Table3 Acceptance rate and effectiveness rate of the consultations
4 Discussion
4.1 Improvement of anti-infection consultation quality
From 2018 to 2020, the number of consultations increased significantly, and anti-infection consultations were still dominant. On the one hand, health administrative authorities in China attached great importance to the rational use of antibacterial drugs, which was included in hospital management and performance evaluation indicators. On the other hand, Chinese clinical pharmacists vigorously invested in anti-infection consultation work, which dramatically improved the consultation effect and expanded their influence in the management of antibacterial drugs[22-24]. The main purpose of anti-infection consultations in our hospital was to adjust the anti-infection scheme, and the main working mode was to adjust the scheme when the bacterial culture result was not available or negative, or screen the scheme if it was available. As a result, how to improve the ability of anti-infection treatment is a crucial problem that clinical pharmacists should always pay attention to.
The top three clinical departments applying for pharmaceutical consultations were Department of Spinal Surgery (99 cases, 18.3%), Department of Urology (68 cases, 12.5%) and Central Intensive Care Unit (CICUs) (55 cases, 10.1%). In our hospital, the amount of spinal surgery is large, so is the number of patients with fever after operation. Surgeons lack experience in using antibiotics, especially the choice of drugs for anti-tuberculosis treatment, which should attract clinical pharmacists’ attention. In terms of Department of Urology, the patients’ characters are more distinct. They tend to be elder with liver and kidney dysfunction and multiple chronic disease, so more needs are for adjusting dosage and identifying drug interactions. Consultations in Intensive Care Units (ICUs) mainly focus on multidisciplinary difficult cases. Our main concern is the individualized medication of patients with multi-drug resistant bacteria or rare pathogenic bacteria infection. In order to provide better pharmacy services for ICUs patients, senior clinical pharmacists regularly hold consultation case discussions and literature reading reports in 4 ICUs. The topics mainly include high-quality anti-infection literature, the rational use of special grade antibiotics such as ceftazidime、avermectin and polymyxin B, and individualized medication experience analysis, which provide a learning and communication platform for physicians.
It is worth noting that with the rapid increase in the incidence of fungal infections [25], there is a corresponding increase in need for the rational use of anti-fungal drugs. Such consultations are often difficult to give recommendations due to the long course of broad-spectrum antibiotics treatment for patients. On the premise of evaluating risk factors with WVUH deep fungal infection score, clinical pharmacists strictly controlled the abuse of antifungal drugs and achieved good therapeutic effects.
4.2 Discussion on the consultation mode of multidisciplinary individualized medication
Pharmacists should take initiative to pay attention to all the medication of patients. Only in this way can we broaden the breadth and depth of clinical pharmacists’ consultations. To create multidisciplinary pharmaceutical consultation is the purpose of developing the mode of multidisciplinary individualized medication consultation in our hospital. According to the data above, there are 11 non-anti-infection consultation cases in 2018, 20 cases in 2019 and 30 cases in 2020, demonstrating an increasing trend year by year. The total number of non-anti-infection consultations in three years accounts for 11.3%, which is equivalent to the average proportion of tertiary hospitals in other regions of China [7]. Among them, anticoagulation consultations accounted for 9 cases (14.8%), and nutrition consultations accounted for 8 cases (13.1%). There is still a certain gap between the breadth of drug selection and the difficulty of consultations, by comparison to national clinical pharmacy specialty hospitals [26-27].
Department of Cardiology is characterized by radiofrequency ablation of heart failure, arrhythmia and atrial fibrillation. It has a high reputation in Shanghai, China. In addition, the Department of Respiration is a rapidly developing specialty in recent years, in which anticoagulant outpatient service is badly in need. The anticoagulant pharmacy services our hospital have carried out are embodied in pharmacy rounds and the support of physician-pharmacist joint anticoagulation outpatient clinics. The addition of anticoagulant recommendations in pharmacists’ consultations is another attempt of pharmaceutical intervention. First, during the intervention process, we found that the both physicians and nursing staffs have established a relatively standardized evaluation process and medication habits for postoperative anticoagulation management. However,for elderly patients with renal insufficiency,physicians are often confused about the choice of medication and dosage; Secondly, for the non-surgical patients, physicians tend to ignore whether they are at high risk of embolism, which leads to inaccurate application timing of anticoagulant drugs. Besides, during the process of medication, hemorrhage risk is not easy to pay attention to, resulting in increased risk of adverse consequences. Finally, how to balance embolic risk and hemorrhage risk, and how to carry out physical prevention are also weak links. In response to the problems above, clinical pharmacists give interventions in consultations and play a certain effect. After intervention, no consultation patients have experienced embolism or hemorrhage due to the unreasonable use of anticoagulants. At present, the participation of clinical pharmacists in anticoagulant work in China is still in the initial stage. The work mainly focuses on patient follow-up and assisting doctors in patient education management. Besides, current anticoagulant management norms and standardized anticoagulant effect evaluation system are also in the exploratory stage[28]. We need to find our own way out to catch up with other countries. In the future, we intend to continue implementing this mode to improve the quality and quantity of anticoagulation consultations.
PPIs are widely used in clinical practice. In the previous pre-prescription review and key monitoring drugs review, we found that physicians had many irrational PPIs use, including inappropriate timing of medication, unreasonable choice of dosage and dosage form, inappropriate use of drugs, etc. After the implementation of the intervention, we gave individualized suggestions to patients. The recommendations mainly include reasonable therapeutic and preventive dose, choice between oral and intravenous drip dosage form and the incidence of adverse reactions caused by drug interaction, which were generally welcomed and accepted by physicians. In China, due to the increasingly serious problems of PPIs abuse, a series of targeted measures have been implemented and preliminary results have been achieved [29-30]. The addition of PPIs recommendations in clinical pharmacists’ consultations is our attempt. With the continuous promotion of this mode, we hope to further rationalize PPIs use and reduce unnecessary drug expenditures.
In China, clinical nutrition support is developed late,so is the work of nutrition pharmacists. Besides, nutrition pharmacists’ work content overlaps with that of the Department of Nutrition, resulting in the relatively slow work progress. The nutritional pharmaceutical care in our hospital is still in its infancy, which does not match the needs of its tumor specialty characteristics. In fact, nutrition support is indeed urgently in need. In the face of the needs of a large number of tumor patients and rapid development of new varieties and dosage forms of nutritional drugs in the market, oncologists need nutrition pharmacists’ support.
At present, although the total number of nutrition consultations is small, we have basically achieved individualized nutritional score screening for each patient, which is related to the low prevalence of malnutrition [31].That means we have taken the first step of nutritional screening at the pharmaceutical level. But it is far from enough to give recommendations on enteral or parenteral nutrition based on screening scores. The next step is to publicize our nutrition support and promote propaganda and education on problems of nutritional risk screening, early low calorie supply, enteral nutrition priority, etc. We plan to sort out the classification of enteral and parenteral preparations in our hospital, and introduce energy density, sugar fat ratio, preparation characteristics and pharmacoeconomic evaluation to physicians, so as to let them know our expertise in nutrition support.
When giving consultation recommendations, it is equally important to focus on the effect of medication advice, the monitoring of adverse reactions, and whether they should ask other departments for help. In the future, we should also pay attention to follow-up monitoring and multidisciplinary cooperation.
4.3 Evaluation of consultation effects
The ARC of the post-intervention group was not significantly increased, compared with the pre-intervention group (96.9% vs 95.7%, P = 0.578). But it was higher than what was reported in domestic literature[8-10]. This was probably due to the frequent interactions with physicians and the general recognition of ability. The ERC in the post-intervention group was significantly higher than that in the pre-intervention group (81.7% vs 70.2%, P < 0.05), but lower than was reported in the domestic literature. It may attribute to the fact that our hospital is the leading phase I tumor clinical research center in China, which attracts large numbers of patients with advanced malignant tumor. The consultation patients are often infected seriously and combined with multiple organ failure, which lead to poor prognosis and affected the effectiveness of consultations.
4.4 Case in point
A 92-year-old female was admitted to our hospital with the diagnosis of malignant tumor of colon. She had a history of peptic ulcer and heart failure. After admission, the patient had repeated fever and was treated with levofloxacin and moxifloxacin hydrochloride injection successively. At present, she was still in fever with liver dysfunction (total bilirubin 42.4 umol·L-1, direct bilirubin 37.1 umol·L-1, AST 66 U·L-1, r-GT 183 U·L-1) and renal dysfunction (creatinine 233 umol·L-1). The infection index was abnormal (WBC 14.59 × 109 L-1, CRP 126.64 mg·L-1) and the mental response was poor.
Purpose of consultation: To adjust the anti-infection scheme.
Clinical pharmacists suggest that: (1) The patient’s current inflammatory indicators are progressively elevated with frequent urination symptoms. Midstream urine culture repeatedly shows multidrug-resistant Klebsiella pneumoniae (+), which needs to be treated with another antibiotic. Considering that the patient is at the advanced age of 92 with abnormal liver and kidney function, polymyxin is not suitable because of its nephrotoxicity and neurotoxicity, neither is compound sulfamethoxazole because of its hepatotoxicity and nephrotoxicity. In addition, the concentration of tigecycline in urinary tract is low, which should not be the primary choice in treating urinary tract infections. Considering the conditions above, we recommend to use ceftazidime avibatam sodium for injection 1.25g q12h ivgtt (creatinine clearance rate of 32ml·min-1). Blood routine, CRP and PCT should be reexamined after 3 days of medication. (2) The patient’s Padua score is 6 points (stay in bed for at least 3 days 3’+advanced age 1’+heart failure 1’+infection 1’), indicating a high risk of embolism. So it is recommended to use low molecular weight heparin 4000 IU qd. (3) The patient has a history of peptic ulcer, uncontrolled infection and liver dysfunction, which are risk factors of stress ulcer. So pantoprazole 40 mg bid ivgtt is recommended. (4) According to NRS2002 nutritional screening score, the patient gets 3 points (malignant tumor1’+ recent weight loss1’+decreased food intake1’), which suggests severe malnutrition. So we suggest to use ENSURE on demand. (5) The patient is currently using compound amino acid injection (18AA). In view of the abnormal liver function, we suggest to select branched chain amino acids preparations. As a result, we suggest to use compound amino acid injection (20AA) instead.
Follow-up: Physicians accepted the consultation recommendations above. After 3 days of treatment, the patient’s temperature decreased and the infection index gradually returned to normal. No thrombosis or upper gastrointestinal bleeding occurred. The nutritional status improved.
4.5 Conclusion
During the specialty construction of Shanghai clinical pharmacy, we strengthened the training of clinical pharmacists, and further improved the pharmaceutical services. In terms of the pharmaceutical consultation work, we created a multidisciplinary individualized medication consultation mode. During the implementation of this mode, we added anticoagulation, PPIs use, nutrition and individualized follow-up monitoring to the consultation recommendations, which increased the total number of consultations year by year. In details, the number of general consultations, multidisciplinary difficult consultations, departments applying for general consultations, departments applying for multidisciplinary difficult consultations, anti-infection consultations and non-anti-infection consultations increased correspondingly. The ARC continued to be higher than the average level in China and the ERC was significantly higher than that in the pre-intervention stage, which reflected clinical pharmacists’ value in rational drug use.
4.6 Limitations
The limitations of this study are listed as follows: 1.This study is a retrospective study, so the baseline is difficult to be flattened when the subjects are included in the study. In addition, some of the consultation subjects are in critical situation and require multidisciplinary diagnosis and treatment. Their outcomes cannot be completely attributed to the acceptance or rejection of clinical pharmacists’ consultations, and the evaluation of effectiveness needs to be viewed objectively. 2. As the study is a single center study, the vast majority of patients are only limited in Pudong New Area of Shanghai, China. In order to further evaluate the impact of the new consultation mode on the consultation effects, multi-center, large sample studies should be carried out.
Acknowledgments
This study was supported by Key Specialties Foundation of Clinical Pharmacy of Shanghai Municipal Health Commission in China (SWLCYXZX-2018-001) and Research on the Epidemiology of Severe Drug-induced Diseases of the Chinese Society of Toxicology (CST2019CT304).
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