Proton Pump Inhibitors Consumption Research Articles

Rational Use of Proton Pump Inhibitors among Patients Admitted in a Tertiary Care Hospital

Background: The prevalent usage of proton pump inhibitors (PPIs) is a testament to the effectiveness of this class of medications, but it also introduces risk associated with inappropriate prescriptive and consumptive practices. Because of the negative effect of incorrect usage and overdose of PPIs, it is very important for physicians to only prescribe these drugs when needed. However, recent studies showed some concerns about long-term PPIs consumption. The rational prescription of medications is vital to ensuring the optimal use of medical resources, providing effective therapy and minimizing adverse drug reactions. Methods: This observational study was conducted in the department of Pharmacology and therapeutics, Sylhet M.A.G. Osmani medical college, Sylhet, in collaboration with the department of Medicine, Surgery, Gastroenterology, Obstetrics and gynaecology, Sylhet M.A.G. Osmani medical college hospital, Sylhet, from July 2022 to June 2023. The sample size for this study was 600. Usage of PPIs was considered to be appropriate on the basis NICE guidelines and recommendations by Scarpignato et al. (2016) committees on behalf of three Italian scientific societies. Result: For 600 PPIs prescriptions, total 705 case sheets were reviewed. The mean age of the study patients was 42.94±17.16 years. Female were found more 359(59.8%) than male 241(40.2%). Out of 600 patients, based on the indications of PPI usage, 287 (47.8%) of prescriptions were found appropriate, whereas inappropriate prescriptions were found in 313 (52.2%) cases. Out of 287 patients who were prescribed PPIs in an appropriate indication, 175 (61%) patients were given PPIs in an appropriate dose, whereas inappropriate dose was found in 112 (39%) of patients. Again, among 175 patients who were prescribed PPIs for appropriate dose, 24 (13.7%) patients were given PPIs in an appropriate frequency, whereas inappropriate frequency was found in 151 (86.3%) of patients. Finally, 24/600 (4%) patients were prescribed in an appropriate indication with an appropriate dose and frequency, whereas inappropriate prescription were found in 576/600 (96%) patients. PPIs were used as prophylaxis for NSAIDs in highest number 147(51.2%) of patients. Oral was the most common 348(58%) route of prescribing PPIs. Omeprazole was the highest 577(96.2%) prescribed PPIs. Conclusion: Based on this study result, it could be concluded that in most of the patients PPIs prescriptions were not following appropriate indications, dose and frequency recommended by reference guidelines. Like any other drugs, PPIs should be prescribed for a clear indication, the minimum dose needed for the expected effect and medication halted when no longer necessary upon re-evaluation.

Proton Pump Inhibitors in Germany: Status Quo of a Growing Market.

The volume of prescriptions for proton pump inhibitors (PPIs) remains high, although the literature increasingly points to excessive prescribing in relation to guideline recommendations. No very recent data is available on the specific situation in Germany, particularly on the proportion of PPI consumption from over-the-counter (OTC) sales and self-selection, following PPI down-scheduling. The aim of this study was to determine the actual amount of prescribed and OTC PPIs in Germany. For this retrospective study, several IQVIA databases were used, representing all prescriptions billed to statutory and private health insurers in Germany, as well as OTC sales. Analyses were performed for the period November 2020 to October 2021 or partially November 2018 to October 2021 and were descriptive in nature. Mainly, data were collected from IQVIATM PharmaScope National® as well as IQVIA TM DPM® databases. A total of 2.87 billion PPI tablets were shown to have been sold between November 2020 and October 2021, with most drugs prescribed in the largest packages and strengths. In addition, the OTC PPI market increased by an average of 14% per year over a 3-year period. The results of this study suggest the substantial size of the PPI market in Germany is based on prescriptions, a consistent increase in OTC PPI purchases and a recent increase in prescriptions.

Hypersensitivity reactions to proton pump inhibitors. An EAACI position paper.

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well-known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%-3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence-based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in-depth investigations in the topic.

What is the role of proton pump inhibitors consumption on the clinical presentation and severity of COVID-19 infection?

Objective: Proton pump inhibitors (PPI) are among the most prescribed drugs worldwide; therefore, assessing their effect on COVID-19 infection symptoms and severity is of great importance. This study was designed to evaluate the role of PPI consumption on the clinical presentation and severity of COVID-19.Patients and Methods: All adult COVID-19 patients were eligible in this observational cross-sectional study. The patients’ demographic and clinical data, history of PPI consumption, and comorbid disease were recorded. Charlson comorbidity index (CCI) and quick COVID-19 severity index (qCSI) score were calculated for each patient. IBM SPSS version 25 was used for statistical analysis.Results: Totally 670 patients completed the study (PPI users=121). The average severity (qCSI) score of PPI user patients with comorbidity score of zero was significantly higher than non-users (P-value=0.001). Mortality rate was 6.6% and 3.8% in PPI-users and non-users respectively (P-value= 0.117). PPI users were significantly more symptomatic compared to non-users (p value=0.001).Conclusion: We found that PPI users were meaningfully more symptomatic and had a higher severity (qCSI) score. Rational prescription of PPIs should be considered by physicians during and after the pandemic.

Association between proton pump inhibitors and severe hematological toxicity in patients receiving pemetrexed-based anticancer treatment: The prospective IPPEM study

ObjectivePemetrexed is associated with hematological toxicity. Drug-drug interactions (DDIs) between methotrexate and proton pump inhibitors (PPIs) induce a higher risk of hematological toxicity due to the inhibition of methotrexate excretion by PPIs. As pemetrexed and methotrexate are both excreted by human organic anion transporter 3 (hOAT3), this study investigates the hypothetical DDI between pemetrexed and PPIs in lung cancer patients. The primary objective was the occurrence of severe (grade ≥ 3) hematological toxicity. The secondary objectives were to describe the type of hematological toxicity and associated clinical consequences (NCT03537833). Materials and MethodsPPI consumption was collected for each patient receiving pemetrexed-based anticancer chemotherapy from May 2018 to October 2020 in a prospective multicentric observational and nonrandomized study. Multivariate Cox regression and propensity score (PS) adjustment, PS matching and inverse weighting on PS (IPTW) methods were used. ResultsPPI consumption (55 among 156 included patients) was associated with a significantly higher risk of severe hematological toxicity in the multivariable Cox regression model (hazard ratio HR = 2.51, 95% confidence interval [1.47–4.26]; p = 0.005). Similar results were found with PS adjustment (HR = 1.91 CI95% [1.14–3.20]; p = 0.002), PS-matching (HR = 1.93 CI95% [1.08–3.45]; p = 0.02) and IPTW method (HR = 2.06 CI95% [1.27–3.35]; p = 0.004). Severe neutropenia and anemia occurred in 32.7% and 14.1% of patients, respectively. This resulted in 48 anticancer chemotherapy postponements and 24 dose adjustments, 26 growth factor prescriptions, 24 red blood cell transfusions, and 20 hospitalizations. ConclusionsThe results strongly suggest an association between PPI consumption and pemetrexed-related severe hematological toxicity. Deprescription of PPIs when feasible should be considered to prevent this DDI.

Curbing proton pump inhibitor overprescribing: Multifaceted strategies in an academic hospital.

Proton pump inhibitors (PPI) have become essential in the management of upper gastrointestinal disorders, yet they are prescribed without an indication in up to 89% of cases and the number of prescribed PPIs is on the rise. A working group developed several multifaceted strategies in our multihospital trust to curb inappropriate PPI use. We describe herein these strategies and assess their impact on PPI consumption in a hospital belonging to this trust. From 2012 to 2019, our actions included the publication and presentation of a review of emergent PPI side effects, the development of an appropriate use leaflet, medication audits, journal club meetings, and prescription analysis. We considered that a decrease in PPI consumption could be a relevant surrogate criterion for the appropriation and acceptance of these interventions; this was assessed from 2012 to 2019 and expressed as defined daily dose (DDD)/1000 patient-days. There was a clear downward trend in the consumption of PPIs, both in medical and surgical wards. The overall PPI use decreased by 17.1% (from 566 to 468 DDD/1000 patient-days). IV PPI consumption dropped by 37.7% (from 146 to 91 DDD/1000 patient-days), while oral PPIs consumption decreased by 10% (from 420 to 378 DDD/1000 patient-days). Sustained strategies aimed at curbing PPI overprescribing led to a sustained decrease in PPI consumption in our hospital. This decrease encourages us to pursue this strategy and to diversify our actions.

Concomitant Use of Levothyroxine and Proton Pump Inhibitors in Patients with Primary Hypothyroidism: a Systematic Review.

The aim of this study was to assess the effect of concomitant use of levothyroxine (LT4) and proton pump inhibitors (PPIs) on thyroid-stimulating hormone (TSH) levels in patients with primary hypothyroidism. A systematic review of interventional and observational studies that compared the TSH levels before and after concomitant use of LT4 and PPI was performed. Articles published in English up to September 1, 2019, were included. PubMed, EMBASE, and Cochrane Library databases. Gray literature was also searched in repositories, websites OpenGrey and Google Scholar, and abstracts of major international congresses. Study quality was assessed with the Newcastle-Ottawa quality assessment scale for observational studies and the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool was used. Five thousand twelve discrete articles were identified. Following assessment and application of eligibility criteria, seven studies were included. There was a considerable heterogeneity among the included studies in design, sample size, inclusion and exclusion criteria, treatment regimen, and baseline demographics. Each of the included studies showed an increase in TSH levels following LT4 and PPI consumption, and in the majority of these, the increase was statistically significant. The concomitant use of LT4 and PPI showed a significant increase in TSH concentration. However, given the small number of studies, further research is needed to clarify the interfering role of PPI on LT4 intestinal absorption. CRD42020047084.

Randomised clinical trial: oesophageal radiofrequency energy delivery versus sham for PPI-refractory heartburn.

Oesophageal radiofrequency reduces use of proton pump inhibitors (PPIs) in patients with gastro-oesophageal reflux disease responding to PPIs. To determine the efficacy of oesophageal radiofrequency in patients with PPI-refractory heartburn. A randomised, double-blind, sham-controlled multicentre study was designed to assess the efficacy of oesophageal radiofrequency in PPI non-responding patients with heartburn. Patients had moderate-to-severe heartburn defined by at least 3 occurrences a week, and not improved by continuous PPI treatment. The primary endpoint was clinical success at week 24, defined by intake of less than 7 PPI doses over the 2 preceding weeks and adequate symptom control determined by the patient. Sixty two patients were randomised, 29 to the oesophageal radiofrequency group and 33 to the sham group. Intention-to-treat analysis showed that 1/29 (3.4%) and 5/33 (15.1%) achieved the primary endpoint in the oesophageal radiofrequency and sham groups, respectively (NS). There was no significant difference between oesophageal radiofrequency and sham regarding the number of days without heartburn, days with PPI consumption in the last 2weeks, and patients not taking PPIs. No pH-impedance parameter was associated with clinical response. The occurrence of adverse events was similar in both groups. This sham-controlled, randomised study did not demonstrate any efficacy of oesophageal radiofrequency for the treatment of PPI-refractory heartburn regarding symptom relief or consumption of PPIs. ClinicalTrials.gov NCT01682265.

Comparison of Immunohistochemistry and Conventional Stains for Helicobacter Pylori Detection in Gastric Biopsies of Patients Receiving Proton Pump Inhibitors

Objective: To evaluate the diagnostic performance of different staining methods for Helicobacter pylori (H. pylori) in patients treated with proton pump inhibitors (PPI) Material and Methods: This is a retrospective study involving 75 gastric biopsies from patients with and without PPI therapy between October 2018 and September 2019. Slides were stained with hematoxylin and eosin (H&E); Giemsa and immunohistochemical staining (IHC) was done using polyclonal anti-H. pylori antibodies. Statistical analysis was performed to determine any association between the results of different staining methods and PPI consumption. Sensitivity, specificity and positive-negative predictive values of H&E and Giemsa stains were calculated. Results: Overall, H. pylori infection was detected in 33.3% of patients using IHC, 26.7% using H&E, and 28.0% via Giemsa staining. A strong correlation was found between PPI consumption and low H. pylori density detected via IHC (p-value=0.015) but not using H&E and Giemsa staining. The sensitivity of H&E and Giemsa was markedly reduced as a result of PPI consumption (57.1% to 18.2% vs. 85.7% to 27.3%, respectively). Conclusion: Identification of H. pylori using IHC in patients treated with PPI was superior to H&E and Giemsa stains. Both H&E and Giemsa stains showed a marked decrease in sensitivity in patients receiving PPI. The results indicate that IHC should be performed in patients with PPI therapy instead of H&E or Giemsa stains, and PPI should be discontinued for at least 14 days before the performance of endoscopy.

A cluster randomized trial to measure the impact on nonsteroidal anti-inflammatory drug and proton pump inhibitor prescribing in Italy of distributing cost-free paracetamol to osteoarthritic patients

BackgroundParacetamol is recommended as first-line treatment for pain control in osteoarthritis because it has fewer side effects than do other therapeutic options, including nonsteroidal anti-inflammatory drugs (NSAIDs). Prescribing proton pump inhibitors (PPIs) as gastric bleeding prophylaxis in chronic NSAID users is also common, although not recommended. In Italy, paracetamol is not reimbursed by the National Health System. The aim of this trial was to test whether the availability to osteoarthritis patients of free paracetamol would decrease their use of NSAIDs and, as a secondary objective, whether opioid and PPI consumption would also decrease.MethodsEight general practitioners (GPs) (59 patients) were randomized to usual care and 8 (58 patients) to the experimental arm, where prescribed paracetamol was directly distributed for free by the local hospital. After 6 months, paracetamol was also available for free in the control arm.The main outcome was the pre/post difference in average NSAID and PPI consumption. Differences between experimental and control arms in pre/post differences are reported, as registered by the drug prescription information system.ResultsAverage NSAID consumption decreased non-significantly, from 6.79 to 2.16 defined daily dose (DDD) in the experimental arm and from 3.19 to 2.97 DDD in the control group (p = 0.067). No changes were observed for PPIs (from 11.27 to 14.65 DDD and from 9.74 to 12.58 DDD in experimental and control arms, respectively, p = 0.788) or opioids (from 1.61 to 1.14 DDD and from 1.41 to 1.56 DDD in experimental and control arms, respectively, p = 0.419). When the intervention was extended to the control arm, no decrease in NSAID consumption was observed (from 2.46 to 2.43 DDD, p = 0.521).ConclusionsRemoving small economic barriers had small or no effect on the appropriateness of opioid or PPI prescribing to patients with osteoarthritis; a reduction in NSAID consumption cannot be ruled out.Trial registration numberNCT02691754 (Approved February 24, 2016).

457 – On Demand Vs Continuous Use of Proton Pump Inhibitors (PPI) on Symptom Burden and Quality of Life: Results of a Real-World Rct in Primary Care Patients with Gastroesophageal Reflux Disease (GORD)

Introduction The aim in the study was to investigate if prescription of on demand vs continuous use of PPI influenced symptom burden, health related quality of life and selfrated health in primary care. Previous trials in this area have used 'willingness to continue' as a proxy outcome measure. The use of an innovative trials platform integrating the electronic record and patient outcomes via smartphone enables symptoms and quality of life profile to be captured. Methods 36 primary care centres participated in the study: 8 in Greece, 10 in Poland, 8 in the Netherlands and 10 in UK. Eligible patients were adults 18 to 65 years of age with GORD, either current or former PPI users, and identified based on primary care electronic health records data. Patients were randomized to either on demand (when the patient experiences bothersome reflux symptoms) or continuous use of PPI. Patient reported demographics, drug use, symptom burden, quality of life and self-rated health at the first visit and the follow-up visit after 8 weeks. The trial was registered with EudraCT as nr 2014-001314-25. The effect of on demand vs continuous PPI use on PPI intake and patient reported outcomes (reflux symptom burden, assessed with RDQ; Health related quality of life, assessed with SF-12) was tested using mixed effect regression model with treatment allocation (on demand vs continuous PPI use), visit and an interaction term between treatment allocation and visit as exposure variables. Change in PPI dose was correlated with change in patient reported outcomes using Spearman correlation. Results A total of 488 patients (median age 51 years, 58 % women) completed the first visit and 360 completed the follow-up visit. There was no significant difference in baseline PPI use, reflux symptom burden or QoL, or in study completion, between treatment allocation. There was no difference between continuous or on-demand advice on PPI use (b=.57, 95 %CI: -.40-1.53), however, PPI use increased between baseline and follow-up in both groups (b=1.33, 95 %CI: .65-2.01). There was no difference between continuous or on-demand on either of the patient reported outcomes. However, symptom burden (b=-.61, 95%CI:-.73- -.49) and health related quality of life (b= 3.31, 95 %CI: 2.17-4.45) improved significantly between baseline and follow up in both groups (Table 2). An increased PPI intake correlated significantly with a reduced reflux symptom score (n=347, rho= -0.12, p=.02) and an improved physical SF-12 subscale score (n=217, rho=0.16, p=0.02), while no significant association was found for SF-12 mental subscale or self-rated health. Conclusion Both continuous and on-demand dosing increase PPI consumption in real-world settings. Reaching a sufficient dose of PPI to reduce reflux symptom burden improves quality of life in patients with GORD.

Increased Risk of Spontaneous Bacterial Peritonitis in Cirrhotic Patients Using Proton Pump Inhibitors

Background: The association between bacterial infections and proton pump inhibitors (PPIs) has recently been studied with debatable results. Aim: The aim of this study was to investigate the relationship between PPIs and the development of spontaneous bacterial peritonitis (SBP) or other bacterial infections in cirrhotic patients. Materials and Methods: Consecutive cirrhotic patients hospitalized from 2007 through 2012 to Hamad General Hospital–, Doha, Qatar, were enrolled and classified as PPI users or non-users according to PPI consumption in the 90 days prior to hospitalization. Cirrhosis was clinically diagnosed by a combination of physical, biochemical, radiological, and endoscopic findings, or by liver biopsy. Results: A total of 333 patients were included in this study, of whom 171 (51.4%) used PPIs and 162 (48.6%) did not use PPIs. PPI users were significantly older in age (p = 0.001). There was no statistical difference between the 2 groups in sex distribution and etiology of cirrhosis (p > 0.05 for both parameters). PPI users had a significantly higher incidence of overall bacterial infection (38%) than non-PPI users (13.6%), p = 0.0001. Statistical significance is observed specifically for SBP and chest infection (p = 0.0006 and p = 0.01, respectively). In multivariate analysis, older age (> 60 years; OR = 1.246, 95% CI 1.021–08.486; p = 0.02), and PPI use (OR = 2.149, 95% CI 1.124–06.188; p = 0.01) were independent predicting factors for SBP and overall bacterial infection. Conclusion: The present study shows that PPI use, as well as older age (> 60 years), was an independent predicting factor for the development of overall infection and SBP in hospitalized cirrhotic patients. Unless it is indicated, PPI therapy should be avoided in this group of patients, particularly in those older than 60 years of age.

Gastroesophageal reflux disease and Barrett’s esophagus after laparoscopic sleeve gastrectomy: a possible, underestimated long-term complication

BackgroundMorbidly obese patients are affected by gastroesophageal reflux disease (GERD) and hiatal hernia (HH) more frequently than lean patients. Because of conflicting results, the indication to sleeve gastrectomy (SG) in patients with GERD is still debated. ObjectivesTo evaluate the incidence of GERD on the basis of clinical, endoscopic, and histologic data in patients undergoing SG. SettingsUniversity hospital, Rome, Italy. MethodsFrom July 2007 to January 2010, 162 patients underwent primary SG. Preoperatively all patients underwent visual analogue scale (VAS) evaluation of GERD symptoms, proton pump inhibitors (PPIs) consumption recording, and esophagogastroduodenoscopy (EGD). Stomach resection started 6 cm from pylorus on a 48Fr bougie. Staple line was reinforced by an oversewing suture. A postoperative clinical control with VAS evaluation, PPI consumption, and EGD was proposed to all patients. Three patients were excluded because of the occurrence of major postoperative complications. ResultsA total of 110 patients accepted to take part in the study (follow-up rate: 69.1%). At a mean 58 months of follow-up, incidence of GERD symptoms, VAS mean score, and PPI intake significantly increased compared with preoperative values (68.1% versus 33.6%: P<.0001; 3 versus 1.8: P = .018; 57.2% versus 19.1%: P<.0001) At EGD, an upward migration of the “Z” line and a biliary-like esophageal reflux was found in 73.6% and 74.5% of cases, respectively. A significant increase in the incidence and in the severity of erosive esophagitis (EE) was evidenced, whereas nondysplastic Barrett’s esophagus (BE) was newly diagnosed in 19 patients (17.2%). No significant correlations were found between GERD symptoms and endoscopic findings. ConclusionIn the present series the incidence of EE and of BE in SG patients was considerably higher than that reported in the current literature, and it was not related to GERD symptoms. Endoscopic surveillance after SG should be advocated irrespective of the presence of GERD symptoms.

Evaluation of methods for H. pylori detection in PPI consumption using culture, rapid urease test and smear examination.

Culture, rapid urease test (RUT) and smear examination have been used as reliable methods for diagnosis of H. pylori infection. Accurate performance of these tests requires good quality biopsies with considerable number of bacterial cells. However, consumption of proton pump inhibitors (PPIs) affects growth and urease activity of H. pylori, leading to false negative results. In this study the efficacy of culture, RUT and smear examination was assessed and the effect of PPI consumption was evaluated. Two antral biopsies from 530 dyspeptic patients with and without PPI consumption were used for RUT, culture and smear examination. Statistical analysis was used to determine the association between results of culture, RUT or smear examination and PPI consumption. Sensitivity and specificity of three tests were calculated by standard methods. H. pylori infection was detected in 40% of patients by culture, 48.3% by RUT and 21.1% by smear examination and the overall detection rate was 54%. A strong correlation was found between PPI consumption and negative results of culture and RUT (P<0.05) but not smear examination. The sensitivity of RUT was reduced as a result of PPI consumption. This reduction was more profound in 1-hr RUT (92.2% to 74.4%) compared with 24-hr RUT (93.9% to 81.6%). Prevalence of H. pylori was declined, compared with previous studies. This decrement could be due to false negative results of H. pylori diagnostic tests, among which culture and RUT are mostly affected by PPI. Accordingly, PPI consumption should be stopped before performance of endoscopy.

Inhibiteurs de la pompe à protons : impact d’une évaluation des pratiques professionnelles sur la pertinence des prescriptions

Objective To improve the quality of proton pump inhibitors (PPI) prescription in an orthopaedic department. Study design Prospective professional practice evaluation study. Patients and methods A specific protocol concerning the best practice for using PPI in the perioperative period was established by anaesthesiologists and validated by all prescribers, according to recent recommendations published by French Afssaps. PPI prescription pertinence, mainly using the oral route, was based upon the presence of clearly identified risk factors. PPI mensual consumption and severe gastric complications were analyzed and compared with those obtained from the previous year. Ten months after the beginning of the protocol, the pertinence of PPI prescription was analyzed in 20 randomly selected medical records. Data are expressed in defined daily dose (DDD). Results After one year, a 35.5% decrease in oral PPI consumption was noted (901 ± 211 before vs 581 ± 235 DDD, after, P < 0.05). A similar trend to a decrease in intravenous PPI consumption was observed (40 ± 23 vs 22 ± 26, P = 0.06). During the same period, the overall incidence of severe gastric complication remained stable. The PPI prescription was pertinent in 85% of selected medical records. Conclusion This study confirmed the interest of professional practice evaluation protocols to improve PPI prescription. A strong implication of all medical staff members is mandatory to maintain such benefits over time.

Are proton pump inhibitors a new antidiabetic drug? A cross sectional study

To investigate the effect of proton pump inhibitors (PPIs) on glycemic control (HbA1c) in type 2 diabetic patients. A cross-sectional study of consecutive in-patients admitted to hospital in any department during the first semester of the year 2010 who had a recent HbA1c measurement. The study excluded those with a diagnosis of hyperglycemic decompensation, diabetic onset or pregnancy. It compared HbA1c levels of those taking PPIs and those not. A total of 97 patients were recruited. The average HbA1C level was 7.0% ± 1.2%. Overall PPI consumption was 55.7%. HbA1c was significantly lower in individuals who took PPIs: -0.6%, 95% CI: -0.12 to -0.83. People who used PPIs with some type of insulin therapy had a HbA1c reduction by -0.8%, 95% CI: -0.12 to -1.48. For the rest of subgroup analysis based on the antidiabetic drug used, PPI consumption always exhibited lower HbA1c levels. PPIs seems to be consistently associated with better glycemic control in type 2 diabetes. HbA1c reduction observed is similar to incretin-based therapies.

Surgical management of refractory gastro-oesophageal reflux

Surgery in the management of gastrooesophageal reflux disease (GORD) is controversial; its availability and frequency show variability between, and even within, countries. GORD is a common chronic condition, with some 20 per cent of the population in Western countries experiencing symptoms of reflux at least once a week1. When gastric juice flows back into the oesophagus, it causes heartburn and acid regurgitation (so-called ‘typical’ symptoms) and/or a variety of symptoms often referred to as ‘atypical’. Atypical symptoms include cough, hoarseness, dental erosions and angina-like chest pain.The regurgitated gastric contents may damage the oesophageal mucosa, inducing erosions, ulcers and even metaplastic change (Barrett’s oesophagus). Most patients with GORD are treated effectively by non-prescription medication or acid-suppressing drugs (proton pump inhibitors (PPIs)), or a combination of the two. Although effective2, surgery has a relatively marginal role. It is generally reserved for those few patients who are unwilling to take drugs or whose condition is considered ‘refractory’ to such treatments (patients whose symptoms or mucosal damage persist or are cured only partially by PPIs)3. When faced with a patientwith refractory disease it falls to the surgeon to decide whether or not an antireflux procedure will confer benefit. As will be shown below, the present difficulty in defining the role of surgery in the management of refractory GORD stems partly from the currently accepted Montreal definition of GORD as ‘a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or syndromes’4. According to this symptom-focused definition, all patients with typical or atypical symptoms related to acid or nonacid reflux have the disease. These patients may be prescribed a trial of medical therapy, even if their overall oesophageal exposure to gastric contents is normal. Four groups of refractory patients who might request surgery can be identified. The first group consists of poorly compliant patients, or those having an inappropriate PPI consumption because of poor timing and/or frequency of dosing. This is probably the largest group and these patients are the simplest to treat, either by correcting themedical treatment (enforcing compliance, modifying the timing and/or frequency of dosage) or, if necessary, by antireflux surgery. The second group contains patients whose refractory symptoms are different to their initial symptoms. PPIs often resolve the severe heartburn felt in the initial stages of GORD but fail to reduce volume reflux and regurgitation while stooping or straining. Cough (especially at night), episodes of wakening and choking, and poor sleep pattern are common refractory symptoms that prompt a patient to seek surgical intervention. The third group of patients have symptoms that are unresponsive to PPIs. Themain reason is a persistence of alkaline or weakly acidic reflux of duodenal contents (bile and pancreatic juice). In this situation PPIs have reduced gastric acid output, but are ineffective with respect to the alkaline component of the refluxate. The final group comprises those whose refractory symptoms are due to an altered sensitivity of the oesophageal mucosa. This results in an abnormal perception of otherwise normal events, often described as ‘acid-sensitive oesophagus’ or ‘functional heartburn’. Although no exact figure is available, it has been estimated that these last two groups account for 10–20 per cent of refractory GORD. Without refractory symptoms, there is little evidence to promote antireflux surgery, except for Barrett’s oesophagus with severe reflux requiring progressively increasing doses of PPI, or when there is an associated large paraoesophageal hernia (to prevent future strangulation or respiratory complications). For a surgeon to operate, something more than a purely symptombased definition ofGORDis required; a trial of treatment by operation is not acceptable if the chance of successful outcome is minimal. An accurate definition of disease before surgery requires the measurement of acid reflux (by 24-h pH monitoring after suspension of PPI therapy) and exclusion of dysmotility disorders (achalasia, diffuse oesophageal spasm). If acid exposure is abnormal, GORD may be regarded as present and surgery as justified, if symptoms warrant it. This diagnostic approach, however, does not deal satisfactorily with the last two of the four groups described above. In

Long-term effects of a multifaceted intervention to encourage the choice of the oral route for proton pump inhibitors: an interrupted time-series analysis

Problem:Drugs are often given intravenously even when the patient is able to swallow and when an oral form would be more cost-effective.Design:Evaluation of the impact of a multifaceted intervention on...

Gastroprotective drugs in Australia: Utilization patterns between 1997 and 2006 in relation to NSAID prescribing

Background: In Australia, the prescribing of proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs) for defined gastrointestinal disorders is approved for subsidy by the universal Australian Pharmaceutical Benefits Scheme. These agents also may be used with NSAIDs, but this prescribing is not approved for subsidy. PPI prescribing increased in Australia between 1997 and 2006, and some authorities are concerned that this increase may be due to prescriptions outside the approved indications.Objectives: The aims of this study were to quantify gastroprotective drug consumption in Australia between 1997 and 2006 and to investigate the relationship over time between this prescribing and NSAID prescribing.Methods: Data from concession beneficiaries (seniors and welfare recipients) were included. Data on PPIs, H2RAs, NSAIDs, and cyclooxygenase (COX)-2 inhibitors dispensed between 1997 and 2006 were gathered from Medicare Australia and are expressed as defined daily doses (DDDs) per 1000 concession beneficiaries per day (CBPDs). Gastroprotective drugs were defined using the World Health Organization Anatomical Therapeutic Chemical classification of 2006. Drug utilization 90% and expenditures in Australian dollars (AUD $, not normalized to an index year) were calculated.Results: H2RA prescribing was stable between 1997 and 2001, at ~60 DDDs/1000 CBPDs. Dispensation of H2RAs began to decrease in 2001 to 20 DDDs/ 1000 CBPDs in 2006. PPI consumption increased consistently, with a sharp change beginning in 2001 (from about 45 to 140 DDDs/1000 CBPDs between 2001 and 2006). The government expenditure for PPIs per concession beneficiary per year also increased from about AUD $26 in 1997 to almost AUD $74 in 2006, whereas the expenditure for H2RAs decreased from about AUD $24 to about AUD $5. Nonselective NSAID prescribing decreased with the introduction of COX-2 inhibitors in 2000. COX-2 inhibitors increased the overall consumption of total NSAIDs in the first 4 years (2000–2003) after their introduction.Conclusions: The prescribing of H2RAs decreased, whereas the prescribing of PPIs increased, between 1997 and 2006 in this population of concession beneficiaries in Australia. During the same period, nonse-lective NSAID prescribing decreased while COX-2 inhibitor prescribing increased.

Influence of generics in prescribing dynamics of proton pump inhibitors in general practice

Use of antisecretory drugs has greatly increased in recent years in Italy. After the launching of generic lansoprazole (early 2006), several Italian Regional Health Authorities have introduced measures to favour the prescription of less expensive PPI. The aim of this study is to evaluate general practitioners’ prescription (GPs) of different Proton Pump Inhibitors (PPIs) in the period between 2005 to 2008. Analysis has been performed on a database of 99 medical practitioners that have managed an average of 150,000 inhabitants. We evaluate the PPIs prescriptions from Jan 2005 to Dec 2008. Evaluations performed are the following: 1) PPI prescription (total and separately for lansoprazole, esomeprazole, pantoprazole, rabeprazole, and omeprazole); 2) prevalence of the reimbursement purpose (Gastroprotection – G; Acid-Related Disease – ARD); 3) PPI prescriptions separately for ARD diagnostic codes. Data were expressed as Compound Annual Growth Rate (CAGR). PPI consumption were quantified using Defined Daily Dose system (DDD). The total volume of PPI’s prescribing increased progressively over the 4 years (CAGR +15%). The proportion of defined daily doses accounted for by lansoprazole increased from 12.0% in 2005 to 30.9% in 2008. The prescription of omeprazole decreased from 42.2% to 26.7%, while that of esomeprazole remained costant. The reimbursement purpose was higher for G (CAGR +43%) than for ARD (CAGR +7%). We found an increase of lansoprazole prescriptions especially for heartburn (CAGR +52.4%), gastroesophageal reflux (CAGR 34,5%) and upper abdominal pain (CAGR 37,2%). Generic PPIs has unexpectedly increased the prescription of whole drug class during the period 2005-2008. Our data suggest that the appropriateness of PPI prescription after generic PPI introduction should be carefully monitored to distinguish between cost-effective from cost-ineffective PPI treatment.