High Flow Nasal Cannula Use Is Associated with Increased Morbidity and Length of Hospitalization in Extremely Low Birth Weight Infants.

OBJECTIVE: To determine differences in the incidence of bronchopulmonary dysplasia (BPD) or death in extremely low birth weight infants managed on high flow nasal cannula (HFNC) vs continuous positive airway pressure (CPAP). STUDY DESIGN: This is a retrospective data analysis from the Alere Neonatal Database for infants born between January 2008 and July 2013, weighing ≤1000 g at birth, and received HFNC or CPAP. Baseline demographics, clinical characteristics, and neonatal outcomes were compared between the infants who received CPAP and HFNC, or HFNC ± CPAP. Multivariable regression analysis was performed to control for the variables that differ in bivariate analysis. RESULTS: A total of 2487 infants met the inclusion criteria (941 CPAP group, 333 HFNC group, and 1546 HFNC ± CPAP group). The primary outcome of BPD or death was significantly higher in the HFNC group (56.8%) compared with the CPAP group (50.4%, P < .05). Similarly, adjusted odds of developing BPD or death was greater in the HFNC ± CPAP group compared with the CPAP group (OR 1.085, 95% CI 1.035-1.137, P = .001). The number of ventilator days, postnatal steroid use, days to room air, days to initiate or reach full oral feeds, and length of hospitalization were significantly higher in the HFNC and HFNC ± CPAP groups compared with the CPAP group. CONCLUSIONS: In this retrospective study, use of HFNC in extremely low birth weight infants is associated with a higher risk of death or BPD, increased respiratory morbidities, delayed oral feeding, and prolonged hospitalization. A large clinical trial is needed to evaluate long-term safety and efficacy of HFNC in preterm infants.

Effects of Multiple Ventilation Courses and Duration of Mechanical Ventilation on Respiratory Outcomes in Extremely Low-Birth-Weight Infants.

IMPORTANCE: Extubation failure is common in extremely preterm infants. The current paucity of data on the adverse long-term respiratory outcomes associated with reinitiation of mechanical ventilation prevents assessment of the risks and benefits of a trial of extubation in this population. OBJECTIVE: To evaluate whether exposure to multiple courses of mechanical ventilation increases the risk of adverse respiratory outcomes before and after adjustment for the cumulative duration of mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study of extremely low-birth-weight (ELBW; birth weight <1000 g) infants born from January 1, 2006, through December 31, 2012, who were receiving mechanical ventilation. Analysis was conducted between November 2014 and February 2015. Data were obtained from the Alere Neonatal Database. EXPOSURES: The primary study exposures were the cumulative duration of mechanical ventilation and the number of ventilation courses. MAIN OUTCOMES AND MEASURES: The primary outcome was bronchopulmonary dysplasia (BPD) among survivors. Secondary outcomes were death, use of supplemental oxygen at discharge, and tracheostomy. RESULTS: We identified 3343 ELBW infants, of whom 2867 (85.8%) survived to discharge. Among the survivors, 1695 (59.1%) were diagnosed as having BPD, 856 (29.9%) received supplemental oxygen at discharge, and 31 (1.1%) underwent tracheostomy. Exposure to a greater number of mechanical ventilation courses was associated with a progressive increase in the risk of BPD and use of supplemental oxygen at discharge. Compared with a single ventilation course, the adjusted odds ratios for BPD ranged from 1.88 (95% CI, 1.54-2.31) among infants with 2 ventilation courses to 3.81 (95% CI, 2.88-5.04) among those with 4 or more courses. After adjustment for the cumulative duration of mechanical ventilation, the odds of BPD were only increased among infants exposed to 4 or more ventilation courses (adjusted odds ratio, 1.44; 95% CI, 1.04-2.01). The number of ventilation courses was not associated with increased risk of supplemental oxygen use at discharge after adjustment for the length of ventilation. A greater number of ventilation courses did not increase the risk of tracheostomy. CONCLUSIONS AND RELEVANCE: Among ELBW infants, a longer cumulative duration of mechanical ventilation largely accounts for the increased risk of chronic respiratory morbidity associated with reinitiation of mechanical ventilation. These results support attempts of extubation in ELBW infants receiving mechanical ventilation on low ventilator settings, even when success is not guaranteed.

TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets.

The Therapeutic Intensification in De Novo Leukaemia (TIDEL)-II study enrolled 210 patients with chronic phase chronic myeloid leukemia (CML) in two equal, sequential cohorts. All started treatment with imatinib 600 mg/day. Imatinib plasma trough level was performed at day 22 and if <1000 ng/mL, imatinib 800 mg/day was given. Patients were then assessed against molecular targets: BCR-ABL1 ≤10%, ≤1%, and ≤0.1% at 3, 6, and 12 months, respectively. Cohort 1 patients failing any target escalated to imatinib 800 mg/day, and subsequently switched to nilotinib 400 mg twice daily for failing the same target 3 months later. Cohort 2 patients failing any target switched to nilotinib directly, as did patients with intolerance or loss of response in either cohort. At 2 years, 55% of patients remained on imatinib, and 30% on nilotinib. Only 12% were >10% BCR-ABL1 at 3 months. Confirmed major molecular response was achieved in 64% at 12 months and 73% at 24 months. MR4.5 (BCR-ABL1 ≤0.0032%) at 24 months was 34%. Overall survival was 96% and transformation-free survival was 95% at 3 years. This trial supports the feasibility and efficacy of an imatinib-based approach with selective, early switching to nilotinib. This trial was registered at www.anzctr.org.au as #12607000325404.

Differences in short-term neonatal outcomes between discordant twins.

PURPOSE: To evaluate short-term outcomes associated with discordant twin pairs admitted to the NICU. DESIGN: A retrospective descriptive study comparing discordant twin pairs. SUBJECTS: Three hundred eighty-four discordant twin pairs were included. Mean gestational age of the twin pairs was 32.6 weeks (range, 24-39). METHODS: The ParadigmHealth database was queried for all twin admissions from January 2001 to June 2004 admitted to 453 NICUs across the United States. Discordance was calculated for each twin set as defined as greater than 20% difference in birth weight. Exclusion criteria were death of a twin, congenital anomalies, or extracorporeal life support. MAIN OUTCOME MEASURES: Demographics, respiratory needs, feeding characteristics, complications, and discharge needs. RESULTS: A total of 384 discordant twin pairs met inclusion criteria. The larger twins required more ventilation/continuous positive airway pressure (55% vs 44%, P < .01) and/or oxygen therapy (50% vs 41%, P = .02) compared with smaller twins. Smaller twins reached full oral (PO) feeds an average of 0.6 weeks later than larger twins (P < .0001) but had more weight gain per day. Smaller twins transitioned to an open crib at lower weights but at slightly greater age. No differences were noted with necrotizing enterocolitis or apnea. Smaller twins had increased nosocomial infections. Mean length of stay was shorter (P = .0036) in the larger twin group. Only 33% of the twin pairs were discharged on the same day. CONCLUSIONS: Larger twins had more acute respiratory issues but achieved certain milestones more rapidly with fewer complications, thus leading to earlier discharge compared with their smaller twin counterparts.

Clinical outcomes and cost of the moderately preterm infant.

PURPOSE: The purpose of this study is to define the incidence of admission and morbidities and the economic impact of moderately preterm infants in the neonatal intensive care unit (NICU). DESIGN: A retrospective descriptive study. SUBJECTS: All infants born between 32 to 34 weeks' gestational age (GA) (n=4932) followed by ParadigmHealth, a care management company, from January 2001 through June 2004 were evaluated. Infants with major congenital anomalies were excluded. This sample represented 453 NICUs in 24 states in the United States. METHODS: Retrospective data analysis. Infants born between 32 and 34 weeks' GA were studied (n=4932). This subset of patients in the NICU was compared to the entire population in the database (n=19,923) for incidence and cost comparison. Infants were followed for 2 weeks after hospital discharge. MAIN OUTCOME MEASURES: Demographics, feeding characteristics, respiratory needs, complications, discharge needs, and patient costs. RESULTS: The 4932 infants admitted to the NICU with gestational ages of 32 to 34 weeks represented 24.8% of the 19,923 admissions during this time period. This cohort experienced low mortality (0.5%) and had an average length of stay (LOS) of 17.6 days. The average cost per case was $31,000, representing 21.6% of total NICU costs. Fifty-four percent of infants experienced respiratory compromise, requiring ventilation, continuous positive airway pressure, or oxygen during their hospital course. Fifty-six percent required intravenous nutrition, and 19% of these patients were discharged home with ongoing medical needs and the use of durable medical equipment. CONCLUSIONS: Although morbidities with long-term consequences were rare, there is a significant burden on the infant, family, and healthcare team for patients 32 to 34 weeks' GA. It is important to understand the characteristics of this group of infants and explore ways of optimizing care to minimize this burden.

Practice variation in suspected neonatal sepsis: a costly problem in neonatal intensive care.

OBJECTIVE: The most common admission to intensive care nurseries is the infant with suspected neonatal sepsis. To determine the clinical practice of neonatologists with respect to this diagnosis, we examined a large neonatal database during a 2-year period of time. The goal of this study was to define whether there were optimal practice strategies that could identify a "benchmark" clinical approach for this diagnosis. DESIGN: The PROACT database of ParadigmHealth was examined for all term infants with an admitting ICD - 9 code for suspected neonatal sepsis between January 1, 2001 and December 31, 2002. Infants had to be asymptomatic by 24 hours of life with no significant respiratory signs and receiving oral feedings. All infants had negative blood cultures. Maternal risk factors were examined to determine if they influenced the duration of therapy. The impact of treatment upon subsequent length of stay was also evaluated. Several areas of the country were individually examined to see if possible regional variations existed with respect to treatment of suspected sepsis. RESULTS: There were no significant differences noted in the management when maternal risk factors for suspected sepsis were assessed. In general, neonates were treated for 3.3+/-1.8 to 3.5+/-2.1 days, regardless of the number of maternal risk factors present at birth (p=NS). Length of stay ranged from 4.2+/-2.1 to 4.4+/-1.9 days in these groups (p=NS). The duration of treatment ranged from 1 to 10 days, even though all infants were clinically well and feeding by 24 hours of life. A total of 170 infants (17.0%) were treated for 4 to 6 days and 116 (11.6%) neonates received antibiotics for 7 to 10 days, even with negative blood cultures. One region of the country appeared to treat infants for a longer period of time than the other four regions examined, increasing the mean length of stay by 1.8 days (p<0.05). CONCLUSIONS: Treatment of neonates with suspected sepsis appears to be influenced by considerations other than maternal risk factors or the infant's clinical condition beyond the first day of life. There appears to be a great deal of practice variation among neonatologists confronted by patients with suspected sepsis. Awareness of this unnecessary variation may be of great value in reducing the duration of antibiotic therapy in the NICU and shortening the length of stay.

Intensive care management of the term neonate: are there regional differences in outcome?

The objective of this study was to evaluate the patterns of hospitalization of term infants in 3 major metropolitan areas. We hypothesized that regional practice variation occurred in the care of term infants and that these differences would be reflected in the hospitalization patterns of infants. All infants cared for in an Intensive Care Nursery (ICN) after maternal discharge in 1 of 3 major metropolitan areas followed up by the same neonatal management company were compared (n=4,487). Term infants were grouped into 1 of 2 categories based on illness severity: Group 1 (G1) infants-those who required supplemental oxygen or ventilation for 24 hours or more (n=611); and Group 2 (G2) infants-those infants without an oxygen or ventilation requirement (n=1,549). Excluded were infants in the following categories: birth weight <2,500 grams, major congenital anomalies, surgical patients, extracorporeal membrane oxygenation (ECMO) support, or babies who died before discharge. The number of infants in each of these categories was compared as a percentage of the total number of infants cared for in that region. The average length of stay (ALOS) and percentage of patient days attributed to infants in each category were compared across regions using multiple comparison tests (Tukey). The total ALOS was greatest in City A, as was the ALOS for sick term infants. Patient days for sick term infants were lowest in City C, and healthier term infants comprised the lowest percentage of patient days in City A. This difference resulted in the lowest percentage of patient days for all term admissions in City A. These data demonstrated that significant variation existed in the delivery of care to term neonates among major metropolitan regions. Cities that admitted fewer term infants for observation periods (G2) tended to have sicker term neonates with higher acuity hospitalizations (GI) and longer lengths of stay (LOS). These findings suggested that a conservative admission policy for this population can decrease overall LOS.