Cognitive behavioral therapy or graded exercise therapy compared with usual care for severe fatigue in patients with advanced cancer during treatment: a randomized controlled trial.

BACKGROUND: Cancer-related fatigue remains a prevalent and burdensome symptom experienced by patients with advanced cancer. Our aim was to assess the effects of cognitive behavioral therapy (CBT) or graded exercise therapy (GET) on fatigue in patients with advanced cancer during treatment with palliative intent. PATIENTS AND METHODS: A randomized controlled trial was conducted from 1 January 2013 to 1 September 2017. Adult patients with locally advanced or metastatic cancer who reported severe fatigue during treatment [Checklist Individual Strength, subscale fatigue severity (CIS-fatigue) ≥35] were accrued across nine centers in The Netherlands. Patients were randomly assigned to either 12 weeks of CBT or GET, or usual care (1 : 1: 1, computer-generated sequence). Primary outcome was CIS-fatigue at 14 weeks. Secondary outcomes included fatigue measured with the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ-C30), quality of life, emotional functioning, physical functioning, and functional impairments at baseline, 14, 18, and 26 weeks. RESULTS: Among 134 participants randomized, the mean age was 63 (standard deviation 9) years and 77 (57%) were women. Common diagnoses included: breast (41%), colorectal (28%), and prostate cancer (17%). A total of 126 participants completed assessment at 14 weeks. Compared with usual care, CBT significantly reduced fatigue [difference -7.2, 97.5% confidence interval (CI) -12.7 to -1.7; P = 0.003, d = 0.7], whereas GET did not (-4.7, 97.5% CI -10.2 to 0.9; P = 0.057, d = 0.4). CBT significantly reduced EORTC-QLQ-C30 fatigue (-13.1, 95% CI -22.1 to -4.0; P = 0.005) and improved quality of life (10.2, 95% CI 2.4 to 17.9; P = 0.011) and physical functioning (7.1, 95% CI 0.5 to 13.7; P = 0.036) compared with usual care. Improvement in emotional functioning and decrease in functional impairments failed to reach significance. GET did not improve secondary outcomes compared with usual care. CONCLUSIONS: Among advanced cancer patients with severe fatigue during treatment, a CBT intervention was more effective than usual care for reducing fatigue. Following GET, patients reported lower fatigue, but results were not significant, probably due to a smaller sample size and lower adherence than anticipated. TRIAL REGISTRATION: Netherlands National Trial Register, identifier: NTR3812.

A randomized controlled trial of web-based cognitive behavioral therapy for severely fatigued breast cancer survivors (CHANGE-study): study protocol.

BACKGROUND: About one third of breast cancer survivors suffer from persistent severe fatigue after completion of curative cancer treatment. Face-to-face cognitive behavioral therapy (F2F CBT), especially designed for fatigue in cancer survivors, was found effective in reducing fatigue. However, this intervention is intensive and treatment capacity is limited. To extend treatment options, a web-based version of CBT requiring less therapist time was developed. This intervention is aimed at changing fatigue-perpetuating cognitions and behaviors. The efficacy of web-based CBT will be examined in a multicenter randomized controlled trial. METHODS: In total, 132 severely fatigued breast cancer survivors will be recruited and randomized to either an intervention condition or care as usual (ratio 1:1). Participants will be assessed at baseline and 6 months thereafter. The intervention group will receive web-based CBT, consisting of three F2F sessions and maximally eight web-based modules over a period of 6 months. The care as usual group will be on a waiting list for regular F2F CBT. The total duration of the waiting list is 6 months. The primary outcome of the study is fatigue severity. Secondary outcomes are functional impairments, psychological distress and quality of life. DISCUSSION: If web-based CBT is effective, it will provide an additional treatment option for fatigue in breast cancer survivors. Web-based CBT is expected to be less time-consuming for therapists than regular F2F CBT, which would result in an increased treatment capacity. Moreover, the intervention would become more easily accessible for a larger number of patients, and patients can save travel time and costs. TRIAL REGISTRATION: Dutch Trial Registry--NTR4309.

Neuropsychiatric symptoms as risk factors for progression from CIND to dementia: the Cache County Study.

OBJECTIVES: To examine the association of neuropsychiatric symptom (NPS) severity with risk of transition to all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD). DESIGN: Survival analysis of time to dementia, AD, or VaD onset. SETTING: Population-based study. PARTICIPANTS: 230 participants diagnosed with cognitive impairment, no dementia (CIND) from the Cache County Study of Memory Health and Aging were followed for a mean of 3.3 years. MEASUREMENTS: The Neuropsychiatric Inventory (NPI) was used to quantify the presence, frequency, and severity of NPS. Chi-squared statistics, t-tests, and Cox proportional hazard ratios were used to assess associations. RESULTS: The conversion rate from CIND to all-cause dementia was 12% per year, with risk factors including an APOE ε4 allele, lower Mini-Mental State Examination, lower 3MS, and higher CDR sum-of-boxes. The presence of at least one NPS was a risk factor for all-cause dementia, as was the presence of NPS with mild severity. Nighttime behaviors were a risk factor for all-cause dementia and of AD, whereas hallucinations were a risk factor for VaD. CONCLUSIONS: These data confirm that NPS are risk factors for conversion from CIND to dementia. Of special interest is that even NPS of mild severity are a risk for all-cause dementia or AD.

A new, simple and objective prognostic score for phase I cancer patients.

AIM: To ensure safety and optimise efficacy, careful patient selection for participation in oncologic phase I trials is warranted. Therefore, we did a validation study on existing phase I prognostic scores, and subsequently aimed to make an even more simple prognostic score. PATIENTS AND METHODS: We retrospectively analysed characteristics and clinical outcome of 122 patients who participated in eight different phase I studies in our centre. A literature search was performed for existing prognostic scores which were validated in our dataset. Additionally, a simple prognostic score able to predict overall survival (OS), progression free survival (PFS), 90-d mortality and duration of participation was developed. RESULTS: In our population the median OS was 31 (range 4-241) weeks, median PFS was 10 (range 3-119) weeks. Thirteen patients (11%) died within 90-d and median participation duration was 11 (range 1-119) weeks. Two out of five existing prognostic scores could be validated in this dataset for OS. Based on multivariate analyses a new, objective and simple score, consisting of LDH, sodium and haemoglobin, was tested. High score (2-3 points) compared to low score (0-1) significantly predicted OS (HR 1.878, p = 0.003), PFS (HR 1.156, p = 0.038), participation duration (HR 1.858, p = 0.004) and 90-d mortality (OR 4.200, p = 0.022). CONCLUSION: We propose a new prognostic model, using LDH, sodium and haemoglobin, helpful to predict OS, PFS, participation duration and 90-d mortality. Larger multicentre studies are needed to validate this score.

Severe fatigue and related factors in cancer patients before the initiation of treatment.

It is generally known that fatigue is a common symptom during cancer treatment, and in cancer survivors. However, fatigue was never studied after diagnosis, before cancer treatment was initiated. This study investigated the prevalence of severe fatigue, and related factors, in cancer patients before the initiation of treatment. One hundred and seventy-nine patients with various malignancies were assessed before start of treatment with curative intention, including the Checklist Individual Strength, Sickness Impact Profile, Beck Depression Inventory Primary Care, Symptom Checklist-90, and six Numeric Rating Scales to measure fatigue, pain and physical activity. To test which factors contributed to severe fatigue a logistic regression analysis was performed. In total 23.5% patients were severely fatigued, varying between diagnoses; prostate cancer (14.3%), breast cancer (20.3%), and gastrointestinal cancer (28.1%). Currently lower physical activity (P=0.013), more depressive mood (P=0.014), impaired sleep and rest during the day and night (P=0.045), and fatigue 1 year before diagnosis (P=0.005) contributed to severe fatigue. Relatively large numbers of cancer patients already experience severe fatigue before initiation of treatment, varying between 14-28%. The factors that contributed to severe fatigue at this stage were physical activity, depressive mood, impaired sleep and rest, and fatigue 1 year before diagnosis.

Phase I and pharmacologic study of oral ZD9331, a novel nonpolyglutamated thymidylate synthase inhibitor, in adult patients with solid tumors.

PURPOSE: To assess the toxicity profile and dose-limiting toxicities (DLTs), to determine the maximum-tolerated dose, and to study the pharmacokinetics of ZD9331 when administered orally to patients with advanced solid tumors. PATIENTS AND METHODS: Patients were treated with oral ZD9331 given once daily (od) or twice daily (bid) for 5, 7, or 10 days; cycles were repeated every 21 days at doses ranging from 2.5 to 40 mg. For pharmacokinetic analysis, plasma sampling was performed during the first course and assayed using a validated liquid chromatographic-tandem mass spectrometry assay. Plasma levels of 2'-deoxyuridine were measured as a surrogate marker for TS inhibition. RESULTS: Forty-two patients received a total of 166 courses. The DLTs were myelosuppression and skin rash. Dose escalation of oral ZD9331 from 2.5 to 40 mg, as a single daily dose, resulted in a less than proportional increase in the plasma area under the concentration-time curve of ZD9331. The plasma drug exposure per cycle for the schedules 20 mg od for 5 days, 10 mg od for 10 days, and 10 mg bid for 5 days, all resulting in a total dose per cycle of 100 mg, were comparable. One partial response was noted in a patient with gastric cancer. CONCLUSION: DLTs in this phase I study of oral ZD9331 were myelosuppression and skin toxicity. The recommended dose for phase II studies of oral ZD9331 is 20 mg od for 5 consecutive days, every 3 weeks.

Respiratory symptoms at age 8 years in a cohort of very low birth weight children.

The childhood respiratory consequences of very low birth weight (birth weight < or =1,500 g) are incompletely understood, especially since the introduction of recent changes in neonatal care. To assess prevalence, trends, and risk factors for respiratory symptoms, the authors followed to age 8 years a cohort of 384 very low birth weight children from six regional neonatal intensive care units in Wisconsin and Iowa who were born between August 1, 1988, and June 30, 1991. A control group of 154 Wisconsin schoolchildren was also assembled. Respiratory symptoms in the past 12 months and history of asthma ("asthma ever") were reported by parents on a questionnaire used in the International Study of Asthma and Allergies in Childhood (ISAAC). Control group prevalence resembled ISAAC prevalence worldwide and in Canada, but respiratory symptoms were twice as common among very low birth weight children. With advent of the availability of pulmonary surfactants, the prevalence of wheezing at age 8 decreased from 50% to 16% (p = 0.002) among children with bronchopulmonary dysplasia, but it increased from 14% to 38% among those with milder neonatal respiratory disease. Bronchopulmonary dysplasia, family history of asthma, smoking in the household, and patent ductus arteriosus were predictive of wheezing in the previous 12 months. Antenatal steroid therapy had a borderline-significant protective association with wheezing (odds ratio = 0.56, 95% confidence interval: 0.29, 1.1). There were interaction effects between several of the predictors.

Prostate cancer: simplicity to complexity.

Prostate cancer is a complex disease to which a multitude of genetic and environmental factors contribute. Two new studies offer insights as to how the disease may arise and progress. The first describes mapping and cloning of a new candidate gene, ELAC2, whereas the second demonstrates how cooperation between Cdkn1b and Pten contribute to suppression of prostate tumors.

Wisconsin cystic fibrosis chest radiograph scoring system: validation and standardization for application to longitudinal studies.

This study was designed to achieve a final modeling, validation, and standardization plan for the Wisconsin cystic fibrosis (CF) chest radiographic scoring system. Sixty chest radiographs were selected to reflect a range of severity of lung pathology in children with CF. Seven experienced volunteer raters (three radiologists and four pediatric pulmonologists) from five institutions were recruited to evaluate and score the films. Analysis of scores revealed that the subcomponents of the Wisconsin system showed considerable variation from rater to rater, but reliability assessment indicated satisfactory Cronbach's alpha coefficients (0.83-0.90) among the seven raters. It was found that an additive method of total score computation is significantly more reliable (P < 0.05) than either the original multiplicative model or the traditional Brasfield scoring system. Comparison of radiologists and pulmonologists revealed a marked, systematic difference in scoring with the former group being more conservative in interpretation of abnormalities than the pulmonologists, and some of the raters showing very limited sensitivity. Quantitative chest radiology applied to children with cystic fibrosis studied long-term in longitudinal research projects requires the careful use of sensitive scoring methods and careful selection and training of multiple raters. This is particularly important since pulmonologists and radiologists can differ systematically in interpreting/scoring abnormalities.

Associations between family history of asthma, bronchopulmonary dysplasia, and childhood asthma in very low birth weight children.

Very low birth weight (VLBW) infants are at risk for childhood wheezing and asthma, as are children with a family history of asthma. Family history of asthma may also be associated with premature labor and, among VLBW infants, with bronchopulmonary dysplasia (BPD) and chronic lung disease (CLD) of prematurity. This study targeted all neonates with birth weight <1,501 g who were admitted to seven perinatal centers in Wisconsin and Iowa between August 1, 1988 and June 30, 1991. Comprehensive information was collected for 723 of the 1,007 30-day survivors, and for 106 full-term controls. A representative subgroup of 257 VLBW children was contacted at age 5 years to ascertain bronchodilator and/or steroid use and diagnosis of asthma. Some evidence of an association between family history of asthma and premature birth was found, but it was not associated with neonatal BPD/CLD or BPD/CLD severity. Among BPD/CLD indicators, radiographic evidence of BPD at age 25-35 days was most strongly associated with bronchodilator use up to age 2 years (odds ratio (OR) = 10.1, 95% confidence interval (CI) 4.07-25.2) and with asthma between ages 2 years and 5 years (OR = 4.83, 95% CI 2.18-10.7). Among children without radiographic evidence of BPD, family history of asthma was associated with childhood asthma and bronchodilator use.

Evaluation of criteria for chronic lung disease in surviving very low birth weight infants. Newborn Lung Project.

Criteria in common use for the diagnosis of chronic lung disease of prematurity or bronchopulmonary dysplasia in the neonatal period have not been sufficiently compared and validated against indicators of later respiratory complications. In this study of all 680 infants < or = 1500 gm birth weight admitted to six perinatal centers August 1, 1988, to July 31, 1990, 524 were alive and had no major congenital anomalies at 5 years old. Of 419 who had given permission to release their names and addresses, 272 were located and participated in a follow-up study. The following diagnostic criteria for bronchopulmonary dysplasia and chronic lung disease of prematurity were used during the initial hospitalization: (1) use of supplemental oxygen on day 30 of life, (2) a comprehensive bronchopulmonary dysplasia severity score applied at 25 to 35 days of life developed by a clinician panel to adjust for practice variation in ventilatory support and blood gases, (3) use of supplemental oxygen on day 30 of life with radiographic evidence consistent with bronchopulmonary dysplasia between days 25 and 35 of life, (4) radiographic evidence consistent with bronchopulmonary dysplasia alone, and (5) use of supplemental oxygen at 36 weeks' postconceptional age. These criteria were assessed against use of bronchodilators or steroids during the first 2 years of life, diagnosis of asthma, and hospitalizations for respiratory causes up to age 5. Although all criteria were significantly associated with all the outcomes, radiographic evidence was most predictive. These results indicate that, during a period when 21% of neonates were exposed to antenatal steroids, 24% received surfactant and 9% received postnatal corticosteroids, radiographic evidence was more predictive of long-term respiratory outcome than other commonly used criteria.

Meter-dosed, inhaled beclomethasone attenuates bronchoalveolar oxyradical inflammation in premature infants at risk for bronchopulmonary dysplasia.

The object of this study was to examine the hypothesis that meter-dosed, inhaled beclomethasone administered to premature infants beginning at birth in a tapering dosage schedule over the first 12 days of life attenuates bronchoalveolar lining fluid oxyradical inflammation concomitant with modulation of bronchopulmonary dysplasia. The design of this study was an unblinded, uncontrolled phase I, pilot investigation of inhaled beclomethasone primarily examining safety and administration. The setting was a tertiary care neonatal intensive care unit. Intubated, premature infants were studied longitudinally to 36 weeks corrected gestational age. Meter-dosed, inhaled beclomethasone was administered in a tapering dosage schedule over the first 12 days of life. Endotracheal tube aspirates were collected on Days 2, 4, and 6 of life and assayed for various markers of bronchoalveolar lining fluid oxyradical stress. Infants were also assessed with regards to a number of relevant clinical variables and presence or absence of bronchopulmonary dysplasia at 36 weeks corrected gestational age. Although no differences in clinical outcome were apparent in comparing nine control infants with nine beclomethasone-treated infants, bronchoalveolar lining fluid from control infants exhibited evidence of apparent phospholipid peroxidation (enhanced polyunsaturated fatty acid consumption) on Day 2 of life compared to beclomethasone-treated infants. Significant differences were noted for percent arachidonic acid, total polyunsaturated fatty acids and ratio of polyunsaturated fatty acids, to saturated fatty acids. The ratio of monohydroxyl linolenic acid to native linoleic acid (a more specific marker of lipid peroxidation) as well as myeloperoxidase activity (a marker of neutrophil oxyradical stress) tended to be higher in the control group but did not achieve statistical significance for this small subject number study. No adverse reactions related to meter-dosed, inhaled beclomethasone were noted in the treatment group; most specifically no evidence of hypothalamic-pituitary-adrenal axis suppression was noted in either control or beclomethasone-treated infants. Meter-dosed, inhaled beclomethasone in the dosage schedule utilized was safe and appeared to moderate bronchoalveolar lining fluid phospholipid peroxidation. Small numbers of infants entered into the present investigation preclude comments on clinical efficacy because of the likelihood of a statistical type 2 error. However, additional investigations of inhaled beclomethasone initiated at birth in premature infants at risk for bronchopulmonary dysplasia, enrolling larger number of subjects and perhaps a higher dosage of beclomethasone, are warranted.

The relation of maternal complications to outcomes in very low birthweight infants in an era of changing neonatal care.

We examine the relation of key neonatal outcomes to pregnancy complications and to the use of antenatal steroids and investigate whether there is evidence of recent change in this relation. Complete information on pregnancy and neonatal course was available for 749 out of 949 singleton births without major congenital anomalies below 1501 g admitted to seven regional neonatal intensive care units between August 1, 1988 and June 30, 1991. Mortality was highest in infants born after labor with spontaneous rupture of fetal membranes of less than 24 hours duration (odds ratio [OR] = 1.6, 95% confidence interval [1.0, 2.6]). Spontaneous rupture of membranes of over 24 hours duration was associated with decreased risk of respiratory distress syndrome (OR = 0.42, [0.28, 0.64]) and decreased risk of patent ductus arteriosus (OR = 43, [0.28, 0.66]). Pregnancy induced hypertension was associated with increased risk of respiratory distress syndrome in those born at less than 20 weeks' gestation (OR = 6.0, [2.0, 17]). Labor with or without rupture of membranes of short duration was associated with increased risk of intraventricular hemorrhage (OR = 1.9, [1.2, 2.5]). These associations were not different in early versus late time periods of the study. Antenatal steroids were associated with dramatically reduced risk of mortality (OR = 0.20, [0.09, 0.50] ), respiratory distress syndrome (OR = 0.52, [0.32, 0.85]), and intraventricular hemorrhage (OR = 0.37, [0.21-0.65]).

A population study. Mortality and morbidity after availability of surfactant therapy. Newborn Lung Project.

OBJECTIVE: To assess the impact of recent changes in neonatal intensive care on the mortality and morbidity of very-low-birth-weight neonates (< 1501 g). DESIGN: Prospective cohort study. SETTING: Six neonatal intensive care units in Wisconsin and Iowa. PARTICIPANTS: All very-low-birth-weight neonates who were admitted to the neonatal intensive care units the year before the availability of exogenous surfactant (n = 333), during the investigational new drug protocol for synthetic surfactant (Exosurf) (n = 347), and after the release of synthetic surfactant (n = 356) (designated as periods 1, 2, and 3, respectively). INTERVENTIONS: None. MAIN RESULTS: The percentage of neonates receiving exogenous surfactant in the three periods was 3%, 37%, and 56%, and the percentage receiving antenatal steroids was 12%, 17%, and 27% (P = .0001 for increase in both modalities). The percentage of neonates dying in the three periods was 23%, 14%, and 19% (P = .05 for downward trend). The percentage of neonates with intraventricular hemorrhage decreased in the subgroup weighing between 700 and 1350 g (35%, 28%, and 24%) (P = .04) and increased in the subgroup weighing below 700 g (8%, 41%, and 45%) (P = .03). The percentage of neonates with bronchopulmonary dysplasia increased from 21% to 36% between periods 1 and 2 (P = .003) and decreased to 27% (P = .04) in period 3. Antenatal steroid use was strongly associated with the decrease in intraventricular hemorrhage (odds ratio, 0.35) and mortality risk (odds ratio, 0.20). CONCLUSIONS: Several developments in care have contributed to changes in mortality risk, incidence of intraventricular hemorrhage, and the severity of respiratory disease in very-low-birth-weight infants.

A new radiographic scoring system for bronchopulmonary dysplasia. Newborn Lung Project.

OBJECTIVES: To develop a simple, clinically meaningful radiographic score for bronchopulmonary dysplasia (BPD). To investigate its reliability, validity, and usefulness and to compare it to the Edwards score. WORKING HYPOTHESIS: Our radiographic scoring of BPD is reliable, correlates with respiratory support, and provides a necessary standardization in comparing severity of respiratory disease between hospitals. STUDY DESIGN: Prospective cohort study. PATIENT SELECTION: The study included all neonates (n = 366) with birth weight below 1501 g admitted to 7 neonatal intensive care units, who had chest radiographs taken at age 25-35 days. METHODOLOGY: A simple radiographic scoring system was developed. Scores ranging from 0 to 6 were assigned based on standard radiographs and descriptors of degree of abnormality. All radiographs taken between days 25 and 35 of age (n = 1087) were graded by a radiologist and a neonatologist. Radiographs from a stratified random sample of 37 neonates (10%) were also scored by the method of Edwards (n = 128 radiographs). A respiratory support index was constructed for days 25-35 and correlated with the radiographic score. RESULTS: Between-reader correlation was r = 0.87 for our score and r = 0.88 for the Edwards score. The two scores correlated with each other at r = 0.94. The respiratory support index correlated with our radiographic score at r = 0.75 overall, and r = 0.56 to 0.88 within hospitals. Higher postnatal corticosteroid use was found at the hospitals with the lower correlations. CONCLUSIONS: Our radiographic scoring is reliable, valid, and gives results similar to the Edwards score. Radiographs play a standardizing role in assessing severity of BPD between hospitals.

Wisconsin cystic fibrosis chest radiograph scoring system.

A new clinical scoring system for patients with cystic fibrosis is needed because of recent advances in diagnosis and treatment which have changed the course of this disease. Chest radiograph scoring is the best objective measure of pulmonary disease for longitudinal studies beginning with infants; however, based on pilot studies, previous scoring systems are not sensitive enough in discriminating between degrees of mild lung disease. Therefore, a new radiographic scoring system was developed with the goal of achieving both sensitivity and reproducibility. This objective was pursued by applying multiattribute utility theory, using a panel of interpreters with expertise in cystic fibrosis radiology, and employing mathematical modeling techniques to weight the various components. The system was developed and validated in three phases including comparison to the Brasfield method of quantitative radiology. The data demonstrate that the new system can be applied reliably and conveniently to generate reproducible scores of pulmonary disease severity. Evaluation of the scores by four independent raters using chest radiographs from 61 patients at an average age of 8.37 years revealed good agreement with a .714 Kendall coefficient of concordance. Assessment of serial changes over time was performed using a group of 176 chest radiographs from 25 patients ranging from 4 weeks to 6 years old; this showed that the Wisconsin system generates score differences that are greater in magnitude with disease progression compared with the Brasfield method. Therefore, the new method is more sensitive to progression of mild disease and should be superior to prior radiographic scoring systems for evaluating therapies designed to modify the early course of disease. The Wisconsin system is designed to be useful in longitudinal clinical studies involving young children with cystic fibrosis and is capable to detecting progression from normality to mild lung disease.

The taste of desserts' packages.

This article reports an experiment on expressing the behavioural meaning of designed objects. Can a designer express the taste of a desert in the form of its packaging and can consumers match these forms when tasting the desserts? Analysis of responses of 12 adults indicates positive answers to these questions.

Multivariate assessment of traditional risk factors for chronic lung disease in very low birth weight neonates. The Newborn Lung Project.

All neonates (n = 581) with birth weights less than 1501 gm admitted to seven neonatal intensive care units in Wisconsin and Iowa were candidates for a study aimed at the multivariate assessment of risk factors for chronic lung disease while controlling for baseline severity of respiratory disease. Data from 361 neonates were analyzed for all risk factors except fluids; only neonates weighing less than 1200 gm were included (n = 220). Information on traditional risk factors for chronic lung disease was abstracted. A total of 110 (30%) of the analyzed neonates were oxygen dependent on day 30 of life. The following baseline factors were associated with increased risk of oxygen dependence in a joint multivariate model: lower birth weight (odds ratio 1.4/100 gm), higher baseline severity score (odds ratio 2.7/doubling at 32 weeks gestational age), lower gestational age (odds ratio 2.4/week at severity 0), Apgar score at 1 minute (odds ratio 1.6/2 points), male gender (odds ratio 1.9), and nonblack race (odds ratio 2.2). After adjustment for all baseline factors, patent ductus arteriosus, ventilator pressure at 96 hours, oxygen at 96 hours, and fluid intake were associated with oxygen dependence. Neonates with a low baseline severity score who remained oxygen dependent had a higher intake of fluid relative to output, whereas neonates with a higher baseline severity score had higher fluid intake and output. Lack of weight loss was associated with increased severity but not with oxygen dependence. The results of this study generally confirm the significance of previously reported risk factors for chronic lung disease in a multivariate setting but show that risk factors may not have the same impact in neonates with different baseline severity.