOSE Proton pump inhibitors (PPIs) are considered to be overprescribed. Consensus on how to attempt discontinuation is, however, lacking. We therefore conducted a systematic review of clinical studies on discontinuation of PPIs. METHODS Systematic review based on clinical studies investigating discontinuation strategies and discontinuation rates for users of antisecretory medication judged eligible for withdrawal. The databases Medline, Embase and Cochrane Library were searched to December 2013 using the terms antisecretory, anti-ulcer, PPI, acid suppressant, discontinuation, step-down, step down, cessation, tapering, withdrawal and withhold. Search terms were used either singularly or in combination. Papers written in English or Scandinavian were included. Concurrent hand searching was undertaken to pursue references of references. The website ClinicalTrials.gov was searched for unpublished results and ongoing studies. A total of 371 abstracts were scrutinized to determine relevancy. RESULTS The thorough search resulted in six clinical studies on strategies for discontinuation of PPIs. All discontinuation regimens used in the studies differed, and several interventions have been tested in order to decrease use of PPIs. Discontinuations were reported across all studies ranging from 14% to 64% without deteriorating symptom control. Tapering seems to be a more effective discontinuation strategy than abrupt discontinuation. CONCLUSION Discontinuation of PPIs is feasible in a clinical setting, and a substantial number of the patients treated without a clear indication can safely reduce or discontinue treatment. Tapering seems to be the most effective way of doing this.

Overlap of symptoms of gastroesophageal reflux disease, dyspepsia and irritable bowel syndrome in the general population

Abstract Introduction. Gastroesophageal reflux disease (GERD), functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common functional gastrointestinal conditions with significant impact on the daily lives of individuals. The objective was to investigate the prevalence and overlap of the three conditions in a Western general population. Material and methods. A nationwide study of 100,000 individuals 20 years and above, randomly selected in the general population. A web-based questionnaire survey formed the basis of this study. Questions regarding FD and IBS were extracted from the ROME III adult questionnaire. Questions regarding GERD were developed based on the Montreal definition. Prevalence estimates for GERD, FD IBS were calculated in total and for each sex separately and for four age groups. A Venn diagram was constructed, illustrating the overlap between the three conditions. Results. The overall response rate was 52.2%. The prevalence of GERD, FD and IBS was 11.2%, 7.7% and 10.5%, respectively, and overlap between two or three of these conditions was seen among 6.5% of the respondents. Among individuals meeting the criteria of one or more of the conditions GERD, FD and IBS, 30.7% had overlap between two or all three conditions. Conclusion. GERD, FD and IBS are common conditions in the general population and the overlap between these conditions is also quite common. When diagnosing patients with GERD, FD and IBS, physicians should keep in mind that these patients could be suffering from more than one of these conditions.

Rapidly increasing prescribing of proton pump inhibitors in primary care despite interventions: A nationwide observational study

Abstract Background: Guideline and reimbursement modifications have been introduced to optimize prescribing of antisecretory medication in Danish general practice. Impacts of the interventions have not been evaluated. Objectives: To analyse developments in prescribing of antisecretory medication in Denmark 2001–2011 and to assess the impacts of interventions on prescribing of antisecretory medication. Methods: Register-based cohort study covering the entire Danish population of currently 5.5 million inhabitants. Developments in the prescribing of antisecretory medication over time in Denmark between 2001 and 2011 and association with age and gender of users along with the impact of interventions on the prescribing of drug subgroups are analysed. Results: 96.8% of all antisecretory drugs sold are proton pump inhibitors (PPIs) and 94.4% of the PPIs are prescribed in primary care. Prescribing of PPIs has increased substantially during the past decade. Both number of users and the average individual use have increased. The prescribing of ulcerogenic drugs to the elderly has stagnated in the same time range. Reimbursement modifications and scientific guidelines do not seem to have had a substantial influence on the steadily increasing prescribing of PPIs. Conclusion: Use of PPIs has increased substantially during the past decade, without a change in indications for use of PPIs in the same time range. Interventions to enhance adherence to guidelines and promote rational use of PPIs do not seem to have had a substantial influence on the overall prescribing rate.

Medical and non-medical predictors of initiating long-term use of proton pump inhibitors: a nationwide cohort study of first-time users during a 10-year period

Studies of the increasing use of proton pump inhibitors (PPIs) have mainly focused on prevalent long‐term use and associations with gastrointestinal morbidity and comedication. Little is known about non‐medical characteristics of first‐time users of PPI, and predictors of initiating long‐term use of PPIs.

Alarm symptoms of upper gastrointestinal cancer and contact to general practice – A population-based study

Abstract Introduction. Survival of upper gastrointestinal (GI) cancer depends on early stage diagnosis. Symptom-based guidelines and fast-track referral systems have been implemented for use in general practice. To improve diagnosis of upper GI cancer, knowledge on prevalence of alarm symptoms in the general population and subsequent healthcare-seeking is needed. Material and methods. A nationwide study of 100,000 adults, who were randomly selected from the general population were invited to participate in an internet-based survey. People aged ≥45 years were included in this study. Items regarding experience of specific and nonspecific alarm symptoms of upper GI cancer within the preceding 4 weeks and contact to general practitioner (GP) were included. Results. Of the 60,562 subjects aged ≥45 years, 33,040 (54.6%) completed the questionnaire. The prevalence of the specific alarm symptoms ranged between 1.1% (“repeated vomiting”) and 3.4% (“difficulty swallowing”). Women had higher odds of experiencing “repeated vomiting” and “persistent and recent-onset abdominal pain”, but lower odds of experiencing “upper GI bleeding”. The proportion of people contacting their GP with each of the four specific alarm symptoms ranged from 24.3% (“upper GI bleeding”) to 39.9% (“repeated vomiting”). For each combination of two specific alarm symptoms, at least 52% contacted their GP. Conclusion. The specific alarm symptoms of upper GI cancer are not very prevalent in the general population. The proportion of GP contacts with each of the four specific symptoms varied between 24.3% and 39.9%. The proportion of GP contacts was higher in the older age and with combinations of two symptoms.

Enteric Coating Can Lead to Reduced Antiplatelet Effect of Low‐Dose Acetylsalicylic Acid

Low-dose acetylsalicylic acid (ASA) is widely used as antithrombotic prophylaxis. Enteric-coated ASA has been developed to decrease the risk of gastrointestinal side effects. The consequences of enteric coating on pharmacokinetics and antiplatelet effect of ASA have not systematically been assessed. This MiniReview demonstrates that data from clinical trials indicate that enteric coating can reduce the antiplatelet effect of ASA compared to plain ASA. This is possibly due to decreased bioavailability of ASA caused by prolonged solvation and absorption of the enteric-coated formulations. Therefore, low-dose enteric-coated ASA might not be bioequivalent to plain ASA, entailing the risk of insufficient cardiovascular prophylaxis.

Barriers to contacting general practice with alarm symptoms of colorectal cancer: a population-based study

Background A prerequisite for general practitioners (GPs) being able to refer patients with cancer alarm symptoms for further investigations is that individuals present to the GP. Knowledge of barriers to help-seeking is, however, sparse. Objectives. The aim of this study was to analyse associations between the experience of recent-onset alarm symptom of colorectal cancer and four different barriers towards GP contact. Methods A nationwide web-based cohort survey was conducted in 100000 individuals aged 20 years or above, randomly selected from the Danish Civil Registration System. Items regarding experience of four predefined alarm symptoms of colorectal cancer (rectal bleeding, abdominal pain, change in stool texture and change in stool frequency), decisions about contact to GPs and barriers towards GP contact were included. Results A total of 37455 respondents over 40 years (51.8%) completed the questionnaire. The proportion of individuals with no contact to the GP varied between 69.8% and 79.8% for rectal bleeding and change in stool frequency, respectively. The most widely reported barriers were being worried about wasting the doctors time and being too busy to make time to visit the doctor. Men with rectal bleeding significantly more often reported being worried about what the doctor might find. The proportion of individuals who reported barriers was, in general, higher among the youngest age group. Conclusion Barriers to contacting the GP were frequent when experiencing alarm symptoms of colorectal cancer. Reporting the different barriers was significantly associated with gender and age.

Side Effects of Long-Term Proton Pump Inhibitor Use: A Review

Proton pump inhibitors (PPIs) are widely used, and concerns about overuse have been raised. Therefore, side effects are important to be aware of and several suggested side effects of long-term use have been studied. In this MiniReview, we sum up the evidence of side effects related to long-term PPI treatment. Suspected side effects are mainly related to increased susceptibility to infections, secondary hypergastrinaemia, impeded absorption of micronutrients or idiosyncratic reactions. Most of the potential side effects have only been evaluated in observational studies demonstrating conflicting and weak associations with a substantial risk of confounding. However, a high probability of causality seems to be established for the side effects increased risk of gastrointestinal infections and rebound acid hypersecretion following discontinuation of treatment due to secondary hypergastrinaemia. The risk of side effects should not be a reason to withhold PPIs from patients with a true indication, and worry about poorly proven side effects should not lead to unnecessary discontinuation. The most important safety issue regarding PPI therapy is to critically evaluate the indication when initiating treatment and reconsidering the indication in long-term-treated patients.

Lifestyle, socioeconomic status and healthcare seeking among women with gynaecological cancer alarm symptoms: a combined questionnaire-based and register-based population study

Objectives To determine the proportion of contacts to general practitioner (GP) with recent onset gynaecological cancer alarm symptoms (pelvic pain, postmenopausal bleeding, bleeding during intercourse or pain during intercourse) and to analyse the associations between lifestyle factors, socioeconomic status and GP contact for these symptoms. Design Cross-sectional survey combined with data from national registers. Setting The general Danish population. Participants A total of 25 866 non-pregnant women ≥20 years completed the survey. Women reporting at least one of four gynaecological alarm symptoms within the preceding 6 months form the study base (n=2957). Results The proportion of women reporting GP contact ranged from 21.1% (pain during intercourse) to 32.6% (postmenopausal bleeding). Women aged 60+ years had higher odds of reporting GP contact for at least one of the four gynaecological cancer alarm symptoms compared with those aged 20–39 years (OR 2.56, 95% CI 1.69 to 3.89), and immigrants had higher odds of reporting GP contact for at least one of the symptoms (OR 1.56, 95% CI 1.13 to 2.15) compared with ethnic Danish individuals. Among those reporting postmenopausal bleeding and/or bleeding during intercourse, women in the age group 60+ years had higher odds of reporting GP contact compared with those aged 20–39 years (OR 2.79, 95% CI 1.33 to 5.87). A high educational level (>12 years) was positively associated with reporting GP contact for postmenopausal bleeding and/or bleeding during intercourse compared with a low educational level (<10 years) (OR 2.23, 95% CI 1.19 to 4.19). No associations were found with lifestyle factors. Conclusions Few women contacted their GP with recent onset gynaecological cancer alarm symptoms. Higher age, being immigrant and higher educational level increased the odds of GP contact. Future studies should explore the reasons for these findings as this may aid in prompting early diagnosis and thereby improve the prognosis of gynaecological cancer.