Statements on the impact of the article on practice Process and structure characteristics may influence the dispensing of undesirable interacting drug combinations in community pharmacies but probably to a minor degree. Medication surveillance in Dutch pharmacies seems to be effective. Introduction 1 4 5 6 8 9 The objective of this study was to assess process and structure characteristics associated with the dispensing of interacting drug combinations, which carry a high risk of adverse patient outcomes. Methods Setting 1 10 11 Table 1 Number of dispensings in the database of the individual drugs involved, the eleven potential D–DIs and the calculated ratio  Drug–drug interaction Number of dispensings drug A × 1,000 (range) Number of dispensings drug B ×  1,000 (range) Number of D–DIs counted (range) a  Drug A Drug B 1 Erythromycin, clarithromycin, azithromycin, roxithromycin Digoxin 440.8 (0–2754) 487.0 (0–3064) 3,993 (0–41) 1.39 (0–18.52) 2 Itraconazole Digoxin 88.7 (0–349) 487.0 (0–3064) 245 (0–7) 0.45 (0–21.69) 3 Ciprofloxacin Theophylline 105.4 (0–769) 100.9 (0–756) 944 (0–14) 6.39 (0–534.38) 4 Miconazole oral gel Acenocoumarol, fenprocoumon 44.6 (0–233) 608.2 (5–3156) 154 (0–3) 0.38 (0–21.30) 5 Erythromycin Carbamazepine 49.7 (0–531) 193.6 (0–871) 35 (0–4) 0.24 (0–40.92) 6 Erythromycin, clarithromycin, azithromycin Disopyramide 426.6 (0–2754) 9.4 (0–151) 61 (0–4) –  7 Erythromycin, clarithromycin Pimozide 274.4 (0–2004) 57.4 (0–394) 70 (0–15) 0.46 (0–46.12) 8 Propranolol, oxprenolol, pindolol beta2-mimetics, inhalation corticosteroids 250.6 (1–1075) 2,546.9 (27–10504) 5,127 (0–94) 0.54 (0–12.98) 9 Erythromycin, clarithromycin Cisapride 274.4 (0–2004) 127.5 (0–821) 586 (0–11) 1.16 (0–40.45) 10 Itraconazole, fluconazole, ketoconazole Cisapride 199.9 (0–727) 127.5 (0–821) 347 (0–12) 0.95 (0–57.10) 11 Acenocoumarol, fenprocoumon Azapropazon 608.2 (5–3156) 8.4 (0–164) 32 (0–19) –  a Procedure 1 9 2 1 Fig. 1 The selection of the pharmacies receiving a questionnaire and IHC visit  Table 2 The subjects and number of questions in the questionnaire Chapter Subject (number of questions) General pharmacy data Ownership of the pharmacy (1), cooperation with other pharmacies (1), cooperation with general practitioners (1), electronic submission of prescriptions (4) Facilities Alterations (2) Quality policy Setting up and implementing a quality system (4), certification (2), attitude towards quality management (12) Quality measurement Measurement of errors (2), complaints (1), patient satisfaction (2), interventions (3), and participation in mystery guest investigations (2) Receipt procedure Number of personnel involved in dispensing a receipt (2), checks in dispensing a receipt (3) Medication surveillance—tuning software a Medication surveillance—organisation The way technicians are instructed to manage medication surveillance signals (5), the way this is supervised (2), number of interventions (1), use of resources (2), participation in courses (4), management of the D–DI between carbamazepine and erythromycin (5) and between Sulfamethoxazole/trimethoprim and Acenocoumarol (7) Medication surveillance—recording management The way the management of signals is recorded (4) Pharmacy preparations The way instructions for pharmacy preparations are recorded (1), the way pharmacy preparations are supervised (3), the number of pharmacy preparations (2), the policy regarding analysing pharmacy preparations (3) Personnel and workload Subjective workload (3), absence through illness (1), number of receipts dispensed per technician (2), personnel and experience of personnel (18) Patient care Information given to patients (6), information exchange with hospitals (4), participation in health care projects (4) Farmacotherapeutic consultation groups Participation in farmacotherapeutic consultation groups (3), agreements made (3) a Formula 1: \documentclass[12pt]{minimal}
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$$ {\hbox{Ratio}}\,{\hbox{2}}\, = \,\frac{{\frac{{k_{i,ab} }} {{N_i \cdot \sum\nolimits_i {k_{i,ab} {\hbox{/}}N_{{\hbox{tot}}} } }}}} {{\frac{{k_{i,a} }} {{N_i \cdot \sum\nolimits_i {k_{i,a} {\hbox{/}}N_{{\hbox{tot}}} } }} \cdot \frac{{k_{i,b} }} {{N_i \cdot \sum\nolimits_{} {k_{i,b} {\hbox{/}}N_{{\hbox{tot}}} } }}}} $$\end{document} k i ,ab i k i,a i k i,b i N i i N tot Statistical analysis 12 p Results 1 1 1 3 Table 3 Significant univariate correlations between the questionnaire and the number of dispensings of the D–DIs between macrolide antibiotics and digoxin (number 1) Question Correlation Significance n n −0.165 0.009 Which medication surveillance system is used in the pharmacy? n −0.261 0.000 n 0.088 0.170 n 0.197 0.002 4 4 5 Table 4 Predictability of the models composed in the multivariate analysis D–DI R 2 a 1 28.9 0.61 2 12.8 −0.22 3 17.3 31.5 4 7.0 −0.18 5 14.4 −0.41 7 6.5 6.4 8 16.1 0.68 9 14.0 −0.43 10 2.6 0.90 a Table 5 The questions in the multivariate model predicting the dispensing of the D–DI between macrolide antibiotics and digoxin (number 1) Variable: Answer (coding) Direction coefficient Constant  3.3679 n n Yes (0) versus no (1) −2.2749 Co-trimoxazole—acenocoumarol: no appointments were made with the GPs. The drug will be dispensed. n Reference Eight options of choice option 1 ‘with all GPs’ and option n 1.0308 Eight ‘with no GPs’ n 0.3788 n −0.4542 n 0.9026 n −0.5100 n −0.1912 n 0.0886 n n Yes (0) versus no (1) 0.1793 n n Yes (0) on the receipt, no not on the receipt (1) 0.2691 n n Yes (0) on the basis of signal lists, no (1) not on the basis of signal lists 0.0723 How many receipts are dispensed per year divided by the number of fte technicians  –4 Discussion In this study, we investigated determinants for the dispensing of 11 undesirable interacting drug combinations. In general, our results are in line with the expectation that the medication surveillance system plays an important role in medication surveillance. Although the 11 potential D–DIs were counted 11,594 times which suggests that a considerable number of patients is exposed to potential and avoidable adverse patient outcomes, these results should be judged against a background of approximately 100 million dispensings. It is possible that in these cases due to particular circumstances any other option, such as substituting or not dispensing one of the drugs, is a less favourable choice than dispensing the D–DI. In 5% of the total number of D–DIs more than one pharmacy was involved, indicating the importance of communication. For the D–DI between macrolide antibiotics and digoxin, two determinants were found. Although the type of medication surveillance system was a determinant, this does not mean that the differences are determined by the quality of the system itself because they may also correlate with the attitude of the pharmacists using the systems. The three medications surveillance systems differ in the extent to which communication with other healthcare providers is possible and developments were made in recent years. The Pharmacom system has the most advanced communication possibilities and compared to the other systems, new developments to the Euroned system were modest. Unexpectedly, pharmacies part of a health care centre dispensed this D–DI more often than other pharmacies. In health care centres, the communication lines between pharmacists and general practitioners are much shorter, suggesting that intervening undesirable D–DIs will be easier. Possibly, pharmacies which are part of a health care centre oppose the opinions from the general practitioners less often, to avoid harming the cooperation within the health care centre but, of course, there may be several other reasons. For the other eight assessed D–DIs no determinants were found in the univariate analysis, neither did the models in the multivariate analysis have a good predictability. A possible explanation is that the quality of medication surveillance in community pharmacies in the Netherlands is high. Therefore, the number of pharmacies dispensing high-risk D–DIs seems to be small. p Fourth, the questionnaire was composed on the basis of a literature search and interviews with experts. It is possible that not all characteristics correlating with the dispensing of undesirable interacting drug combinations were disclosed, such as differences in population characteristics between pharmacies. For example, pharmacies with an elderly population using more drugs simultaneously have a higher risk of dispensing interacting drug combinations than pharmacies with a younger population. Also, it is possible that in areas with many general practitioners who use a medication surveillance system for prescribing, the background chance of a D–DI is much smaller. Fifth, it is possible that the differences between pharmacies were too small compared with the power of this study to distinguish determinants. All associations found in this study were directly related to the management of signals. In our questionnaire, we also included other topics, such as pharmacy preparations and patient care. Future research should focus on the management of a larger variety of signals than the ones in our study and on how D–DI associated dispensing could be further reduced. Conclusion In conclusion, both medication surveillance systems and being part of a health care centre may play an important role in the management of D–DIs and the avoidance of adverse patient outcomes. Pharmacies in a healthcare centre dispensed D–DIs more often. For most D–DIs, no determinants were found possibly indicating that the quality of medication surveillance in the Netherlands is high.