Effect of an antimicrobial stewardship programme on antimicrobial utilisation and costs in patients with leukaemia: a retrospective controlled study.

OBJECTIVES: To examine the effectiveness of an antimicrobial stewardship programme on utilization and cost of antimicrobials in leukaemia patients in Canada. METHODS: We conducted a multisite retrospective observational time series study from 2005 to 2013. We implemented academic detailing as the intervention of an antimicrobial stewardship programme in leukaemia units at a hospital, piloted February-July 2010, then fully implemented December 2010-March 2013, with no intervention in August-November 2010. Internal control was the same hospital's allogeneic haematopoietic stem-cell transplantation unit. External control was the combined leukaemia-haematopoietic stem-cell transplantation unit at another hospital. Primary outcome was antimicrobial utilization (antibiotics and antifungals) in defined daily dose per 100 patient-days (PD). Secondary outcomes were antimicrobial cost (Canadian dollars per PD); cost and utilization by drug class; length of stay; 30-day inpatient mortality; and nosocomial Clostridium difficile infection. We used autoregressive integrated moving average models to evaluate the impact of the intervention on outcomes. RESULTS: The intervention group included 1006 patients before implementation and 335 during full implementation. Correspondingly, internal control had 723 and 264 patients, external control 1395 and 864 patients. Antimicrobial utilization decreased significantly in the intervention group (p <0.01, 278 vs. 247 defined daily dose per 100 PD), increased in external control (p = 0.02, 237.4 vs. 268.9 defined daily dose per 100 PD) and remained stable in internal control (p = 0.66). Antimicrobial cost decreased in the intervention group (p = 0.03; $154.59 per PD vs. $128.93 per PD), increased in external control (p = 0.01; $109.4 per PD vs. $135.97 per PD) but was stable in internal control (p = 0.27). Mortality, length of stay and nosocomial C. difficile rate in intervention group remained stable. CONCLUSIONS: The antimicrobial stewardship programme reduced antimicrobial use in leukaemia patients without affecting inpatient mortality and length of stay.

A population-based assessment of the drug interaction between levothyroxine and warfarin.

Most drug interaction resources suggest that levothyroxine can dramatically potentiate the effect of warfarin. However, the mechanistic basis of the interaction is speculative, and little evidence supports a meaningful drug interaction. We conducted a population-based nested case-control study to examine the risk of hospitalization for hemorrhage following the initiation of levothyroxine in a cohort of 260,076 older patients receiving warfarin. In this group, we identified 10,532 case subjects hospitalized for hemorrhage and 40,595 controls. In the primary analysis, we found no association between hospitalization for hemorrhage during warfarin therapy and initiation of levothyroxine in the preceding 30 days (adjusted odds ratio 1.11, 95% confidence interval 0.67-1.86). Secondary analyses using more remote initiation of levothyroxine also found no association. These findings suggest that concerns about a clinically meaningful levothyroxine-warfarin drug interaction are not justified. Drug interaction resources that presently characterize this interaction as important should reevaluate this classification.

Progressive trends in the prevalence of benzodiazepine prescribing in older people in Ontario, Canada.

OBJECTIVES: The extensive use of benzodiazepines has been a concern of healthcare providers and policy makers in Canada and around the world. The purpose of this study was to examine temporal trends in benzodiazepine prescriptions dispensed in older people from 1993-1998. DESIGN: Retrospective population-based cross-sectional study using administrative databases. SETTING: Ontario, Canada. PARTICIPANTS: The over 1 million residents of Ontario age 65 and older covered by the provincial universal drug benefit program. MEASUREMENTS: The main outcome measures were the prevalence, overall and with respect to age and gender, of benzodiazepine prescriptions dispensed and the ratio of the number of people to whom short- versus long-acting benzodiazepine prescriptions were dispensed in each study year. The annual rates of switching to other psychotropic agents were examined for those patients that discontinued filling benzodiazepine prescriptions. RESULTS: The annual prevalence of benzodiazepine prescriptions dispensed decreased consistently over time (25.1% in 1993 to 22.5% in 1998; P < .001). Benzodiazepine dispensing prevalence increased with increasing age (approximately 20% of those age 65 to 69 to approximately 30% of those age > or =85; P < .001) and more females than males received the medication (relative risk = 1.50, 95% confidence interval = 1.49-1.51). The ratio of short- to long-acting benzodiazepine prescriptions filled increased over time (3.6 in 1993 to 5.8 in 1998; P < .001), in line with guideline recommendations. Rates of switching to antidepressants increased over time (8.5% in 1993 to 10.2% in 1998; P < .001), whereas switching to barbiturates was consistently low (0.12%; P = .403). CONCLUSION: The prevalence of benzodiazepine therapy for older people in Ontario has steadily declined between 1993 and 1998. There is a trend of dispensing relatively more short-acting than long-acting benzodiazepines and of replacing benzodiazepines with antidepressants in older people without a remarkable increase in barbiturate consumption. These findings suggest that, without undue regulation, physicians are making progress in the prescribing of benzodiazepine therapy on the basis of current knowledge available.

Use of antidepressants among elderly subjects: trends and contributing factors.

OBJECTIVE: The authors assessed changes over time in antidepressant utilization among elderly subjects regarding the prevalence of antidepressant users, shifts in prescription patterns, and related financial implications. METHOD: The authors conducted a population-based study of more than 1.4 million Ontario residents aged 65 years or older. Cross-sectional data regarding annual antidepressant utilization were obtained from administrative databases for 1993 to 1997. Time series analysis was used to assess trends over time and to make future projections. RESULTS: The proportion of antidepressant users increased from 9.3% of the elderly population in 1993 to 11.5% in 1997. Prescriptions for selective serotonin reuptake inhibitors (SSRIs) accounted for 9.6% of antidepressant prescriptions dispensed in the first 30 days of 1993 and 45.1% of those dispensed by the last 30 days of 1997 and were projected to increase to approximately 56% by the end of 2000. Prescriptions for tricyclic antidepressants fell from 79.0% in the first 30 days of 1993 to 43.1% by the last 30 days of 1997 and were projected to decline to approximately 28% by the end of 2000. Annual antidepressant costs (in Canadian dollars) increased by 150%, from $10.8 million in 1993 to $27.0 million in 1997. Population shifts and an increase in the prevalence of antidepressant users accounted for at least 20% of this increase, whereas the prescribing transition from tricyclic antidepressants to SSRIs accounted for at least 61% of the increase. CONCLUSIONS: The introduction of SSRIs has had a substantial financial impact at the drug utilization level. Future research should address the appropriate balancing of the cost of newer agents versus their ostensible advantages.

Clinical and economic effectiveness of an inpatient anticoagulation service.

We conducted a prospective cohort study to evaluate clinical and economic end points achieved by a pharmacist-managed anticoagulation service compared with usual care (50 patients/group). The primary therapeutic end point was the time between starting heparin therapy and surpassing the activated partial thromboplastin time therapeutic threshold. The primary economic end point was the direct variable cost of hospitalization from admission to discharge. No significant differences between groups were noted for the primary therapeutic end point. Total hospital costs were significantly lower for patients receiving pharmacist-managed care than for those receiving usual care ($1594 and $2014, respectively, 1997 dollars, p=0.04). Earlier start of warfarin (p=0.05) and shorter hospital stay (5 and 7 days, p=0.05) were associated with the pharmacist-managed group.

Thromboembolic prophylaxis in moderate-risk patients undergoing elective abdominal surgery: decision and cost-effectiveness analyses.

We conducted a retrospective, literature-based decision analysis to compare the cost-effectiveness of conventional low-dose heparin, dalteparin, and intermittent pneumatic compression (IPC) as thromboembolic prophylaxis to a no-prophylaxis option in patients at moderate risk of developing thromboembolic complications after major elective abdominal surgery. The analysis was conducted through an institutional perspective. Probability and incidence rate data were summarized from the literature. Cost data were obtained from the Detroit Medical Center's cost accounting systems and from national diagnosis-related group estimates. Mortality and complications avoided were the main outcome measures on which cost-effectiveness was based. Overall costs associated with conventional low-dose heparin, dalteparin, intermittent pneumatic compression, and no prophylaxis were $84, $122, $102, and $112, respectively in the primary analysis, which included costs of labor. Corresponding cost-effectiveness ratios in terms of costs/complication-free patient were $86, $124, $103, and $118, respectively. Compared with no prophylaxis, incremental cost-effectiveness analysis in terms of cost/mortality avoided involved savings of $6087 and $3125 with conventional low-dose heparin and IPC, respectively, and expenses of $2857 with dalteparin. A secondary analysis excluding costs of labor showed similar results. The results of the study consistently showed conventional low-dose heparin to provide the most cost-effective thromboembolic prophylaxis of the methods considered in terms of reducing both morbidity and mortality in the patient population studied.