Jeffrey H. Silber

Recommendations for the Use of Antiemetics: Evidence-Based, Clinical Practice Guidelines

THE GOAL OF ANTIEMETIC therapy is to prevent nausea and vomiting completely. This goal is achieved for many patients receiving chemotherapy or radiation therapy, and is based on clinical and basic research that has steadily improved the control of emesis over the last 20 years. As therapy has become more effective, it has also become safer, with few side effects associated with the most commonly used regimens. These regimens are convenient for patients to receive and for health care professionals to administer. However, despite improvements, a significant number of patients still experience emesis, and efforts to reduce this side effect of treatment must continue. As antiemetic usage has grown, the classes of agents available for antiemetic treatment, the number of agents, and the indications for antiemetics have all increased as well. The prevention of delayed emesis and anticipatory emesis is equal in importance to the need to prevent acute chemotherapyand radiation-induced emesis. Additionally, managing special and difficult emetic problems and selecting the proper antiemetic approach necessitate identification of the patient’s emetic risk. Although the neuropharmacologic basis of emesis is still incompletely understood, the selection of an appropriate antiemetic regimen is possible and can have an impact on several aspects of clinical care. Goals related to the complete control of emesis, ie, no vomiting, include providing care that is convenient for the patient, treatment that reduces hospitalization and time in the ambulatory setting, and therapy that enhances the patient’s quality of life. Additionally, practitioners need to be mindful of reducing costs of treatment while achieving these goals. 1-3

Hospital and patient characteristics associated with death after surgery. A study of adverse occurrence and failure to rescue.

We asked if the factors that predict overall mortality following two common surgical procedures are different from those that predict adverse occurrences (complications) during the hospitalization or death after an adverse occurrence, which we refer to as “failure to rescue.” We examined 5,972 Medicare patients undergoing elective cholecystectomy or transurethral prostatectomy using three outcome measures: 1) the death rate (number of deaths/number of patients); 2) the adverse occurrence rate (number of patients who developed an adverse occurrence/number of patients); and 3) the failure rate (number of deaths in patients who developed an adverse occurrence/number of patients with an adverse occurrence). The death rate was associated with both hospital and patient characteristics. The adverse occurrence rate was associated primarily with patient characteristics. In contrast, failure to rescue was associated more with hospital characteristics, and was less influenced by patient admission severity of illness as measured by the MedisGroups score. We concluded that factors associated with hospital failure to rescue are different from factors associated with adverse occurrences or death. Understanding the reasons behind variation in mortality rates across hospitals should improve our ability to use mortality statistics to help hospitals upgrade the quality of care.

Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score.

PURPOSE Decline in intelligence can occur after whole-brain cranial irradiation for childhood malignancy. The purpose of this analysis was to estimate better the impact of dose and age at time of irradiation on IQ decline. PATIENTS AND METHODS A total of 48 children were studied. We combined two previously reported studies that included 15 patients with pediatric acute lymphocytic leukemia (ALL) and 18 pediatric patients with medulloblastoma/posterior fossa primitive neural ectodermal tumors (PNETs) in whom serial IQ tests were administered. Another 15 patients (nine ALL and six PNET) were studied subsequent to these reports. This experience included ALL patients who were treated with whole-brain irradiation at doses of 18 Gy (n = 9) and 24 Gy (n = 15), and PNET patients who were treated with 18 Gy (n = 5), 22 to 24 Gy (n = 2), and 32 to 40 Gy (n = 17). Multiple regression models were constructed to estimate expected IQ score after treatment based on initial IQ score, age at treatment, and dose of whole-brain irradiation. RESULTS Using a multiple linear regression model to correct for initial IQ and age at treatment, patients who received a dose of 36 Gy to the whole brain were estimated to score 8.2 points less on IQ testing than those with 24 Gy (95% confidence interval [CI], 1.8 to 14.6) and 12.3 points less than those who received 18 Gy (95% CI, 2.7 to 21.7). Older age at the time of irradiation resulted in less decline in subsequent IQ score. The predicted IQ decline is 11.9 points less in a 10-year-old patient than in a 3-year-old patient (95% CI, 4.2 to 19.6) for equivalent doses of irradiation. The model to predict IQ accounts for half the total variation in IQ score. There was no significant difference between the coefficients that reflected IQ decrease from radiation dose between subgroups who had ALL versus those with PNET. CONCLUSIONS One can forecast final IQ score based on the initial IQ score, dose of irradiation, and age at time of irradiation. Our findings should aid in the selection of appropriate therapy when whole-brain irradiation is needed.

Hospital nurse practice environments and outcomes for surgical oncology patients.

OBJECTIVE To examine the effect of nursing practice environments on outcomes of hospitalized cancer patients undergoing surgery. DATA SOURCES Secondary analysis of cancer registry, inpatient claims, administrative and nurse survey data collected in Pennsylvania for 1998-1999. STUDY DESIGN Nurse staffing (patient to nurse ratio), educational preparation (proportion of nurses holding at least a bachelors degree), and the practice environment (Practice Environment Scale of the Nursing Work Index) were calculated from a survey of nurses and aggregated to the hospital level. Logistic regression models predicted the odds of 30-day mortality, complications, and failure to rescue (death following a complication). PRINCIPAL FINDINGS Unadjusted death, complication, and failure to rescue rates were 3.4, 35.7, and 9.3 percent, respectively. Nurse staffing and educational preparation of registered nurses were significantly associated with patient outcomes. After adjusting for patient and hospital characteristics, patients in hospitals with poor nurse practice environments had significantly increased odds of death (odds ratio, 1.37; 95 percent confidence interval, 1.07-1.76) and of failure to rescue (odds ratio, 1.48; 95 percent confidence interval, 1.07-2.03). Receipt of care in National Cancer Institute-designated cancer centers significantly decreased the odds of death, which can be explained partly by better nurse practice environments. CONCLUSIONS This study is one of the first to examine the predictive validity of the National Quality Forums endorsed measure of the nurse practice environment. Improvements in the quality of nurse practice environments could reduce adverse outcomes for hospitalized surgical oncology patients.

Enalapril to Prevent Cardiac Function Decline in Long-Term Survivors of Pediatric Cancer Exposed to Anthracyclines

PURPOSE To determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index [MCI] on exercise testing or increase in left ventricular end-systolic wall stress [LVESWS]) in long-term survivors of pediatric cancer. PATIENTS AND METHODS This was a randomized, double-blind, controlled clinical trial comparing enalapril to placebo in 135 long-term survivors of pediatric cancer who had at least one cardiac abnormality identified at any time after anthracycline exposure. RESULTS There was no difference in the rate of change in MCI per year between enalapril and placebo groups (0.30 v 0.18 L/min/m(2); P =.55). However, during the first year of treatment, the rate of change in LVESWS was greater in the enalapril group than in the placebo group (-8.59 v 1.85 g/cm(2); P =.033) and this difference was maintained over the study period, resulting in a 9% reduction in estimated LVESWS by year 5 in the enalapril group. Six of seven patients removed from random assignment to treatment because of cardiac deterioration were initially treated with placebo (P =.11), and one has died as a result of heart failure. Side effects from enalapril included dizziness or hypotension (22% v 3% in the placebo group; P =.0003) and fatigue (10% v 0%; P =.013). CONCLUSION Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year; this reduction was maintained over the study period. Any theoretical benefits of LVESWS reduction in this anthracycline-exposed population must be weighed against potential side effects from ACE inhibitors when making treatment decisions.

Comparing the Contributions of Groups of Predictors: Which Outcomes Vary with Hospital Rather than Patient Characteristics?

Abstract In a model, such as a logit regression model, we wish to compare the relative importance of two groups of predictors for various objectives. In the example that motivated this work, the model predicts patient outcomes during hospital stays, and we wish to measure the relative contribution of patient and hospital characteristics to the variation in outcomes among patients and among hospitals. This is done using the relative dispersion of patient and hospital contributions to the fitted outcomes. As is seen, this question is distinct from other common questions, including the quality of the overall fit, the degree to which the outcome is accurately predicted, the statistical significance of groups of predictors, and the correlations among and between groups of predictors. Relevant point estimates, confidence intervals, and hypothesis tests are developed. In the example, we examine three outcome measures and find that nearly all of the predictable variation in patient outcomes and most of the predic...

Failure-to-rescue: comparing definitions to measure quality of care.

Objectives: Use of failure-to-rescue (FTR) as an indicator of hospital quality has increased over the past decade, but recent authors have used different sets of complications and deaths to define this measure. This study examines the reliability and validity of different FTR measures currently in use. Research Design: We studied 3 definitions: (1) “original” FTR (using all deaths); (2) FTR-N, a “nursing sensitive” definition that uses only specific complications and deaths; and (3) FTR-A [another restricted definition of FTR used by Agency for Healthcare Research and Quality (AHRQ) for analyzing Healthcare Cost and Utilization Project (HCUP) data]. Each FTR measure was applied to 403,679 general surgical patients across 1567 hospitals reported in 1999–2000 Medicare MEDPAR data. Results: Although FTR used all deaths, FTR-N and FTR-A definitions omitted 49% and 42% of deaths, respectively. Reliability was better for FTR than FTR-A or FTR-N (ρ = 0.32 vs. 0.18 vs. 0.18, respectively). Validity: Hospitals ranked by adjusted mortality were highly correlated with FTR (Kendall’s τ = 0.83) and less correlated with FTR-A (τ = 0.43) and FTR-N (τ = 0.41). Adjusting for patient characteristics, all FTR measures showed strong associations with bed-to-nurse ratio, nursing mix, teaching status, and hospital size; however, hospital “high technology” was not as well associated with FTR-N. Conclusions: For general surgery, more limited definitions used by FTR-N and FTR-A omit over 40% of deaths, display less reliability, and may have more questionable validity than the original FTR measure. We encourage analysts to use the original FTR definition that uses all deaths when analyzing hospital quality of care.

Surveillance scanning of children with medulloblastoma.

BACKGROUND The standard follow-up care for children with medulloblastoma includes regular clinical evaluations and surveillance scanning of the central nervous system with computed tomography or magnetic resonance imaging. The evaluations and scanning assess the response of the tumor to treatment, detect any recurrence of disease, and monitor any complications of treatment. We compared the effectiveness of a periodic history taking and physical examination with that of surveillance scanning in detecting recurrent tumors. METHODS We reviewed the medical records, including 794 scanning reports or scans, of 86 children with posterior fossa medulloblastoma who were followed regularly between 1980 and 1991. Recurrent tumors were classified as symptomatic if neuroimaging studies had been prompted by clinical symptoms or signs and as radiographic if the tumor had been detected by imaging in an asymptomatic patient. RESULTS Twenty-three of the 86 children (27 percent) had a recurrence of tumor. Four recurrences (17 percent) were detected on scanning only, and 19 (83 percent) were associated with symptoms arising a median of four months after the previous scan. The median and range of survival after a recurrence of the tumor were 5 months and < 1 to 38 months, respectively, for a symptomatic recurrence and 20 months and 10 to 32 months, respectively, for a radiographic recurrence (P = 0.03). No patient survived after a recurrence. The longer survival of patients with recurrent tumors detected by scanning most likely reflects the small number of patients and lead-time and length biases associated with screening. CONCLUSIONS Among children with medulloblastoma, surveillance scanning is of little clinical value. Scanning detected a minority of recurrences, and no patient who had a recurrence survived.

Characteristics Associated With Differences in Survival Among Black and White Women With Breast Cancer

IMPORTANCE Difference in breast cancer survival by race is a recognized problem among Medicare beneficiaries. OBJECTIVE To determine if racial disparity in breast cancer survival is primarily attributable to differences in presentation characteristics at diagnosis or subsequent treatment. DESIGN, SETTING, AND PATIENTS Comparison of 7375 black women 65 years and older diagnosed between 1991 to 2005 and 3 sets of 7375 matched white control patients selected from 99,898 white potential controls, using data for 16 US Surveillance, Epidemiology and End Results (SEER) sites in the SEER-Medicare database. All patients received follow-up through December 31, 2009, and the black case patients were matched to 3 white control populations on demographics (age, year of diagnosis, and SEER site), presentation (demographics variables plus patient comorbid conditions and tumor characteristics such as stage, size, grade, and estrogen receptor status), and treatment (presentation variables plus details of surgery, radiation therapy, and chemotherapy). MAIN OUTCOMES AND MEASURES 5-Year survival. RESULTS The absolute difference in 5-year survival (blacks, 55.9%; whites, 68.8%) was 12.9% (95% CI, 11.5%-14.5%; P < .001) in the demographics match. This difference remained unchanged between 1991 and 2005. After matching on presentation characteristics, the absolute difference in 5-year survival was 4.4% (95% CI, 2.8%-5.8%; P < .001) and was 3.6% (95% CI, 2.3%-4.9%; P < .001) lower for blacks than for whites matched also on treatment. In the presentation match, fewer blacks received treatment (87.4% vs 91.8%; P < .001), time from diagnosis to treatment was longer (29.2 vs 22.8 days; P < .001), use of anthracyclines and taxols was lower (3.7% vs 5.0%; P < .001), and breast-conserving surgery without other treatment was more frequent (8.2% vs 7.3%; P = .04). Nevertheless, differences in survival associated with treatment differences accounted for only 0.81% of the 12.9% survival difference. CONCLUSIONS AND RELEVANCE In the SEER-Medicare database, differences in breast cancer survival between black and white women did not substantially change among women diagnosed between 1991 and 2005. These differences in survival appear primarily related to presentation characteristics at diagnosis rather than treatment differences.

Anesthesiologist direction and patient outcomes.

Background Anesthesia services for surgical procedures may or may not be personally performed or medically directed by anesthesiologists. This study compares the outcomes of surgical patients whose anesthesia care was personally performed or medically directed by an anesthesiologist with the outcomes of patients whose anesthesia care was not personally performed or medically directed by an anesthesiologist. Methods Cases were defined as being either “directed” or “undirected,” depending on the type of involvement of the anesthesiologist, as determined by Health Care Financing Administration billing records. Outcome rates were adjusted to account for severity of disease and other provider characteristics using logistic regression models that included 64 patient and 42 procedure covariates, plus an additional 11 hospital characteristics often associated with quality of care. Medicare claims records were analyzed for all elderly patients in Pennsylvania who underwent general surgical or orthopedic procedures between 1991–1994. The study involved 194,430 directed and 23,010 undirected patients among 245 hospitals. Outcomes studied included death rate within 30 days of admission, in-hospital complication rate, and the failure-to-rescue rate (defined as the rate of death after complications). Results Adjusted odds ratios for death and failure-to-rescue were greater when care was not directed by anesthesiologists (odds ratio for death = 1.08, P < 0.04; odds ratio for failure-to-rescue = 1.10, P < 0.01), whereas complications were not increased (odds ratio for complication = 1.00, P < 0.79). This corresponds to 2.5 excess deaths/1,000 patients and 6.9 excess failures-to-rescue (deaths) per 1,000 patients with complications. Conclusions Both 30-day mortality rate and mortality rate after complications (failure-to-rescue) were lower when anesthesiologists directed anesthesia care. These results suggest that surgical outcomes in Medicare patients are associated with anesthesiologist direction, and may provide insight regarding potential approaches for improving surgical outcomes.