{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T10:56:25Z","timestamp":1790592985947,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":270,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018636","name":"Xuzhou Science and Technology Program","doi-asserted-by":"publisher","award":["KC23184"],"award-info":[{"award-number":["KC23184"]}],"id":[{"id":"10.13039\/501100018636","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Canadian Respiratory Journal"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Persistent pulmonary hypertension of the newborn (PPHN) may respond incompletely to inhaled nitric oxide (iNO) when poorly recruited lung limits delivery to ventilated alveoli. We evaluated whether high\u2010frequency oscillatory ventilation (HFOV) combined with iNO improved clinical and physiologic outcomes compared with conventional mechanical ventilation (CMV)\u2009+\u2009iNO or HFOV alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective, single\u2010center, 3\u2010arm, open\u2010label randomized clinical trial, 138 neonates born at 34\u2009weeks of gestation or later with echocardiographically confirmed PPHN and an oxygenation index of 25 or greater were randomized 1:1:1 to HFOV\u2009+\u2009iNO, CMV\u2009+\u2009iNO, or HFOV alone. The principal complete\u2010case per\u2010protocol analysis included 126 infants (42 per group) with ascertainable 120\u2010day primary outcomes who completed the assigned strategy without a major protocol deviation. The possible influence of the 12 unavailable primary outcomes was evaluated in post hoc randomized\u2010denominator extreme\u2010case sensitivity analyses. The primary outcome was death or extracorporeal membrane oxygenation (ECMO) within 120\u2009days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the complete\u2010case per\u2010protocol population, death or ECMO occurred in 3 of 42 infants (7.1%) assigned to HFOV\u2009+\u2009iNO, 11 of 42 (26.2%) assigned to CMV\u2009+\u2009iNO, and 14 of 42 (33.3%) assigned to HFOV alone (overall\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.012). For HFOV\u2009+\u2009iNO versus CMV\u2009+\u2009iNO, the risk ratio was 0.27 (95% CI, 0.08\u20130.91), and the risk difference was \u221219.0 percentage points (95% CI, \u221234.5 to \u22123.6; Holm\u2010adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.038). For HFOV\u2009+\u2009iNO versus HFOV alone, the risk ratio was 0.21 (95% CI, 0.07\u20130.69) and the risk difference was \u221226.2 percentage points (95% CI, \u221242.4 to \u22129.9; Holm\u2010adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011). The mean oxygenation index at 72\u2009h was 7.1 (SD, 2.8), 11.0 (SD, 3.8), and 15.9 (SD, 4.5), respectively (group\u2010by\u2010time interaction\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The overall primary comparison remained significant under symmetric extreme\u2010case assignments for the unavailable outcomes but not under the differential worst\u2010case assumption for HFOV\u2009+\u2009iNO (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.222).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In the observed per\u2010protocol population, HFOV\u2009+\u2009iNO was associated with fewer deaths or ECMO events and faster improvement in oxygenation and right\u2010ventricular echocardiographic measures than either comparator. Because 12 randomized infants were excluded and the overall comparison was not robust to the differential worst\u2010case missing\u2010outcome assumption, confidence in the apparent treatment effect is limited. These findings are exploratory and hypothesis\u2010generating, do not establish efficacy, and require confirmation in a prospectively registered multicenter trial with complete outcome ascertainment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/carj\/8717590","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T10:03:56Z","timestamp":1790589836000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High\u2010Frequency Oscillatory Ventilation Combined With Inhaled Nitric Oxide for Persistent Pulmonary Hypertension of the Newborn: A Single\u2010Center Randomized Clinical 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