Awareness, attitude and behavior regarding proton pump inhibitor among medical staff in the Southwest of China

Proton pump inhibitors (PPIs) were proved to be currently the most effective drugs inhibiting hydrochloric acid secretion [1] and were widely used for the treatment and prophylaxis of upper gastrointestinal tract disorders including gastroesophageal reflux disease (GERD), peptic ulcer disease and its complications, Helicobacter pylori eradication therapy, dyspepsia, nonsteroidal anti-inflammatory drugs (NSAIDs)-induced ulcers, stress ulcers, and other hypersecretory conditions [2]. Since the first PPI omeprazole was introduced in 1989, other drugs in the class have been marketed: lansoprazole, pantoprazole, rabeprazole, esomeprazole and ilaprazole. There has been a substantial, continuing and unexplained rise in prescribing of PPIs. PPIs remain one of the world’s most frequently prescribed medications. In the United States, PPIs were prescribed in 4% of outpatients in 2002 and 9.2% in 2009, sales of PPIs accounted for about 10 billion dollars in 2007 and 13.9 billion dollars with 113 million prescriptions filled annually in 2010 [3]. In addition, PPIs have become the 8th therapeutic class on the prescription list in 2013. In Scotland, there was a threefold increase in PPI utilization between 2001 and 2017, however total expenditure on PPIs was 66.7% lower in 2017 compared to that in 2001 [4]. In the Netherlands, there was a threefold increase in PPI utilization between 2000 and 2010, whereas there imbursed expenditure fell by 58% in 2010, helped by increasing utilization of generic omeprazole at only 2% of the prepatent loss price in 2010 [5]. There was an eightfold increase in PPI utilization between 1997 and 2009, but only a twofold increase in reimbursed expenditure in Belgium [6]. Similar to other countries, there were considerable differences in the utilization of generics and patent-protected PPIs among Western European countries [7]. Several studies reported that the utilization and expenditure of PPIs had increased by 6 to 10 times over the past decade in several tertiary general hospitals in China [8, 9]. In China, although generic drugs are encouraged to use, their prices are only slightly lower than original drugs, which make the utilization and expenditure of PPI increase synchronously.

Overutilization is defined as prescribing PPIs without an appropriate indication or inappropriate continuation of PPIs upon discharge from the hospital. Unexplained abdominal pain was the main driver for prescribing intravenous PPIs empirically, out of which (68.9%) were for suspected upper gastrointestinal bleed [10]. The utilization of injectable PPIs increased substantially over the past decade at a tertiary hospital in China [8, 9]. A recent research showed that 86% of patients who were prescribed PPIs did not have appropriate indications in the general medical ward of a tertiary Jordanian hospital [2]. Another study showed that PPIs were taken by 25.4% of the patients hospitalized in an internal medicine department of a tertiary Greek hospital, but as many as 81.2% of them had no indications [11]. In our previous studies, all patients under going elective operations in hepatobiliary surgical were prescribed PPIs, but 82.41% of them had unlicensed indication. In addition, 35.59% of inpatients were prescribed PPIs, of which 57% had no indications [9, 12]. Furthermore, PPIs overuse in the clinical setting is often the result of incorrect stress ulcer prophylaxis (SUP) in non-intensive care unit patients, and failure to discontinue this therapy before hospital discharge, even in the absence of a therapeutic indication. Despite their perceived safety and reasonable costs, overutilization of PPIs would pose significant health risks such as gastrointestinal discomfort, dyspepsia, elevated liver transaminase, allergic reactions, visual abnormalities, osteoporosis, hypomagnesemia, community-acquired pneumonia, as well as Clostridium difficile colitis [4, 13].

Several postulated factors are responsible for inappropriate PPIs overutilization in China including misunderstandings about PPIs in medical staff (doctors, nurses and pharmacists), over prescribing of more expensive PPIs (injectable, original), tense physician-patient relationship and consumer-oriented advertising. Currently, in China, doctors prescribe prescriptions for patients, and then medication instruction is provided by nurses or pharmacists. Therefore, the knowledge and attitude towards PPIs in doctors, nurses and pharmacists can all affect the utilization and clinical efficacy of drugs. For example, previous studies indicated that clinical pharmacist’s real-time interventions facilitated the rational use of PPIs and resulted in favorable economic outcomes [12, 14]. If these medical staff do not fully understand the relevant knowledge of PPI, such as drug characteristics, pharmacological action, mechanism, indication, administration time, administration method, duration, drug interaction and adverse reaction, it is easy to cause overuse of PPIs, reduce efficacy and increase adverse reactions. But only a few studies focus on the awareness of PPI issues in medical staff. Therefore, given the current situation and possible causes of PPI overutilization in China, the purpose of this study was to investigate the awareness, attitude and behavior toward PPI use among doctors, nurses, and pharmacists in China so as to find some methods to improve the rationality of PPI application.

Knowledge about PPI therapy among the residents or medical staff of many countries including China has only been studied to a limited extent. This study surveyed medical staff from more than 20 hospitals in the Southwest of China to assess their awareness, attitude and behavior regarding PPIs in the form of questionnaires.

The result of awareness studies indicated that medical staff did not have good overall PPI knowledge. In particular, nurses got less information about PPIs than doctors or pharmacists, especially in aspects of physical and chemical properties, action mechanism, time and method of taking medicine and the characteristics of various PPI. For example, a randomized research have shown that inhibition hours (on 24hintragastric pH > 4.0) of esomeprazole 40 mg, rabeprazole 20 mg, omeprazole 20 mg, lansoprazole 30 mg and pantoprazole 40 mg inpatients with heartburn symptoms was 14.02, 12.13, 11.08, 11.52, 10.07, respectively [19]. While, in this study, only 29.48% of nurses knew esomeprazole has the longest acid inhibition time. Prescribers should take into account that use of PPI can cause toxicity risks, which remain to be fully characterized in pregnancy and children. PPIs, except omeprazole, can be given considering the benefit-harm ratio for the mother and fetus after the first trimester [20]. Recently researcher reviewed the reported adverse effects of PPIs (omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole) used in the treatment of pediatric GERD and found the rate of at least one adverse effect was 34, 43.7, 40, 61.5, 34.8%, respectively [21]. Therefore, omeprazole is recommended in pregnancy and children. Our survey indicated that less than half of the medical staff mastered this knowledge. Several clinical practice guidelines recommend that SUP should be discontinued until no high risk factors, or able to tolerate enteral feeding, or not receiving mechanical ventilation or not in ICU [15, 22]. However, we found that only 12.46% of the respondents responded correctly to the duration of PPI prophylaxis in present study. The score of PPI knowledge was related to gender, age, occupation, education level, professional title, hospital nature and grade. In China, the nurse professional is still a mainly female domain, and the education level and the professional title of nurses are lower than those of doctors and pharmacists. Moreover, hospital nature and grade can also affect the awareness about PPI knowledge. Medical staff in public hospitals got high score than staff in private hospitals. This is probably due to the fact that private hospitals usually put more focus on economic benefits, whereas public hospitals pay more attention to the professional training of their medical staff [23]. So, in public hospitals, medical staff has more opportunity of getting clinical practice experience and new knowledge, which will lead to more abundant knowledge about the reasonable use of PPIs.

There is increasing evidence supporting the overuse of PPIs in clinical practice in the world. More recently, researches have uncovered similar phenomena regarding PPI overuse in China [9, 24, 25]. Our previous study showed that 35.59% of inpatients were prescribed PPIs, of which 57% had no indications. Two other studies also found that the majority of surgical patients (59.26 and 67.03%, respectively) had received PPIs for SUP without indications and for long durations. This overutilization of PPIs for SUP in hospital can cause large economic waste and side effects such as gastrointestinal discomfort, dyspepsia, allergic reactions and visual abnormalities [4, 13]. Fortunately, in the present survey, the majority of respondents were aware of the prevalence of PPI overuse in China. Furthermore, respondents thought overuse of PPI was closely related to the misuse of the PPI by doctors or patients, and it was necessary to launch certain large scale education on rational use of PPI for medical staff to promote better understanding on PPI. Besides using PPIs for SUP in hospital, it is common to use PPIs for community long-term therapy, such as treating GERD. In China, oral omeprazole is the only over-the-counter (OTC) PPIs medicine. However, all oral PPIs, whether OTC or not, are available at community pharmacies without doctor’s prescription and the purchase quantity is not limited. Owing to this easy access to PPIs and poor knowledge of patients, there also remains overutilization of PPIs in community pharmacy. Some research have found that inappropriate long term use of PPIs can increase side effects such as community-acquired pneumonia, fragility fractures, hypomagnesemia, and Clostridium difficile infections [4]. In addition, except ilaprazole, the other five available PPIs (omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole) are all listed in the national medical insurancecatalogue. If a patient buys PPIs in a hospital, the cost can be co-payment. However, if a patient purchases PPIs at a community pharmacy, he will have to pay all by himself. Consequently, the overutilization in community pharmacy can increase patients’ medical burden. As a result, it is imperative to strengthen the management of community pharmacy and implement education on rational use of PPIs for community pharmacists and for the public. Unfortunately, only 37.02% of medical staff paid close attention to the community pharmacy management.

Nearly half of the respondents used PPIs in the past 1 year. In addition, nearly half of respondents used two or more than two kinds of PPIs. Compared to other PPIs, omeprazole was more frequently used, which was mainly related to the following reasons: First, omeprazole is the only OTC drug and consumer-oriented advertising about effectiveness and safety of omeprazole is easily acquired. Second, omeprazole is first introduced and applied clinically for the longest time, with the highest clinical evidence. Third, among all the six available PPIs, omeprazole, is the only one which is listed in the catalogue of national essential medicine in China.

Despite the useful information learnt from this study, several limitations require mention. First, our findings about knowledge, attitude and behavior regarding PPI among medical staff are based on self-reported instruments, which may introduce reporting bias and overestimation of positive knowledge, attitude and behavior. Second, because this was a survey from one geographic location in the Southwest of China, generalization of the results from these data may be limited. Another limitation of this study was the use of a self-designed questionnaire. Therefore, this scoring system may have some defects. In order to reduce defects, the questionnaire was designed and modified based on the advice of experts and pilot study. Finally, the number of respondents might be a little bit small owing to the shortage of research funding.

The present study indicated that medical staff did not have satisfied PPIs awareness, attitude and behavior in more than 20 hospitals in the Southwest of China, especially nurses. This survey also truly reflected some of the potential causes of PPI abuse in the typical Chinese hospitals. To promote awareness of medical staff and to avoid PPI misuse, the authors suggest a number of fundamental keystones as followings: (1) Carrying out periodic training about PPI rational use for medical personnel. (2) Using all media means to establish educational programs about the illness that require PPI therapy and to emphasize when PPI will not do any good. (3) Emphasizing pharmacists’ role and responsibility in stopping PPI sale without prescription, except for OTC drugs. (4) Offering special course to medical, pharmaceutical, and nursing students, which emphasizes the specific behavior of rational PPI use. All those methods might facilitate the rational use of PPI.