Biomedical subjects

Kathleen A Kennedy

Publications and source records attributed to Kathleen A Kennedy.

10 recordsLinked to original sources

PubMed2005

Inhaled nitric oxide for premature infants with severe respiratory failure.

BACKGROUND: Inhaled nitric oxide is a controversial treatment for premature infants with severe respiratory failure. We conducted a multicenter, randomized, blinded, controlled trial to determine whether inhaled nitric oxide reduced the rate of death or bronchopulmonary dysplasia in such infants. METHODS: We randomly assigned 420 neonates, born at less than 34 weeks of gestation, with a birth weight of 401 to 1500 g, and with respiratory failure more than four hours after treatment with surfactant to receive placebo (simulated flow) or inhaled nitric oxide (5 to 10 ppm). Infants with a response (an increase in the partial pressure of arterial oxygen of more than 10 mm Hg) were weaned according to protocol. Treatment with study gas was discontinued in infants who did not have a response. RESULTS: The rate of death or bronchopulmonary dysplasia was 80 percent in the nitric oxide group, as compared with 82 percent in the placebo group (relative risk, 0.97; 95 percent confidence interval, 0.86 to 1.06; P=0.52), and the rate of bronchopulmonary dysplasia was 60 percent versus 68 percent (relative risk, 0.90; 95 percent confidence interval, 0.75 to 1.08; P=0.26). There were no significant differences in the rates of severe intracranial hemorrhage or periventricular leukomalacia. Post hoc analyses suggest that rates of death and bronchopulmonary dysplasia are reduced for infants with a birth weight greater than 1000 g, whereas infants weighing 1000 g or less who are treated with inhaled nitric oxide have higher mortality and increased rates of severe intracranial hemorrhage. CONCLUSIONS: The use of inhaled nitric oxide in critically ill premature infants weighing less than 1500 g does not decrease the rates of death or bronchopulmonary dysplasia. Further trials are required to determine whether inhaled nitric oxide benefits infants with a birth weight of 1000 g or more.

Administration, Inhalation↗

PubMed2005

Vitamin A supplementation for extremely low birth weight infants: outcome at 18 to 22 months.

BACKGROUND: A National Institute of Child Health and Human Development Neonatal Research Network randomized trial showed that vitamin A supplementation reduced bronchopulmonary dysplasia (O2 at 36 weeks' postmenstrual age) or death in extremely low birth weight (ELBW) neonates (relative risk [RR]: 0.89). As with postnatal steroids or other interventions, it is important to ensure that there are no longer-term adverse effects that outweigh neonatal benefits. PRIMARY OBJECTIVE: To determine if vitamin A supplementation in ELBW infants during the first month after birth affects survival without neurodevelopmental impairment at a corrected age of 18 to 22 months. DESIGN/METHODS: Infants enrolled in the National Institute of Child Health and Human Development vitamin A trial were evaluated at 18 to 22 months by carefully standardized assessments: Bayley Mental Index (MDI) and Psychomotor Index (PDI), visual and hearing screens, and physical examination for cerebral palsy (CP). The medical history was also obtained. Neurodevelopmental impairment (NDI) was predefined as > or =1 of MDI <70, PDI <70, CP, blind in both eyes, or hearing aids in both ears. RESULTS: Of 807 enrolled infants, 133 died before and 16 died after discharge. Five hundred seventy-nine (88%) of the 658 remaining infants were followed up. The primary outcome of NDI or death could be determined for 687 of 807 randomized infants (85%). Baseline characteristics and predischarge and postdischarge mortality were comparable in both study groups. NDI or death by 18 to 22 months occurred in 190 of 345 (55%) infants in the vitamin A group and in 204 of 342 (60%) of the control group (RR: 0.94; 95% confidence interval: 0.80-1.07). RRs for low MDI, low PDI, and CP were also <1.0. We found no evidence that neonatal vitamin A supplementation reduces hospitalizations or pulmonary problems after discharge. CONCLUSION: Vitamin A supplementation for ELBW infants reduces bronchopulmonary dysplasia without increasing mortality or neurodevelopmental impairment at 18 to 22 months. However, this study was not powered to evaluate small magnitudes of change in long-term outcomes.

Bronchopulmonary Dysplasia↗

PubMed2005

Sterile water gastric drip in extremely low birthweight premature infants: a randomized trial.

This study was performed to test the hypothesis that sterile water gavage drip (SWGD) used in the fluid management of extremely low birthweight (ELBW) infants will decrease the incidence of hypernatremia. Secondary hypotheses included decreased hyperkalemia, hyperglycemia, and hyperbilirubinemia. Sixty ELBW infants were randomized before 36 hours of age to receive SWGD (up to 30 mL/kg/d) and intravenous fluid or conventional intravenous fluid management. SWGD was well tolerated in 89% of the infants. No difference was seen in the incidence of hypernatremia, hyperkalemia, hyperglycemia, or hyperbilirubinemia. A significant reduction in the incidence of treated patent ductus arteriosus (PDA) was noted in the study group (36% versus 69%; relative risk, 0.52; 95% confidence interval, 0.30 to 0.90; p = 0.02). SWGD may provide an alternative means of safely administering free water to the ELBW infant. The observed reduction in treated PDA requires further investigation.

Ductus Arteriosus, Patent↗

PubMed2004

Integration with the human genome of peptide sequences obtained by high-throughput mass spectrometry.

A crucial aim upon the completion of the human genome is the verification and functional annotation of all predicted genes and their protein products. Here we describe the mapping of peptides derived from accurate interpretations of protein tandem mass spectrometry (MS) data to eukaryotic genomes and the generation of an expandable resource for integration of data from many diverse proteomics experiments. Furthermore, we demonstrate that peptide identifications obtained from high-throughput proteomics can be integrated on a large scale with the human genome. This resource could serve as an expandable repository for MS-derived proteome information.

Amino Acid Sequence↗

PubMed2004

Evidence for multiple pathways in the assembly of the Escherichia coli maltose transport complex.

We used the maltose transport complex MalFGK2 of the Escherichia coli cytoplasmic membrane as a model for the study of the assembly of hetero-oligomeric membrane protein complexes. Analysis of other membrane protein complexes has led to a general model in which a unique, ordered pathway is followed from subunit monomers to a final oligomeric structure. In contrast, the studies reported here point to a fundamentally different mode for assembly of this transporter. Using co-immunoprecipitation and quantification of interacting partners, we found that all subunits of the maltose transport complex efficiently form heteromeric complexes in vivo. The pairwise complexes were stable over time, suggesting that they all represent assembly intermediates for the final MalFGK2 transporter. These results indicate that several paths can lead to assembly of this oligomer. We also characterized MalF and MalG mutants that caused reduced association between some or all of the subunits of the complex with this assay. The mutant analysis highlights some important motifs for subunit contacts and suggests that the promiscuous interactions between these Mal proteins contribute to the efficiency of complex assembly. The behaviors of the wild type and mutant proteins in the co-immunoprecipitations support a model of multiple assembly pathways for this complex.

ATP-Binding Cassette Transporters↗

PubMed2004

Early surfactant for neonates with mild to moderate respiratory distress syndrome: a multicenter, randomized trial.

OBJECTIVE: We studied the efficacy and safety of electively providing surfactant to preterm infants with mild to moderate respiratory distress syndrome (RDS) not requiring mechanical ventilation. STUDY DESIGN: A 5-center, randomized clinical trial was performed on 132 infants with RDS, birth weight >or=1250 grams, gestational age or=40% for >or=1 hour, and no immediate need for intubation. Infants were randomly assigned to intubation, surfactant (Survanta, Ross Laboratories, Columbus, Ohio) administration, and expedited extubation (n=65) or expectant management (n=67) with subsequent intubation and surfactant treatment as clinically indicated. The primary outcome was duration of mechanical ventilation. RESULTS: Infants in the surfactant group had a median duration of mechanical ventilation of 2.2 hours compared with 0.0 hours for control infants, since only 29 of 67 control infants required mechanical ventilation (P=.001). Surfactant-treated infants were less likely to require subsequent mechanical ventilation for worsening respiratory disease (26% vs 43%, relative risk=0.60; 95% CI, 0.37, 0.99). There were no differences in secondary outcomes (duration of nasal continuous positive airway pressure, oxygen therapy, hospital stay, or adverse outcomes). CONCLUSIONS: Routine elective intubation for administration of surfactant to preterm infants >or=1250 grams with mild to moderate RDS is not recommended.

Female↗

PubMed2003

Evaluating the evidence about therapies. What the clinician needs to know about statistics.

Study design is the most important determinant of whether the study conclusions are likely to be biased or misleading. Clinical practice should be based on the most rigorously designed studies to address a particular question. If a study is well designed and sufficiently powered to give an unbiased and precise estimate of treatment effect, the statistical analyses are usually straightforward and evaluating the statistical methods is not difficult. The statistical methods used in observational studies are more complex and much more difficult to evaluate, but study design (selection of subjects and controls, selection and measurement of confounders) is still a critical determinant of bias in the study results. When clinical practice is based on observational studies, extreme caution must be exercised in concluding that associations imply a causal relationship between the treatment or exposure and the outcome.

Biomedical Research↗

PubMed2003

Understanding and using diagnostic tests.

Every diagnostic test causes additional cost if not additional risk. The cost and risk are justified if the test result is likely to change what is done for patients. This includes a diagnostic test that does not alter therapy but provides important prognostic information for the parents. Whether the test result changes therapy depends on: the action threshold (the probability of disease at which the clinician offers the therapy or intervention because it would do more good than harm). the patient's pretest probability of disease. the test performance (measured by LRs, sensitivity, and specificity). For all tests there is an inverse relationship or trade-offbetween sensitivity and specificity. A good diagnostic test is one in which this trade-off is relatively small within the range of sensitivities and specificities that are clinically relevant. When diagnostic tests are used in low-risk subjects (as in screening tests), the performance of the test is critical because missing a significant number of cases is considered unacceptable and subjecting healthy individuals to the repercussions of false-positive test results is also problematic. The decision to introduce a screening program also depends on the availability and cost of screening and diagnostic tests, the potential for testing to cause harm, the prevalence and prognosis of the condition, the availability of effective treatment, and the importance of presymptomatic treatment.

Diagnostic Tests, Routine↗

PubMed2003

Risk factors predicting vasopressor use after patent ductus arteriosus ligation.

Ligation of the patent ductus arteriosus (PDA) is sometimes complicated by postoperative hypotension requiring vasopressor(s). It is unclear which infants are at risk for this complication. We conducted a retrospective and prospective cohort study to identify risk factors predicting vasopressor use after PDA ligation. Our patients were infants < 37 weeks of gestation who underwent PDA ligation. The primary outcome was the use of vasopressor(s) within 72 hours after PDA ligation, defined as beginning vasopressor(s) or increasing the dose of vasopressor(s). Thirty-two of 100 (32%) study infants required vasopressor(s) after PDA ligation. Infants who had lower birth weights, lower gestational ages, higher ventilator support, or whose mothers had received antenatal steroids had a higher risk of vasopressor use. Infants who required vasopressor(s) were at increased risk of dying before 36 weeks postmenstrual age. Lower birth weight, lower gestational age, and higher respiratory support define a high-risk subgroup of patients in whom the prophylactic administration of vasopressor(s) could be studied.

Cohort Studies↗

PubMed2003

A comparison of three vitamin A dosing regimens in extremely-low-birth-weight infants.

OBJECTIVE: Vitamin A supplementation reduces bronchopulmonary dysplasia (BPD)/death in extremely low birth weight neonates. It was hypothesized that compared with the standard regimen of 5000 IU 3 times per week for 4 weeks, (1) a higher dose (10,000 IU 3 x per week) would increase serum retinol and retinol binding protein (RBP) and lower relative dose responses (RDR), and (2) once-per-week dosing (15,000 IU once per week) would lead to equivalent levels, RBP, and RDR. STUDY DESIGN: Extremely low birth weight neonates (n = 120) receiving O(2)/mechanical ventilation at 24 hours were randomly assigned to (1) standard, (2) higher dose, or (3) once-per-week regimens. Measures of vitamin A deficiency were serum retinol <20 microg/dL, RBP <2.5 mg/dL, and/or RDR >10% on day 28. BPD was defined as O(2)/mechanical ventilation at 36 weeks' postmenstrual age. RESULTS: Groups were similar at enrollment (median gestational age, 25 weeks; birth weight, 689 g). Possible toxicity was seen in <5%. The higher dose regimen did not increase retinol or RBP, decrease RDR, or improve outcomes. Infants in the once-per-week regimen had lower retinol levels and higher RDR without an effect on outcomes. CONCLUSIONS: Compared with the standard regimen, once-per-week dosing worsened, and higher doses did not reduce, vitamin A deficiency. Therefore, the standard regimen is recommended.

Bronchopulmonary Dysplasia↗