Inhaled nitric oxide in preterm infants: an individual-patient data meta-analysis of randomized trials.

BACKGROUND: Inhaled nitric oxide (iNO) is an effective therapy for pulmonary hypertension and hypoxic respiratory failure in term infants. Fourteen randomized controlled trials (n = 3430 infants) have been conducted on preterm infants at risk for chronic lung disease (CLD). The study results seem contradictory. DESIGN/METHODS: Individual-patient data meta-analysis included randomized controlled trials of preterm infants (<37 weeks' gestation). Outcomes were adjusted for trial differences and correlation between siblings. RESULTS: Data from 3298 infants in 12 trials (96%) were analyzed. There was no statistically significant effect of iNO on death or CLD (59% vs 61%: relative risk [RR]: 0.96 [95% confidence interval (CI): 0.92-1.01]; P = .11) or severe neurologic events on imaging (25% vs 23%: RR: 1.12 [95% CI: 0.98-1.28]; P = .09). There were no statistically significant differences in iNO effect according to any of the patient-level characteristics tested. In trials that used a starting iNO dose of >5 vs ≤ 5 ppm there was evidence of improved outcome (interaction P = .02); however, these differences were not observed at other levels of exposure to iNO. This result was driven primarily by 1 trial, which also differed according to overall dose, duration, timing, and indication for treatment; a significant reduction in death or CLD (RR: 0.85 [95% CI: 0.74-0.98]) was found. CONCLUSIONS: Routine use of iNO for treatment of respiratory failure in preterm infants cannot be recommended. The use of a higher starting dose might be associated with improved outcome, but because there were differences in the designs of these trials, it requires further examination.

Foot-and-mouth disease control and eradication in the Bicol Surveillance Buffer Zone of the Philippines.

Following the onset of an epidemic of foot and mouth disease (FMD) commencing in 1994 and affecting mainly pigs in the Philippines, a National Plan for the Control and Eradication of the disease was initiated. A disease surveillance buffer zone in the southern Luzon region of Bicol was established to protect the Visayas and Mindanao from infection and enable eventual elimination of the disease in Luzon. With achievement of Office International Epizooties (OIE)-certified FMD freedom with vaccination in the Philippines now imminent, the four components of the disease control strategy are reviewed, including quarantine and animal movement controls, strategic vaccination, surveillance and disease investigation, and enhanced public awareness with school on the air radio programmes. Although numbers of outbreaks declined following widespread vaccination, evaluation of serological responses in vaccinates suggested low levels of immune protection. The cessation of outbreaks was considered more likely a result of animal movement controls, improved surveillance and emergency response capability, and reduction in FMD-risk behaviours by livestock owners, particularly through efforts to enhance public awareness of biosecurity measures by the training of traders, livestock industry personnel and both commercial and smallholder farmers. A two-stage random sampling serosurveillance strategy enabled identification of residual infection that was not detected through opportunistic sampling and negative incident reporting. Intensive investigations of FMD outbreaks, particularly in Albay province in 1999, enabled improved understanding of the risk factors involved in disease transmission and implementation of appropriate interventions. The findings from this review are offered to assist development of FMD control and eradication programmes in other countries in south-east Asia that are now being encouraged to support the OIE goal of FMD freedom with vaccination by 2020.

Inhaled nitric oxide in preterm infants: a systematic review and individual patient data meta-analysis.

BACKGROUND: Preterm infants requiring assisted ventilation are at significant risk of both pulmonary and cerebral injury. Inhaled Nitric Oxide, an effective therapy for pulmonary hypertension and hypoxic respiratory failure in the full term infant, has also been studied in preterm infants. The most recent Cochrane review of preterm infants includes 11 studies and 3,370 participants. The results show a statistically significant reduction in the combined outcome of death or chronic lung disease (CLD) in two studies with routine use of iNO in intubated preterm infants. However, uncertainty remains as a larger study (Kinsella 2006) showed no significant benefit for iNO for this combined outcome. Also, trials that included very ill infants do not demonstrate significant benefit. One trial of iNO treatment at a later postnatal age reported a decrease in the incidence of CLD. The aim of this individual patient meta-analysis is to confirm or refute these potentially conflicting results and to determine the extent to which patient or treatment characteristics may explain the results and/or may predict benefit from inhaled Nitric Oxide in preterm infants. METHODS/DESIGN: The Meta-Analysis of Preterm Patients on inhaled Nitric Oxide (MAPPiNO) Collaboration will perform an individual patient data meta-analysis to answer these important clinical questions. Studies will be included if preterm infants receiving assisted ventilation are randomized to receive inhaled Nitric Oxide or to a control group. The individual patient data provided by the Collaborators will be analyzed on an intention-to-treat basis where possible. Binary outcomes will be analyzed using log-binomial regression models and continuous outcomes will be analyzed using linear fixed effects models. Adjustments for trial differences will be made by including the trial variable in the model specification. DISCUSSION: Thirteen (13) trials, with a total of 3567 infants are eligible for inclusion in the MAPPiNO systematic review. To date 11 trials (n = 3298, 92% of available patients) have agreed to participate. Funding was successfully granted from Ikaria Inc as an unrestricted grant. A collaborative group was formed in 2006 with data collection commencing in 2007. It is anticipated that data analysis will commence in late 2009 with results being publicly available in 2010.