Understanding physicians’ behavior toward alerts about nephrotoxic medications in outpatients: a cross-sectional analysis

Background: Although most outpatients are relatively healthy, many have chronic renal insufficiency, and high override rates for suggestions on renal dosing have been observed. To better understand the override of renal dosing alerts in an outpatient setting, we conducted a study to evaluate which patients were more frequently prescribed contraindicated medications, to assess providers’ responses to suggestions, and to examine the drugs involved and the reasons for overrides. Methods: We obtained data on renal alert overrides and the coded reasons for overrides cited by providers at the time of prescription from outpatient clinics and ambulatory hospital-based practices at a large academic health care center over a period of 3 years, from January 2009 to December 2011. For detailed chart review, a group of 6 trained clinicians developed the appropriateness criteria with excellent inter-rater reliability (κ = 0.93). We stratified providers by override frequency and then drew samples from the high- and low-frequency groups. We measured the rate of total overrides, rate of appropriate overrides, medications overridden, and the reason(s) for override. Results: A total of 4120 renal alerts were triggered by 584 prescribers in the study period, among which 78.2% (3,221) were overridden. Almost half of the alerts were triggered by 40 providers and one-third was triggered by high-frequency overriders. The appropriateness rates were fairly similar, at 28.4% and 31.6% for high- and low-frequency overriders, respectively. Metformin, glyburide, hydrochlorothiazide, and nitrofurantoin were the most common drugs overridden. Physicians’ appropriateness rates were higher than the rates for nurse practitioners (32.9% vs. 22.1%). Physicians with low frequency override rates had higher levels of appropriateness for metformin than the high frequency overriders (P = 0.005). Conclusion: A small number of providers accounted for a large fraction of overrides, as was the case with a small number of drugs. These data suggest that a focused intervention targeting primarily these providers and medications has the potential to improve medication safety

Fluconazole for empiric antifungal therapy in cancer patients with fever and neutropenia

BACKGROUND: Several clinical trials have demonstrated the efficacy of fluconazole as empiric antifungal therapy in cancer patients with fever and neutropenia. Our objective was to assess the frequency and resource utilization associated with treatment failure in cancer patients given empiric fluconazole antifungal therapy in routine inpatient care. METHODS: We performed a retrospective cohort study of cancer patients treated with oral or intravenous fluconazole between 7/97 and 6/01 in a tertiary care hospital. The final study cohort included cancer patients with neutropenia (an absolute neutrophil count below 500 cells/mm(3)) and fever (a temperature above 38°C or 100.4°F), who were receiving at least 96 hours of parenteral antibacterial therapy prior to initiating fluconazole. Patients' responses to empiric therapy were assessed by reviewing patient charts. RESULTS: Among 103 cancer admissions with fever and neutropenia, treatment failure after initiating empiric fluconazole antifungal therapy occurred in 41% (95% confidence interval (CI) 31% – 50%) of admissions. Patients with a diagnosis of hematological malignancy had increased risk of treatment failure (OR = 4.6, 95% CI 1.5 – 14.8). When treatment failure occurred the mean adjusted increases in length of stay and total costs were 7.4 days (95% CI 3.3 – 11.5) and $18,925 (95% CI 3,289 – 34,563), respectively. CONCLUSION: Treatment failure occurred in more than one-third of neutropenic cancer patients on fluconazole as empiric antifungal treatment for fever in routine clinical treatment. The increase in costs when treatment failure occurs is substantial

Provider variation in responses to warnings: do the same providers run stop signs repeatedly?

OBJECTIVE: Variation in the use of tests and treatments has been demonstrated to be substantial between providers and geographic regions. This study assessed variation between outpatient providers in overriding electronic prescribing warnings. METHODS: Responses to warnings were prospectively logged. Random effects models were used to calculate provider-to-provider variation in the rates for the decisions to override warnings in 6 different clinical domains: medication allergies, drug-drug interactions, duplicate drugs, renal recommendations, age-based recommendations, and formulary substitutions. RESULTS: A total of 157 482 responses were logged. Differences between 1717 providers accounted for 11% of the overall variability in override rates, so that while the average override rate was 45.2%, individual provider rates had a wide range with a 95% confidence interval (CI) (13.7%-76.7% ). The highest variations between providers were observed in the categories age-based (25.4% of total variability; average override rate 70.2% [95% CI, 29.1%-100% ]) and renal recommendations (24.2%; average 70% [95% CI, 29.5%-100% ]), and provider responses within these 2 categories were most often clinically inappropriate according to prior work. Among providers who received at least 10 age-based recommendations, 64 of 238 (27%) overrode ≥ 90% of the warnings and 13 of 238 (5%) overrode all of them. Of those who received at least 10 renal recommendations, 36 of 92 (39%) overrode ≥ 90% of the alerts and 9 of 92 (10%) overrode all of them. CONCLUSIONS: The decision to override prescribing warnings shows variation between providers, and the magnitude of variation differs among the clinical domains of the warnings; more variation was observed in areas with more inappropriate overrides

Mortality and drug exposure in a 5-year cohort of patients with chronic liver disease

Chronic liver diseases are common in the general population. Drug treatment in this group may be challenging, as many drugs are hepatically metabolised and hepatotoxic.; We aimed to assess the mortality of patients with chronic liver disease according to specific drug exposures and the three laboratory parameters creatinine, bilirubin and International Normalised Ratio (INR).; We conducted a multicentre, 5-year retrospective cohort study in two tertiary university referral hospitals and a secondary referral hospital, using a research database to evaluate the crude and adjusted mortality.; Of 1159362 individual patients 1.7% (n = 20158) had chronic liver disease and in this group 36.8% had unspecified chronic non-alcoholic liver disease, 30.1% chronic hepatitis C and 11.9% cirrhosis of the liver. 8.4% of patients presented a diagnosis associated with alcohol. The 4-year survival rates were significantly higher in the group with the most normal laboratory values (94.3%) versus 34.5% in the group with elevated parameters (p >0.001). Overall, drug exposure was not associated with higher mortality; in adjusted multivariate analysis the hazard ratio for anti-cancer drugs was 2.69 (95% CI 1.32-5.46). Of individual drugs, mortality hazard ratios for amiodarone, morphine oral, acetazolamide, sirolimus and lamivudine were 2.46 (95% CI 1.68-3.61), 2.26 (95% CI 1.78-2.86), 2.10 (95% CI 1.19-3.70), 1.81 (95% CI 1.02-3.21) and 1.72 (95% CI 1.17-2.53) respectively.; Drug exposure in general was not associated with higher mortality except for a few categories. Mortality in patients with chronic liver disease was high and is associated with simple laboratory values

The costs of adverse drug events in community hospitals

BACKGROUND: Adverse drug events (ADEs) occur often in hospitals, causing high morbidity and a longer length of stay (LOS), and are costly. However, most studies on the impact of ADEs have been conducted in tertiary referral centers, which are systematically different than community hospitals, where the bulk of care is delivered, and most available data about ADE costs in any setting are dated. Costs in community settings are generally lower than in academic hospitals, and the costs of ADEs might be as well. To assess the additional costs and LOS associated with patients with ADEs, a multicenter retrospective cohort study was conducted in six community hospitals with 100 to 300 beds in Massachusetts during a 20-month observation period (January 2005-August 2006). METHODS: A random sample of 2,100 patients (350 patients per study site) was drawn from a pool of 109,641 patients treated within the 20-month observation period. Unadjusted and adjusted cost of ADEs as well as LOS were calculated. RESULTS: ADEs were associated with an increased adjusted cost of $3,420 and an adjusted increase in length of stay (LOS) of 3.15 days. For preventable ADEs, the respective figures were +$3,511 and +3.37 days. The severity of the ADE was also associated with higher costs--the costs were +$2,852 for significant ADEs (LOS +2.77 days), +$3,650 for serious ADEs (LOS +3.47 days), and +$8,116 for life-threatening ADEs (LOS +5.54 days, all p > .001). CONCLUSIONS: ADEs in community hospitals cost more than$3,000 dollars on average and an average increase of LOS of 3.1 days--increments that were similar to previous estimates from academic institutions. The LOS increase was actually greater. A number of approaches, including computerized provider order entry and bar coding, have the potential to improve medication safety

Tiering drug-drug interaction alerts by severity increases compliance rates.

OBJECTIVE: Few data exist measuring the effect of differentiating drug-drug interaction (DDI) alerts in computerized provider order entry systems (CPOE) by level of severity ("tiering"). We sought to determine if rates of provider compliance with DDI alerts in the inpatient setting differed when a tiered presentation was implemented. DESIGN: We performed a retrospective analysis of alert log data on hospitalized patients at two academic medical centers during the period from 2/1/2004 through 2/1/2005. Both inpatient CPOE systems used the same DDI checking service, but one displayed alerts differentially by severity level (tiered presentation, including hard stops for the most severe alerts) while the other did not. Participants were adult inpatients who generated a DDI alert, and providers who wrote the orders. Alerts were presented during the order entry process, providing the clinician with the opportunity to change the patient's medication orders to avoid the interaction. MEASUREMENTS: Rate of compliance to alerts at a tiered site compared to a non-tiered site. RESULTS: We reviewed 71,350 alerts, of which 39,474 occurred at the non-tiered site and 31,876 at the tiered site. Compliance with DDI alerts was significantly higher at the site with tiered DDI alerts compared to the non-tiered site (29% vs. 10%, p < 0.001). At the tiered site, 100% of the most severe alerts were accepted, vs. only 34% at the non-tiered site; moderately severe alerts were also more likely to be accepted at the tiered site (29% vs. 10%). CONCLUSION: Tiered alerting by severity was associated with higher compliance rates of DDI alerts in the inpatient setting, and lack of tiering was associated with a high override rate of more severe alerts