METHODS Study design

A survey was performed in a convenience sample of 33 hospital pharmacies in the Netherlands.

The study was carried out from April 2009 to September 2010 and was focused on the medication safety alerts that were disseminated to hospital pharmacies only. In the study period the CMR disseminated the alerts solely to hospital pharmacies because only hospitals participated in the CMR.

Study population

A convenience sample of 33 Dutch hospital pharmacies in the Utrecht Pharmacy Practice network for Education and Research (UPPER) of the Department of Pharmaceutical Sciences, Utrecht University was invited to participate in this study. The hospitals received an invitation for the study when a traineeship pharmacy student was scheduled in the study period by the UPPER organisation. UPPER is a network consisting of hospital pharmacies and community pharmacies that regularly participate in research and traineeships for pharmacy students of this department.

The Netherlands has 93 hospitals and almost all Dutch hospital pharmacies are part of the UPPER network. The hospital pharmacy has a role in medication surveillance and dispensing in the hospital. In all hospitals the pharmacy technicians visit the wards to replenish the ward stocks daily and the hospital pharmacies are responsible for the ward stock list. Routine visits by clinical pharmacists are not generally performed, but they review all prescriptions in the hospital and apply medication surveillance by using a clinical decision support system of the pharmacy medication system. Hospitals always have a pharmacy medication system for entering the prescription whether a hospital has implemented computerized physician order entry (CPOE) or not. This is a centralized activity (performed in the hospital pharmacy) and does not require daily ward visits. The hospitals do not differ in these procedures.

Data collection

The researchers selected three CMR alerts by using the following criteria: the alert should be targeted primarily to hospital pharmacists, the alert had been disseminated at least 2 years ago (in the period 2006 and 2007) and clear recommendations were issued with the alert or could easily be derived from the alert. All the CMR alerts have been published on the website of the CMR organisation.^9,15 The selected alerts concerned the following errors: the daily administration of methotrexate after incorrect labelling of once a day instead of once a week; the administration of undiluted potassium sodium-phosphate concentrate; and the administration of glucose 50%

instead of glucose 5%. From these three CMR alerts and recommendations the researchers prepared a structured questionnaire referring to the practical implementation. The research team developed the questions (indicators for correct implementation) directly from the recommendations in the three alerts. Table 1 summarizes the selected CMR alerts, their recommendations and the derived indicators for the correct implementation (ie, questions in the questionnaire). Within the UPPER network 33 pharmacy students went to their hospitals (n=33, each student went to one hospital) for their internship. During the internship each student was assigned to perform face-to-face interviews with the hospital pharmacist who supervised the student. The students used a structured questionnaire during the interview. Hospital pharmacists responsible for the training of residents and interns were generally interviewed. These hospital pharmacists have at least 5 years working experience and they belong to the senior staff of the hospital pharmacy. If necessary the students could perform onsite observations to support the answers in the questionnaire, but whether or not observations were carried out was not documented. The onsite observations were not compulsory and the students independently decided whether the observations were necessary. Both the face-to-face interview and the onsite observations were performed during the traineeship in the hospitals. Before the start of the traineeship the students received a briefing about this research at the university.

Measures

The indicators for the degree of uptake of the three CMR alerts varied from four to five per alert (table 1). The indicators concerned the presence of medication in the pharmacy stock, a protocol and cautionary text added to the pharmacy stock. Some indicators were related to the operating procedures during prescribing and dispensing.

On the basis of common sense and their knowledge of the field, the researchers selected the following potential determinants which could be associated with the uptake: the number of beds (including nursing homes and other institutions where the hospital pharmacy dispensed medication), the number of employees in the hospital pharmacy (divided into pharmacists, pharmacy technicians, and others, e.g. management staff), the use of CPOE for prescribing medication and the number of medication errors reported to the CMR in the last 12 months.

Additionally, some characteristics of the hospital (type of hospital (university, teaching, general) and its region (north, east, south and west)) were collected.

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Table 1. CMR alerts.

Description of the medication error which was published in the CMR alert (year of dissemination of the CMR alert)

Recommendations as a result of the described medication error in the CMR alert

Administration of methotrexate with a labelled dosage of once a day instead of once a week (2006)

During admission the nurse entered the home medication of the patient in the CPOE as provisional prescriptions. For methotrexate 7.5 mg the nurse entered a dose of one tablet per day instead of one tablet per week. The physician forgot to authorize the provisional prescriptions of the patient in the CPOE. In spite of this, the patient received the medication and methotrexate 7.5 mg had been administrated for 9 days in a row. The patient died after a few days.

• Withdraw all methotrexate tablets in the stocks of the wards.

• Dispense methotrexate tablets only for one day to the wards.

Administration of undiluted potassium-sodium-phosphate concentrate (2006)

A patient on intravenous drip feed on the pulmonary ward was prescribed potassium-sodium-phosphate concentrate. The nurse read ‘one phial potassium-sodium-phosphate concentrate once-only intravenous’.

The nurse administrated the undiluted potassium-sodium-phosphate concentrate intravenously to the patient. Within a few minutes the patient died from a cardiac arrest caused by high dose of potassium.

• No specific recommendation was mentioned in the alert. In the alert the hospital pharmacists could read that the hospital has changed the potassium-sodium-phosphate concentrate to glyceropotassium-sodium-phosphate

concentrate in the stock, and removed the potassium-sodium-phosphate concentrate from the ward stocks.

Furthermore, from the error description it is also clear that one should have a protocol containing information on the maximum infusion rate.

Administration of glucose 50% instead of glucose 5%

(2007)

A resident received an order from a cardiologist over the telephone for 1 litre of glucose 5% for a patient with dehydration. The resident did not hear what the cardiologist said and he thought the cardiologist wanted 1 litre of glucose 50%. The resident commissioned the nurse to administer 1 litre of glucose 50% in 6 h.

Although the nurse mentioned that it was an unusual dose the resident insisted it was an order from the cardiologist. The nurse used the free text space in the CPOE to order 1 litre of glucose 50%. The 100 ml glucose 50% phials were available in the ward and 10 phials were infused. During the night the patient had agonal respiration, bradycardia, low tension and high blood sugar level. The patient died the next morning.

• Make instruction about how to handle an order over the telephone (repeat the order).

• Avoid using the free text space in the computer system because of the absence of medication surveillance.

Though a check by the pharmacist is necessary.

• Education about therapy to physicians and residents.

• Change glucose 50% to glucose 40% in the stock of the wards.

• Mention in the procedure that the pharmacy should be consulted if there are any doubts.

• Pay attention to the hierarchy and attitude between physicians, supervisor, residents and nurses.

a Questions were developed by the research team. The questions were derived directly from the recommendations.

b Weighting of each response to the questions.

CMR Central Medication incidents Registration; CPOE computerized physician order entry.

Questions for the hospital pharmacist ^a (questionnaire) Weighting^b

• Is there any methotrexate in the stock of the wards? No = 20%

• Is there any caution text to warn personnel about the high dispensing volume of methotrexate tablets or injections in the central stock of the hospital pharmacy?

Yes = 20%

• Is there any medication surveillance of the methotrexate dose in the pharmacy computer system? Yes = 20%

• Does the pharmacy dispense methotrexate in a once per week dose? Yes = 20%

• Does the pharmacy record the date of dispensing methotrexate? Yes = 20%

• Does the hospital pharmacy have glycerophosphate as the only phosphate for injection ? (if yes, the following three questions don not need answering)

Yes = 100%

• Is there any stock of phosphate injection with potassium at the wards? No = 33.3%

• Does the protocol about parenterals describe a maximum concentration of phosphate to administer?

Yes = 33.3%

• Does the protocol about parenteral describe a maximum rate of infusion? Yes = 33.3%

• Is there a protocol about how to handle an order by telephone? Yes = 25%

• Is it allowed to prescribe (CPOE) or enter (Pharmacy Medication System) a dose in the free text space?

(if it is allowed, still a score of 25% is possible if the following question was answered yes: does the pharmacist check all free text information?)

No = 25%

Yes = 25%

• Is there any glucose 50% in stock of the wards? No = 25%

• Is there a protocol with the advice to call the pharmacy if there is any doubt on the number of phials to administer?

Yes = 25%

The primary outcome was the degree of uptake of the specific recommendations per alert. For analysis the indicators that were derived from the recommendations were scored (weighted) as to whether or not the specific recommendation had been adopted (see table 1 for potential weighting in % for each indicator). For each alert the hospital pharmacy was able to score a maximum of 100% (complete uptake).

For the number of employees as a potential determinant, the researcher calculated the ratio of the number of full-time equivalents (FTEs) of pharmacists or pharmacy technicians or total personnel (including other staff like management staff) per 100 beds. The total number of beds

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consisted of beds in the hospital, nursing homes and other institutions to which the hospital pharmacy dispensed medication. Beds in the hospital are more time consuming and therefore these beds were given double weight in the calculation of the ratio. Another potential determinant was the use of CPOE, which was considered to be actively used when at least 80% of the prescriptions were entered in the CPOE by the physicians. The last potential factor was the number of medication errors reported to the CMR in the last 12 months.⁹

Data analysis

Data were documented in Microsoft Office Excel 2003 SP3 sheets. The students could upload the results on a dedicated website, which were downloaded by the researchers. The separate Excel sheets were merged into a single data file, which was analysed with IBM Predictive Analytics SoftWare (PASW) Statistics V.18.

The degree of uptake was divided into two groups: complete uptake (score 100%) and non-complete uptake (score 0-99%). The potential determinants were also divided into two groups for further statistical analysis. We used the median as a cut-off value to divide FTE pharmacist per 100 beds, FTE pharmacy technicians per 100 beds, total FTE pharmacy staff per 100 beds into two categories: hospital with low FTE per 100 beds and hospital with high FTE per 100 beds. The use of CPOE was divided into two groups: hospitals using CPOE and hospitals not using CPOE. A hospital was considered to use CPOE when at least 80% of the prescriptions were entered in the CPOE by the physicians. The reporting to CMR was also divided into two groups: hospitals actively reporting medication errors to the CMR and hospitals not actively reporting. Hospitals can report all kinds of medication errors to the CMR.⁹ The researchers used the median of the number of reported medication errors to divide this potential determinant into two groups and the hospitals that did not report any reports were excluded from the calculation of the median because these hospitals were already included as not actively reporting.

Descriptive statistics were used for the degree of uptake of the recommendations and the general characteristics. For analysis of the association between the degrees of uptake and the potential determinants, Fisher’s exact test with risk estimate was used.

RESULTS