CPAP Versus NIPPV Postextubation in Preterm Neonates: A Comparative-Effectiveness Study.

BACKGROUND AND OBJECTIVES: Nasal intermittent positive pressure ventilation (NIPPV) has been shown to be superior to nasal continuous positive airway pressure (CPAP) postextubation in preterm neonates. However, studies have not permitted high CPAP pressures or rescue with other modes. We hypothesized that if CPAP pressures >8 cmH2O and rescue with other modes were permitted, CPAP would be noninferior to NIPPV. METHODS: We conducted a pragmatic, comparative-effectiveness, noninferiority study utilizing network-based real-world data from 22 Canadian NICUs. Centers self-selected CPAP or NIPPV as their standard postextubation mode for preterm neonates <29 weeks' gestation. The primary outcome was failure of the initial mode ≤72 hours. Secondary outcomes included failure ≤7 days, and reintubation ≤72 hours and ≤7 days. Groups were compared using a noninferiority adjusted risk-difference (aRD) margin of 0.05, and margin of no difference. RESULTS: A total of 843 infants extubated to CPAP and 974 extubated to NIPPV were included. CPAP was not noninferior (and inferior) to NIPPV for failure of the initial mode ≤72 hours (33.0% vs 26.3%; aRD 0.07 [0.03 to 0.12], Pnoninferiority(NI) = .86), and ≤7 days (40.7% vs 35.8%; aRD 0.09 [0.05 to 0.13], PNI = 0.97). However, CPAP was noninferior (and equivalent) to NIPPV for reintubation ≤72 hours (13.2% vs 16.1%; aRD 0.01 [-0.05 to 0.02], PNI < .01), and noninferior (and superior) for reintubation ≤7 days (16.4% vs 22.8%; aRD -0.04 [-0.07 to -0.001], PNI < .01). CONCLUSIONS: CPAP was not noninferior to NIPPV for failure ≤72 hours postextubation; however, it was noninferior to NIPPV for reintubation ≤72 hours and ≤7 days. This suggests CPAP may be a reasonable initial postextubation mode if alternate rescue strategies are available.

Non Breast-Milk-Fed Very Preterm Infants Are at Increased Risk of Iron Deficiency at 4-6-Months Corrected Age: A Retrospective Population-Based Cohort Study.

Iron supplementation is routinely recommended for breast-milk-fed preterm infants. However, the Canadian Pediatric Society recommends no additional iron supplementation for preterm infants fed primarily with iron-rich formula. Other pediatric societies don't provide specific guidance on supplemental iron for formula-fed preterm infants. This study investigated how feeding type influences iron status of very preterm infants at 4-6-months corrected age (CA). A retrospective cohort study was conducted using a population-based database on all very preterm infants (<31 weeks gestational age) born in Nova Scotia, Canada from 2005-2018. Information about feeding type, iron intake from formula, supplemental iron therapy and iron status at 4-6-months CA was extracted. Iron deficiency (ID) was defined as serum ferritin <20 and <12 µg/L at 4-and 6-months CA, respectively. Of 392 infants, 107 were "breast-milk-fed" (exclusively or partially) and 285 were "not breast-milk-fed" (exclusively fed with iron-rich formula) at 4-6-months CA. Total daily iron intake was higher in the non-breast-milk-fed group (2.6 mg/kg/day versus 2.0 mg/kg/day). Despite this, 36.8% of non-breast-milk-fed infants developed ID versus 20.6% of breast-milk-fed infants. ID is significantly more prevalent in non-breast-milk-fed infants than breast-milk-fed infants despite higher iron intake. This suggests the need to revisit recommendations for iron supplementation in non-breast-milk-fed preterm infants.

Accuracy of reticulocyte hemoglobin for diagnosing iron deficiency in former very preterm infants: a population-based cohort study.

Background: Serum ferritin (SF) is commonly used to diagnose iron deficiency (ID) but has limitations. Reticulocyte hemoglobin (Ret-He) is being increasingly used for ID diagnosis. This study aimed to assess accuracy of Ret-He for ID diagnosis in former very preterm infants (VPI) at 4-6 months corrected age (CA). Methods: A retrospective population-based cohort study was conducted on all live VPI born between 23 and 30 weeks of gestational age (GA) in Nova Scotia from 2012 to 2018. Infants underwent SF and Ret-He testing at 4-6 months CA. ID was defined using two definitions. The first defined ID as SF < 20 mcg/L at both 4- and 6-months CA, and the second as SF < 30 mcg at at both 4- and 6-months CA. The accuracy of Ret-He for identifying ID was assessed using the area under the receiver operating characteristic curve (AUC). Results: ID was present in 39.7% (62) of 156 infants in the first definition and 59.6% (93) in the second at 4-6 months CA. The AUC of Ret-He for ID diagnosis was 0.64 (p = 0.002) in the first definition and 0.59 (p = 0.04) in the second. The optimal cut-off was 29.4pg in the first and 29.7 in the second definition. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) at the 29.4 pg cut-off were 50.0%, 78.7%, 60.8%, and 70.5% for definition 1 and 44.1%, 74.6%, 71.9%, and 47.5% at the 29.7pg cut-off for definition 2. Conclusion: Ret-He had low diagnostic accuracy for ID diagnosis in former VPI. Caution is advised when using Ret-He alone for ID diagnosis. Further research is needed to establish optimal approaches for identifying ID in VPI.

Does the long-term administration of proton pump inhibitors increase the risk of adverse cardiovascular outcomes? A ChatGPT powered umbrella review.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for the treatment of acid-related disorders. In the context of coronary artery disease (CAD), PPIs are commonly prescribed along with antiplatelet medications. In fact, the potential interaction between these two classes of medications has been subject to much debate. This review aimed to summarise the findings from systematic reviews and meta-analyses on the casual relationship between PPI use (alone) and major adverse cardiovascular events (MACE). Furthermore, the recent release of ChatGPT has provided reviewers with a powerful natural language processing tool. We therefore aimed to assess the utility of ChatGPT in the systematic review process. METHODS: A comprehensive search of PubMed was conducted to identify relevant systematic reviews and meta-analyses published up to March 2023. Two independent reviewers assessed the eligibility of the studies, extracted the data, and assessed the methodological quality using AMSTAR 2.0. The population of interest was adults that received the medications of interest (PPIs) for a minimum of three months, regardless of indication. Control groups were defined as placebo or active comparators. The outcomes of interest were described under the general term MACE, which include cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. There were no restrictions with regards to time, but we only included reports in English. A different group of independent reviewers simultaneously ran the same process using ChatGPT. The results were then compared with the human generated results. RESULTS: Seven systematic reviews and meta-analyses were included, involving a total of 46 randomised controlled trials and 33 observational studies. The studies examined the association between PPI use and MACE, including stroke, myocardial infarction, and all-cause mortality. The results of the individual studies were conflicting, with some showing a positive association between PPI use and MACE, some showing no association, and others showing mixed results. However, the majority of the studies that included observational data reported a positive association between PPI use and MACE. Sensitivity analyses conducted in some studies did not significantly alter the primary results, suggesting that the findings were robust. Furthermore, ChatGPT was successfully prompted to execute most tasks involved in this review. We therefore present text that was generated by ChatGPT, including the abstract, introduction, results, and discussion sections. CONCLUSION: The findings of this umbrella review suggest that a causal relationship between PPI use and an increased risk of MACE cannot be ruled out. Further research is needed to better understand this relationship, particularly the underlying mechanisms and potential confounding factors. Healthcare professionals should consider the long-term use of PPIs and carefully weigh the risks and benefits for each patient. Finally, ChatGPT was successfully prompted to execute most of the tasks involved in this review. We therefore feel that this tool will be of great assistance in the field of evidence synthesis in the near future.

Poractant alfa versus bovine lipid extract surfactant: prospective comparative effectiveness study.

OBJECTIVE: To compare short term respiratory outcomes in preterm infants treated with bovine lipid extract surfactant or poractant alfa. STUDY DESIGN: Prospective comparative effectiveness cohort study of infants <32 weeks' gestational age requiring surfactant in thirteen centers. Each center provided bovine lipid extract surfactant for a set period of time in the year 2019 and then changed to poractant alfa for the remainder of the year. The primary outcome was total duration of respiratory support. RESULT: 968 infants were included. 494 received bovine lipid extract surfactant and 474 received poractant alfa. No difference was observed in the total duration of respiratory support (mechanical ventilation or non-invasive) (median 38 vs 40.5 days), need to re-dose surfactant, bronchopulmonary dysplasia, survival to discharge, or length of admission. CONCLUSION: In this pragmatic study, we did not identify any difference in short term outcomes between the groups based on the type of surfactant received.

Evaluation of a Modified SBAR Report to Physician Tool to Standardize Communication on Neonatal Transport.

OBJECTIVE: SBAR (situation, background, assessment and recommendation) is a structured format for the effective communication of critically relevant information. This tool was developed as a generic template to provide structure to the communication of clinical information between health care providers. Neonatal transport often presents clinically stressful circumstances where concise and accurate information is required to be shared clearly between multidisciplinary health care providers. A modified SBAR communication tool was designed to facilitate structured communication between nonphysician bedside care providers operating from remote sites and physicians providing decision-making support at receiving care facilities. Prospective interventional study was designed to evaluate the reliability of a "SBAR report to physician tool" in sharing clinically relevant information between multidisciplinary care providers on neonatal transport. STUDY DESIGN: The study was conducted between 2011 and 2014 by a dedicated neonatal transport service based at McMaster Children's Hospital which provides care for approximately 500 infants in Southern Ontario annually. In the preintervention phase, 50 calls were randomly selected for the evaluation and 115 consecutively recorded transport calls following adoption of the reporting tool. The quality of calls prior to and after the intervention was assessed by reviewers independently. Inter-rater agreement was also assessed for both periods. RESULTS: Inter-rater agreement between raters was moderate to perfect in most components of the SBAR "report to the physician tool" except for the assessment component, which showed fair agreement during both preintervention and postintervention periods. There was an improvement in global score (primary outcome) with a mean difference of 0.95 (95% confidence interval [CI]: 0.77-1.14; p < 0.001) and in cumulative score with a mean difference of 8.55 (95% CI: 7.26-9.84; p < 0.001) in postintervention period. CONCLUSION: The use of the SBAR report to physician tool improved the quality of clinical information shared between nonphysician members of the neonatal transport team and neonatal transport physicians. KEY POINTS: · Long-Accurate and concise information sharing is crucial for decision-making in neonatal transport.. · Information sharing between multidisciplinary teams can be enhanced by using a commonly understood information sharing template.. · The SBAR report to physician tool improves the quality of information shared between multidisciplinary team members in neonatal transport..

A call for a streamlined ethics review process for multijurisdictional, child health research studies.

To be time and resource efficient in neonatal research and to answer clinically relevant questions with validity and generalizability, large numbers of infants from multiple hospitals need to be included. Multijurisdictional research in Canada is currently fraught with research ethics review process hurdles that lead to delays, administrative costs, and possibly termination of projects. We describe our experience applying for ethics review to 13 sites in 7 provinces for a project comparing two standard of care therapies for preterm born infants with respiratory distress syndrome. We welcome the current opportunity created by the Institute of Human Development Child and Youth Health and the Institute for Genetics, to collaboratively identify practical solutions that would benefit Canadian researchers, Research Ethics Boards, and children and families.

Epidemiology of thrombosis in Canadian neonatal intensive care units.

OBJECTIVE: To assess the rate, location, risk factors, management, and outcomes of neonatal thrombosis (NT). DESIGN: A retrospective study investigating infants admitted to NICUs in Canadian Neonatal Network between January 2014 and December 2016 and diagnosed with NT. Each infant with NT was matched with an infant without NT. RESULTS: Of 39,971 infants, 587 (1.5%) were diagnosed with NT: 440 (75%) venous, 112 (19%) arterial, 29 (5%) both. NT rate was 1.4% in full-term and 1.7% in preterm infants. Venous thrombi occurred most commonly in the portal vein and arterial thrombi in the cerebral artery. Conservative management and low molecular weight heparin were the most common treatment modalities. Hospital stay was longer (p < 0.001) in the NT patients, but mortality was similar. CONCLUSIONS: NT was diagnosed in ~15/1000 NICU admissions and most commonly in the portal vein and cerebral arteries. Management varied based on the type and location of thrombi. Large multicenter trials are needed to address the best management strategies.

Probiotics for preterm infants: A National Retrospective Cohort Study.

OBJECTIVE: To evaluate the effect of prophylactic probiotic (PP) administration on rates of necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and mortality in preterm infants. STUDY DESIGN: We conducted a retrospective cohort study of infants < 29 weeks' gestation, admitted to neonatal intensive care units participating in the Canadian Neonatal Network between 1 January 2014 and 31 December 2015. Infants in the exposure group received PP. A multiple logistic regression model with generalized estimation equation was used. RESULTS: A total of 3093 infants were included, 652 infants (21%) received PP. The adjusted odds ratios (aOR) of NEC (aOR 0.64, 95% confidence interval [CI] 0.410, 0.996), mortality (aOR 0.41, 95% CI 0.26, 0.63), and a composite of NEC or mortality were significantly lower in the PP group. There was no significant difference in the aOR of LOS. CONCLUSION: Prophylactic probiotic administration is associated with a reduction in NEC and mortality in preterm infants.

Pharmacological Treatments for Neonatal Abstinence Syndrome: A Systematic Review and Network Meta-analysis.

Importance: Incidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment. Objective: To compare pharmacological therapies for neonatal abstinence syndrome. Data Sources: Systematic review and network meta-analysis of Medline (1946-June 2018), Embase (1974-June 2018), Cochrane CENTRAL (1966-June 2018), Web of Science (1900-June 2018), and ClinicalTrials.gov (June 2018). Study Selection: Randomized clinical trials of pharmacological treatments for neonatal abstinence syndrome alone or in combination with adjuvant treatments. Abstract, title, and full-text screening were conducted independently by 2 reviewers (T.D. and C.G.). Data Extraction and Synthesis: Data extraction was conducted independently by 2 reviewers (T.D. and C.G.) according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-Network Meta-Analyses guidelines. Quality was assessed with the Cochrane Risk of Bias tool and data were pooled with fixed-effect models as a result of the low number of trials that were included in the analysis. Main Outcomes and Measures: The primary outcome was the length of treatment. The length of stay, need for adjuvant therapy, and adverse events were considered as secondary outcomes. Results: Eighteen trials (N = 1072) were eligible for inclusion. The treatments that were included in the length of treatment analysis were buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted tincture of opium, morphine, methadone, and phenobarbital. Sublingual buprenorphine was considered the optimal treatment for a reduction in the length of treatment (days: mean difference vs morphine, -12.75 [95% CI, -17.97 to -7.58]; median rank, 1 [3-1]) and length of stay (days: mean difference vs morphine, -11.43 [95% CI, -16.95 to -5.82]; median rank, 1 [3-1]) but not the need for adjuvant treatment (odds ratio vs morphine, 1.23 [95% CI, 0.46-3.44]; median rank, 3 [5-1]). The results were robust to bias but sensitive to imprecision. Conclusions and Relevance: The current evidence suggests that buprenorphine is the optimal treatment for neonatal abstinence treatment, but limitations are considerable and wide-scale adoption requires a large multisite trial. Morphine, which is considered standard of care in most hospitals, was the lowest-ranked opioid for length of treatment and length of stay.

Gastric Residual Volume in Feeding Advancement in Preterm Infants (GRIP Study): A Randomized Trial.

OBJECTIVE: To evaluate the effect of not relying on prefeeding gastric residual volumes to guide feeding advancement on the time to reach full feeding volumes in preterm infants, compared with routine measurement of gastric residual volumes. We hypothesized that not measuring prefeeding gastric residual volumes can shorten the time to reach full feeds. STUDY DESIGN: In this single-center, randomized, controlled trial, we included gavage fed preterm infants with birth weights (BW) 1500-2000 g who were enrolled within 48 hours of birth. Exclusion criteria were major congenital malformations, asphyxia, and BW below the third percentile. In the study group, the gastric residual volume was measured only in the presence of bloody aspirates, vomiting, or an abnormal abdominal examination. In the control group, gastric residual volume was assessed routinely, and feeding advancement was based on the gastric residual volume. The primary outcome was the time to reach feeding volumes of 120 mL/kg per day. Secondary outcomes were time to regain BW, episodes of feeding interruptions, sepsis, and necrotizing enterocolitis. RESULTS: Eighty-seven infants were enrolled. There were no differences between the study and control groups with respect to time to reach full feeds (6 days [95% CI, 5.5-6.5] vs 5 days [95% CI, 4.5-5.5]; P = .82), time to regain BW, episodes of feeding interruptions, or sepsis. Two infants in the control group developed necrotizing enterocolitis. CONCLUSIONS: Avoiding routine assessment of gastric residual volume before feeding advancement did not shorten the time to reach full feeds in preterm infants with BW between 1500 and 2000 g. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01337622.

Automated versus manual control of inspired oxygen to target oxygen saturation in preterm infants: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review of clinical trials comparing automated versus manual fraction of inspired oxygen (FiO2) control to target oxygen saturation (SpO2) in preterm infants. DESIGN: The authors searched MEDLINE, Embase, CENTRAL, and CINAHL from inception upto December 2016, reviewed conference proceedings and sought results of unpublished trials. Studies were included if automated FiO2 control was compared to manual control in preterm infants on positive pressure respiratory support. The primary outcome was percentage of time spent within the target SpO2 range. Summary mean differences (MD) were computed using random effects model. RESULTS: Out of 276 identified studies 10 met the inclusion criteria. Automated FiO2 control significantly improved time being spent within the target SpO2 range [MD: 12.8%; 95% CI: 6.5-19.2%; I2 = 90%]. Periods of hyperoxia (MD:-8.8%; 95% CI: -15 to -2.7%), severe hypoxia(SpO2 < 80%)(MD: -0.9%;95%CI: -1.5 to -0.4%) and hypoxic events (MD: -5.6%; 95% CI: -9.1 to -2.1%) were significantly reduced with automated control. CONCLUSION: Automated FiO2 adjustment provides significant improvement of time in target saturations, reduces periods of hyperoxia, and severe hypoxia in preterm infants on positive pressure respiratory support.

Guidelines for feeding very low birth weight infants.

Despite the fact that feeding a very low birth weight (VLBW) neonate is a fundamental and inevitable part of its management, this is a field which is beset with controversies. Optimal nutrition improves growth and neurological outcomes, and reduces the incidence of sepsis and possibly even retinopathy of prematurity. There is a great deal of heterogeneity of practice among neonatologists and pediatricians regarding feeding VLBW infants. A working group on feeding guidelines for VLBW infants was constituted in McMaster University, Canada. The group listed a number of important questions that had to be answered with respect to feeding VLBW infants, systematically reviewed the literature, critically appraised the level of evidence, and generated a comprehensive set of guidelines. These guidelines form the basis of this state-of-art review. The review touches upon trophic feeding, nutritional feeding, fortification, feeding in special circumstances, assessment of feed tolerance, and management of gastric residuals, gastro-esophageal reflux, and glycerin enemas.

Use of noninvasive high-frequency ventilation in the neonatal intensive care unit: a retrospective review.

OBJECTIVE: The aim of the article is to review the effectiveness of neonatal noninvasive high-frequency ventilation (NIHFV) in preventing endotracheal mechanical ventilation. STUDY DESIGN: Retrospective case series including all 79 instances of NIHFV use at four participating centers between July 2010 and September 2012. RESULTS: In 73% of cases, NIHFV was used as rescue after another noninvasive mode, and prophylactically (postextubation) in the remainder. In 58% of cases, infants transitioned to another noninvasive mode, without requiring intubation. There were significant reductions in the mean (SD) number of apneas, bradycardias, or desaturations (over 6 hours) (3.2 [0.4] vs. 1.2 [0.3]; p < 0.001), FiO2 (48 [3] vs. 40 [2]%; p < 0.001) and CO2 levels (74 [6] vs. 62 [4] mm Hg; p = 0.025] with NIHFV. No NIHFV-related complications were noted. CONCLUSIONS: NIHFV is a promising NIV mode that may help prevent or delay intubation and deserves further clinical research.

A systematic review and meta-analysis of caudal block as compared to noncaudal regional techniques for inguinal surgeries in children.

This systematic review and meta-analysis were designed to compare the analgesic effectiveness and adverse effects with the use of caudal analgesia as compared to noncaudal regional analgesia techniques in children undergoing inguinal surgeries. MEDLINE, EMBASE, and CENTRAL (Cochrane) databases were searched for randomized control trials published in English language from 1946 up to 2013. Use of rescue analgesia and adverse effects were considered as primary and secondary outcomes, respectively. Outcomes were pooled using random effects model and reported as risk ratio (RR) with 95% CI. Out of 3240 hits and 24 reports for final selection, 17 were included in this review. Caudal analgesia was found to be better in both early (RR = 0.81 [0.66, 0.99], P = 0.04) and late (RR = 0.81 [0.69, 0.96], P = 0.01) periods, but with a significant risk of motor block and urinary retention. According to GRADE, the quality of evidence was moderate. Although potentially superior, caudal analgesia increases the chance of motor block and urinary retention. There are limited studies to demonstrate that the technical superiority using ultrasound translates into better clinical success with the inguinal nerve blocks.

Evaluation of implementation status of national policy on Indian systems of medicine and homeopathy 2002: Stakeholders' perspective.

BACKGROUND: National Policy on Indian systems of medicine and homoeopathy (ISM and H policy) was formulated in 2002 to encourage the development of Ayurveda, Sidhha, Unani, Yoga, Naturopathy and Homoeopathy in India. This study proposes to assess the views of public health experts on current implementation of ISM and H Policy. METHODS: An online questionnaire was designed to ascertain the views of public health experts on ISM and H Policy and mailed to 100 public health experts. The tool was tested for content validity and a pilot study was done. Results were analyzed with the help of SPSS version 16. RESULTS AND CONCLUSION: Response rate was 61%. Majority of experts considered implementation status of ISM and H Policy as poor. Lack of quality education was mentioned as major factor responsible for current scenario of ISM and H Policy by most of experts. Lack of funds and government support were emerged as major bottlenecks in implementation of ISM and H Policy.