Vibhuti Shah

Infants experience distress from repeated vaccine injections in the first year of life. This systematic review evaluated oral nutritive and non-nutritive interventions to reduce distress including: breastfeeding (pre-injection and during), bottle-feeding, sucrose solution, glucose/dextrose solutions, other sweet-tasting oral liquids, and non-nutritive sucking. Cochrane methodology and GRADE were used. Searches were conducted in MEDLINE, EMBASE, APA PsycINFO, CINAHL, and ProQuest Dissertations to identify relevant randomized and quasi-randomized controlled trials. Distress was the critical outcome. Placebo-controlled trials were prioritized when possible. Eligible studies were reviewed and data extracted by at least 2 reviewers. A random-effects model was used to pool the data; results are presented as standardized mean differences (SMDs) with 95% CIs. The certainty of evidence (graded from high, moderate, low, to very low) and the magnitude of effect were used to develop summary statements. Fifty-nine distinctive studies were included, with certainty of evidence ranging from moderate to very low. The magnitude of effect exceeded the minimum threshold (SMD ≥0.2) for all interventions. Breastfeeding during vaccinations likely results in a large reduction in distress (SMD=-2.38, moderate certainty). Breastfeeding pre-injection (SMD=-1.19, low certainty) and bottle-feeding (SMD=-1.65, low certainty) may both result in a large reduction in distress. Evidence from placebo-controlled trials shows that sucrose solution likely results in a large decrease in distress (SMD=-1.02, moderate certainty) and glucose/dextrose solutions likely reduce distress (SMD=-0.78, moderate certainty). Other sweet-tasting oral liquids likely result in a large decrease in distress (SMD=-1.47, moderate certainty). Non-nutritive sucking may reduce distress, but the evidence is very uncertain (SMD=-1.98, very low certainty). In infants, breastfeeding, sweet-tasting solutions, and other oral sweet-tasting liquids are preferred oral interventions to reduce vaccine injection-related distress.

This is an update of a review published in 2012. A related review "Inhaled versus systemic corticosteroids for preventing bronchopulmonary dysplasia in ventilated very low birth weight preterm neonates" has been updated as well. Bronchopulmonary dysplasia (BPD) is a serious and common problem among very low birth weight infants, despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. Due to their anti-inflammatory properties, corticosteroids have been widely used to treat or prevent BPD. However, the use of systemic steroids has been associated with serious short- and long-term adverse effects. Administration of corticosteroids topically through the respiratory tract may result in beneficial effects on the pulmonary system with fewer undesirable systemic side effects. To compare the effectiveness of inhaled versus systemic corticosteroids administered to ventilator-dependent preterm neonates with birth weight ≤ 1500 g or gestational age ≤ 32 weeks after 7 days of life on the incidence of death or BPD at 36 weeks' postmenstrual age. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 1), MEDLINE via PubMed (1966 to 23 February 2017), Embase (1980 to 23 February 2017), and CINAHL (1982 to 23 February 2017). We also searched clinical trials registers, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised or quasi-randomised controlled trials comparing inhaled versus systemic corticosteroid therapy (irrespective of dose and duration) starting after the first week of life in ventilator-dependent very low birth weight infants. We used standard methodological procedures expected by the Cochrane Collaboration. We included three trials that involved a total of 431 participants which compared inhaled versus systemic corticosteroids to treat BPD. No new trials were included for the 2017 update. Although one study randomised infants at < 72 hours (N = 292), treatment started when infants were aged > 15 days. In this larger study, deaths were included from the point of randomisation and before treatment started. Two studies (N = 139) randomised and started treatment at 12 to 21 days. Two trials reported non-significant differences between groups for the primary outcome: incidence of death or BPD at 36 weeks' postmenstrual age among all randomised infants. Estimates for the largest trial were Relative risk (RR) 1.04 (95% Confidence interval (CI) 0.86 to 1.26), Risk difference (RD) 0.03 (95% CI -0.09 to 0.15); (moderate-quality evidence). Estimates for the other trial reporting the primary outcome were RR 0.94 (95% CI 0.83 to 1.05), RD -0.06 (95% CI -0.17 to 0.05); (low-quality evidence). Secondary outcomes that included data from all three trials showed no significant differences in the duration of mechanical ventilation or supplemental oxygen, length of hospital stay, or the incidence of hyperglycaemia, hypertension, necrotising enterocolitis, gastrointestinal bleed, retinopathy of prematurity or culture-proven sepsis moderate- to low-quality evidence). In a subset of 75 surviving infants who were enrolled from the United Kingdom and Ireland, there were no significant differences in developmental outcomes at seven years of age between groups (moderate-quality evidence). One study received grant support and the industry provided aerochambers and metered dose inhalers of budesonide and placebo for the same study. No conflict of interest was identified. We found no evidence that inhaled corticosteroids confer net advantages over systemic corticosteroids in the management of ventilator-dependent preterm infants. There was no evidence of difference in effectiveness or adverse event profiles for inhaled versus systemic steroids. A better delivery system guaranteeing selective delivery of inhaled steroids to the alveoli might result in beneficial clinical effects without increasing adverse events. To resolve this issue, studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for administration of these medications. The long-term effects of inhaled steroids, with particular attention to neurodevelopmental outcomes, should be addressed in future studies.

Background Chronic lung disease (CLD) remains a common complication among preterm infants. There is increasing evidence that inflammation plays an important role in the pathogenesis of CLD. Due to their strong anti‐inflammatory properties, corticosteroids are an attractive intervention strategy. However, there are growing concerns regarding short‐ and long‐term effects of systemic corticosteroids. Theoretically, administration of inhaled corticosteroids may allow for beneficial effects on the pulmonary system with a lower risk of undesirable systemic side effects. Objectives To determine the impact of inhaled corticosteroids administered to preterm infants with birth weight up to 1500 grams (VLBW) beginning in the first two weeks after birth for the prevention of CLD as reflected by the requirement for supplemental oxygen at 36 weeks' postmenstrual age (PMA). Search methods Randomised and quasi‐randomised trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 12) in the Cochrane Library (searched 5 January 2016), MEDLINE (1966 to 5 January 2016), Embase (1980 to 5 January 2016), CINAHL (1982 to 5 January 2016), reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies web‐site (1990 to May 2016). Selection criteria We included in this review randomised controlled trials of inhaled corticosteroid therapy initiated within the first two weeks of life in VLBW preterm infants. Data collection and analysis We evaluated data regarding clinical outcomes, including: CLD at 28 days or 36 weeks' PMA; mortality; combined outcome of death or CLD at 28 days of age and at 36 weeks' PMA; the need for systemic corticosteroids; failure to extubate within 14 days; and adverse effects of corticosteroids. All data were analysed using Review Manager (RevMan) 5. Meta‐analyses were performed using relative risk (RR) and risk difference (RD), along with their 95% confidence intervals (CI). If RD was significant, the number needed to treat for an additional beneficial outcome (NNTB) was calculated. We used the GRADE approach to assess the quality of evidence. Main results According to GRADE the quality of the studies was moderate. Three additional trials are included in this update. The present review includes data analyses based on 10 qualifying trials that enrolled 1644 neonates. There was no significant difference in the incidence of CLD at 36 weeks' PMA in the inhaled steroid versus the placebo group (5 trials, 429 neonates) among all randomised (typical RR 0.97, 95% CI 0.62 to 1.52; typical RD −0.00, 95% CI −0.07 to 0.06). There was no heterogeneity for this outcome (typical RR I² = 11%; typical RD I² = 0%). There was a significant reduction in the incidence of CLD at 36 weeks' PMA among survivors (6 trials, 1088 neonates) (typical RR 0.76, 95% CI 0.63 to 0.93; typical RD −0.07, 95% CI −0.13 to −0.02; NNTB 14, 95% CI 8 to 50). There was a significant reduction in the combined outcome of death or CLD at 36 weeks' PMA among all randomised neonates (6 trials, 1285 neonates) (typical RR 0.86, 95% CI 0.75 to 0.99; typical RD −0.06, 95% CI −0.11 to −0.00) (P = 0.04); NNTB 17, 95% CI 9 to infinity). There was no significant heterogeneity for any of these analyses (I² = 0%). A lower rate of reintubation was noted in the inhaled steroid group compared with the control group in one study. There were no statistically significant differences in short‐term complications between groups and no differences in adverse events at long‐term follow‐up reported. Long‐term follow‐up of infants enrolled in the study by Bassler 2015 is ongoing. Authors' conclusions Based on this updated review, there is increasing evidence from the trials reviewed that early administration of inhaled steroids to VLBW neonates is effective in reducing the incidence of death or CLD at 36 weeks' PMA among either all randomised infants or among survivors. Even though there is statistical significance, the clinical relevance is of question as the upper CI limit for the outcome of death or CLD at 36 weeks' PMA is infinity. The long‐term follow‐up results of the Bassler 2015 study may affect the conclusions of this review. Further studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. Studies need to address both the short‐ and long‐term benefits and adverse effects of inhaled steroids with particular attention to neurodevelopmental outcome.

Professional organizations recommend car seat testing of preterm infants before discharge from hospital. Late preterm infants (LPIs, 34^0/7 to 36^6/7 weeks’ gestational age) are at the greatest risk for failure, despite often being well. To determine the incidence of car seat testing failure in LPIs and associative factors. A retrospective chart review was performed of inborn LPIs admitted to all levels of newborn care between July 1, 2012 and June 30, 2013. Data collected included maternal demographics, labour and delivery history, and neonatal course. Data were analyzed using backward logistic regression. A total of 511 charts were reviewed and 367 LPIs were eligible for inclusion. Of the 313 LPIs tested (mean [± SD] gestational age 36 weeks ±6 days and birth weight 2614±405 g), 80 (26%) failed (95% CI 21% to 31%). Most failed due to desaturations (≥2) of <88% for ≥10 s (n=33 [41%]). Multiple gestation was associated with failure (adjusted OR 2.45 [95% CI 1.44 to 4.18]; P=0.001), and there was a trend toward statistical significance for the variable postnatal age (0.996 [95% CI 0.99 to 1.00]; P=0.05). Infants who passed their car seat test had higher postnatal ages than those who failed (mean difference 39.4 h [95% CI 12.7 h to 66.0 h]; P=0.004). Twenty-six percent of LPIs failed car seat testing. Ideally, infants should be tested after an appropriate transitional period. The authors identified factors that may be important in designing future, prospective studies in this area. Future research should evaluate the clinical significance of car seat testing and resource utilization.

This systematic review assessed the effectiveness and safety of pharmacotherapy and combined interventions for reducing vaccine injection pain in individuals across the lifespan. Electronic databases were searched for relevant randomized and quasi-randomized controlled trials. Self-reported pain and fear as well as observer-rated distress were critically important outcomes. Data were combined using standardized mean difference (SMD) or relative risk with 95% confidence intervals (CI). Fifty-five studies that examined breastfeeding (which combines sweet-tasting solution, holding, and sucking), topical anesthetics, sweet-tasting solutions (sucrose, glucose), vapocoolants, oral analgesics, and combination of 2 versus 1 intervention were included. The following results report findings of analyses of critical outcomes with the largest number of participants. Compared with control, acute distress was lower for infants breastfed: (1) during vaccination (n=792): SMD -1.78 (CI, -2.35, -1.22) and (2) before vaccination (n=100): SMD -1.43 (CI, -2.14, -0.72). Compared with control/placebo, topical anesthetics showed benefit on acute distress in children (n=1424): SMD -0.91 (CI, -1.36, -0.47) and self-reported pain in adults (n=60): SMD -0.85 (CI, -1.38, -0.32). Acute and recovery distress was lower for children who received sucrose (n=2071): SMD -0.76 (CI, -1.19, -0.34) or glucose (n=818): SMD -0.69 (CI, -1.03, -0.35) compared with placebo/no treatment. Vapocoolants reduced acute pain in adults [(n=185), SMD -0.78 (CI, -1.08, -0.48)] but not children. Evidence from other needle procedures showed no benefit of acetaminophen or ibuprofen. The administration of topical anesthetics before and breastfeeding during vaccine injections showed mixed results when compared with topical anesthetics alone. There were no additive benefits of combining glucose and non-nutritive sucking (pacifier) compared with glucose or non-nutritive sucking (pacifier) alone or breastfeeding and sucrose compared with breastfeeding or sucrose alone. Breastfeeding, topical anesthetics, sweet-tasting solutions, and combination of topical anesthetics and breastfeeding demonstrated evidence of benefit for reducing vaccine injection pain in infants and children. In adults, limited data demonstrate some benefit of topical anesthetics and vapocoolants.

Adapting educational tools to meet user needs is a critical aspect of translating research evidence into best clinical practices. The objectives of this study were to evaluate usability and effectiveness of educational tools about infant vaccination pain management directed to postnatal nurses. Mixed methods design. A template pamphlet and video included in a published clinical practice guideline were subjected to heuristic usability evaluation and then the revised tools were reviewed by postnatal hospital nurses in three rounds of interviews involving 8 to 12 nurses per round. Nurses’ knowledge about evidence-based pain management interventions was evaluated at three time points: baseline, after pamphlet review, and after video review. Of 32 eligible postnatal nurses, 29 agreed to participation and data were available for 28. Three overarching themes were identified in the interviews: 1) utility of information, 2) access to information, and 3) process for infant procedures. Nurses’ knowledge improved significantly (p < 0.05) from the baseline phase to the pamphlet review phase, and again from the pamphlet review phase to the video review phase. This study demonstrated usability and knowledge uptake from a nurse-directed educational pamphlet and video about managing infant vaccination pain. Future studies are needed to determine the impact of implementing these educational tools in the postnatal hospital setting on parental utilization of analgesic interventions during infant hospitalization and future infant vaccinations.

Background: Neonatal sepsis is a cause of mortality and long-term morbidity worldwide. Objectives: To describe longitudinal trends in the cumulative incidence of early- and late-onset sepsis (EOS and LOS), mortality, and causative organisms in a Thai Hospital before and after construction of a new neonatal intensive care unit (NICU). Methods: Review of NICU admissions with blood cultures positive for bacteria or fungi for the periods 1995 to 2002 (preconstruction) and 2004 to 2010 (postconstruction). Sepsis was categorized into EOS (within first 3 days of life) and LOS (after first 3 days of life). Results: Of 5,570 admissions, 241 (4.3%) neonates with 276 episodes of sepsis were identified. There was no difference in the rate of sepsis overall (P = 0.90), LOS (P = 0.30), or sepsis-related mortality (P = 0.61) over the two periods, but the rate of EOS increased significantly from 0.34% to 0.81% (P = 0.04). Rates of Klebsiella species and Escherichia coli sepsis increased from 13.6% to 25.6% (P = 0.01) and from 5.3% to 12.2% (P = 0.04), respectively, while rates of Staphylococcus aureus sepsis decreased from 12.9% to 4.3% (P < 0.007). Sepsisrelated mortality was 1.8%. Conclusions: Although direct causality cannot be proven, the rate of EOS and the pattern of causative organisms changed following construction of the new NICU. Building a new unit does not necessarily result in a reduction in the rate of sepsis. This data may provide a baseline for implementing evidence-based infection control strategies to prevent/reduce sepsis and improve neonatal care.

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.

Objectives To evaluate the impact of implementing a simple, user-friendly eLearning module on hand hygiene (HH) compliance and infection rates. Design Preintervention and postintervention observational study. Participants All neonates admitted to the neonatal intensive care unit (NICU) over the study period were eligible for participation and were included in the analyses. A total of 3422 patients were admitted over a 36-month span (July 2009 to June 2012). Interventions In the preintervention and postintervention periods (phases I and II), all healthcare providers were trained on HH practices using an eLearning module. The principles of the ‘4 moments of HH’ and definition of ‘baby space’ were incorporated using interactive tools. The intervention then extended into a long-term sustainability programme (phase III), including the requirement of an annual recertification of the module and introduction of posters and screensavers throughout the NICU. Primary and secondary outcome measures The primary outcome was HH compliance rates among healthcare providers in the three phases. The secondary outcome was healthcare-associated infection rates in the NICU. Results HH compliance rates declined initially in phase II then improved in phase III with the addition of a long-term sustainability programme (76%, 67% and 76% in phases I, II and III, respectively (pConclusions Interventions to improve HH compliance are challenging to implement and sustain with the need for ongoing reinforcement and education.

Although numerous evidence-based and feasible interventions are available to treat pain from childhood vaccine injections, evidence indicates that children are not benefitting from this knowledge. Unrelieved vaccination pain puts children at risk for significant long-term harms including the development of needle fears and subsequent health care avoidance behaviours. Parents report that while they want to mitigate vaccination pain in their children, they lack knowledge about how to do so. An evidence-based clinical practice guideline for managing vaccination pain was recently developed in order to address this knowledge-to-care gap. Educational tools (pamphlet and video) for parents were included to facilitate knowledge transfer at the point of care. The objectives of this study were to evaluate usability and effectiveness in terms of knowledge acquisition from the pamphlet and video in parents of newly born infants. Mixed methods design. Following heuristic usability evaluation of the pamphlet and video, parents of newborn infants reviewed revised versions of both tools and participated in individual and group interviews and individual knowledge testing. The knowledge test comprised of 10 true/false questions about the effectiveness of various pain management interventions, and was administered at three time points: at baseline, after review of the pamphlet, and after review of the video. Three overarching themes were identified from the interviews regarding usability of these educational tools: receptivity to learning, accessibility to information, and validity of information. Parents’ performance on the knowledge test improved (p≤0.001) from the baseline phase to after review of the pamphlet, and again from the pamphlet review phase to after review of the video. Using a robust testing process, we demonstrated usability and conceptual knowledge acquisition from a parent-directed educational pamphlet and video about management of vaccination pain. Future studies are planned to determine the impact of these educational tools when introduced in clinical settings on parent behaviors during infant vaccinations.