Measuring practice preference variation for quality improvement in neonatal respiratory care.

OBJECTIVES: The authors sought to measure and compare practice preference variation in neonatal respiratory care within and between neonatal intensive care units (NICUs) using the Neonatology Survey of Interdisciplinary Groups in Healthcare Tool (NSIGHT). STUDY DESIGN: Eleven NICUs completed the NSIGHT between 2019 and 2021. Net preference was measured by mean response; agreement was ranked by standard distribution of response values. Heat maps showed comparisons between NICUs and disciplines. RESULTS: NICUs and individuals agreed most often on use of pressure support with mandatory ventilation and on use of non-invasive positive pressure ventilation for apnea. High preference variation surrounded decisions for invasive ventilation versus continuous positive airway pressure for extremely low birth weight infants. Preference difference was most frequent between neonatologists and nurses. CONCLUSIONS: Patterns of practice preference variation in neonatal respiratory care are specific to clinical scenario. Measuring preference variation may inform psychology of change and strengthen quality improvement efforts.

Measuring practice preference variation for quality improvement: development of the Neonatology Survey of Interdisciplinary Groups in Healthcare Tool (NSIGHT).

BACKGROUND: Understanding behavioural psychology and the human side of change are guiding principles for quality improvement (QI). Tools to measure these to guide improvement efforts are lacking. METHODS: We created a clinical vignette-based survey to measure provider preferences for respiratory care in the neonatal intensive care unit. Fourteen vignettes were included, each vignette offering two reasonable practice choices. Responses were based on a 5-point Likert scale, ranging from neutral to strong preference for either choice. The survey was completed by physicians, nurses, advanced practice providers and respiratory therapists in 2017 and again in 2019. Net preference was measured as the median value of responses, and agreement was measured as the SD of responses. Net preference and agreement were assessed for all responses, by discipline, and by year. RESULTS: Response rates were 51% of all staff in 2017 and 57% in 2019. Vignettes asking about non-invasive respiratory support showed more defined net preferences and higher agreement between years, coinciding with QI efforts and guideline implementation in this area during the interval time. Results on other areas of practice were consistent between years. Discipline comparisons showed nurses and physicians agreed the least often. Six response patterns were identified, ranging from net preference and high agreement to no net preference and low agreement. CONCLUSION: We propose this survey, called the Neonatology Survey of Interdisciplinary Groups in Healthcare Tool, is a novel method for measurement of hospital unit psychology and culture. Demonstrated improvement where QI efforts were focused and consistency in results in other areas support the validity of this tool. Measuring the human side of change may impact QI efforts.

Changes in Assessment of and Satisfaction With Discharge Preparation From the Neonatal Intensive Care Unit.

BACKGROUND: A successful transition from the neonatal intensive care unit (NICU) to home is aided by a comprehensive discharge planning program that keeps families involved and engaged with the discharge preparation process. PURPOSE: To compare the assessment of parental NICU discharge preparedness with parental satisfaction with the NICU discharge preparation. METHODS: Families were surveyed 4 to 6 weeks after NICU discharge, and those selecting "very prepared" were considered "satisfied" with their discharge preparation. On discharge day, families were considered "prepared" for discharge based on their overall level of preparedness and their nurse's rating of them on a discharge readiness assessment tool. RESULTS: In total, 1104 families (60%) reported being both "satisfied" and "prepared"; 293 families (16%) were "satisfied" but not "prepared"; 297 families (16%) were not "satisfied" but were "prepared"; and 134 families (7%) were neither "satisfied" nor "prepared." Compared with families that were both "satisfied" and "prepared," families that were neither "satisfied" nor "prepared" were more likely to be raising the infant alone, of Black race, and to have sicker infants. IMPLICATIONS FOR PRACTICE: Some families are at a higher risk and merit more consideration during NICU discharge planning. Assess the discharge readiness of all families prior to discharge. Those at an increased risk may benefit from more discharge education and training, specifically for single mothers, those with limited resources, or others considered at high risk.

Glucose concentrations in enterally fed preterm infants.

OBJECTIVES: Determine the prevalence of glucose concentrations below the Pediatric Endocrine Society (PES) term and late preterm-focused guideline target for mean glucose concentrations (≥70 mg/dL) among preterm NICU infants on full enteral nutrition and assess the impact on monitoring practices. STUDY DESIGN: Retrospective cohort study. RESULTS: We analyzed 1717 infants who were at least 2 days old and 48 hours after parenteral fluids were discontinued. Glucose concentrations were ≥70, 60-69, 50-59, and <50 mg/dL in 76.6, 16.2, 5.9, and 1.3% of measurements, respectively. In multivariate models, concentrations <60 mg/dL were common among male infants at lower postnatal age, small-for-gestational age, and born to women with hypertension (p < 0.05). After PES guideline, infants were more likely to have >3 glucose measurements (p < 0.05). CONCLUSIONS: Glucose concentrations <70 mg/dL are not uncommon among preterm infants receiving full enteral nutrition. Monitoring increased after guideline publication. Applying PES threshold to well-appearing preterm infants may promote increased monitoring and intervention without clear long-term benefit.

Predicting Successful Neonatal Retro-Transfer to a Lower Level of Care.

Up to 20% of newborn infants retro-transferred to a lower level of care require readmission to a higher-level facility. In this study, we developed and validated a prediction rule (The Rule for Elective Transfer between Units for Recovering Neonates [RETURN]) to identify clinical characteristics of infants at risk for failing retro-transfer.

Outcomes of Implementation of a NICU-Based Late Preterm Infant Feeding Guideline.

BACKGROUND AND OBJECTIVES: Late preterm (LPT) infants are at risk for feeding difficulties. Our objectives were to reduce the use of intravenous (IV) fluids and increase breastfeeding at discharge among LPT infants admitted to our NICU. METHODS: We implemented a feeding guideline and evaluated its effect using a pre-post design. We examined rates of our main outcomes, IV fluid use, and any or exclusive breastfeeding at discharge, as well as several secondary outcomes, including hypoglycemia (glucose <50 mg/dL) at >8 hours of life, by using χ2 and t tests. We excluded infants that were <2000 g, admitted to the NICU at >8 hours of life, or needed IV fluids at ≤8 hours of life for a medical reason. We used multivariable logistic regression to examine odds ratios and 95% confidence intervals of our main outcomes. RESULTS: Fifty percent of infants were eligible. Of those eligible, 18 of 52 (35%) vs 14 of 65 (22%) received IV fluids at >8 hours of life (P = .06). In the 24 hours before discharge, 35 of 52 (75%) vs 46 of 65 (78%) received any breast milk (P = .67), and 10 of 52 (30%) vs 10 of 65 (21%) received exclusive breast milk (P = .43). More infants had hypoglycemia in the posttime period (16 of 65 [25%]) compared with the pretime period (3 of 52 [6%]; P = .01). CONCLUSIONS: After implementation of a LPT feeding guideline in our NICU that defined specific expected feeding volumes, we did not find changes in IV fluid use or breastfeeding.

Do-Not-Resuscitate Orders in the Neonatal ICU: Experiences and Beliefs Among Staff.

OBJECTIVES: Studies in adult patients have shown that do-not-resuscitate orders are often associated with decreased medical intervention. In neonatology, this phenomenon has not been investigated, and how do-not-resuscitate orders potentially affect clinical care is unknown. DESIGN: Retrospective medical record data review and staff survey responses about neonatal ICU do-not-resuscitate orders. SETTING: Four academic neonatal ICUs. SUBJECTS: Clinical staff members working in each neonatal ICU. INTERVENTIONS: Survey response collection and analysis. MEASUREMENTS AND MAIN RESULTS: Participating neonatal ICUs had 14-48 beds and 120-870 admissions/yr. Frequency range of do-not-resuscitate orders was 3-11 per year. Two-hundred fifty-seven surveys were completed (46% response). Fifty-nine percent of respondents were nurses; 20% were physicians. Over the 5-year period, 44% and 17% had discussed a do-not-resuscitate order one to five times and greater than or equal to 6 times, respectively. Fifty-seven percent and 22% had cared for one to five and greater than or equal to 6 patients with do-not-resuscitate orders, respectively. Neonatologists, trainees, and nurse practitioners were more likely to report receiving training in discussing do-not-resuscitate orders or caring for such patients compared with registered nurses and respiratory therapists (p < 0.001). Forty-one percent of respondents reported caring for an infant in whom interventions had been withheld after a do-not-resuscitate order had been placed without discussing the specific withholding with the family. Twenty-seven percent had taken care of an infant in whom interventions had been withdrawn under the same circumstances. Participants with previous experiences withholding or withdrawing interventions were more likely to agree that these actions are appropriate (p < 0.001). CONCLUSIONS: Most neonatal ICU staff report experience with do-not-resuscitate orders; however, many, particularly nurses and respiratory therapists, report no training in this area. Variable beliefs with respect to withholding and withdrawing care for patients with do-not-resuscitate orders exist among staff. Because neonatal ICU patients with do-not-resuscitate orders may ultimately survive, withholding or withdrawing interventions may have long-lasting effects, which may or may not coincide with familial intentions.

Implementation of a Donor Milk Program Is Associated with Greater Consumption of Mothers' Own Milk among VLBW Infants in a US, Level 3 NICU.

BACKGROUND: It is unclear whether use of donor milk (DM) changes the provision of mothers' own milk (MOM) to very low birth weight (VLBW) infants in the neonatal intensive care unit (NICU). OBJECTIVES: To determine whether (1) the rates of any MOM and human milk consumption at feeding initiation and discharge and (2) the proportion of VLBW infants who stopped consuming any MOM and human milk during hospitalization changed in the 2 years after versus before implementation of a DM program in a US, inner-city, level 3 NICU. METHODS: We studied VLBW infants admitted to Boston Medical Center in the 2 years before (n = 74) and after (n = 80) implementation of a DM program (June 2011). We used multivariable logistic regression to compare milk consumption at feeding initiation and discharge and Cox proportional hazards to compare the proportion of infants that stopped consuming milk during the hospitalization pre and post our DM program. RESULTS: After adjustment for maternal race, age, insurance, delivery type, gestational age, and birth weight, we found a 6.0-fold increased odds (95% CI, 2.0-17.7) of consuming MOM at discharge and a 49% reduction in the cessation of MOM consumption during hospitalization (hazard ratio [HR], 0.51; 95% CI, 0.28-0.93) in the 2 years after versus before our DM program. CONCLUSION: Implementation of a DM program was associated with greater consumption of MOM throughout hospitalization and at discharge among VLBW infants. Implementation of DM programs may augment support of mothers to provide breast milk in level 3 NICUs.

Stochastic Resonance Effects on Apnea, Bradycardia, and Oxygenation: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of stochastic resonance (SR) stimulation on preterm infant oxygen desaturation, bradycardia, and apnea events. We hypothesized that SR stimulation will reduce these events. METHODS: This was a randomized crossover study conducted from April 2012 to July 2014. Eligible preterm infants were not receiving ventilation support and had at least 1 clinically documented apnea, bradycardia, and/or oxygen desaturation event. The 3 outcome variables were as follows: oxygen desaturation, bradycardia, and apnea events. Infants received up to two 3- or 4-hour intervention periods of 30-minute alternating intervals of SR stimulation and no SR stimulation. The first intervention period was randomly assigned to begin with SR stimulation either on or off, whereas the next intervention period automatically began with the opposite on/off state. We compared the SR stimulation "on" periods with the SR stimulation "off" periods with each infant serving as his or her own control. RESULTS: The sample consisted of 36 infants with a mean (±SD) gestational age of 30.5 ± 3 weeks and a birth weight of 1409 ± 450 g. SR stimulation decreased the number of apneic events by 50%. SR stimulation ameliorated every aspect of clinically significant oxygen desaturation events, with a 20% to 35% decrease in the number, duration, and intensity of oxygen desaturation events when SR stimulation was on. Also, SR stimulation produced a nearly 20% reduction in the intensity of bradycardia events. CONCLUSIONS: SR stimulation may be a noninvasive and nonpharmacologic treatment option for apnea, oxygen desaturation, and some aspects of bradycardia in premature infants.

Late Preterm Infants and Neurodevelopmental Outcomes at Kindergarten.

BACKGROUND AND OBJECTIVE: Late preterm infants (LPIs) (gestation 34 weeks and 0 days to 36 weeks and 6 days) compared with full-term infants (FTIs) are at increased risk for mortality and short- and long-term morbidity. The objective of this study was to assess the neurodevelopmental outcomes in a longitudinal cohort study of LPIs from infancy to school age and determine predictive values of earlier developmental testing compared with school-age testing. METHODS: We used general estimating equations to calculate the odds of school readiness in a nationally representative cohort of 4900 full-term and 950 late preterm infants. We generated positive and negative predictive values of the ability of the 24-month Mental Developmental Index (MDI) scores of the Bayley Short Form, Research Edition, to predict Total School Readiness Score (TSRS) at kindergarten age. RESULTS: In multivariable analysis, late preterm infants had higher odds of worse TSRSs (adjusted odds ratio 1.52 [95% confidence interval 1.06-2.18], P = .0215). The positive predictive value of a child having an MDI of <70 at 24 months and a TSRS <5% at kindergarten was 10.4%. The negative predictive value of having an MDI of >70 at 24 months and a TSRS >5% was 96.8%. Most infants improved score ranking over the study interval. CONCLUSIONS: LPIs continue to be delayed at kindergarten compared with FTIs. The predictive validity of having a TSRS in the bottom 5% given a MDI <70 at 24 months was poor. A child who tested within the normal range (>85) at 24 months had an excellent chance of testing in the normal range at kindergarten.

Improvement in Perinatal HIV Status Documentation in a Massachusetts Birth Hospital, 2009-2013.

BACKGROUND AND OBJECTIVES: Despite recommendations for universal HIV testing during routine prenatal care, maternal HIV status is not always available at the time of delivery, which may lead to missed opportunities for antiretroviral prophylaxis. We completed a quality improvement project focused on increasing the availability of maternal HIV status documentation at our perinatal facility. Our primary aim was to improve documentation rates from 50% to 100% between 2009 and 2013. Our secondary aim was to identify predictors of documentation. METHODS: After an initial needs assessment, we performed a multidisciplinary quality improvement effort to address lack of HIV documentation in perinatal charts. The interventions included a switch to a verbal-only consent process, a rapid HIV testing protocol, and a simplified newborn admission document. To assess the impact of our intervention, we audited 100 charts per month and formally analyzed a second random sample of 200 charts in the postimplementation phase. RESULTS: Rates of HIV status documentation improved between 2009 and 2013, from 55.5% to 96.5%. Multivariable models revealed that before our interventions, mothers receiving care at freestanding offices (versus community-based outreach clinics) and those privately insured (versus publicly) were less likely to have HIV status documented. In 2013, neither ambulatory site nor insurance type predicted documentation. CONCLUSIONS: We demonstrated improvement in maternal HIV status documentation on admission to labor and delivery after implementation of a 3-pronged intervention. Next steps include investigating persistent barriers to achieving universal screening and documentation.

2010 perinatal GBS prevention guideline and resource utilization.

OBJECTIVES: To quantify differences in early-onset sepsis (EOS) evaluations, evaluation-associated resource utilization, and EOS cases detected, when comparing time periods before and after the implementation of an EOS algorithm based on the Centers for Disease Control and Prevention (CDC) 2010 guidelines for prevention of perinatal Group B Streptococcus (GBS) disease. METHODS: Retrospective cohort study of infants born at ≥36 weeks' gestation from 2009 to 2012 in a single tertiary care center. One 12-month period during which EOS evaluations were based on the CDC 2002 guideline was compared with a second 12-month period during which EOS evaluations were based on the CDC 2010 guideline. A cost minimization analysis was performed to determine the EOS evaluation-associated costs and resources during each time period. RESULTS: During the study periods, among well-appearing infants ≥36 weeks' gestation, EOS evaluations for inadequate GBS prophylaxis decreased from 32/1000 to <1/1000 live births; EOS evaluation-associated costs decreased by $6994 per 1000 live births; and EOS evaluation-associated work hours decreased by 29 per 1000 live births. We found no increase in EOS evaluations for other indications, total NICU admissions, frequency of infants evaluated for symptoms before hospital discharge, or incidence of EOS during the 2 study periods. CONCLUSIONS: Implementation of an EOS algorithm based on CDC 2010 GBS guidelines resulted in a 25% decrease in EOS evaluations performed among well-appearing infants ≥36 weeks' gestation, attributable to decreased evaluation of infants born in the setting of inadequate indicated GBS prophylaxis. This resulted in significant changes in EOS evaluation-associated resource expenditures.

Building collaborative teams in neonatal intensive care.

The complex multidisciplinary nature of neonatal intensive care combined with the numerous hand-offs occurring in this shift-based environment, requires efficient and clear communication and collaboration among staff to provide optimal care. However, the skills required to function as a team are not typically assessed, discussed, or even taught on a regular basis among neonatal personnel. We developed a multidisciplinary, small group, interactive workshop based on Team STEPPS to provide staff with formal teamwork skills, and to introduce new team-based practices; 129 (95%) of the eligible 136 staff were trained. We then compared the results of the pretraining survey (completed by 114 (84%) of staff) with the post-training survey (completed by 104 (81%) of participants) 2 years later. We found an improvement in the overall teamwork score from 7.37 to 8.08 (p=<0.0001) based on a range of poor (1) to excellent (9). Respondents provided higher ratings in 9 out of 15 team-based categories after the training. Specifically, staff found improvements in communication (p=0.037), placed greater importance on situation awareness (p=<0.00010), and reported that they supported each other more (p=<0.0001). Staff satisfaction was rated higher post-training, with responses showing that staff had greater job fulfilment (p=<0.0001), believed that their abilities were being utilised properly (p=0.003), and felt more respected (p=0.0037). 90% of staff found the new practice of team meetings to help increase awareness of unit acuity, and 77% of staff noted that they had asked for help or offered assistance because of information shared during these meetings. In addition to summarising the results of our training programme, this paper also provides practical tools that may be of use in developing team training programmes in other neonatal units.

Prospective economic evaluation of a peer support intervention for prevention of postpartum depression among high-risk women in Ontario, Canada.

OBJECTIVE: A previous multisite, randomized, controlled trial of peer support compared with usual care for prevention of postpartum depression demonstrated a reduction in depression symptoms at 12 weeks postbirth. Our objective was to determine the cost-effectiveness of this intervention. STUDY DESIGN: Prospectively planned economic evaluation alongside the clinical trial to determine the cost per case of postpartum depression averted, using individual patient data (n = 610) and societal perspective. All costs were expressed in 2011 Canadian dollars. RESULTS: The mean cost per woman was $4,497 in the peer support group and $3,380 in the usual care group (difference of $1,117, p < 0.0001). There was a 95% probability that the program would cost less than $20,196 per case of postpartum depression averted. CONCLUSIONS: Although this is a volunteer-based program, it results in a net cost to the health care system and society. However, this cost is within the range for other accepted interventions for this population.

Effect of early educational intervention on younger siblings: the Infant Health and Development Program.

OBJECT: To assess whether younger siblings of participants in an early (preschool) educational program would benefit in terms of developmental and educational outcomes. DESIGN: Assessment of a cohort of siblings of intervention participants at a mean age of 13.5 years. SETTING: The Infant Health and Development Program (IHDP), an 8-site randomized trial of 3 years of early education for premature low-birth-weight infants who were followed up through 18 years of age. PARTICIPANTS: Siblings born within 5 years of the IHDP study participants. MAIN EXPOSURE: A sibling born no more than 5 years earlier who participated in the IHDP. MAIN OUTCOME MEASURES: Observed IQ; youth report of behavioral problems, their expectations of future success, and their relationship with their parents; and the caregiver's report on the youth's school progress and their expectations of the youth's educational attainment. RESULTS: Of 878 IHDP participants who were followed up, 466 (53.1%) had an eligible younger sibling, and 229 of those siblings (49.1%) agreed to participate. No differences were seen between the siblings of those who did and did not receive the IHDP intervention on any of the outcome measures. Adjusting for maternal race/ethnicity, age, and educational attainment at the birth of the study participant; study site; sex of the sibling; and losses to the cohort did not alter the results. CONCLUSION: Participation in an early educational program confers no apparent benefit on younger siblings in their early adolescent years.

Economic evaluation alongside the Premature Infants in Need of Transfusion randomised controlled trial.

BACKGROUND: The Premature Infants in Need of Transfusion (PINT) Outcome Study showed no significant difference in the primary outcome of death or neurodevelopmental impairment (NDI) in extremely low birthweight (ELBW) infants. However, a post-hoc analysis expanding the definition of NDI to include borderline intellectual functioning (Mental Development Index (MDI) <85) found an improvement in outcomes in the group maintained at higher haemoglobin levels. OBJECTIVE: To determine the cost effectiveness of more frequent red blood cell transfusions (high-Hb threshold) compared with less frequent transfusions (low-Hb threshold) in ELBW infants. DESIGN/METHODS: The authors performed an economic evaluation using patient-level data collected during the PINT randomised trial. The authors measured comprehensive costs from a third-party payer's perspective over a time horizon from birth through 18-21 months corrected age. RESULTS: The average total cost in the high-Hb threshold group was CAN$149 767 compared with CAN$150 227 in the low-Hb threshold group (difference of CAN$460, p=0.96). Cost-effectiveness analysis estimated savings of CAN$6879 for every additional infant surviving without severe NDI. There was a 48% chance that the high-Hb threshold reduced costs while improving outcome and a 90% chance that it would be cost effective at a willingness-to-pay threshold of CAN$250 000 per additional survivor without severe NDI. Post-hoc analysis defining cognitive delay as MDI score <85, instead of <70, revealed savings in the high-Hb threshold group of CAN$4457 per additional survivor without NDI. Results were robust to deterministic sensitivity analyses. CONCLUSION: A high-Hb threshold for transfusion, as measured in ELBW PINT study infants through 18 months corrected gestational age, may be an economically appealing intervention. The estimates were associated with moderate statistical uncertainty that should be targeted in larger, future studies.

Economic evaluation of caffeine for apnea of prematurity.

OBJECTIVE: To determine the cost-effectiveness of treatment with caffeine compared with placebo for apnea of prematurity in infants with birth weights less than 1250 g, from birth through 18 to 21 months' corrected age. METHODS: We undertook a retrospective economic evaluation of the cost per survivor without neurodevelopmental impairment by using individual-patient data from the Caffeine for Apnea of Prematurity clinical trial (N = 1869). We included direct medical costs either to the insurance payer or the hospital but excluded costs to parents and society, such as lost productivity. We used a price of $0.21/mg of generic caffeine citrate for our base-case analysis. All costs were expressed in 2008 Canadian dollars and discounted at 3%. The time horizon for this analysis extended through 18 to 21 months' corrected age to match the clinical trial. RESULTS: The mean cost per infant was $124 466 in the caffeine group and $133 505 in the placebo group (difference: $9039 [-14 749 to -3375]; adjusted P = .014). Cost-effectiveness analysis showed caffeine to be a dominant or "win-win" therapy: in >99% of 1000 bootstrap replications of the analysis, caffeine-treated infants had simultaneously better outcomes and lower mean costs. These results were robust to a 1000% increase in the individual resource items, including the price of caffeine citrate. CONCLUSIONS: In comparison with placebo, caffeine therapy for apnea of prematurity in infants weighing less than 1250 g is economically appealing for infants up to 18 to 21 months' corrected age.

Variation in diagnosis of apnea in moderately preterm infants predicts length of stay.

OBJECTIVE: Apnea of prematurity is one of the most common diagnoses in the NICU. Because resolution of apnea is a usual precondition for discharge from the hospital, different monitoring practices might affect length of stay for premature infants. Our objective was to compare the proportion of 33 to 34 weeks' gestational age infants diagnosed with apnea in different NICUs and to assess whether variability in length of stay would be affected by the rate of documented apnea. METHODS: This was a prospective cohort study of moderately preterm infants who survived to discharge in 10 NICUs in Massachusetts and California. RESULTS: The study population comprised 536 infants born between 33 and 34/7 weeks of which 264 (49%) were diagnosed with apnea. The mean postmenstrual age at discharge was higher in infants diagnosed with apnea compared with those without apnea (36.4 ± 1.3 vs 35.7 ± 0.8; P < .001, analysis of variance). Significant inter-NICU variation existed in the proportion of infants diagnosed with apnea (range: 24%-76%; P < .001). Postmenstrual age at discharge also varied between NICUs (range: 35.5 ± 0.6 to 36.7 ± 1.5 weeks; P < .001). As much as 28% of the variability in postmenstrual age at discharge between NICUs could be explained by the variability in the proportion of infants diagnosed with apnea. CONCLUSIONS: NICUs vary in the proportion of moderately preterm infants diagnosed with apnea, which significantly affects length of stay. Standardization of monitoring practices and definition of clinically significant cardiorespiratory events could have a significant impact on reducing the length of stay in moderately preterm infants.

Mixture modeling of microarray gene expression data.

About 28% of genes appear to have an expression pattern that follows a mixture distribution. We use first- and second-order partial correlation coefficients to identify trios and quartets of non-sex-linked genes that are highly associated and that are also mixtures. We identified 18 trio and 35 quartet mixtures and evaluated their mixture distribution concordance. Concordance was defined as the proportion of observations that simultaneously fall in the component with the higher mean or simultaneously in the component with the lower mean based on their Bayesian posterior probabilities. These trios and quartets have a concordance rate greater than 80%. There are 33 genes involved in these trios and quartets. A factor analysis with varimax rotation identifies three gene groups based on their factor loadings. One group of 18 genes has a concordance rate of 56.7%, another group of 8 genes has a concordance rate of 60.8%, and a third group of 7 genes has a concordance rate of 69.6%. Each of these rates is highly significant, suggesting that there may be strong biological underpinnings for the mixture mechanisms of these genes. Bayesian factor screening confirms this hypothesis by identifying six single-nucleotide polymorphisms that are significantly associated with the expression phenotypes of the five most concordant genes in the first group.

Assessing the effects of racemic and single-enantiomer albuterol on airway secretions in long-term intubated patients.

OBJECTIVE: In vitro data suggest that the S-enantiomer of albuterol can induce mucociliary dysfunction. This clinical study assesses the clinical significance of standard doses of the S-enantiomer on airway secretions in long-term intubated patients by comparing a racemic formulation of albuterol, an R-enantiomer formulation, and normal saline solution. DESIGN: A placebo-controlled crossover study. PATIENTS: Fourteen stable intubated patients with a median duration of intubation of 21 months and a median age of 72 years. SETTING: Long-term ventilator unit in skilled nursing facility. INTERVENTIONS: Following a 2-week washout period during which regularly scheduled beta2-agonists were discontinued, tracheal aspirates were collected for 4 h/d for a 5-day period to establish baseline values, and the patients were then randomized in crossover manner to each of three nebulized treatments: normal saline solution, racemic albuterol, and R-albuterol. Each treatment was administered three times daily for 5 days, followed by a 2-day washout. MEASUREMENTS: Tracheal aspirates were analyzed for volume, sodium, chloride, bicarbonate, interleukin (IL)-8, IL-1beta, soluble intercellular adhesion molecule, and tumor necrosis factor-alpha. RESULTS: There were no consistent significant differences among the three treatment periods either in terms of volume of secretions or in the concentrations of the electrolytes or the inflammatory indexes. However, all three treatments, including saline solution, were associated with increased secretion volume after the first dose, but this effect was not apparent on subsequent doses. CONCLUSION: There were no significant differences between racemic albuterol and R-albuterol observed in this study for any of the parameters studied, suggesting that the S-enantiomer does not adversely affect airway secretions at recommended doses. In addition, the routine administration of nebulized beta(2)-sympathomimetic agonists to stable patients undergoing prolonged intubation, for the sole purpose of changing the volume and composition of secretions of airway secretions, is not supported by the results of this study.