Early hospital discharge of children with cancer treated for fever and neutropenia: identification and management of the low-risk patient

Children with leukemia and solid tumors are often hospitalized for empiric broad-spectrum antibiotic therapy because of fever during periods of chemotherapy-induced neutropenia. Conventional practice dictates that parenteral antibiotics be continued until the patient is afebrile and has recovered from neutropenia, ie, until the absolute neutrophil count (ANC) exceeds 500 cells per cubic millimeter. However, the practice in our center has been to discontinue parenteral antibiotic therapy and discharge many such patients before resolution of neutropenia. Since the feasibility and safety of this approach has not been studied, we reviewed the records of 114 consecutive hospitalizations for fever and neutropenia in 61 patients during a 13-month period. Seventy-seven children (68%) were discharged to their homes while still neutropenic after they had been afebrile for 1 to 2 days on parenteral antibiotics, had negative blood cultures, appeared well, and usually had some evidence of bone marrow recovery. Five patients (4.4%) developed recurrent fever and required rehospitalization within 7 days of discharge. Only three of the 77 patients (3.9%) who were sent home with neutropenia had recurrent fever. Each had a brief and uneventful second hospitalization. Two of the 37 children discharged with an ANC over 500 cells per cubic millimeter required rehospitalization. A declining ANC and advanced malignancy were risk factors in predicting recurrence of fever following discharge. A rising monocyte count was a predictor of imminent recovery from neutropenia. These results suggest that "early" discharge of an afebrile yet still neutropenic patient is safe when the patient is in remission, has no evidence of serious infection, appears clinically stable, and has indications of bone marrow recovery. The conventional approach of routinely continuing the hospitalization until resolution of neutropenia may be unnecessary in such low-risk patients.     

Diagnosis and management of relapse in acute lymphoblastic leukemia

Although the results are steadily improving, the treatment of the child with lymphoblastic leukemia in relapse remains unsatisfactory. Owing to the very nature of relapse, it is highly unlikely that future chemotherapy protocols will provide curative treatment for the majority of patients with recurrent disease. Therefore, the greatest possible emphasis must be given to further improvements and refinements in front-line (initial) therapy so as to prevent relapse from ever occurring. Our goal should be to put the relapse leukemia specialist "out of business."     

The financial impact of investigational drug services

The pharmacy-based investigational drug service plays an important role in the clinical research process. Investigators and sponsors often rely on the research pharmacist to assure drug accountability and to assist in educating staff about drug studies, reporting adverse reactions, and providing drug information. While many pharmacy departments across the country have established investigational drug services, there is an increasing need to justify these services from a financial perspective. Our pharmacy department currently provides investigational drug services for over 100 protocols. We have established a fee-for-service billing mechanism, but only 61% of our protocols are drug-company or investigator-sponsored, which reimburse for pharmacy services. As a result, we are unable to collect all operating costs through our billing mechanism. Many protocols, however, are sponsored by the National Cancer Institute (NCI), which provides free drugs for cancer protocols. Some NCI drugs are also on the market, so the hospital experiences savings in drug costs when patients are placed on certain NCI protocols. When we combine direct costs recovered through billing with the indirect cost savings from dispensing "free drugs, we find that the total benefit of operating an investigational drug service more than outweighs the cost of operating the service.     

Copper in drinking water, Nebraska, 1994

In 1993, the levels of copper (Cu) in much of Nebraska's drinking water exceeded the U.S. Environmental Protection Agency's (EPA) action level of 1.3 mg/L. To determine the association of copper with gastrointestinal (GI) illness in August 1994 the authors interviewed persons living in households with 1993 Cu levels > 3 mg/L (51 households), 2-3 mg/L (54 households), and < 1.3 mg/L (43 households). Cases were defined as persons who had experienced the rapid onset of vomiting or nausea with abdominal pain during the preceding two weeks. To validate their exposure index, the authors immediately resampled drinking water in the households of 25 cases and 27 controls matched for age. Reassessment in December 1994 of the exposure and case status of the original cohort showed no association between copper in drinking water in 1993 and case status in 1994. The risk of GI illness seemed no greater with Cu > 3 mg/L (RR = 1.03; 95% CI = 0.43, 2.49) or 2-3 mg/L (RR = 0.50; 95% CI = 0.18, 1.41) than with Cu < 1.3 mg/L. The 1993 Cu concentrations could not be reproduced in August 1994; resampling in December 1994 again showed no association between GI illness and Cu exposure (RR > 1.3-2.9 mg/L, < or = 1.3 mg/L = 0.25, 95% CI = 0.10, 0.64, and RR > or = 3.0 mg/L, < or = 1.3 mg/L = 0.36, 95% CI = 0.09, 1.49).     

Regulatory peptides in the heart and major vessels of man and mammals

Studies on the distribution of peptides in human tissues have been made either by measuring responses to localized stimuli or by subjecting extracts of different regions to radioimmunoassay (RIA). Attempts at isolating regulatory peptides from the mammalian tissues have resulted in the isolation of many bioactive fragments. Later, modification of initial isolation methods led to the identification of the native molecules in various tissues and body fluids. The present study examined atrial natriuretic peptide (ANP) and several other peptides in cardiac tissues of several species of laboratory mammal and human beings; using a sensitive and highly specific radioimmunoassays.In all the species studied, ANP-like immunoreactivity appeared to be highest in the heart tissue of rat. The peptide was highest in the right atrium (RA) of rat and lowest in the RA of guinea pig (P< 0.002). Neuropeptide Y (NPY) another abundant cardiac peptide was present in the cardiac tissues of all species but was more in the left atrium (LA) than the RA of all species (P<0.05). Calcitonin gene-related peptide (CGRP) was present throughout the cardiovascular system of the rat and guinea pig. Small but detectable amount of Neurotensin (NT) immunoreactivity was found in the rat but was consistently negative in the guinea pig cardiac tissues (P< 0.05). Substance P (SP) immunoreactivity was detected in the rat and higher quantities being in the Aorta but no trace of the peptide was detected in the left ventricle, aorta nor the pulmonary vein of post mortem human.Though the structure of most of the species studied has been elucidated, the primary structure of guinea pig ANP has not been fully generated. Thus the data obtained may suggest that in keeping with these mammalian peptides, the primary structures may be variant. With most of the peptides studied (e.g. ANP, Neuropepdide Y), immunoreactivity occurs predominantly in the atrial tissues, but is also present in vessels outside the heart, a finding which may be of functional significance.