Articleonimprovingmedicationerror.pdf

Improving Medication Safety in Psychiatry – A ControlledIntervention Study of Nurse Involvement in Avoidance of
Potentially Inappropriate PrescriptionsAnn L. Soerensen1,2, Marianne Lisby3, Lars P. Nielsen4, Birgitte K. Poulsen4 and Jan Mainz5,6,7
1Danish Center for Healthcare Improvements, Faculty of Social Science, Aalborg University, Aalborg, Denmark, 2University College of NorthernDenmark, Aalborg, Denmark, 3Research Center for Emergency Medicine, Aarhus University Hospital, Aarhus, Denmark, 4Department of Clinical
Pharmacology, Aarhus University Hospital, Aarhus, Denmark, 5Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark,6Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark and 7Department of Community Mental Health, The
University of Haifa, Haifa, Israel
(Received 9 October 2017; Accepted 12 February 2018)
Abstract: The aim of this controlled, before-and-after study in the Department of Psychiatry in a university hospital in Denmarkwas to examine the potential effects and characteristics of nurses reviewing psychiatric patients’ medication records to identifypotentially inappropriate prescriptions (PIPs). The control group and the intervention group each consisted of two bed units cho-sen based on patients’ diagnoses and age categories. There were 396 patients (age ≥18 years) included in the study. Senior clini-cal pharmacology physicians performed medication reviews for all patients in the study; these medication reviews wereconsidered gold standard. The intervention group: nurses were given a pharmacology course after which the nurses reviewedmedication lists and subsequently conferred any identified PIPs with physicians. The control group: medication was reviewed asusual and nurses did not participate. Primary outcome measure was the potential difference in PIPs between the control groupand the intervention group, analysed in two ways: (i) difference in mean number of PIPs and (ii) difference in number of patientsexposed to ≥1 PIP, using regression analysis with an approximated difference-in-difference (DID) approach. Secondary outcomemeasure was characteristics of PIPs where physicians responded to nurse-identified PIPs. The DID between intervention groupand control group for mean number of PIPs per patient was �0.23 (�1.07 to 0.60), and for number of patients receiving ≥1 PIP,the odds ratio was 0.61 (0.25 to 1.46). Physicians changed most prescriptions in the category interaction between drugs. Nursescould not significantly reduce the prevalence of PIPs for psychiatric patients.
Potentially inappropriate prescriptions (PIPs) are common andsignificant in older patients [1,2] and present a specific chal-lenge in psychiatry [3–6]. There appears to be limited researchon PIP in general psychiatric populations that include youngerpatients. However, a Danish study estimated the prevalence ofPIPs in newly admitted psychiatric patients to affect 59% ofpatients, and 12% of the identified PIPs were assessed as poten-tially fatal [7]. There is a need to reinforce medication safety ini-tiatives in psychiatry by exploring new initiatives and engagingother staff groups such as nurses [8]. Nurses are professionalswho have received training in pharmacology and medicinesmanagement during their education. However, researchers sug-gest nurses have insufficient knowledge of the medications theyhandle [9,10] and should receive regular medication manage-ment courses [11]. Nurses are also the staff group who spendmost time at the patients’ bedside, continually observing andmonitoring the patient for both effects and side effects of medi-cations [12]. Nurses are key members of the psychiatric teamsurrounding the patient [13,14] and provide continuous vitalknowledge about patients and their medications [15].In studies on nurses’ role in identifying and mitigating medi-
cal errors, nurses often appear to be the last barricade between
patients and many medical errors [16–19]. In much of the litera-ture mentioned above, errors relating to medications are themost prevalent issue. Studies demonstrate how nurses identifydrug-related problems (DRP) and improve medicines manage-ment [20–24], but similar studies are scarce in psychiatry. OneJapanese study demonstrated improvement in Global Assess-ment of Functioning and a trend towards better acceptance ofmedication by psychiatric patients when physicians – based onnurses’ reports and suggestions – changed medications [25], anda British cluster randomized study demonstrated significantimprovement in total Positive and Negative Syndrome Scale(PANSS) score in patients with schizophrenia after a medicationmanagement training course for mental health nurses [26]. Theaim of this study was to examine the characteristics and magni-tude of PIPs as well as the potential effect of nurses’ systematicreviews of medication records on the appropriateness of medica-tions prescribed to newly admitted psychiatric patients. Ourhypothesis was that pharmacological training of nurses and ageneral increased awareness of medication safety have thepotential to reduce PIPs in adult psychiatric inpatients.
Method
Definitions. Potentially inappropriate prescription is defined asprescribing that introduces a significant risk of an adverse drug-relatedevent where there is evidence of an equally or more effective but lower-
Author for correspondence: Ann Lykkegaard Soerensen, AalborgUniversity, Department of Clinical Medicine, Danish Center forHealthcare Improvements, Fibigerstraede 11, 9220 Aalborg, Denmark(e-mail: als@business.aau.dk).
© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)
Basic & Clinical Pharmacology & Toxicology, 2018, 123, 174–181 Doi: 10.1111/bcpt.12989

risk alternative therapy available for the same condition [2,27].Additionally, PIP includes the use of drug combinations with knowndrug–drug interactions, drug–disease interactions, overdosing, use ofdrugs for a longer time than clinically indicated, as well as the omissionof prescribing drugs that are clinically indicated [2,27]. Studies onelderly patients provide this understanding of PIP but do not include thescenario of omission of therapeutic drug monitoring (TDM). TDM is aquantification of drug concentrations in blood plasma or serum to titratethe dose of individual patients. This quantification helps to obtain a drugconcentration associated with the highest possible probability ofresponse and tolerability with an acceptably low risk of toxicity [28].TDM is central to the prescribing of, for example, tricyclicantidepressants and certain antipsychotic- as well as mood-stabilizingdrugs [28]. In this study, omission of TDM was included and extendedto encompass electrocardiography and other general paraclinical datarequired for appropriate prescribing, for example, electrolytes in bloodplasma. Categories and elaboration on definitions of PIPs are given inTable S1.
Setting and study design. This controlled, interventional before-and-after study took place in the Aalborg University Hospital of Psychiatryand enrolled patients from November 2014 until June 2015. Thebaseline measurements were performed for a 2-month period inNovember 2014 and December 2014, and the intervention wasperformed for a 6-month period from January to June 2015. Thepsychiatric hospital has 249 beds across 14 bed units. Two bed unitswith 18 beds each were selected as the intervention group, and two bedunits with 12 and 22 beds were selected as the control group. Theintervention group and the control group each contained one bed unitspecializing in psychotic disorders and one bed unit specializing inaffective disorders. The bed units were purposely selected and matchedon patients’ diagnoses and age categories to prevent, if possible, otherfactors influencing outcome.
Ethical considerations. The Regional Ethical Committee for MedicalResearch in the North Denmark Region assessed the study and reportedthat ethical approval was not required according to Danish national lawon medical research. The Danish Health and Medicines Authority, TheDanish Data Protection Agency and hospital management approved thestudy. Furthermore, the study was registered with Clinicaltrials.gov,NCT02052505, 29 January 2014. Patients’ informed consent was notrequired according to Danish regulations as all measures to maintainpatients’ anonymity were taken. Senior clinical pharmacologyphysicians (SCPPs) performed medication reviews during the studywhich were only used descriptively and not in patients’ treatment.However, the SCPPs were ethically obliged to intervene in cases wherepatients’ safety was assessed acutely endangered. This happened onthree separate occasions.
Participants. The study included all patients admitted to the four bedunits, either from the psychiatric emergency department or through thepatient’s general practitioner, between November 2014 and June 2015.Exclusion criteria were as follows: terminally ill patients with ananticipated short life expectancy; an expected length of stay of lessthan 48 hr; patients transferred from another psychiatric unit orprevious inclusion in the study; and patients whom nurses failed toinclude and consequently whose medication lists were not reviewed.
Intervention. Senior clinical pharmacology physicians performedmedication reviews in both intervention and control bed units duringthe baseline and the intervention period according to the method usedand described in a previous study [7]. It was not possible to blind theSCPPs to time period nor allocation of group. A graphical overviewof the medication review procedure is provided as Figure S1. Themedication reviews served as a gold standard against which to
compare the intervention period and as a benchmark for the nurses’observations. After the baseline period, the intervention consisted of a5-day course for the participating nurses from the intervention bedunits followed by the same nurses carrying out reviews of medicationlists for newly admitted patients. The 5-day course covered generalpharmacology, psychopharmacology and treatment principles for someof the major mental disorders, principles for medication reviews,exercises in identifying PIPs and how to systematically documentrelevant observations. Lecturers were SCPPs (authors LPN and BKP),psychiatrists, physicians, a pharmacist and the course leader (authorALS). After the course, 22 registered nurses, across the twointerventional bed units, would review patients’ electronic medicationrecords to identify PIPs. The review was carried out within 1–2 daysafter admission and after the physician reviewed and released themedications to be administered. The nurses used the electronicmedication records, the electronic patient records, paraclinical data,their clinical knowledge in general and their knowledge of theindividual patient and consulted with nursing colleagues.The nurses recorded their observations and supplemented these
records with a short text explaining the rationale for assessing the pre-scription(s) as a PIP. The nurses also recorded the physicians’ subse-quent responses to the reported observations.
Data collection. Data included demographic details, clinical status,medications and a medication review performed by the SCPP. Allpatient records and medication records were electronic. The primaryoutcome was the potential difference in PIPs between the controlgroup and the intervention group following the nurses’ observations inthe intervention group. Secondary outcome included prevalence andtypes of PIPs where physicians responded to nurses’ observations andchanged medications.
Data analysis. The primary outcome was analysed in two ways:firstly, an estimation of potential difference in mean number of PIPs,and secondly, an estimation of potential difference in patientsreceiving ≥1 PIP using linear regression and logistic regression withan approximated difference-in-difference (DID) approach, respectively.The DID method permits an interpretation of data similar to arandomized controlled trial as differences that are constant over timeare taken into account [29]. An illustration of the DID method hasbeen provided as Figure S2. Regarding the first analysis of theprimary outcome, mean number of PIPs was considered the dependentvariable and time (before/after), group (control/intervention bed units)and interaction between time and the group as independent variablesin a linear regression. The estimated interaction variable is a DIDbetween intervention and control bed units. Regarding the secondanalysis of the primary outcome: patients receiving ≥1 PIP (presenceof PIP was coded: 1 and for absent: 0) were considered the dependentvariable and time, group and interaction between time and the groupas independent variables in a logistic regression. The DID approach asdescribed above was applied; however, due to the nonlinear nature ofthe logistic regression, this cannot be interpreted as a genuine DID.The estimated odds ratio for the interaction variable is an estimatedDID between intervention and control bed units. A statisticalsignificance level of 0.05 was applied for both main outcomes.Secondary outcome included prevalence and types of PIPs where
physicians responded to nurses’ observations and changed medications.Characteristics of the study population were provided using descrip-
tive statistics. Baseline measurements by the SCPPs were descriptiveand consisted of prevalence, categories and potential severity of PIPsfor all four bed units. The presentation of prevalence and proportionsof PIPs were in absolute numbers and percentages. Sample size calcu-lations preceded the intervention. Based on a previous study investi-gating PIP in a psychiatric population, the mean number of PIPs perpatient was assumed to be 1.8, the standard deviation 2.19 [7], and a
© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)
IMPROVING MEDICATION SAFETY IN PSYCHIATRY 175

reduction by 50% considered clinically relevant. To detect a reductionfrom 1.8 to 0.9 in mean number of PIPs per patient, at a two-sided0.05 significance level, a sample size of 94 patients per group duringthe intervention period was needed to ensure 80% power. Also basedon a previous study [7], and the composition of diagnoses representedin the included bed units, it was assumed that 50% of patients wouldbe affected by at least one PIP at baseline [7], and a reduction to 30%of patients affected by at least one PIP would be clinically relevant.To detect a difference of 20 percentage points in the proportion of
patients receiving at least one PIP, at a two-sided 0.05 significancelevel, a sample size of 94 patients per group during the interventionperiod was needed to ensure 80% power. It was eventually decided toset the sample size at 120 patients to account for potential loss ofpatients. Data analysis was performed in Stata/IC 14.0 (Stata Corp,College Station, TX, USA).
Results
Characteristics of patients.Inclusion and exclusion of patients, as illustrated in fig. 1,resulted in 396 patients in the study during baseline and inter-vention. Furthermore, there was no observable differencebetween the two groups regarding patient characteristics
(table 1). Moreover, during the intervention, there were no dif-ferences between patients reviewed by the nurses (n = 121)and included in the analysis and patients whom the nursesfailed to include (n = 15); these differences had been evalu-ated based on the following variables: age (p = 0.43), gender(p = 0.21), primary psychiatric disorder (p = 0.75), comorbidi-ties (p = 0.89), alcohol or substance abuse (p = 0.93) andmedication characteristics (p = 0.47).
Potentially inappropriate prescriptions.The distribution of PIPs was consistent on intervention andcontrol wards for the baseline period and the subsequent fol-low-up period indicating no other external factors influencingthe prevalence of PIP in the control wards.Over the 8-month data collection period, 396 patients and
2625 prescriptions, differentiated as 1894 regular prescriptionsand 758 pro re nata (p.r.n. (medication administered ‘asneeded’)) prescriptions, were reviewed by the SCPPs. Allmedication reviews by the SCPPs yielded a prevalence ofpatients with at least one PIP (n = 262) of (262/396) 66%. In
Fig. 1. Flow chart illustrating the inclusion and exclusion of patients in the study (n = 396).
© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)
176 ANN L. SOERENSEN ET AL.

total, 761 PIPs were identified by the SCPPs. The leading cat-egories of PIPs were interactions between drugs (232/761(30%)), omission of indication for treatment (119/761 (16%)),drug dosage too high (96/761 (13%)) and interaction between
drug and disease (84/761 (11%)). The primary outcome is dis-played in table 2 and demonstrates the scenario of potentialimprovement if all PIPs identified by SCPPs and nurses hadreceived relevant alterations.
Table 1.Characteristics of the entire study population (n = 396).
Patient characteristicsTotal
(n = 396)Intervention
bed unit A (n = 85)Intervention bedunit B (n = 94)
Control bedunit A (n = 56)
Control bedunit B (n = 161)
Age distributionMedian (years), IQR (years) 43, 30–56 42, 32–53 44, 26–61 36, 26–47 46, 32–58
Age category (years), n (%)