Mark T. Holdsworth

Impact of computerized prescriber order entry on the incidence of adverse drug events in pediatric inpatients.

OBJECTIVES. This study was conducted to determine the impact of a computerized physician order entry system with substantial decision support on the incidence and types of adverse drug events in hospitalized children. METHODS. A prospective methodology was used for the collection of adverse drug events and potential adverse drug events from all patients admitted to the pediatric intensive care and general pediatric units over a 6-month period. Data from a previous adverse drug event study of the same patient care units before computerized physician order entry implementation were used for comparison purposes. RESULTS. Data for 1197 admissions before the introduction of computerized physician order entry were compared with 1210 admissions collected after computerized physician order entry implementation. After computerized physician order entry implementation, it was observed that the number of preventable adverse drug events (46 vs 26) and potential adverse drug events (94 vs 35) was reduced. Reductions in overall errors, dispensing errors, and drug-choice errors were associated with computerized physician order entry. There were reductions in significant events, as well as those events rated as serious or life threatening, after the implementation of computerized physician order entry. Some types of adverse drug events continued to persist, specifically underdosing of analgesics. There were no differences in length of stay or patient disposition between preventable adverse drug events and potential adverse drug events in either study period. CONCLUSIONS. This study demonstrated that a computerized physician order entry system with substantive decision support was associated with a reduction in both adverse drug events and potential adverse drug events in the inpatient pediatric population. Additional system refinements will be necessary to affect remaining adverse drug events. Preventable events did not predict excess length of stay and instead may represent a sign, rather than a cause, of more complicated illness.

Risk determinants for catheter‐associated blood stream infections in children and young adults with cancer

Catheter‐associated blood stream infections (CABSI) are frequent complications encountered with cancer treatment. In order to understand which factors might predispose to CABSIs in children and young adults, we evaluated risk for infection in association with tumor type, catheter type, and setting of occurrence.

Guideline for the Prevention of Acute Nausea and Vomiting Due to Antineoplastic Medication in Pediatric Cancer Patients

This guideline provides an approach to the prevention of acute antineoplastic‐induced nausea and vomiting (AINV) in children. It was developed by an international, inter‐professional panel using AGREE and CAN‐IMPLEMENT methods. Evidence‐based interventions that provide optimal AINV control in children receiving antineoplastic agents of high, moderate, low, and minimal emetogenicity are recommended. Recommendations are also made regarding selection of antiemetic agents for children who are unable to receive corticosteroids for AINV control, the role of aprepitant and optimal doses of antiemetic agents. Gaps in the evidence used to support the recommendations were identified. The contribution of this guideline to AINV control in children requires prospective evaluation. Pediatr Blood Cancer 2013; 60: 1073–1082.

Pain and Distress from Bone Marrow Aspirations and Lumbar Punctures

OBJECTIVE To compare the efficacy of 3 different pharmacologic regimens to relieve pain and distress in children with cancer undergoing bone marrow aspirations (BMAs) and lumbar punctures (LPs). DESIGN Retrospective cohort study with crossovers for some patients. PATIENTS AND METHODS The pain and distress ratings of patients undergoing BMAs (n = 73) and LPs (n = 105) were examined in a comparison of 3 different interventions: (1) a topical eutectic mixture of lidocaine and prilocaine (EMLA cream), (2) oral midazolam and EMLA cream, or (3) propofol/fentanyl general anesthesia. The choice of the intervention depended on patient/parent request. A validated faces pain scale was completed by the child or parent following each BMA or LP. The faces pain scale includes ratings of the severity of pain (from 0 = none to 5 = severe) and ratings of how frightened (from 0 = not scared to 5 = scared) the child was prior to each procedure. Comparisons of the pain and distress ratings were made among all patients for their first procedure and also within individual patients who had received >1 of the 3 interventions. Independent comparisons between the first treatments received by each patient were analyzed using Kruskal–Wallis tests. Comparisons of different crossover treatments received by individual patients were analyzed using Wilcoxon tests. RESULTS For all first procedures, mean ± SD pain and distress ratings during LPs were significantly lower when propofol/fentanyl was used (n = 43; 0.4 ± 1.0 and 1.4 ± 1.7) versus either EMLA (n = 29; 2.4 ± 1.7 and 2.9 ± 1.9) or midazolam/EMLA (n = 33; 2.4 ± 1.8 and 2.7 ± 1.8), respectively. Pain and distress ratings during BMAs were also significantly lower with propofol/fentanyl (n = 29; 0.5 ± 1.0 and 1.2 ± 1.7) versus EMLA (n = 21; 3.5 ± 1.6 and 3.3 ± 1.8) or midazolam/EMLA (n = 23; 3.3 ± 1.5 and 3.0 ± 1.9), respectively. When data were analyzed within each patient, these differences were also present. CONCLUSIONS Children receiving propofol/fentanyl general anesthesia experienced significantly less procedure-related pain and distress than did those receiving either EMLA or oral midazolam/EMLA.

Guideline for the classification of the acute emetogenic potential of antineoplastic medication in pediatric cancer patients.

This guideline provides clinicians caring for children with an approach to assessing the acute emetogenic potential of antineoplastic therapies. It was developed by an international, inter‐professional panel of clinicians and researchers using AGREE and CAN‐ADAPTE methods. The emetogenicity of antineoplastic agents was evaluated and ranked as high, moderate, low, or minimal. The emetogenicity of multiple‐agent and multiple‐day antineoplastic therapy was also classified. Gaps in the evidence used to underpin the guideline recommendations were identified. The contribution of this guideline to the prevention of antineoplastic‐induced nausea and vomiting in individual children about to receive antineoplastic therapy requires prospective evaluation. Pediatr Blood Cancer 2011; 57: 191–198.

Assessment of Chemotherapy-Induced Emesis and Evaluation of a Reduced-Dose Intravenous Ondansetron Regimen in Pediatric Outpatients with Leukemia

Objective: To measure the severity of nausea and vomiting in pediatric patients receiving intravenous or intrathecal chemotherapy for acute lymphoblastic leukemia and to evaluate the effectiveness of 2 intravenous doses of ondansetron for this condition. Design: Patients were surveyed during repeated treatments of maintenance chemotherapy, given with or without ondansetron, using a repeated measures pretest/posttest design. Setting: Outpatient pediatric oncology clinic. Patient population: Sixteen pediatric patients (aged 2–15 years, mean 6.2) with acute lymphoblastic leukemia. Methods: Surveys to assess nausea and vomiting and the extent of interference with daily activities were administered following emetogenic chemotherapy with or without ondansetron. Results: A total of 255 surveys following emetogenic chemotherapy with daunorubicin, cyclophosphamide, carmustine, and etoposide and cytarabine combined, as well as intrathecal therapy with methotrexate, hydrocortisone, and cytarabine, were analyzed. Analysis was performed on surveys of 149 courses without antiemetic therapy and 106 courses after 2 doses of ondansetron 0.15 mg/kg iv. The most emetogenic chemotherapy treatment was the etoposide/cytarabine combination (p<0.05). Ondansetron completely protected patients (defined as no nausea or no vomiting) during most (>50%) of the chemotherapy treatments, except for those in which cyclophosphamide was used. Ondansetron provided greater control of nausea and vomiting, a higher percentage of complete protection, and decreased the daily activity interference rating for carmustine and etoposide/cytarabine compared with courses of chemotherapy without antiemetics (p<0.05). Two intravenous doses of ondansetron also provided durable antiemetic efficacy over time for the most emetogenic chemotherapy treatment (etoposide/cytarabine). Conclusions: Etoposide/cytarabine proved to be the most emetogenic of the chemotherapy treatments studied. A reduced-dose regimen of intravenous ondansetron was shown to be an effective antiemetic for the outpatient treatments with etoposide/cytarabine and carmustine, but not with cyclophosphamide.

Impact of Pharmacists’ Directive Guidance Behaviors on Patient Satisfaction

OBJECTIVE To determine the impact of directive guidance (DG) behaviors by pharmacists on patient satisfaction with pharmaceutical care services. DG behaviors are social support behaviors and include such activities as supplying information about medications and providing encouragement and feedback regarding drug therapy. DESIGN Cross-sectional observational study using a self-administered survey. SETTING Two university-affiliated ambulatory care clinics, two chain pharmacies, and one independent pharmacy. PATIENTS One hundred sixty patients with a chronic disease (e.g., asthma, hypertension, diabetes). MAIN OUTCOME MEASURE Patient satisfaction with pharmaceutical care services. RESULTS A total of 160 completed questionnaires were collected from patients at 5 sites. Overall, patients patronizing ambulatory care clinics perceived higher rates of DG behaviors and were more satisfied with pharmaceutical care services, compared with patients in community pharmacies (P < .05). The hierarchical regression model was significant (F(13,112) = 4.9091, P < .001). DG behaviors explained 32.4% (P < .001) of the variance in patient satisfaction with pharmaceutical care services. CONCLUSION Higher rates of DG behaviors by pharmacists are associated with greater patient satisfaction with pharmaceutical care services.

Continuous Midazolam Infusion for the Management of Morphine-Induced Myoclonus

Objective: To describe a patient with morphine-induced myoclonus treated with a continuous infusion of midazolam and continued morphine dose escalation. Design: Single case report. Setting: Delivery, monitoring, and titration of morphine and midazolam in the patients home by a homecare agency. Results: The use of high dosages of morphine (i.e., 500 mg/h) produced myoclonic spasms in this patient, which in turn resulted in increasing pain. To allow for continuation of effective analgesia and to control the myoclonic spasms, an infusion of midazolam was initiated and titrated. The midazolam infusion allowed for continuation of the morphine dosage and also permitted further dosage escalation. As morphine dosages were further escalated, it was also necessary to increase the midazolam infusion to control additional myoclonic spasms. Conclusions: Use of a concomitant midazolam infusion with high doses of morphine appears to be safe and is an effective means of controlling morphine-induced myoclonus. If further dosage increases of morphine are necessary in this setting, increases in the midazolam infusion also may be required.

Stratified Administration of Serotonin 5-HT3 Receptor Antagonists (Setrons) for Chemotherapy-Induced Emesis: Economic Implications

The serotonin 5-HT3 receptor antagonists or ‘setrons’ have become the standard of care for the prevention of chemotherapy-induced emesis (CIE) and are first-line therapy for acute CIE in healthcare organisations worldwide. However, their superior efficacy versus standard antiemetics comes at a significant cost. Currently, 3 agents are available in the US: ondansetron, granisetron and dolasetron.The most important treatment-related factor contributing to CIE is the emetogenicity of chemotherapy. The ability to customise, or stratify, the setron dose to match the emetogenic challenge of the chemotherapy administered has potential benefits, both clinically and economically. In adults, there is an appreciable amount of clinical literature addressing stratified administration; however, the amount of ‘hard’ economic data is rather limited. Intuitively, if clinical outcomes are equivalent, then stratified administration should be associated with economic benefits, as it generally promotes the use of doses lower than those recommended by the manufacturer. The literature strongly substantiates this for ondansetron, but is not as favourable for granisetron or dolasetron.As the rationale and justification for dose stratification is contained in the clinical literature, the authors have reviewed the pertinent literature supporting the clinical and economic benefits of dose stratification in both adult and paediatric patients. The authors also provide a discussion of various additional strategies that can be employed to ensure the appropriate and cost-effective use of setrons in real-world practice settings. These strategies include the use of lower doses than recommended by manufacturers, use for acute versus delayed phase emesis, enhancing the antiemetic efficacy by the addition of a corticosteroid, use of oral versus injectable formulations (when appropriate) and the implementation and use of local, national and international drug use guidelines.

Availability of Narcotics and Pharmacists' Attitudes toward Narcotic Prescriptions for Cancer Patients

OBJECTIVE: To determine narcotic availability and pharmacist apprehension toward dispensing narcotics for cancer patients. DESIGN: Mailing of a one-page survey. SETTING: All pharmacies in the state of New Mexico. PARTICIPANTS: Of the 309 pharmacies, 76.1 percent (235) completed the survey. MEASUREMENTS AND MAIN RESULTS: Apprehension was significantly elevated for methadone, hydromorphone, and for morphine doses >500 mg/d (p<0.001). The most common reasons listed for apprehension were forgery (46.4 percent), theft (40.4 percent), high dosages (23.8 percent), narcotic investigations (18.7 percent), and patient addiction (9.4 percent). Hydromorphone was available (in stock) in 80.5 percent of the pharmacies, followed by morphine 30-mg sustained-release tablets (64.5 percent) and methadone (53.4 percent). The vast majority of pharmacists were willing to order strong narcotics for specific patients. Pharmacists working in chain stores expressed a higher level of apprehension toward dispensing methadone and more frequently cited forgery as a reason for apprehension. Distance from a metropolitan area and practice setting best predicted apprehension to forgery (p=0.01). CONCLUSIONS: Pharmacists do not appear to be a major obstruction to adequate analgesia for cancer patients in New Mexico but may require further education regarding lack of narcotic addiction and dosing in patients with cancer.