Medication-related problems are responsible for 3–10% of acute hospital admissions, of which approximately half are potentially preventable [1–11]. Hospital admissions can lead to additional functional decline [12, 13], unintentional harm [14], and increased costs. Medication monitoring and management are methods used to avoid medication-related complications.

In 2008, the Dutch HARM study group established seven independent risk factors for medication-related hospital admissions: (a) impaired cognition, (b) four or more diseases in the patient’s medical history, (c) dependent living situation, (d) impaired renal function before hospitalization, (e) non-adherence to medication regimen, (f) the use of five or more medications at the time of admission (polypharmacy), and (g) age over 65 [11]. In the industrialized world, the proportion of the population that is 65 years or older is rapidly increasing. Elderly patients more often suffer from multiple morbidities, use more medications, and are treated by more healthcare professionals than younger patients [15]. Drug consumption is three times higher among people aged 65 years or older, and four times higher in people aged 75 years or older, than it is in people younger than 65 years. The majority of these drugs are taken chronically (http://www.SFK.nl). The increased use of prescription drugs by the elderly is a consequence of their longer lifespan, their increasing use of health services, and the availability of new drugs [16]. From a clinical perspective, prescription changes are a risk factor for medication-related hospital admission. During the course of a disease, it may be necessary to change the dosage of medication, to switch to a similar medication, to temporarily withdraw the drug, or to start a new drug. With the exception of the study of Koecheler [17], who reported ‘medication regimen changes in four or more times during the past 12 months’ to be one of the six prognostic indicators for identifying ambulatory patients who need pharmacist monitoring, there have been no other studies that evaluated the association between the number of prescription changes and hospital admission. For this reason, we investigated whether the frequency of prescription changes is associated with hospital admission, and, if so, whether the strength of this association changes in the months before hospital admission.

The Chronic Disease Score (CDS), a well-established instrument to predict hospital admission, measures comorbidity on the basis of the 1-year pharmacy dispensing data for 17 therapeutic groups of somatic medications intended for chronic use [18]. The latter makes the CDS a static instrument. In contrast, the Prescription Changes Frequency (PCF) is based on prescription changes over a 3-month period.

The objectives of this study were (1) to assess the association between the PCF and hospital admission at different times before admission and (2) to compare the PCF with the CDS for predicting hospital admission.

The risk of hospital admission also increased per CDS category. A higher CDS score was associated with an increased risk of hospitalization: OR 1.5 (95% CI 1.4-1.6]) for CDS 1–2, OR 1.7 (95% CI 1.6-1.9) for CDS 3–4, and OR 3.6 (95% CI 3.3-3.9) for CDS 5 or higher.

Stratification by age (< 65 years ≥ 65 years), admission type (planned or emergency admission), CDS score, and polypharmacy resulted in comparable increases in OR with increasing PCF score. For participants on polypharmacy, the OR of PCF 4 or more decreased between 9 and 3 months before the index date, from 3.5 (95% CI 1.9-6.67) to 2.2 (95% CI 1.0-5.4). When stratified by CDS, the likelihood of being hospitalized also increased with increasing PCF score (Figure 1).

A two-tailed Spearman’ correlation coefficient showed a significant but poor correlation between CDS 0 and PCI 0 (0.019, p= 0.01) and CDS 5 or higher and PCI 4 or higher (0.027, p=0.01) and no significant correlation between CDS 1 or 2 and PCF 1 and CDS 3 or 4 and PCF 2 or 3 at 3 months before the index date.

The main finding of this study is that the frequency of prescription changes (PCF) is associated with an increased risk of hospital admission. We also confirmed the known association between the Chronic Disease Score (CDS) and hospital admission. While the PCF and CDS were both associated with hospital admission, the correlation between the two instruments was poor. The CDS measures comorbidity on the basis of the 1-year pharmacy dispensing data. In contrast, the PCF is based on prescription changes over a 3-month period. The results showed that the PCF within a three month period is comparable with the one year period of the CDS. Therefore, the PCF is more useful in practice.

We found that among patients with a low CDS score, an increasing number of prescription changes was associated with an increased risk of hospital admission. Stratified analysis of the CDS scores into the four categories confirmed this finding: at each CDS category, we found a comparable increase in the risk of hospitalization caused by the number of prescription changes.

Stratification by age (<65 or ≥65 year) and medication use (< 5 or ≥5 medications used) showed an increasing risk of hospitalization with increasing PCF (Figure 1). Several studies have reported age and polypharmacy as risk factors for hospital admission. We found that, based on PCF scores, even patients younger than 65 years and patients without polypharmacy were at increased risk of hospital admission. It is plausible that the risk was lower for planned than for emergency admissions, but this was not confirmed after stratification by type of hospitalization. Unexpectedly, patients on polypharmacy had a decreased risk of hospital admission: PCF 4 or higher decreased between 9 and 3 months before the index date. On the basis of this finding, the most common reason for prescription changes, namely, stopping medication, would appear to be protective against hospital admission in patients on polypharmacy. As we do not know which medications were stopped, this finding does not mean that stopping specific medications is protective.

The CDS has the disadvantage that it is based on information about medication history collected for at least 1 year prior to the event under investigation. We showed that it is possible to predict the risk of hospitalization on the basis of the number of prescription changes in 3 months. On the other hand, the CDS is based on the use for 17 therapeutic groups of somatic medications, whereas the PCF is based on all medications and thus requires detailed medication histories. The CDS was developed to measure a patient’s overall health status, but the PCF is not suitable for this. A potential weakness of the CDS, which was developed in 1992, is that it has never been adjusted to accommodate new medication classes, unlike the PCF, which is based on all medications used. Despite this, the CDS is still associated with hospital admissions.

This longitudinal study of a large group of patients over 24 months demonstrated that the frequency of prescription changes (PCF) over a 3-month period is associated with hospital admission, which suggests that the PCF could be used as an alternative to the CDS for predicting hospital admission. In the ambulant setting, the PCF score could function as a warning signal for an increased risk of hospitalization and as such contribute to medication safety programmes. The PCF might be particularly useful for older patients, who tend to use more medications. District nurses and social workers care should be alerted if the frequency of prescription changes increases in their patients. Community pharmacists can use the PCF as a clinical rule to facilitate early identification of potential drug-related problems. Further research is needed to determine the predictive value of the PCF in practice as a clinical rule.