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Biomedical subjects

D L Phelps

Publications and source records attributed to D L Phelps.

At least 19 recordsLinked to original sources

Erythromycin for the prevention of chronic lung disease in intubated preterm infants at risk for, or colonized or infected with Ureaplasma urealyticum.

BACKGROUND: Controversy exists over whether or not Ureaplasma urealyticum colonization or infection of the respiratory tract contributes to the severity of chronic lung disease (CLD), a major cause of morbidity and mortality in preterm infants. OBJECTIVES: To evaluate the efficacy and safety of prophylactic or therapeutic erythromycin in preventing chronic lung disease in intubated preterm infants with unknown U. urealyticum status or proven positivity. SEARCH STRATEGY: Searches were done of MEDLINE (1966-June 9, 2003), EMBASE (1980-May 5, 2003), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), previous reviews including cross-references, and abstracts of conference proceedings (Pediatric Academic Societies 2000-2003, American Thoracic Society 2001-2003). There were no language restrictions. Expert informants were contacted. SELECTION CRITERIA: Randomized or quasi-randomized studies comparing either prophylactic or therapeutic administration of oral or intravenous erythromycin (regardless of dose and duration) versus no treatment or placebo among intubated preterm infants <37 weeks and <2500 grams with either unknown U. urealyticum status or proven positivity by culture or polymerase chain reaction. DATA COLLECTION AND ANALYSIS: Data were extracted by all of the authors independently and differences were resolved by consensus. Treatment effects for categorical outcomes were expressed as relative risk, with 95% confidence intervals. MAIN RESULTS: Two small controlled studies, both involving intubated babies <30 weeks gestation, were eligible for inclusion. Lyon 1998 tested prophylactic erythromycin in babies whose U. urealyticum status was unknown at the time of initiation of treatment. Jonsson 1998 tested erythromycin in babies known to be culture positive for U. urealyticum. Neither trial showed a statistically significant effect of erythromycin on CLD, death or the combined outcome CLD or death. Because the two studies differed importantly in their design, the results were not combined in meta-analyses. No adverse effects of a 7-10 day course of erythromycin were reported in either study. REVIEWER'S CONCLUSIONS: Current evidence does not demonstrate a reduction in CLD/death when intubated preterm infants are treated with erythromycin prophylactically before U. urealyticum culture/PCR results are known or when Ureaplasma colonized, intubated preterm infants are treated with erythromycin. However, a true benefit could easily have been missed with the small sample sizes in the two eligible studies. The studies were greatly underpowered to detect uncommon adverse effects such as pyloric stenosis. Additional controlled trials are required to determine whether antibiotic therapy of Ureaplasma reduces CLD and/or death in intubated preterm infants.

Anti-Bacterial Agents↗

Does cryotherapy affect refractive error? Results from treated versus control eyes in the cryotherapy for retinopathy of prematurity trial.

PURPOSE: To evaluate the effect of cryotherapy on refractive error status between ages 3 months and 10 years in children with birth weights of less than 1251 g in whom severe retinopathy of prematurity (ROP) developed in one or both eyes during the neonatal period. DESIGN: Randomized clinical trial. PARTICIPANTS: Two hundred ninety-one children in whom severe ROP developed during the neonatal period. INTERVENTION: Cryotherapy for ROP. MAIN OUTCOME MEASURES: Cycloplegic Refraction METHODS: The children underwent repeated follow-up eye examinations, including cycloplegic retinoscopy, between 3 months and 10 years after term due date. Refractive error data from all eyes that were randomized to cryotherapy were compared with data from all eyes that were randomized to serve as controls. Refractive error data were also compared for a subset of children who had both a treated and a control eye that could be refracted. RESULTS: At all ages, the proportion of treated eyes that were unable to be refracted because of retinal detachment, media opacity, or pupillary miosis was approximately half the proportion of the control eyes that were unable to be refracted. When data from all eyes that could be refracted were considered, the distribution of refractive errors between fewer than 8 diopters (D) of myopia and more than 8 D of hyperopia was similar for treated and control eyes at all ages. The proportion of eyes with 8 D or more of myopia was much higher in treated than in control eyes at all ages after 3 months. In the subset of children who had a treated eye and a control eye that could be refracted, distributions of refractive errors in treated versus control eyes were similar at most ages. CONCLUSIONS: In both treated and control eyes, there was an increase in the prevalence of high myopia between 3 and 12 months of age. Between 12 months and 10 years of age, there was little change in distribution of refractive error in treated or control eyes. The higher prevalence of myopia of 8 D or more in treated eyes, as compared with control eyes, may be the result of cryotherapy's preservation of retinal structure in eyes that, in the absence of cryotherapy, would have progressed to retinal detachment.

Astigmatism↗

Do urinary levels of vascular endothelial growth factor predict proliferative retinopathy?

PURPOSE: Vascular endothelial growth factor (VEGF) is elevated in the vitreous of patients with proliferative retinopathies (PR). Angiogenic factors like VEGF are elevated in the urine of subjects with cancers, including those distant from the genitourinary tract. We hypothesized that local increases in VEGF in the vitreous would be reflected in the urine of subjects with PR. METHODS: Urine samples were collected from adults with absent, mild, or severe (requiring laser photocoagulation) PR. VEGF was measured by enzyme linked immunosorbent assay. RESULTS: Of 42 subjects, 16 had no PR and 26 had PR (8 mild, 18 severe). Thirty subjects had diabetes mellitus; 24 of these had PR. Subjects with PR were older than controls. Subjects with PR tended to have higher urinary VEGF (median 123 pg/ml Cr, range 3--1738) than controls without PR (median 93 pg/ml Cr, range 2--200) (p = 0.08). None of 16 controls, but 11/15 subjects with PR had >200 mg VEGF/mg Cr (p = 0.003), yielding high specificity (100%), but poor sensitivity (42%) of elevated urinary VEGF for PR. Urinary VEGF was also modestly correlated with urinary protein excretion (r(2 ) = 0.23). Correction of VEGF values for urinary protein abrogated any correlation with PR. CONCLUSIONS: Urinary levels of VEGF are associated with PR, but this relationship may be caused by concurrent renal diseases that result in proteinuria and/or renal VEGF production. The insensitivity of the association may preclude its use in screening to avoid eye examinations.

Diabetic Retinopathy↗

Using cluster analysis of alcohol use disorders to investigate 'diagnostic orphans': subjects with alcohol dependence symptoms but no diagnosis.

The purpose of this paper is to examine the characteristics of community subjects with one or two alcohol dependence symptoms who did not satisfy the criteria for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) alcohol dependence or abuse (sub-diagnostic group or diagnostic orphans). Variables not included in the DSM-IV alcohol abuse and dependence criteria are used to compare the different alcohol statuses. The results indicate that the sub-diagnostic group 'diagnostic orphans' formed a cluster distinct from that of the non-problem drinkers group, and appeared to be closer to those with alcohol abuse than to those with alcohol dependence. The diagnosis of DSM-IV alcohol dependence (with three, four, or five or more symptoms) appeared to be its own entity. The findings lend credence to the requirement of three symptoms (in any 12 months) for the diagnosis of alcohol dependence in DSM-IV. However, those with one or two symptoms of alcohol dependence should be considered along with alcohol abuse as an entity in future DSM classifications.

Adult↗

Early light reduction for preventing retinopathy of prematurity in very low birth weight infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To answer the question: "Among very low birth weight infants, what is the effect of reducing early environmental light exposure on the incidence of any "Acute ROP", or "Poor ROP Outcomes"? SEARCH STRATEGY: Searches were made of the Cochrane Neonatal Group Register of Controlled Trials, Medline, EMBASE, the Cochrane Library, previous reviews including cross references, abstracts, conference and symposia proceedings, and expert informants. The search terms used were [retrolental fibroplasia or retinopathy of prematurity] and [light or light/ae or lighting or lighting/ae or light/tu or lighting/st]. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that reduced light exposure to premature infants within the first 7 days following birth were considered for this review. DATA COLLECTION AND ANALYSIS: Data on clinical outcomes including any Acute ROP and Poor ROP Outcome were excerpted by both reviewers independently and consensus reached. Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group. MAIN RESULTS: Data from four recent randomized trials, and one much older quasi-randomized trial failed to show any reduction in Acute ROP, or Poor ROP Outcome with the reduction of light to premature infants' retinas. The number of infants studied to date allows 95% confidence that IF there were a true difference being missed, it would be smaller than 7 percentage points on a background of 54% of all infants under 2 kg developing ROP. REVIEWER'S CONCLUSIONS: Decreasing retinal light exposure in premature infants is very unlikely to reduce the incidence of ROP.

Humans↗

D-Penicillamine for preventing retinopathy of prematurity in preterm infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To answer the question: Among very low birth weight infants, what is the effect of prophylactic administration of d-penicillamine on the incidence of acute ROP or severe ROP, and side effects including death? SEARCH STRATEGY: Searches were made of multiple electronic databases, previous reviews including cross references, abstracts, conference/symposia proceedings, and expert informants. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that administered d-penicillamine to infants less than 2000g birth weight within the day following birth were considered relevant to this review. Additional case series were examined for potential side effects. DATA COLLECTION AND ANALYSIS: Data on clinical outcomes were excerpted by 3 reviewers independently, and consensus reached. Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group. MAIN RESULTS: Two randomized trials on the effects on ROP were identified. When combined, they showed a significantly lower incidence of acute ROP in the treated infants, relative risk of 0.09, 95% CI [0.01,0.71]. Severe stages of ROP could not be analyzed. There was no effect on death rates, relative risk 0.99 95% CI [0.70,1.39]. No side effects were reported, and follow up at one year revealed no significant differences in spasticity or developmental delay, although there were more rehospitalizations among the controls. In other reports of using d-penicillamine in over 140 infants for hyperbilirubinemia, skin rashes were reported in 2 infants and one had vomiting that may have been related. REVIEWER'S CONCLUSIONS: D-penicillamine is unlikely to affect survival, and may reduce the incidence of acute ROP among survivors. Studies to date justify further investigation of this drug in a broader population; careful attention to possible side effects is needed.

Chelating Agents↗

Peripheral retinal ablation for threshold retinopathy of prematurity in preterm infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: In premature infants with threshold retinopathy of prematurity (ROP) does peripheral retinal ablation, by any means, reduce the incidence of adverse ophthalmic outcome? SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included a search of the Cochrane Neonatal Group Register of Clinical Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts from pediatric and ophthalmologic meetings, letters and expert informants. Search terms included "Retinopathy of Prematurity" [MeSH Terms], "Retrolental Fibroplasia" [All Fields] and "Lightcoagulation" [All Fields] or "Cryosurgery" [All Fields]. In addition, a personal bibliographic database was used as a cross-reference. SELECTION CRITERIA: All trials in human premature infants with threshold ROP utilizing random or quasi random allocation to either peripheral retinal ablation of the avascular retina, by any means, or concurrent control group with independent outcome assessment were initially selected for review. Following methodologic review, only studies using random allocation were selected for data extraction. DATA COLLECTION AND ANALYSIS: Relevance and validity were assessed by the two authors and consensus reached. Each author extracted clinical outcomes from valid reports independently. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Two randomised trials were identified. Data from these studies show that peripheral retinal ablation reduces the risk of (1) early unfavorable retinal structure from 47. 9% to 28.1% (absolute risk reduction 19.8% [95% CI 27.9 - 11.8%]), (2) unfavorable retinal structure in early childhood from 44.3% to 26.3% (absolute risk reduction 18% [95% CI 27.0 - 9.1%]) and (3) unfavorable visual acuity in early childhood from 63% to 50.6% (absolute risk reduction 12.2% [95% CI 21.2 - 3.1]). In addition, visual fields in sighted eyes were slightly smaller in the treated (51.3 degrees +/- 11.8 degrees ) group as compared to the control (58.2 degrees +/- 14.5 degrees ) group. REVIEWER'S CONCLUSIONS: Peripheral retinal ablation reduces the incidence of adverse ophthalmic outcome in premature infants with threshold ROP. In sighted eyes, peripheral retinal ablation may reduce the size of the visual field. At this stage, long term outcomes remain unknown.

Cryosurgery↗

Substance dependence and other psychiatric disorders among drug dependent subjects: race and gender correlates.

Persons in drug treatment with drug dependence were interviewed with the NIMH Diagnostic Interview Schedule to ascertain DSM-III-R disorders. Lifetime prevalence rates were 64% for alcohol dependence, 44% for antisocial personality disorder (ASPD), 39% for phobic disorders, 24% for major depression, 12% for dysthymia, 10% for generalized anxiety disorder, 3% for panic disorder, 3% for mania, 3% for obsessive compulsive disorder, 2% for bulimia, 1% for schizophrenia, and 1% for anorexia. When stratified by race and age, significant main effects were seen, but there were no significant interactions except in "any non-substance disorder" and in the mean number of non-substance use disorders. Caucasians had a higher mean number of drug dependence disorders and higher overall rates of "any other" disorder than African-Americans, and Caucasians and males had higher mean numbers of non-substance use disorders than African-Americans and females, respectively. This was related to rates of alcohol, cannabis, and hallucinogen dependence, and ASPD rates that were higher among men than women and higher among Caucasian respondents than African-American for alcohol, cannabis, hallucinogen, opiate and sedative dependence, major depression, dysthymia, and generalized anxiety disorder. In contrast, women had higher rates than men of amphetamine dependence, phobic disorder, major depression, dysthymia, panic disorder, obsessive compulsive disorder, and mania. African-Americans had higher rates than Caucasians of amphetamine, cocaine, and phencyclidine dependence, but for no comorbid disorders were the rates higher among African-Americans than Caucasians. The differences according to gender in rates of disorders among substance dependent persons are consistent with the results of general population surveys, but the differences in rates according to race are in contrast to these same community surveys. Limitations in the utility of the concept of race as a valid category diminish the generalizability of the findings; however, one possible explanation is differential treatment seeking in African-American and Caucasian populations that would result in the differences seen.

Adult↗

Psychiatric disorders among drug dependent subjects: are they primary or secondary?

The relationship between substance use disorders and comorbid psychiatric conditions was investigated among 425 persons in drug treatment who met DSM-III-R criteria for drug dependence. Using the NIMH Diagnostic Interview Schedule to ascertain DSM-III-R psychiatric disorders among these drug dependent subjects, lifetime prevalence rates were 64% for alcohol abuse/dependence, 44% for antisocial personality disorder, 39% for phobic disorders, 24% for major depression, 12% for dysthymia, and 10% for generalized anxiety disorder. We found that antisocial personality disorder and phobias generally had onsets prior to the onset of drug dependence (that is, they were primary disorders). The majority of drug dependent persons with generalized anxiety disorder reported an onset after the onset of drug dependence (that is, they had secondary generalized anxiety). Alcohol dependence, depression, and dysthymia were divided nearly evenly between earlier (primary disorder) and later (secondary disorder). These results are consistent with the body of literature indicating the importance of antisocial syndromes in the etiology of substance abuse and the literature indicating the complex, varying nature of the relationship of psychiatric disorders to substance dependence. Finally, a precise nomenclature for "age of onset," "primary," and "secondary" was developed for this study that is critical to understanding these issues and is recommended for other studies.

Adult↗

Early dexamethasone-attempting to prevent chronic lung disease.

BACKGROUND: We previously demonstrated improved survival and early outcomes in a pilot trial of 2 doses of intravenous dexamethasone for infants with surfactant-treated respiratory distress syndrome. (1) A multicenter, randomized, double-blind trial was undertaken to confirm these results. METHODS: Infants <30 weeks' gestation were eligible if they had respiratory distress syndrome, required mechanical ventilation at 12 to 18 hours of age, and had received at least 1 dose of exogenous surfactant. Infants were excluded if sepsis or pneumonia was suspected or if congenital heart disease or chromosomal abnormalities were present. A total of 384 infants were enrolled-189 randomized to dexamethasone (.5mg/kg birth weight at 12-18 hours of age and a second dose 12 hours later) and 195 to an equal volume of saline placebo. RESULTS: No differences were found in the dexamethasone versus placebo groups, respectively, regarding the primary outcomes of survival (79% vs 83%), survival without oxygen at 36 weeks' corrected gestational age (CGA; both 59%), and survival without oxygen at 36 weeks' CGA and without late glucocorticoid therapy (46% vs 44%). No significant differences between the groups in estimates from Kaplan-Meier survival analyses were found for median days on oxygen (50 vs 56 days), ventilation (20 vs 27 days), days to regain birth weight (15.5 vs 14 days), or length of stay (LOS; 88 vs 89 days). Infants given early dexamethasone were less likely to receive later glucocorticoid therapy for bronchopulmonary dysplasia during their hospitalization (27% vs 35%). No clinically significant side effects were noted in the dexamethasone group, although there were transient elevations in blood glucose and blood pressure followed by a return to baseline by study day 10. Among infants who died (40 vs 33), there were no differences in the median days on oxygen, ventilation, nor LOS. However, in survivors (149 vs 162), the following were observed: median days on oxygen 37 versus 45 days, ventilation 14 versus 19 days, and LOS 79 versus 81 days, for the dexamethasone versus placebo groups, respectively. CONCLUSIONS: This dose of early intravenous dexamethasone did not reduce the requirement for oxygen at 36 weeks' CGA and survival was not improved. However, early dexamethasone reduced the use of later prolonged dexamethasone therapy, and among survivors, reduced the median days on oxygen and ventilation. We conclude that this course of early dexamethasone probably represents a near minimum dose for instituting a prophylactic regimen against bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗

Severity of neonatal retinopathy of prematurity is predictive of neurodevelopmental functional outcome at age 5.5 years. Behalf of the Cryotherapy for Retinopathy of Prematurity Cooperative Group.

OBJECTIVE: The purpose of this study was to assess the relation between neonatal retinopathy of prematurity (ROP) in very low birth weight infants and neurodevelopmental function at age 5.5 years. METHODS: Longitudinal follow-up of children occurred in 2 cohorts of the Multicenter Cryotherapy for Retinopathy of Prematurity Study. The extended natural history cohort followed 1199 survivors of <1251 g birth weight from 5 centers. The threshold randomized cohort (ThRz) followed 255 infants <1251 g from 23 centers who developed threshold ROP and who consented to cryotherapy to not more than 1 eye. At 5.5 years both cohorts had ophthalmic and acuity testing and neurodevelopmental functional status determined with the Functional Independence Measure for Children (WeeFIM). RESULTS: Evaluations were completed on 88.7% of the extended natural history cohort; 87% had globally normal functional skills (WeeFIM: >95). As ROP severity increased, rates of severe disability increased from 3.7% among those with no ROP, to 19.7% of those with threshold ROP. Multiple logistic regression analysis demonstrated that better functional status was associated with favorable visual acuity, favorable 2-year neurological score, absence of threshold ROP, having private health insurance, and black race. Evaluations were completed on 87.4% of the ThRz children. In each functional domain, the 134 children with favorable acuity in their better eye had fewer disabilities than did the 82 children with unfavorable acuity: self-care disability 25.4% versus 76.8%, continency disability 4.5% versus 50.0%, motor disability 5.2% versus 42.7%, and communicative-social cognitive disability 22.4% versus 65.9%, respectively. CONCLUSION: Severity of neonatal ROP seems to be a marker for functional disability at age 5. 5 years among very low birth weight survivors. High rates of functional limitations in multiple domains occur in children who had threshold ROP, particularly if they have unfavorable visual acuity.

Child, Preschool↗

Atypical chronic lung disease patterns in neonates.

OBJECTIVE: To determine, in the postsurfactant era, the incidence and clinical characteristics of infants with atypical versus traditionally defined bronchopulmonary dysplasia (BPD) among premature infants with birth weights <1251 g. DESIGN: Retrospective cohort study. SETTING: A single regional neonatal intensive care unit (level III/IV). PATIENTS: Two hundred thirty-two premature infants <1251 g at birth consecutively admitted during a 2-year period. MAIN OUTCOME MEASURE: Incidence of classic BPD and atypical chronic lung disease (CLD) (occurring without preceding respiratory distress or after recovery from respiratory distress). RESULTS: Among 177 infants <1251 g who survived to 28 days, 27 (15%) had atypical CLD and 61 (34.5%) had classic BPD. Atypical CLD infants were significantly heavier and more mature than classic BPD infants (mean birth weights, 922 +/- 152 g vs 854 +/- 173 g; and mean gestational age, 26.8 +/- 1.3 weeks vs 26.1 +/- 1.6 weeks). Median duration of ventilator support (31 days; range, 2 to 127 vs 42 days; range, 4-145 days) and oxygen therapy (30 days; range, 11 to 163 vs 48 days; range, 19-180 days) were shorter in atypical CLD infants than in classic BPD infants. CONCLUSION: Atypical CLD comprised 31% of total cases of CLD. Atypical CLD appears to be less severe than classic BPD. These data suggest that initial, acute lung injuries are not the sole antecedents of neonatal CLD.

Bronchopulmonary Dysplasia↗

School-age follow-up of prophylactic versus rescue surfactant trial: pulmonary, neurodevelopmental, and educational outcomes.

BACKGROUND: Exogenous surfactant replacement has improved survival and reduced pulmonary complications of prematurity. Improved early outcomes for infants of <30 weeks' gestation treated with a strategy of prophylactic versus rescue surfactant, if needed, were demonstrated in a multicenter, randomized trial conducted between 1985 and 1988. We reevaluated a subset of survivors from this trial to determine the pulmonary and neurodevelopmental outcomes at school age. METHODS: At 4.5 to 8 years of age, all survivors from one of the three centers were located, and 96% were evaluated. The original randomization included stratification by center and followed an intention-to-treat methodology in assessing the efficacy of prophylactic versus rescue treatment with surfactant. The follow-up test battery included a health-assessment questionnaire, spirometry, 88% saturation test, neurologic examination, and the McCarthy Scales of Children's Abilities (MSCA) and the Conners' Parent Rating Scale-48. Educational achievement was determined by school class placement and teachers' reports of achievement. RESULTS: Of the 192 children originally enrolled, 154 survived. Evaluations were performed on 148 of these infants. An abnormal pulmonary history was found in 45 (30%) of the children: 16 (22%) in the prophylactic group and 29 (39%) in the rescue group. Formal pulmonary function was evaluated in 81 children; 29 (78%) in the prophylactic group and 33 (75%) in the rescue group were considered abnormal. No significant differences were found between the two groups on either cognitive or motor subscales of the MSCA, the Conners' Parent Rating Scale-48, the neurologic examination, the education services received in school, or the teacher ratings of below-average academic performance. Intelligence scores measured on the MSCA were low-normal for both groups. Some level of educational assistance was being provided to 72 (49%) of the cohort studied, and both groups had below average educational performance and increased needs for educational assistance. CONCLUSIONS: Prophylactic surfactant administration to infants of <30 weeks' gestation was associated with fewer long-term clinical pulmonary complications than assignment to rescue administration. Formal pulmonary testing at school age did not reveal significant differences between treatment groups in those infants who could be tested. There also were no group differences found on neurologic, cognitive, behavioral, or educational assessments at school age.

Child↗