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Clinical pharmacy and CDI patient clinical outcomes


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A retrospective investigation on hospitalised patients with Clostridium difficile showed the importance of clinical pharmacy services in reducing the length of hospital stay
Feras Darwish Elhajji PhD
Clinical and Practice Research Group,
School of Pharmacy, Queen’s University Belfast, Northern Ireland, UK
Faculty of Pharmacy and Applied Science,
Amman, Jordan
Michael Scott PhD
Pharmacy and Medicines Management Centre, Northern Health and Social Care Trust, Ballymena, Northern Ireland, UK
Mamoon Aldeyab PhD
Clinical and Practice Research Group,
School of Pharmacy, Queen’s University Belfast; Pharmacy and Medicines Management Centre, Northern Health and Social Care Trust, Ballymena, Northern Ireland, UK; Faculty of Pharmacy, Applied Science Private University, Amman, Jordan
Patricia Kearney MD
Microbiology Department,
Northern Health and Social Care Trust, Ballymena, Northern Ireland, UK
James McElnay PhD
Clinical and Practice Research Group, School of Pharmacy, Queen’s University Belfast, Northern Ireland, UK
In recent years, pharmacy staff have faced significant challenges in order to meet the changing needs of patients, and to ensure that patients are more confident in the quality and accessibility of the advice and medicine use support offered by the pharmacist. In 2001, within this context, the concept of integrated medicines management (IMM) was proposed and implemented in Antrim Area Hospital (AAH) in Northern Ireland.1,2 IMM clinical pharmacy services have resulted in promising positive outcomes, for example, reduced length of hospital stay, increased time to readmission and reduced number of readmissions, and an improvement in the appropriateness of prescribed medications.1,2
In January 2008, a major Clostridium difficile infection (CDI) outbreak occurred in the AAH, details of which have been published elsewhere.3 CDI can cause a range of complications ranging from self-limiting diarrhoea to death, through suffering from sepsis, colonic perforation and pseudomembranous colitis.4,5 The clinical pharmacist is seen as an essential member of the antimicrobial stewardship team in the hospital site in which the current work was conducted. This role dovetails with the IMM team, because they focus both on improving patient care and healthcare outcomes.6 The objective of this study was to assess the impact of clinical pharmacy services on one CDI patient specific clinical outcome, namely length of hospital stay (LOS).
The study was carried out in the AAH in Northern Ireland, UK for the period April 2007–December 2008. The present work was carried out in the form of an audit as part of the hospital’s clinical service development programme and therefore ethical approval was not required. The study was registered with, and approved by, the Trust’s research and development department.
The following data were collected:
  • demographic profile and past medical history (PMH)
  • clinical pharmacy interventions received by patients during their hospitalisation and CDI risk factors, including antibiotic administration profile, administration of proton pump inhibitors, immunosuppressive agents and prolonged laxative therapy, as well as exposure to gastrointestinal surgery, nasogastric or percutaneous endoscopic gastrotomy (PEG) tube-feeding
  • severity of the CDI at the time of the toxin-positive results
  • CDI exposure based on time and place of onset of CDI symptoms.
The main outcome measure was a longer hospital stay than expected, and this was calculated based on risk-adjusted length of stay index (RALI). RALI is a predictive tool that aims to predict length of hospital stay for patients based on a range of criteria.7,8 Accordingly, longer hospital stay than expected was identified as having a CDI-episode LOS days ≥ 150% of the RALI scores. RALI scores were calculated using an algorithm developed by CHKS Ltd, a specialist company that provides benchmarking and analytical services to the UK National Health Service (NHS).9 All data required for this study were obtained from the hospital computer system. Definitions regarding CDI, hospital- and community-acquired classifications, and severity of disease have been outlined elsewhere.3 The aims and description of the IMM programme have also been described.1,2 
Statistical analysis
The Pearson chi square (X2) test, the independent samples t-test and the Mann–Whitney U-tests were used. Univariate analysis was used as an initial step in identifying significant relationships between the studied variables and the outcomes.  Having completed the univariate analyses, variables with ρ≤0.25 were studied using backward logistic regression analysis, where finally only the significant variables (that is, ρ≤0.05) were considered as the predictive and determinant of the patient characteristics. All data analyses were performed using PASW® statistics (SPSS) for Windows (version 18.0).
In the period between April 2007 and December 2008, 178 patients in the AAH were diagnosed with CDI. The patients received 318 recorded clinical pharmacy interventions on admission, inpatient stay and/or discharge, and the average number of interventions per patient was 1.79. The number of recorded interventions ranged from 0 to 12 interventions per CDI patient. Of the 178 CDI patients, 89 patients had CDI-episode LOS longer than their respective RALI. Univariate analysis showed that eight variables had relationships with longer hospital stay than expected with ρ≤0.25. These variables were:
(1) Gender
(2) Belonging to the community onset – community associated CDI
(3) Belonging to the indeterminate CDI exposure groups
(4) Clinical severity of CDI at time of positive toxin results
(5) If the patient had a nervous, mental or behavioural related PMH
(6) Receipt of metronidazole within the 12 weeks before disease onset
(7) If the patient did not receive clinical pharmacy service at admission stage
(8) If the patient did not receive clinical pharmacy service during their inpatient hospital stay (see Table 1).
The only variables that indicated a significant relationship, by Pearson chi square analysis, with longer hospital stay than expected were those related to the provision of clinical pharmacy services at admission and inpatient stages (ρ=0.026 and 0.010, respectively).
However, when backward logistic regression involving the eight variables versus the dependent variable was undertaken, only one parameter, that is, not receiving clinical pharmacy service interventions during the inpatient hospital stay, had a statistically significant relationship with longer hospital stay than expected (odds ratio= 2.87, 95% CI: 1.38–5.96; Table 2).
Measurement of the quality of healthcare services provided by hospitals is essential to help implement plans and actions that can ultimately improve the quality of patient outcomes. Such improvement in quality standards can often be achieved by better delivery of services, such as clinical pharmacy services, rather than searching for new treatments. Hospital clinical pharmacists are expected to identify and target patients at high risk of CDI, especially when there is a C. difficile outbreak threat in the hospital. Analysis of data showed that receiving clinical pharmacy interventions during the inpatient stage of the hospital stay was the only measured parameter that influenced the risk of staying in the hospital for longer time than expected (that is, CDI-episode LOS ≥ 150% RALI). Receiving inpatient clinical pharmacy service interventions decreased the probability (had an inverse relationship) of a longer hospital stay than expected. CDI patients who received inpatient clinical pharmacy interventions are more likely to have received adjustments to their treatment regimens, especially antibiotics, as an integral part of the IMM programme enhanced clinical pharmacy services in the hospital that includes an antimicrobial stewardship programme. That antimicrobial stewardship involves the optimal selection, dosage and duration of antimicrobial treatment, with the aim to result in the best clinical outcome for the patient, with both minimal toxicity and impact on subsequent resistance.10
It is also interesting to note that the significant relationship (ρ≤0.05 by univariate analysis) between not receiving clinical pharmacy service on admission and the longer than expected hospital stay may suggest a positive potential of receiving clinical pharmacy service at that stage.
In conclusion, this study shows the importance of clinical pharmacy services in improving healthcare outcome measures for a specific group of patients, that is, decreasing the required duration of hospitalisation for patients infected with C. difficile.
Key points
  • Clostridium difficile infection (CDI) can cause a range of complications leading to increased length of hospital stay.
  • IMM clinical pharmacy can reduce the length of hospital stay, increase the time to readmission and improve the appropriateness of prescribed medicines.
  • RALI (risk adjusted length of stay index) is a useful tool in standardising length of stay in hospitalised patients.
  • Provision of clinical pharmacy services can decrease RALI in CDI patients.
  • Improvement in quality standards can be achieved by delivery of clinical pharmacy services rather than searching for new treatments.
  1. Scullin C et al. An innovative approach to integrated medicines management. J Eval Clin Pract 2007;13:781–8.
  2. Burnett KM et al. Effects of an integrated medicines management program on medication appropriateness in hospitalized patients. Am J Health Syst Pharm 2009;66:854–9.
  3. Aldeyab MA et al. Multihospital outbreak of Clostridium difficile ribotype 027 infection: epidemiology and analysis of control measures. Infect Control Hosp Epidemiol 2011;32:210–19.
  4. Owens RC. Clostridium difficile-associated disease: Changing epidemiology and implications for management. Drugs 2007;67:487–502.
  5. Owens RC. Clostridium difficile-associated disease: An emerging threat to patient safety: Insights from the society of infectious diseases pharmacists. Pharmacotherapy 2006;26:299–311.
  6. Dellit TH et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 2007;44:159–77.
  7. Rosenthal GE. Weak associations between hospital mortality rates for individual diagnoses: Implications for profiling hospital quality. Am J Public Health 1997;87:429–33.
  8. Thomas JW et al. Interpreting risk-adjusted length of stay patterns for VA hospitals. Med Care 1998;36:1660–75.
  9. CHKS insight for better healthcare.
  10. Owens RC Jr, Fraser GL, Stogsdill P, Society of Infectious Diseases Pharmacists. Antimicrobial stewardship programs as a means to optimize antimicrobial use. insights from the society of infectious diseases pharmacists. Pharmacotherapy 2004;24:896–908.

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