Improving Vancomycin Stewardship in Critically Ill Children.

BACKGROUND AND OBJECTIVES: Inappropriate vancomycin use is common in children's hospitals. We report a quality improvement (QI) intervention to reduce vancomycin use in our tertiary care PICU. METHODS: We retrospectively quantified the prevalence of infections caused by organisms requiring vancomycin therapy, including methicillin-resistant Staphylococcus aureus (MRSA), among patients with suspected bacterial infections. Guided by these data, we performed 3 QI interventions over a 3-year period, including (1) stakeholder education, (2) generation of a consensus-based guideline for empiric vancomycin use, and (3) implementation of this guideline through clinical decision support. Vancomycin use in days of therapy (DOT) per 1000 patient days was measured by using statistical process control charts. Balancing measures included frequency of bacteremia due to an organism requiring vancomycin not covered with empiric therapy, 30-day mortality, and cardiovascular, respiratory, and renal organ dysfunction. RESULTS: Among 1276 episodes of suspected bacterial infection, a total of 19 cases of bacteremia (1.5%) due to organisms requiring vancomycin therapy were identified, including 6 MRSA bacteremias (0.5%). During the 3-year QI project, overall vancomycin DOT per 1000 patient days in the PICU decreased from a baseline mean of 182 DOT per 1000 patient days to 109 DOT per 1000 patient days (a 40% reduction). All balancing measures were unchanged, and all cases of MRSA bacteremia were treated empirically with vancomycin. CONCLUSION: Our interventions reduced overall vancomycin use in the PICU without evidence of harm. Provider education and consensus building surrounding indications for empiric vancomycin use were key strategies.

Clinical Application of Prophylactic Ethanol Lock Therapy in Pediatric Patients With Intestinal Failure.

Patients with intestinal failure have an increased risk for catheter-related bloodstream infections that can necessitate central venous line replacement and result in morbidity, prolonged hospitalization, or mortality. For pediatric patients with intestinal failure, the severe loss of intestinal absorptive ability leads to reliance on parenteral nutrition to meet minimal needs required for growth and development. Reliance on parenteral nutrition, in turn, forces dependency on central venous lines. Recent research concentrating on the pediatric population with intestinal failure indicates that prophylactic ethanol lock therapy can reduce the rate of catheter-related bloodstream infections and decrease central venous line removal rates in this high-risk population. Prevention of catheter-related bloodstream infections is critical for patients with intestinal failure. Ethanol lock therapy policies and protocols are increasingly being developed in healthcare institutions. Despite these efforts, no standard guidelines currently exist for ethanol lock therapy, and research in this area, specifically involving the pediatric population, is limited. This article presents the evidence to date as a means for assisting nursing professionals to make informed clinical decisions regarding the use of ethanol lock therapy for pediatric patients with intestinal failure.

Delirium in an adult acute hospital population: predictors, prevalence and detection.

BACKGROUND: To date, delirium prevalence and incidence in acute hospitals has been estimated from pooled findings of studies performed in distinct patient populations. OBJECTIVE: To determine delirium prevalence across an acute care facility. DESIGN: A point prevalence study. SETTING: A large tertiary care, teaching hospital. PATIENTS: 311 general hospital adult inpatients were assessed over a single day. Of those, 280 had full data collected within the study's time frame (90%). MEASUREMENTS: Initial screening for inattention was performed using the spatial span forwards and months backwards tests by junior medical staff, followed by two independent formal delirium assessments: first the Confusion Assessment Method (CAM) by trained geriatric medicine consultants and registrars, and, subsequently, the Delirium Rating Scale-Revised-98 (DRS-R98) by experienced psychiatrists. The diagnosis of delirium was ultimately made using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria. RESULTS: Using DSM-IV criteria, 55 of 280 patients (19.6%) had delirium versus 17.6% using the CAM. Using the DRS-R98 total score for independent diagnosis, 20.7% had full delirium, and 8.6% had subsyndromal delirium. Prevalence was higher in older patients (4.7% if <50 years and 34.8% if >80 years) and particularly in those with prior dementia (OR=15.33, p<0.001), even when adjusted for potential confounders. Although 50.9% of delirious patients had pre-existing dementia, it was poorly documented in the medical notes. Delirium symptoms detected by medical notes, nurse interview and patient reports did not overlap much, with inattention noted by professional staff, and acute change and sleep-wake disturbance noted by patients. CONCLUSIONS: Our point prevalence study confirms that delirium occurs in about 1/5 of general hospital inpatients and particularly in those with prior cognitive impairment. Recognition strategies may need to be tailored to the symptoms most noticed by the detector (patient, nurse or primary physician) if formal assessments are not available.

Phase 1 study of arsenic trioxide, high-dose cytarabine, and idarubicin to down-regulate constitutive signal transducer and activator of transcription 3 activity in patients aged <60 years with acute myeloid leukemia.

BACKGROUND: Constitutive activation of signal transducer and activator of transcription-3 (STAT3) was detected in blasts from approximately 50% of patients with acute myeloid leukemia (AML) and was correlated with an adverse outcome. In vitro treatment of AML blasts with arsenic trioxide (ATO) down-regulated STAT3 activity within 6 hours associated with a reduced viability within 48 hours. METHODS: A phase 1 clinical trial to evaluate the biologically effective dose and/or the maximally tolerated dose (MTD) of ATO in vivo in conjunction with high-dose cytarabine (Hidac) and idarubicin (Ida) in patients with AML aged <60 years was conducted. Data were compared with 117 historic AML patients who had received treatment with Hidac/Ida. RESULTS: In total, 61 patients were enrolled onto 11 different dose levels (from 0.01 to 0.65 mg/kg ideal body weight). The MTD was 0.5 mg/kg. Compared with historic controls, patients who received ATO/Hidac/Ida, although they had similar pretreatment characteristics, had better overall survival (P = .039). CONCLUSIONS: ATO priming may have improved the outcome of patients aged <60 years with AML who received Hidac/Ida. The current data suggested that ATO may enhance the effect of chemotherapy. The authors concluded that further studies of this novel combination are warranted.

Five years of ECT: the relationship between consent status and treatment experiences.

OBJECTIVES: ECT has received limited systematic study in the Irish setting. Amendments to the Mental Health Act (2001) propose limiting the use of ECT to patients who can provide written informed consent. We report on the use of ECT in Limerick specifically addressing the issue of patient consent and how it relates to response rate. METHOD: Since 2003, the use of ECT within Limerick Mental Health Services has been monitored by a data gathering process that includes the documentation of mood disturbance before and after the procedure. RESULTS: In the five years between 2003 and 2007, 153 courses of ECT were given to 126 different patients (frequency 16.7/100,000; Female:Male = 2:1). The principal indication for ECT was depressive illness (95%). Bilateral electrode application was the preferred mode comprising 83% of use. A total of 60% experienced at least a 50% reduction in MADRS score over the course of ECT with 78% experiencing a reduction of 10 points or more on the MADRS. Higher response rate was linked to use of bilateral ECT (p = 0.007; 95% CI 1.3-13.6). A total of 14% of patients were unable to provide written informed consent and these patients had more severe depression at outset (p = 0.007; 95% CI 1.8-11.1) and a trend towards greater reduction in MADRS scores during ECT (p = 0.08). The commonest adverse incident associated with ECT was cognitive impairment (33 patients). The risk of cognitive problems was not related to age, ECT dose, number of treatments, severity of depressive symptoms, treatment response, or consent status. CONCLUSIONS: Frequency of use, response and adverse effect rates for ECT in Limerick Mental Health Services are similar to other centres. Cognitive impairment was the most frequent adverse event. The choice of electrode placement for ECT requires further consideration. Restricting ECT to patients that can provide written informed consent would prevent its use in many patients with severe illness who experience significant response to treatment.

An overview of the central control of weight regulation and the effect of antipsychotic medication.

Weight regulation is a complex system necessary for maintaining health. Obesity and cachexia are consequences of dysregulation and cause significant physical morbidity and mortality. In the developed world, obesity is a growing epidemic. A greater understanding of the neuroanatomy of weight regulation has been gained through advances in imaging and neural mapping techniques. The neural connections between key hypothalamic and other central nuclei have been elucidated. Advances in molecular biology have led to the identification and cloning of important peripheral and central weight regulating peptides. Weight gain as a consequence of antipsychotic use is increasingly being recognized as a serious clinical issue. The weight regulation system provides a framework upon which antipsychotics exert their weight-inducing effects. Some studies have sought, with inconsistent results, to establish associations between antipsychotic use and levels of weight regulating mediators. The receptor pharmacology of antipsychotics known to increase weight can be studied with a view to establishing genetic variants contributing to the risk. To date, the 5-HT(2C) receptor 759C/T polymorphism shows most promise. Further studies are required to replicate previous findings and establish new associations.