BUN as an Independent Predictor of Post-Hospital-Discharge Mortality among Older Veterans.

BACKGROUND/OBJECTIVES: An elevated blood urea nitrogen (BUN) in known to be an important prognostic indicator in patients with end-stage heart or kidney disease or certain other life-threatening illnesses. However, it is less certain as to whether an elevated BUN is an independent predictor of long-term mortality risk in less seriously ill patients. To address this issue, we examined the relationship between BUN and long-term mortality after adjusting for potential confounders and other indicators of health status/disease severity, in a select population of older medically stable Veterans. DESIGN: Long-term prospective cohort study. SETTING: Outpatient follow-up of patients discharged from a recuperative care and rehabilitation unit (RCRU) of a Department of Veterans Affairs Community Living Center. PARTICIPANTS: 383 older Veterans (mean age = 78.6±7.6 years, 98% male, and 87% white) discharged alive and in stable medical condition. MEASUREMENTS: At discharge, each subject completed a comprehensive assessment and was then monitored as an outpatient for up to 9.3 years. Associations between blood urea nitrogen at RCRU discharge and mortality were identified utilizing Cox proportional hazards (PH) regression analyses adjusting for conditions known to confound this relationship. RESULTS: Within the follow-up period, 255 subjects (67%) died. In the unadjusted Cox PH model, a BUN ≥ 30 mg/dL was associated with a nearly 2-fold increased risk of mortality (hazard ratio 1.90, 95%CI 1.41 - 2.56). The association between BUN and long-term mortality remained highly significant after adjusting for potential confounders (hazard ratio 1.78, 95%CI 1.29 - 2.44). CONCLUSION: Our findings support BUN levels as an independent predictor of long-term mortality in older, medically stable Veterans. An elevated BUN may be reflective of global health status rather than solely an indicator of the severity of acute illness or unstable chronic disease.

Dodecafluoropentane Emulsion Extends Window for tPA Therapy in a Rabbit Stroke Model.

Dodecafluoropentane emulsion (DDFPe) nanodroplets are exceptional oxygen transporters and can protect ischemic brain in stroke models 24 h without reperfusion. Current stroke therapy usually fails to reach patients because of delays following stroke onset. We tested using DDFPe to extend the time window for tissue plasminogen activator (tPA). Longer treatment windows will allow more patients more complete stroke recovery. We test DDFPe to safely extend the time window for tPA thrombolysis to 9 h after stroke. With IACUC approval, randomized New Zealand white rabbits (3.4-4.7 kg, n = 30) received angiography and 4-mm blood clot in the internal carotid artery for flow-directed middle cerebral artery occlusion. Seven failed and were discarded. Groups were IV tPA (n = 11), DDFPe + tPA (n = 7), and no therapy controls (n = 5). DDFPe (0.3 ml/kg, 2 % emulsion) IV dosing began at 1 h and continued at 90 min intervals for 6 doses in one test group; the other received saline injections. Both got standard IV tPA (0.9 mg/kg) therapy starting 9 h post stroke. At 24 h, neurological assessment scores (NAS, 0-18) were determined. Following brain removal percent stroke volume (%SV) was measured. Outcomes were compared with Kruskal-Wallis analysis. For NAS, DDFPe + tPA was improved overall, p = 0.0015, and vs. tPA alone, p = 0.0052. For %SV, DDFPe + tPA was improved overall, p = 0.0003 and vs. tPA alone, p = 0.0018. NAS controls and tPA alone were not different but %SV was, p = 0.0078. With delayed reperfusion, DDFPe + tPA was more effective than tPA alone in preserving functioning brain after stroke. DDFPe significantly extends the time window for tPA therapy.

Dodecafluoropentane Emulsion (DDFPe) Decreases Stroke Size and Improves Neurological Scores in a Permanent Occlusion Rat Stroke Model.

BACKGROUND: Dodecafluoropentane emulsion (DDFPe), given IV one hour after stroke, has been shown to greatly reduce the percent stroke volume (%SV) in rabbits. With repeated doses its effect continued for 24 hours. PURPOSE: Test DDFPe as neuroprotective agent in permanent occlusion rat stroke models in Sprague Dawley (SD) and Spontaneously Hypertensive Rats (SHR) measuring both %SV and neurological assessment scores (NAS). METHODS: The male rats received either saline (control), or one or four doses (1x or 4x) of DDFPe (0.6ml/kg IV) one hour post stroke. Treatment groups were SD (n=26) (control, 1x and 4x; n=12, 7 and 7) and SHR (n=14) (control, 1x and 4x; n=7, 3 and 4). The 4x doses were given at 1.5 hour intervals. At six hours post stroke, the rats received a NAS using standard tests for balance, reflexes, and motor performance. Then rats were euthanized and brains removed for TTC evaluation of %SV. RESULTS: For %SV analysis strain differences were not significant therefore strains were combined. DDFPe significantly decreased %SV in 1x and 4xDDFPe groups compared to control groups (2.59±1.81 and 0.98±0.88 vs. 9.24±6.06, p≤0.001 each; p≤0.0001 for the overall test for treatment effect). The 1x versus 4xDDFPe groups were not significantly different (p=0.40). In NAS analysis both strains showed significant improvement with 4xDDFPe therapy vs. controls, (SD: 5.00+2.45 vs. 9.36+3.56, p=0.01; SHR: 7.75+4.43 vs. 12.14+3.08, p=0.05). Differences between the 1x DDFPe group and controls were not significant (SD: 8.43+3.69; SHR: 9. 33+3.51). CONCLUSION: DDFPe treatment provides significant neuroprotection when assessed six hours post stroke.

Investigation of effect of variations in bone fraction and red marrow cellularity on bone marrow dosimetry in radio-immunotherapy.

A method is described for computing patient-specific absorbed dose rates to active marrow which accounts for spatial variation in bone volume fraction and marrow cellularity. A module has been added to the 3D Monte Carlo dosimetry program DPM to treat energy deposition in the components of bone spongiosa distinctly. Homogeneous voxels in regions containing bone spongiosa (as defined on CT images) are assumed to be comprised only of bone, active (red) marrow and inactive (yellow) marrow. Cellularities are determined from biopsy, and bone volume fractions are computed from cellularities and CT-derived voxel densities. Electrons are assumed to deposit energy locally in the three constituent components in proportions determined by electron energy absorption fractions which depend on energy, cellularity, and bone volume fraction, and which are either taken from the literature or are derived from Monte Carlo simulations using EGS5. Separate algorithms are used to model primary ß particles and secondary electrons generated after photon interactions. Treating energy deposition distinctly in bone spongiosa constituents leads to marrow dosimetry results which differ from homogeneous spongiosa dosimetry by up to 20%. Dose rates in active marrow regions with cellularities of 20, 50, and 80% can vary by up to 20%, and can differ by up to 10% as a function of bone volume fraction. Dose to bone marrow exhibits a strong dependence on marrow cellularity and a potentially significant dependence on bone volume fraction.

The Interrelationships among albumin, nutrient intake, and inflammation in elderly recuperative care patients.

OBJECTIVES: To examine the interrelationships among low serum albumin, nutritional depletion, and ongoing inflammation in older patients recovering from illness. DESIGN: A prospective cohort study. SETTING: A transitional care unit (TCU) within a Department of Veterans Affairs hospital nursing home care unit. PARTICIPANTS: 275 older veterans (mean age=78.9 ± 7.5y, 99% male) admitted for recuperative care and rehabilitation. MEASUREMENTS: At admission and discharge (median LOS 24d, IQR 16 to 44d), each subject completed a comprehensive standardized evaluation including a nutritional assessment and measurement of serum albumin, C-reactive protein (CRP), interleukin-6 (IL-6) and its soluble receptor, and tumor necrosis factor-alpha (TNF-α) and its soluble receptors (sTNF-RI and II). Complete nutrient intake assessments (calorie counts) were performed daily. RESULTS: Both the discharge albumin and the change in albumin (discharge minus admission) were strongly and inversely correlated with various indicators of inflammation, particularly CRP and IL-6. Change in CRP was the strongest correlate of change in albumin (R2 = 0.21, P<.001) and discharge IL-6 the strongest correlate of discharge albumin (R2 = 0.21, P<.001). Nutrient intake also correlated with albumin and its change, but entered the multivariable models after inflammatory indicators and explained a smaller portion of the variance. Although there were significant interactions between time and both nutrient intake and inflammation, the relative importance of inflammation as a potential determinant of the serum albumin concentration appeared to remain unchanged with longer periods of observation. CONCLUSIONS: Among elderly patients admitted to a TCU, inflammation appears to be a more powerful determinant of albumin and its change during the hospitalization than is nutrient intake. Further study is needed to prove causality and to determine whether the relative importance of inflammation on the albumin concentration diminishes with more prolonged periods of observation.

Radioprotectant Activity of Dicopper(II) Tetrakis(3,5- Diisopropylsalicylate) and Manganese(II) bis(3,5- Diisopropylsalicylate) Alone and in Combination.

Dicopper(ll) tetrakis(3,5-diisopropylsalicylate), (Cu(II)(2)(3,5-DIPS)(4), manganese(II) bis(3,5-diisopropylsalicylate), Mn(II)3,5-DIPS)(2) or combinations of them were used to treat gamma-irradIated mice in examining the possibility that combination treatments might be more effective in increasing survival than treatment with either complex alone. Doses of 0, 10, 20, or 40 mumol of each complex per kilogram of body mass were administered subcutaneously in a factorial design before 9 Gy gamna irradiation, an LD(90) dose of irradiation. Doses of 0, 10, 20, or 40 mumol Cu(II)(2)(3, 5-DIPS)(4) per kg of body mass produced 12, 28, 28, or 36 % survival, respectively, while doses of 0, 10, 20, or 40 mumol (II)(3), 5-DIPS)(2) per kg of body mass prduced 12, 36, 20, or 24 % survival, respectively. However, the combination of 20 mumol Cu(II)(2)(3, 5-DIPS)(4) and 10 mumol Mn(II)(3, 5-DIPS)(2) produced the greatest survival, 48 %, which was 300 % greater than vehicle-treated mice (P=0.01). It is concluded that specific combination treatments can be used to maximize survival of lethally irradiated mice.

A randomised clinical trial of nicotine patches for treatment of spit tobacco addiction among adolescents.

BACKGROUND: This study tested the efficacy of nicotine patches in combination with behavioural therapy for the treatment of adolescent spit tobacco addiction. Prior interventions had resulted in mean cessation rates below 15% at one year. METHODS: This study, the PATCH Project, used a three group, placebo controlled, randomised clinical trial design. The control group received a standard 3-5 minute counselling followed by a two week follow up phone call. The two intervention groups received a six week behavioural intervention; in addition, one group received active nicotine patches while the other group received placebo patches. Both groups received quarterly stage based telephone counselling. RESULTS: At one year, the usual care group's spit tobacco cessation rate was 11.4% (exact 95% confidence interval (CI) 6.1% to 19.1%), placebo patch 25.0% (95% CI 16.9% to 34.7%), and the active patch 17.3% (95% CI 10.4% to 26.3%). When both patch groups were combined, the cessation rate was 21.2% (95% CI 15.7% to 27.6%). The cessation rates for active and placebo patch were not significantly different (exact two sided p = 0.22), while the combined patch groups had a significantly greater cessation rate than usual care (exact two sided p = 0.04). CONCLUSIONS: The behavioural intervention proved to be about twice as successful as previous interventions, but the nicotine patch offered no improvement in cessation rates. The behavioural intervention is based on publicly available materials and can be easily adapted for widespread use, particularly in high schools.

Comparison of MRI pulse sequences in defining prostate volume after permanent implantation.

PURPOSE: To determine the relative value of three MRI pulse sequences in defining the prostate volume after permanent implantation. METHODS AND MATERIALS: A total of 45 patients who received a permanent 125I implant were studied. Two weeks after implantation, an axial CT scan (2 mm thickness) and T1-weighted, T1-weighted fat saturation, and T2-weighted axial MRI (3-mm) studies were obtained. The prostate volumes were compared with the initial ultrasound planning volumes, and subsequently the CT, T1-weighted, and T1-weighted fat saturation MRI volumes were compared with the T2-weighted volumes. Discrepancies in volume were evaluated by visual inspection of the registered axial images and the registration of axial volumes on the sagittal T2-weighted volumes. In a limited set of patients, pre- and postimplant CT and T2-weighted MRI studies were available for comparison to determine whether prostate volume changes after implant were dependent on the imaging modality. RESULTS: T1-weighted and T1-weighted fat saturation MRI and CT prostate volumes were consistently larger than the T2-weighted MRI prostate volumes, with a volume on average 1.33 (SD 0.24) times the T2-weighted volume. This discrepancy was due to the superiority of T2-weighted MRI for prostate definition at the following critical interfaces: membranous urethra, apex, and anterior base-bladder and posterior base-seminal vesicle interfaces. The differences in prostate definition in the anterior base region suggest that the commonly reported underdose may be due to overestimation of the prostate in this region by CT. The consistent difference in volumes suggests that the degree of swelling observed after implantation is in part a function of the imaging modality. In patients with pre- and postimplant CT and T2-weighted MRI images, swelling on the T2-weighted images was 1.1 times baseline and on CT was 1.3 times baseline, confirming the imaging modality dependence of prostate swelling. CONCLUSION: Postimplant T2-weighted MRI images provided superior prostate definition in all critical regions of the prostate compared with CT and the other MRI sequences tested. In addition to defining an optimal technique, these findings call two prior observations into question. Under dosing at the anterior base region may be overestimated because of poor definition of the prostate-bladder muscle interface. The swelling observed after implantation was lower on T2-weighted images as well, suggesting that a fraction of postimplant swelling is a function of the imaging modality. These findings have implications for preimplant planning and postimplant evaluation. As implant planning techniques become more conformal, and registration methods become more efficient, T2-weighted MRI after implantation will improve the accuracy of postimplant dosimetry.

Intralesional injection of mumps or Candida skin test antigens: a novel immunotherapy for warts.

BACKGROUND: Warts are common and induce physical and emotional discomfort. Numerous therapies exist, yet none is optimal. Despite theoretical advantages, immunotherapeutic modalities are often neglected as first-line wart therapies. OBJECTIVE: To compare treatment with intralesional skin test antigen injection of 1 wart vs cryotherapy of all warts. DESIGN: Pilot study. SETTING: University dermatology outpatient clinic. PATIENTS: A total of 115 consecutive patients with at least 1 nongenital wart. INTERVENTIONS: Patients with warts were tested for immunity to mumps and Candida using commercial antigens. Nonresponders received cryotherapy and immune individuals received cryotherapy or intralesional injection of 1 antiserum. RESULTS: Thirty-four (30%) of the 115 patients did not respond to the test injections and 81 (70%) had detectable immunity. Of the immune group, 26 (32%) received cryotherapy, 45 (56%) received intralesional mumps antiserum, and 10 (12%) received intralesional Candida antiserum. Of the anergic patients, 28 (82%) were treated with cryotherapy; 6 (18%) refused cryotherapy. Of the 39 patients who were treated with immunotherapy and completed the protocol, 29 (74%) had complete clearing of the treated wart. Fourteen (78%) of 18 patients with complete resolution of their immunotherapy-treated wart also had resolution of untreated, distant warts. CONCLUSIONS: Intralesional injection of mumps or Candida antigens into warts of immune individuals represents effective treatment. Observation of clearing of anatomically distinct and distant warts suggests acquisition of human papillomavirus-directed immunity in some patients. We conclude that this novel approach to immunotherapy may serve as first-line treatment in immune individuals with multiple or large warts and as second-line treatment in immune patients for whom cryotherapy fails.

Attenuation of the self-renewal of transit-amplifying osteoblast progenitors in the murine bone marrow by 17 beta-estradiol.

In agreement with evidence that estrogens slow the rate of bone remodeling by suppressing the production of both osteoclasts and osteoblasts, loss of estrogens leads to an increase in the number of osteoclast as well as early osteoblast progenitors (CFU-osteoblasts; CFU-OBs) in the murine bone marrow. Here we show that CFU-OBs are early transit-amplifying progenitors, i.e., dividing cells capable of limited self-renewal, and that 17 beta-estradiol acts in vivo and in vitro to attenuate their self-renewal by approximately 50%. Consistent with a direct receptor-mediated action of estrogens on early mesenchymal cell progenitors, anti-estrogen receptor-alpha (anti-ER alpha) Ab's stain a small number of marrow cells that exhibit characteristics of primitive undifferentiated cells, including a high nucleus/cytoplasm ratio and lack of lineage-specific biochemical markers; the effect of 17 beta-estradiol on CFU-OB self-renewal is absent in mice lacking ER alpha. Because both osteoblasts and the stromal/osteoblastic cells that are required for osteoclast development are derived from CFU-OBs, suppression of the self-renewal of this common progenitor may represent a key mechanism of the anti-remodeling effects of estrogens.

Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity.

The relationship of the classical receptors and their transcriptional activity to nongenotropic effects of steroid hormones is unknown. We demonstrate herein a novel paradigm of sex steroid action on osteoblasts, osteocytes, embryonic fibroblasts, and HeLa cells involving activation of a Src/Shc/ERK signaling pathway and attenuating apoptosis. This action is mediated by the ligand binding domain and eliminated by nuclear targeting of the receptor protein; ERalpha, ERbeta, or AR can transmit it with similar efficiency irrespective of whether the ligand is an estrogen or an androgen. This antiapoptotic action can be dissociated from the transcriptional activity of the receptor with synthetic ligands, providing proof of principle for the development of function-specific-as opposed to tissue-selective-and gender-neutral pharmacotherapeutics.

Recruitment experience in the first phase of the African American Hereditary Prostate Cancer (AAHPC) study.

The African American Hereditary Prostate Cancer (AAHPC) Study is an ongoing multicenter genetic linkage study organized by Howard University and the National Human Genome Research Institute (NHGRI), with support from the Office for Research on Minority Health and the National Cancer Institute. The goals of the study are to: (i) look for evidence of involvement of chromosome 1q24-25 (HPC1) in African American men with hereditary prostate cancer (HPC) and (ii) conduct a genome-wide search for other loci associated with HPC in African American men. To accomplish these goals, a network has been established including Howard University, the NHGRI, and six Collaborative Recruitment Centers (CRCs). The CRCs are responsible for the identification and enrollment of 100 African American families. To date, 43 families have been enrolled. Recruitment strategies have included mass media campaigns, physician referrals, community health-fairs/prostate cancer screenings, support groups, tumor registries, as well as visits to churches, barber shops, and universities. By far, the most productive recruitment mechanisms have been physician referrals and tumor registries, yielding a total of 35 (81%) families. Approximately 41% (n = 3400) of probands initially contacted by phone or mail expressed interest in participating; the families of 2% of these met the eligibility criteria, and 75% of those families have been enrolled in the study, indicating a 0.5% recruitment yield (ratio of participants to contacts). As the first large-scale genetic linkage study of African Americans, on a common disease, the challenges and successes of the recruitment process for the AAHPC Study should serve to inform future efforts to involve this population in similar studies.

Oral cefixime is similar to continued intravenous antibiotics in the empirical treatment of febrile neutropenic children with cancer.

Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization, but the safety of this approach has not been adequately studied in children. We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation. Two hundred episodes of febrile neutropenia were studied (156 patients), and 100 episodes were randomized to receive each treatment. Failure to respond to therapy was defined by documented or suspected bacterial infection, recurrent fever, or discontinuation of assigned therapy for any reason before neutropenia resolved. Rates of treatment failure were similar in the oral cefixime group (28%) and in the iv antibiotic group (27%; P=1.0). Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children, a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment.

Intracranial resistive index (RI) values in normal term infants during the first day of life.

PURPOSE: The purpose of this study was to determine normal resistive index (RI) values for term neonates during the first day of life as part of an ongoing prospective study of RI values in term infants with perinatal asphyxia. MATERIALS AND METHODS: Forty normal term neonates underwent cranial sonography and Doppler during the first 24 h after birth. Transfontanelle Doppler was performed of the internal carotid, anterior cerebral, and middle cerebral arteries bilaterally. In addition, transtemporal Doppler was performed of the middle cerebral arteries bilaterally. Mean and median RI values were calculated in all vessels interrogated. The transfontanelle and transtemporal middle cerebral artery measurements were compared using paired t-tests. RESULTS: The overall mean RI of all interrogated vessels was 0.726 with a standard deviation of 0.057. The mean RI value in the middle cerebral arteries was not significantly different with the two different measurement techniques. CONCLUSION: Normal intracranial RI values for a term infant in the first day of life were calculated for comparison with RI values in term infants with perinatal asphyxia.

Relationship of pediatric overall performance category and pediatric cerebral performance category scores at pediatric intensive care unit discharge with outcome measures collected at hospital discharge and 1- and 6-month follow-up assessments.

OBJECTIVE: Given the current focus on outcomes, there is a crucial need for easily utilized measures that can effectively quantify morbidity or disability after a child's critical illness or injury. The purpose of this study is to significantly extend the research on two such promising measures: the Pediatric Overall Performance Category (POPC) and the Pediatric Cerebral Performance Category (PCPC). DESIGN: Cross-sectional analysis of a sample of pediatric intensive care unit (PICU) discharges and a prospective follow-up of this cohort of children. SETTING: Arkansas Children's Hospital. PATIENTS: Two hundred children (ranging in age from birth to 21 yrs) discharged from a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were collected at PICU discharge, hospital discharge, and 1- and 6-month follow-up assessments after hospital discharge. Measures utilized included the POPC (at PICU discharge), PCPC (at PICU discharge), Stanford-Binet Intelligence Scale, fourth edition (at hospital discharge), Bayley Scales of Infant Development, second edition (at hospital discharge), and the Vineland Adaptive Behavior Scales (at 1 and 6 months after discharge). Stanford-Binet Intelligence Quotients and Bayley Mental Developmental Index scores were significantly different across PCPC categories (p < .0001). Bayley Psychomotor Developmental Index scores and Vineland Adaptive Behavior Scales scores varied significantly across POPC categories (p < .0001). The test for linear trend was also significant for each of the comparisons. CONCLUSIONS: The results of this study offer additional support for the use of the PCPC and POPC. These brief and easily completed measures can provide useful information regarding probable outcomes for pediatric intensive care patients when more extensive psychometric testing is not feasible or desirable.

Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities.

High-dose therapy (HDT) has increased complete remission (CR) rates and survival in multiple myeloma (MM). We now report on continuous CR (CCR) and associated prognostic factors in 1000 consecutive patients receiving melphalan-based tandem HDT. Five-year CCR was 52% among 112 CR patients without chromosome 13 (triangle up13) abnormalities and with beta-2-microglobulin

Prostate position late in the course of external beam therapy: patterns and predictors.

PURPOSE: To examine prostate and seminal vesicles position late in the course of radiation therapy and to determine the effect and predictive value of the bladder and rectum on prostate and seminal vesicles positioning. METHODS AND MATERIALS: Twenty-four patients with localized prostate cancer underwent a computerized tomography scan (CT1) before the start of radiation therapy. After 4-5 weeks of radiation therapy, a second CT scan (CT2) was obtained. All patients were scanned in the supine treatment position with instructions to maintain a full bladder. The prostate, seminal vesicles, bladder, and rectum were contoured. CT2 was aligned via fixed bony anatomy to CT1. The geometrical center and volume of each structure were obtained and directly compared. RESULTS: The prostate shifted along a diagonal axis extending from an anterior-superior position to a posterior-inferior position. The dominant shift was to a more posterior-inferior position. On average, bladder and rectal volumes decreased to 51% (+/-29%) and 82% (+/-45%) of their pretreatment values, respectively. Multiple regression analysis (MRA) revealed that bladder movement and volume change and upper rectum movement were independently associated with prostate motion (p = 0.016, p = 0. 003, and p = 0.052 respectively). CONCLUSION: Patients are often instructed to maintain a full bladder during a course of external beam radiation therapy, in the hopes of decreasing bladder and small bowel toxicity. However, our study shows that large bladder volumes late in therapy are strongly associated with posterior prostate displacement. This prostate displacement may result in marginal miss.

Relationship of illness severity and length of stay to functional outcomes in the pediatric intensive care unit: a multi-institutional study.

OBJECTIVE: The purpose of this study was to establish relationships between illness severity, length of stay, and functional outcomes in the pediatric intensive care unit (PICU) by using multi-institutional data. We hypothesized that a positive relationship exists between functional outcome scores, severity of illness, and length of stay. DESIGN: The study used a prospective multicentered inception cohort design. SETTING: The study was conducted in 16 PICUs across the United States that were member institutions of the Pediatric Critical Care Study Group of the Society of Critical Care Medicine. PATIENTS: In total, 11,106 patients were assessed, representing all admissions to these intensive care units for 12 consecutive months. MEASUREMENTS: Functional outcomes were measured by the Pediatric Overall Performance Category (POPC) and Pediatric Cerebral Performance Category (PCPC) scales. Both scales were assessed at baseline and discharge from the PICU. Delta scores were formed by subtracting baseline scores from discharge scores. Other measurements included admission Pediatric Risk of Mortality scores, age, operative status, length of stay in the PICU, and diagnoses. Interrater reliability was assessed by using a set of ten standardized cases on two occasions 6 months apart. MAIN RESULTS: Baseline, discharge, and delta POPC and PCPC outcome scores were associated with length of stay in the PICU and with predicted risk of mortality (p < .01). Incorporation of baseline functional status in multivariate length of stay analyses improved measured fit. Mild baseline cerebral deficits in children were associated with 18% longer PICU stays after controlling for other patient and institutional characteristics. Moderate and severe baseline deficits for both the POPC and PCPC score predict increased length of stay of between 30% and 40%. On the standardized cases, interrater consensus was achieved on 82% of scores with agreement to within one neighboring class for 99.7% of scores. CONCLUSIONS: These data establish current relationships for the POPC and PCPC outcome scales based on multi-institutional data. The reported relationships can be used as reference values for evaluating clinical programs or for clinical outcomes research.