Pertuzumab-associated diarrhea in HER2/neu-positive breast cancer patients: A comparison of trials to actual practice.

BACKGROUND: Although landmark trials in the metastatic (CLEOPATRA) and neo-adjuvant (NeoSphere; TRYPHAENA) settings identified all-grade diarrhea as a pertuzumab-associated adverse event, it was not classified as dose-limiting. In actual practice, diarrhea is often a reason for treatment modifications. OBJECTIVES: To compare the risk of pertuzumab-associated diarrhea in actual practice to the risks in randomized controlled trials. METHODS: We conducted a retrospective cohort study of HER2/neu-positive breast cancer patients who received a pertuzumab-containing regimen between January 2012 and August 2015. We calculated the risk of diarrhea with 95% confidence limits (CLs), and then used two-sample t-tests to compare the risk between trials and actual practice. RESULTS: A total of 27 patients in the study cohort received a pertuzumab-containing treatment regimen for HER2/neu-positive breast cancer. The overall risk of all-grade and severe diarrhea in actual practice was 70% (95% CLs 55-90%) and 37% (95% CLs 20-66%), respectively. No severe diarrhea was observed in the metastatic setting, and the risk of all-grade diarrhea (44%, 95% CLs 21-92%) was similar to the CLEOPATRA study (67%). The risk of all-grade diarrhea in the neo-adjuvant setting was 83% (95% CLs 68-100%), compared to 46% in the NeoSphere trial (p = 0.03). The risk of severe diarrhea (Grade 3-4) in the neo-adjuvant setting was 47% (95% CLs 27-80%) versus 6% in the NeoSphere (p < 0.0001) and 12% in the TRYPHAENA (p < 0.01) trials. CONCLUSIONS: The risk of all-grade and severe diarrhea associated with neoadjuvant pertuzumab use for HER2/neu-positive breast cancer was greater in actual practice than in trials.

Overuse and underuse of pegfilgrastim for primary prophylaxis of febrile neutropenia.

INTRODUCTION: Guidelines recommend pegfilgrastim for primary prophylaxis of febrile neutropenia after highly myelosuppressive chemotherapy. While deviations from guidelines could result in overuse and increased costs, underuse is also a concern and could compromise quality of care. Our objectives were to evaluate guideline adherence and quantify the extent to which physician heterogeneity may influence pegfilgrastim use. METHODS: We randomly sampled 550 patients from a retrospective cohort of those who received infusions at an academic cancer center between 1 September 2013 and 1 September 2014. Electronic medical and drug dispensing records provided information on patient characteristics, chemotherapy characteristics, prescribing physician, and pegfilgrastim administration. RESULTS: We included 154 patients treated by 25 physicians. About half of patients were male and mean age was 61.3 years. Forty (26.1%) patients had no febrile neutropenia risk factors, 62 (40.5%) had one, and 51 (33.3%) had two or more. Thirty patients (19.5%) received pegfilgrastim, of which 12 (40%) received palliative chemotherapy. Nine (60%) of 15 patients on a regimen with a febrile neutropenia risk ≥ 20% received pegfilgrastim. Pegfilgrastim use significantly varied by cancer type (p < 0.01), chemotherapy regimen (p < 0.001), and regimen febrile neutropenia risk (p < 0.001). Multivariable analysis reaffirmed the association between chemotherapy regimen febrile neutropenia risk ≥ 20% and pegfilgrastim use (odds ratio (OR) = 10.1, 95% confidence interval (CI): 1.6-62.7) and suggested that 31% (95% CI: 8%-71%) of the variation in use was attributable to physician characteristics. CONCLUSION: Pegfilgrastim was potentially overused for palliative chemotherapy and underused for chemotherapy regimens with febrile neutropenia risk ≥ 20%. Successful interventions to modify prescribing practices likely require an understanding of the relationship between specific physician characteristics and pegfilgrastim use.

Outcomes of "diabetes-friendly" vs "diabetes-unfriendly" ß-blockers in older nursing home residents with diabetes after acute myocardial infarction.

AIMS: To assess whether nursing home (NH) residents with type 2 diabetes mellitus (T2D) preferentially received "T2D-friendly" (vs "T2D-unfriendly") ß-blockers after acute myocardial infarction (AMI), and to evaluate the comparative effects of the two groups of ß-blockers. MATERIALS AND METHODS: This new-user retrospective cohort study of NH residents with AMI from May 2007 to March 2010 used national data from the Minimum Data Set and Medicare system. T2D-friendly ß-blockers were those hypothesized to increase peripheral glucose uptake through vasodilation: carvedilol, nebivolol and labetalol. Primary outcomes were hospitalizations for hypoglycaemia and hyperglycaemia in the 90 days after AMI. Secondary outcomes were functional decline, death, all-cause re-hospitalization and fracture hospitalization. We compared outcomes using binomial and multinomial logistic regression models after propensity score matching. RESULTS: Of 2855 NH residents with T2D, 29% initiated a T2D-friendly ß-blocker vs 24% of 6098 without T2D (P < 0.001). For primary outcomes among residents with T2D, T2D-friendly vs T2D-unfriendly ß-blockers were associated with a reduction in hospitalized hyperglycaemia (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.21-0.97), but unassociated with hypoglycaemia (OR 2.05, 95% CI 0.82-5.10). For secondary outcomes, T2D-friendly ß-blockers were associated with a greater rate of re-hospitalization (OR 1.26, 95% CI 1.01-1.57), but not death (OR 1.06, 95% CI 0.85-1.32), functional decline (OR 0.91, 95% CI 0.70-1.19), or fracture (OR 1.69, 95% CI 0.40-7.08). CONCLUSIONS: In older NH residents with T2D, T2D-friendly ß-blocker use was associated with a lower rate of hospitalization for hyperglycaemia, but a higher rate of all-cause re-hospitalization.

Concordance between Activated Partial Thromboplastin Time and Antifactor Xa Assay for Monitoring Unfractionated Heparin in Hospitalized Hyperbilirubinemic Patients.

BACKGROUND: Activated partial thromboplastin time (aPTT) and antifactor Xa (anti-Xa) monitoring methods for unfractionated heparin (UFH) often disagree. The extent of discordance for those with elevated bilirubin remains unclear. Our objective was to evaluate concordance between activated aPTT and anti-Xa methods for hyperbilirubinemic patients on UFH. METHODS: This was a retrospective cohort study of 26 patients hospitalized at Rhode Island Hospital between August 2014 and September 2014. Patients had at least one bilirubin measurement >5 mg/dL. After categorizing lab values, percent agreement and kappa were used to examine concordance between aPTT and anti-Xa. RESULTS: Overall percent agreement between aPTT and anti-Xa was 50%. A nontherapeutic aPTT and therapeutic anti-Xa accounted for 98% of all disagreement. Specifically, 76.7% of disagreement was due to a subtherapeutic aPTT and a therapeutic anti-Xa. Unweighted kappa was 0.141 (95%CI: 0.048-0.235). CONCLUSION: Concordance between aPTT and anti-Xa values was poor in hyperbilirubinemic patients.

Effects of an integrated clinical information system on medication safety in a multi-hospital setting.

PURPOSE: The implementation of vendor-based integrated clinical information technology was studied, and its effect on medication errors throughout the medication-use process in a health care system was evaluated. METHODS: The integrated systems selected for implementation included computerized physician order entry, pharmacy and laboratory information systems, clinical decision-support systems (CDSSs), electronic drug dispensing systems (EDDSs), and a bar-code point-of-care medication administration system. The primary endpoint was the reduction in related medication errors. Secondary endpoints included the reductions in medication order turnaround time and EDDS override transactions. RESULTS: Integrated clinical information system technology was implemented in a multihospital health care system with a phased-in approach. A positive effect of this integration on medication errors throughout the medication-use process was demonstrated. Most prescribing errors decreased significantly in the selected categories monitored, specifically drug allergy detection, excessive dosing, and incomplete or unclear orders. Pharmacists were also twice as likely to identify dosages requiring adjustment for renal insufficiency when the integrated technology was in place and more than six times as likely for drug levels outside of the therapeutic range. A positive effect on medication administration safety was also demonstrated: 73 administration-related errors were intercepted through electronic bar-code scanning for every 100,000 doses charted. CONCLUSION: Integration of clinical information system technology decreased selected types of medication errors throughout the medication-use process in a health care system and improved therapeutic drug monitoring in patients with renal insufficiency and in patients receiving drugs with narrow therapeutic ranges through the use of CDSS alerts.