An educational intervention to optimize use of proton pump inhibitors in a Greek university hospital

Introduction

Proton pump inhibitors (PPIs) are among the most frequently prescribed classes of drugs worldwide [1] and this trend has increased over the last decade [2]. Although their use is guided by well-defined indications [3], inappropriate PPIs prescription has been observed in primary care [4] and the hospital setting [5].

Long-term use of PPIs has been associated with serious adverse effects, such as Clostridium difficile infection, community-acquired pneumonia, bone fractures, dementia, chronic kidney disease, and micronutrient deficiencies [6], and it imposes a significant burden on the healthcare costs of developed countries [7]. In hospitalized patients, uncritical continuation of medications at admission can prolong unneeded PPI use during hospital stay and after discharge [8]. Furthermore, unnecessary PPI use is often initiated in hospitalized patients because of poor compliance with guidelines and liberal interpretation of indications in favor of a minimal expected beneficial effect on the clinical outcome [9]. Hence, strategies for PPIs discontinuation have been proposed to limit their inappropriate use [10]. Conversely, underutilization of PPIs is also a significant aspect of PPI misuse, since patients with a valid treatment indication are prone to serious complications and worse clinical outcomes [11].

In this context, hospitalization status may become a critical checkpoint to control the proper prescription of PPIs, and educational initiatives to inform physicians about correct PPI use are of the utmost importance [12]. We therefore conducted a study aiming to document inappropriate prescription of PPIs in a Greek university general hospital and to evaluate the impact of an educational intervention on limiting PPI misuse.

Patients and methods

Results

The study phases are shown in Fig. 1 and the patients’ clinical and demographic characteristics retrieved from their records and charts in Phases I and III of the study are shown in Table 1.

Figure 1 Flow diagram of the study PPI, proton pump inhibitor; GI, gastrointestinal

Table 1 Characteristics of patients receiving PPIs

Primary endpoint

Phase I of the study was conducted in March 2017. Overall, files from 470 patients admitted in 3 consecutive on-call days were assessed (Table 1). Among admitted patients, 32.5%, 65.6% and 33.2% received PPIs before admission, during hospitalization and at discharge, respectively. The rates of inappropriate PPI administration were 25.9%, 49.2% and 21.4%, respectively. More specifically, PPI overuse was documented in 15.7% of patients before admission, in 41.1% of those hospitalized and in 12.4% of the discharged patients, while the respective percentages for PPI underuse were 10.2%, 8.1% and 9%. The duration of hospitalization (10.03±11.86 vs. 9.41±11.84 days, P=0.257) and patients’ outcomes (complete healing and improvement: 50.5% vs. 49.5%, P=0.205) were not related to inappropriate PPI use.

Table 2 summarizes the risk for inappropriate PPI use during hospitalization in the departments of the hospital as compared to the Gastroenterology unit. The patients in the internal medicine department were more likely to be exposed to inappropriate use of PPIs than patients in other departments. As shown in Table 3, patients discharged from the internal medicine sector of the hospital were at a significantly increased risk of inappropriate PPI use compared to patients discharged from the surgery sector (OR 3.79, 95%CI 1.98-7.19; P<0.001), with this difference being significant for both PPI overuse and underuse (OR 3.37, 95%CI 1.48-7.69; P=0.002 and 3.33, 95%CI 1.27-8.67; P=0.011). Moreover, significant PPI underuse during hospitalization was detected among patients admitted to the internal medicine sector compared to those admitted to the surgery sector of the hospital (OR 5.35, 95%CI 1.62-17.86; P= 0.001).

Table 2 Inappropriate use of PPIs during hospitalization during Phase I, by department

Table 3 Administration of PPIs in internal medicine and surgical sectors during Phase I of the study

Secondary endpoints

Phase II of the study was conducted between September 2018 and January 2019. Based on the results of Phase I, the medical staff of the internal medicine sector, where the inappropriate use of PPIs was more frequent, underwent—apart from the information campaign for all medical staff of the Hospital—2 additional intensive educational seminars on the appropriate use of PPIs, as described in the Patients and methods section.

Therefore, Phase III of the study (June and July 2019) focused on the internal medicine departments. Overall, the records and charts of 317 patients admitted in 4 consecutive on-call days were assessed during Phase III. Among them, PPIs were prescribed in 21.9%, 64.5% and 29.7% before admission, during hospitalization and at discharge, respectively. Inappropriate use of PPIs was documented in 22.3%, 48.6% and 23.6% at the same time points.

As shown in Table 4, the rates of inappropriate use of PPIs were not significantly different during hospitalization (51.7% vs. 48.6%, P=0.478) and at discharge (26.9% vs. 23.6%, P=0.391) between Phases I and III. However, we observed a 3-fold decrease in PPI underuse during Phase III compared to the initial assessment. Hospitalization duration was longer in patients with inappropriate PPI use (9.62±9.50 vs. 7.78±10.28 days, P=0.03), while patients’ outcomes (complete healing and improvement: 46% vs. 54%, P=0.297) were not related to inappropriate PPI use during Phase III of the study.

Table 4 Administration of PPIs in internal medicine sector during study Phases I and III

During study Phase I, the average cost of PPIs (omeprazole, lansoprazole, pantoprazole, esomeprazole) administered in our hospital was 3.435 euro and 0.235 euro for the iv and the per os dose, respectively. During the same period, we detected that 1850 iv and 430 per os doses of PPIs were administered in 193 patients without indication during the 10 (mean value) days of their hospitalization. Of these patients, 80% received the medications iv (80% q.d. and 20% b.i.d.) and the rest orally (90% q.d. and 10% b.i.d.). Assuming that these numbers and rates of inappropriate PPI use could be applied to all 90 on-call days of the hospital per year, the annual expenses of the hospital due to PPI overuse was calculated at 193,674 euros. Using the same model, we estimated that 1200 patients (40 patients every 3 hospital on-call days) would be at risk of GI complications annually, due to under-prescribing of PPIs at discharge from the hospital.

Discussion

Following a worldwide trend, PPI overuse is a concern for the Greek healthcare system. Ntaios et al retrospectively studied the discharge letters of 1693 adult patients, revealing that 81.4% of PPI prescriptions had an improper indication [14], and Voukelatou et al showed that 84% of PPIs were prescribed inappropriately among 758 admitted elderly patients [15]. Our findings indicate a lower PPI misuse rate in Greece compared to previously published studies. However, we estimated that the annual cost of the inappropriate prescription of PPIs in a Greek tertiary hospital exceeds the cost of purchasing one modern, fully equipped endoscopy system, and that 1200 patients would be at risk of developing GI complications due to under-prescribing of PPIs at their discharge. We also detected that the patients discharged from the internal medicine sector clinics/departments were at a higher risk of PPI misuse compared to those discharged from the surgical sector. This finding contrasts with the results of 2 studies where a larger proportion of surgical patients were found to receive PPIs inappropriately and in higher doses compared to the internal medicine patients [5,12].

During the second phase of the study, we implemented an educational campaign to present the study Phase I results and to highlight the indications and potential harms of PPI misuse. Finally, we examined the effects of the intervention in the third phase of the study only in the internal medicine sector, where we detected the larger deviation from the correct PPI administration. Phase III was conducted long after Phase I, when the medical stuff were unaware of being monitored.

Our educational intervention failed to reduce the inappropriate use of PPIs. We may speculate that the lack of a close feedback program in our comprehensive educational intervention was one of the contributing factors for this failure. Similar educational interventions accompanied by visual stimulation throughout various hospital sites were also inconclusive, yet implied a reduction in inappropriate PPI use elsewhere [16,17]. Moreover, interventions which included continuous and regular review and benchmarking, apart from educational sessions, were more effective in reducing PPI overuse during hospitalization and after discharge [18,19]. Unfortunately, these studies lacked a long follow up, for clinicians’ prescription habits and for patients’ clinical outcomes. However, it seems that a combination of educational sessions, along with a close feedback program engaging and motivating clinicians to prescribe appropriately, might be more effective. Measures such as clearly written and easily applicable local clinical guidelines, in both printed and electronic form, frequent reminders such as email newsletters, as well as live or web platforms where physicians can view current data and address questions and concerns, could be important steps in this direction [12,20].

On the other hand, our intervention showed for the first time the effectiveness of an educational intervention in reducing the underutilization of PPIs in a hospital setting. PPI underutilization is an underappreciated but concerning issue, mainly reported in patients under NSAID treatment [21]. The burden of potential upper GI complications in high-risk hospitalized patients (NSAIDs, antiplatelet or anticoagulant treatment users, critically ill patients in need of stress ulcer prophylaxis) as well as their greater risk of death and length of hospitalization are well established [22]. However, our observation is limited by the fact we found no difference regarding patients’ outcomes according to the appropriateness of PPI use.

Surprisingly, we observed that the rate of PPI misuse doubled during hospitalization compared to the pre-admission rate, but it returned to pre-hospitalization levels at discharge. This motif was observed in both phases I and III of the study, showing from a different perspective that our intervention had no impact on physicians’ PPI prescription habits. Moreover, any explanation of this motif is difficult and highly speculative. Uncertainty about patients’ outcomes, ignorance of PPIs’ indications and risks, inadequate long-term monitoring of the medications administered, and reliance on the correctness of the pre-hospitalization treatment might, at least partially, explain why the opportunity of correcting long-term PPI misuse was lost during hospitalization [12]. Routine prophylaxis for stress ulcer, gastroprotection for NSAID, antiplatelet, anticoagulant or corticosteroid therapy without other bleeding risk factors, and uncritical PPI use in cirrhosis, cancer or pancreatic diseases, are some well-defined and widespread wrong indications for PPI use in hospitalized patients [21].

Our study is the first to evaluate the effect of an educational intervention on the administration of PPIs in Greece and one of the very few worldwide. The multifaceted character of the intervention and the large number of patients that were included in the study strengthens the reliability of our results. The fact that the exact dates of the phases of the study were unknown to the hospital staff limited the potential bias of the hospital physicians to act as if under review. On the other hand, our study was a cross-sectional data recording, preventing the estimation of a potential relationship between clinical or demographic factors and PPI prescribing and the follow up of PPI administration after the patients’ discharge from hospital. Evaluation of the effect of the educational intervention only on the internal medicine sector can also be considered a study limitation.

In conclusion, inappropriate PPI prescription in the hospital setting is a worrisome issue, and Greece is no exception. Since hospitalization provides an opportunity for a thorough medical assessment, intervention programs training hospital physicians to prescribe PPIs properly should be conducted. The failure of our intervention to control PPIs prescribing might, at least, be explained by the lack of close monitoring, feedback and benchmarking to further motivate medical staff to improve PPI use in clinical practice.