The latest medical research on Paediatric Physician

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about paediatric physician gathered by our medical AI research bot.

The selection below is filtered by medical specialty. Registered users get access to the Plexa Intelligent Filtering System that personalises your dashboard to display only content that is relevant to you.

Want more personalised results?

Request Access

Results of Two Cases of Pig-to-Human Kidney Xenotransplantation.

N Engl J

Xenografts from genetically modified pigs have become one of the most promising solutions to the dearth of human organs available for transplantation. The challenge in this model has been hyperacute rejection. To avoid this, pigs have been bred with a knockout of the alpha-1,3-galactosyltransferase gene and with subcapsular autologous thymic tissue.

We transplanted kidneys from these genetically modified pigs into two brain-dead human recipients whose circulatory and respiratory activity was maintained on ventilators for the duration of the study. We performed serial biopsies and monitored the urine output and kinetic estimated glomerular filtration rate (eGFR) to assess renal function and xenograft rejection.

The xenograft in both recipients began to make urine within moments after reperfusion. Over the 54-hour study, the kinetic eGFR increased from 23 ml per minute per 1.73 m2 of body-surface area before transplantation to 62 ml per minute per 1.73 m2 after transplantation in Recipient 1 and from 55 to 109 ml per minute per 1.73 m2 in Recipient 2. In both recipients, the creatinine level, which had been at a steady state, decreased after implantation of the xenograft, from 1.97 to 0.82 mg per deciliter in Recipient 1 and from 1.10 to 0.57 mg per deciliter in Recipient 2. The transplanted kidneys remained pink and well-perfused, continuing to make urine throughout the study. Biopsies that were performed at 6, 24, 48, and 54 hours revealed no signs of hyperacute or antibody-mediated rejection. Hourly urine output with the xenograft was more than double the output with the native kidneys.

Genetically modified kidney xenografts from pigs remained viable and functioning in brain-dead human recipients for 54 hours, without signs of hyperacute rejection. (Funded by Lung Biotechnology.).

Validation of the Pediatric Sequential Organ Failure Assessment Score and Evaluation of Third International Consensus Definitions for Sepsis and Septic Shock Definitions in the Pediatric Emergency Department.

JAMA Pediatrics

Pediatric sepsis definitions have evolved, and some have proposed using the measure used in adults to quantify organ dysfunction, a Sequential Organ Failure Assessment (SOFA) score of 2 or more in the setting of suspected infection. A pediatric adaptation of SOFA (pSOFA) showed excellent discrimination for mortality in critically ill children but has not been evaluated in an emergency department (ED) population.

To delineate test characteristics of the pSOFA score for predicting in-hospital mortality among (1) all patients and (2) patients with suspected infection treated in pediatric EDs.

This retrospective cohort study took place from January 1, 2012, to January 31, 2020 in 9 US children's hospitals included in the Pediatric Emergency Care Applied Research Network (PECARN) Registry. The data was analyzed from February 1, 2020, to April 18, 2022. All ED visits for patients younger than 18 years were included.

ED pSOFA score was assigned by summing maximum pSOFA organ dysfunction components during ED stay (each 0-4 points). In the subset with suspected infection, visit meeting criteria for sepsis (suspected infection with a pSOFA score of 2 or more) and septic shock (suspected infection with vasoactive infusion and serum lactate level >18.0 mg/dL) were identified.

Test characteristics of pSOFA scores of 2 or more during the ED stay for hospital mortality.

A total of 3 999 528 (female, 47.3%) ED visits were included. pSOFA scores ranged from 0 to 16, with 126 250 visits (3.2%) having a pSOFA score of 2 or more. pSOFA scores of 2 or more had sensitivity of 0.65 (95% CI, 0.62-0.67) and specificity of 0.97 (95% CI, 0.97-0.97), with negative predictive value of 1.0 (95% CI, 1.00-1.00) in predicting hospital mortality. Of 642 868 patients with suspected infection (16.1%), 42 992 (6.7%) met criteria for sepsis, and 374 (0.1%) met criteria for septic shock. Hospital mortality rates for suspected infection (599 502), sepsis (42 992), and septic shock (374) were 0.0%, 0.9%, and 8.0%, respectively. The pSOFA score had similar discrimination for hospital mortality in all ED visits (area under receiver operating characteristic curve, 0.81; 95% CI, 0.79-0.82) and the subset with suspected infection (area under receiver operating characteristic curve, 0.82; 95% CI, 0.80-0.84).

In a large, multicenter study of pediatric ED visits, a pSOFA score of 2 or more was uncommon and associated with increased hospital mortality yet had poor sensitivity as a screening tool for hospital mortality. Conversely, children with a pSOFA score of 2 or less were at very low risk of death, with high specificity and negative predictive value. Among patients with suspected infection, patients with pSOFA-defined septic shock demonstrated the highest mortality.

Association Between High-Need Education-Based Funding and School Suspension Rates for Autistic Students in New Zealand.

JAMA Pediatrics

Autistic students often experience poor educational outcomes that have implications for later life, including unemployment, interactions with the criminal justice system, increased risk for substance abuse, and low socioeconomic status. Improving educational outcomes is critical for ensuring that autistic young people can reach their potential.

To quantify differences in suspension rates between autistic and nonautistic students and to assess whether high-need education-based funding for autistic students is associated with reduced rates of school suspension.

This national cohort study used linked health and education data from New Zealand's Integrated Data Infrastructure. Data were obtained for students aged 5 to 16 years from January 1 to December 31, 2018, and analyzed July 7, 2021, to January 1, 2022. A novel case identification method was used to identify autistic students.

High-need education-based funding (Ongoing Resourcing Scheme [ORS]) obtained before 2019.

Rates of suspension from school. Crude and adjusted analyses of the association between suspension rates and autism among the full population with adjustment made for sociodemographic characteristics (sex, age, ethnicity, deprivation, and urban or rural profile of residence) were conducted using complete-case, 2-level random intercept logistic multivariable regressions. To assess the association between ORS funding and suspension, analysis was restricted to autistic students.

Of the 736 911 students in the study population, 9741 (1.3%) were identified as autistic (median [SD] age, 10 [3.2] years; 7710 [79.1%] boys), and 727 170 (98.7%) as nonautistic (median [SD] age, 10 [3.4] years; 369 777 [50.9%] boys). School suspension was experienced by 504 autistic students (5.2%) and 13 845 nonautistic students (1.9%). After adjustment for demographic characteristics, autistic students had significantly higher odds of suspension than their nonautistic peers (adjusted odds ratio, 2.81; 95% CI, 2.55-3.11). Of the 9741 autistic students, 2895 (29.7%) received high-need education-based (ORS) funding. Suspensions were experienced by 57 autistic students (2.0%) with high-need funding and 447 autistic students (6.5%) without high-need funding. After adjustment for demographic characteristics, co-occurring conditions, and level of disability support need, autistic students with high-need funding had significantly lower odds of suspension than autistic students without high-need funding (adjusted odds ratio, 0.29; 95% CI, 0.21-0.40).

In this cohort study, the findings of disparities in suspension rates between autistic and nonautistic students underscore the challenges faced in providing inclusive education for all young people, regardless of disability status. This study found that high-need funding was associated with reduced suspension rates among autistic students, suggesting that if appropriate supports are afforded to autistic students, a more inclusive education can be provided.

Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma.

N Engl J

As asthma symptoms worsen, patients typically rely on short-acting β2-agonist (SABA) rescue therapy, but SABAs do not address worsening inflammation, which leaves patients at risk for severe asthma exacerbations. The use of a fixed-dose combination of albuterol and budesonide, as compared with albuterol alone, as rescue medication might reduce the risk of severe asthma exacerbation.

We conducted a multinational, phase 3, double-blind, randomized, event-driven trial to evaluate the efficacy and safety of albuterol-budesonide, as compared with albuterol alone, as rescue medication in patients with uncontrolled moderate-to-severe asthma who were receiving inhaled glucocorticoid-containing maintenance therapies, which were continued throughout the trial. Adults and adolescents (≥12 years of age) were randomly assigned in a 1:1:1 ratio to one of three trial groups: a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide (with each dose consisting of two actuations of 90 μg and 80 μg, respectively [the higher-dose combination group]), a fixed-dose combination of 180 μg of albuterol and 80 μg of budesonide (with each dose consisting of two actuations of 90 μg and 40 μg, respectively [the lower-dose combination group]), or 180 μg of albuterol (with each dose consisting of two actuations of 90 μg [the albuterol-alone group]). Children 4 to 11 years of age were randomly assigned to only the lower-dose combination group or the albuterol-alone group. The primary efficacy end point was the first event of severe asthma exacerbation in a time-to-event analysis, which was performed in the intention-to-treat population.

A total of 3132 patients underwent randomization, among whom 97% were 12 years of age or older. The risk of severe asthma exacerbation was significantly lower, by 26%, in the higher-dose combination group than in the albuterol-alone group (hazard ratio, 0.74; 95% confidence interval [CI], 0.62 to 0.89; P = 0.001). The hazard ratio in the lower-dose combination group, as compared with the albuterol-alone group, was 0.84 (95% CI, 0.71 to 1.00; P = 0.052). The incidence of adverse events was similar in the three trial groups.

The risk of severe asthma exacerbation was significantly lower with as-needed use of a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide than with as-needed use of albuterol alone among patients with uncontrolled moderate-to-severe asthma who were receiving a wide range of inhaled glucocorticoid-containing maintenance therapies. (Funded by Avillion; MANDALA number, NCT03769090.).

Trial of a Preferential Phosphodiesterase 4B Inhibitor for Idiopathic Pulmonary Fibrosis.

N Engl J

Phosphodiesterase 4 (PDE4) inhibition is associated with antiinflammatory and antifibrotic effects that may be beneficial in patients with idiopathic pulmonary fibrosis.

In this phase 2, double-blind, placebo-controlled trial, we investigated the efficacy and safety of BI 1015550, an oral preferential inhibitor of the PDE4B subtype, in patients with idiopathic pulmonary fibrosis. Patients were randomly assigned in a 2:1 ratio to receive BI 1015550 at a dose of 18 mg twice daily or placebo. The primary end point was the change from baseline in the forced vital capacity (FVC) at 12 weeks, which we analyzed with a Bayesian approach separately according to background nonuse or use of an antifibrotic agent.

A total of 147 patients were randomly assigned to receive BI 1015550 or placebo. Among patients without background antifibrotic use, the median change in the FVC was 5.7 ml (95% credible interval, -39.1 to 50.5) in the BI 1015550 group and -81.7 ml (95% credible interval, -133.5 to -44.8) in the placebo group (median difference, 88.4 ml; 95% credible interval, 29.5 to 154.2; probability that BI 1015550 was superior to placebo, 0.998). Among patients with background antifibrotic use, the median change in the FVC was 2.7 ml (95% credible interval, -32.8 to 38.2) in the BI 1015550 group and -59.2 ml (95% credible interval, -111.8 to -17.9) in the placebo group (median difference, 62.4 ml; 95% credible interval, 6.3 to 125.5; probability that BI 1015550 was superior to placebo, 0.986). A mixed model with repeated measures analysis provided results that were consistent with those of the Bayesian analysis. The most frequent adverse event was diarrhea. A total of 13 patients discontinued BI 1015550 treatment owing to adverse events. The percentages of patients with serious adverse events or severe adverse events were similar in the two trial groups.

In this placebo-controlled trial, treatment with BI 1015550, either alone or with background use of an antifibrotic agent, prevented a decrease in lung function in patients with idiopathic pulmonary fibrosis. (Funded by Boehringer Ingelheim; 1305-0013 number, NCT04419506.).

Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age.

N Engl J

Vaccination of children to prevent coronavirus disease 2019 (Covid-19) is an urgent public health need. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in children 6 to 11 years of age are unknown.

Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled expansion evaluation of the selected dose. In part 2, we randomly assigned children (6 to 11 years of age) in a 3:1 ratio to receive two injections of mRNA-1273 (50 μg each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of the vaccine in children and the noninferiority of the immune response in these children to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives included determination of the incidences of confirmed Covid-19 and severe acute respiratory syndrome coronavirus 2 infection, regardless of symptoms. Interim analysis results are reported.

In part 1 of the trial, 751 children received 50-μg or 100-μg injections of the mRNA-1273 vaccine, and on the basis of safety and immunogenicity results, the 50-μg dose level was selected for part 2. In part 2 of the trial, 4016 children were randomly assigned to receive two injections of mRNA-1273 (50 μg each) or placebo and were followed for a median of 82 days (interquartile range, 14 to 94) after the first injection. This dose level was associated with mainly low-grade, transient adverse events, most commonly injection-site pain, headache, and fatigue. No vaccine-related serious adverse events, multisystem inflammatory syndrome in children, myocarditis, or pericarditis were reported as of the data-cutoff date. One month after the second injection (day 57), the neutralizing antibody titer in children who received mRNA-1273 at a 50-μg level was 1610 (95% confidence interval [CI], 1457 to 1780), as compared with 1300 (95% CI, 1171 to 1443) at the 100-μg level in young adults, with serologic responses in at least 99.0% of the participants in both age groups, findings that met the prespecified noninferiority success criterion. Estimated vaccine efficacy was 88.0% (95% CI, 70.0 to 95.8) against Covid-19 occurring 14 days or more after the first injection, at a time when B.1.617.2 (delta) was the dominant circulating variant.

Two 50-μg doses of the mRNA-1273 vaccine were found to be safe and effective in inducing immune responses and preventing Covid-19 in children 6 to 11 years of age; these responses were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; KidCOVE number, NCT04796896.).

Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection.

N Engl J

Patients with multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection have limited treatment options. Lenacapavir is a first-in-class capsid inhibitor that showed substantial antiviral activity in a phase 1b study.

In this phase 3 trial, we enrolled patients with multidrug-resistant HIV-1 infection in two cohorts, according to the change in the plasma HIV-1 RNA level between the screening and cohort-selection visits. In cohort 1, patients were first randomly assigned in a 2:1 ratio to receive oral lenacapavir or placebo in addition to their failing therapy for 14 days; during the maintenance period, starting on day 15, patients in the lenacapavir group received subcutaneous lenacapavir once every 6 months, and those in the placebo group received oral lenacapavir, followed by subcutaneous lenacapavir; both groups also received optimized background therapy. In cohort 2, all the patients received open-label oral lenacapavir with optimized background therapy on days 1 through 14; subcutaneous lenacapavir was then administered once every 6 months starting on day 15. The primary end point was the percentage of patients in cohort 1 who had a decrease of at least 0.5 log10 copies per milliliter in the viral load by day 15; a key secondary end point was a viral load of less than 50 copies per milliliter at week 26.

A total of 72 patients were enrolled, with 36 in each cohort. In cohort 1, a decrease of at least 0.5 log10 copies per milliliter in the viral load by day 15 was observed in 21 of 24 patients (88%) in the lenacapavir group and in 2 of 12 patients (17%) in the placebo group (absolute difference, 71 percentage points; 95% confidence interval, 35 to 90). At week 26, a viral load of less than 50 copies per milliliter was reported in 81% of the patients in cohort 1 and in 83% in cohort 2, with a least-squares mean increase in the CD4+ count of 75 and 104 cells per cubic millimeter, respectively. No serious adverse events related to lenacapavir were identified. In both cohorts, lenacapavir-related capsid substitutions that were associated with decreased susceptibility developed in 8 patients during the maintenance period (6 with M66I substitutions).

In patients with multidrug-resistant HIV-1 infection, those who received lenacapavir had a greater reduction from baseline in viral load than those who received placebo. (Funded by Gilead Sciences; CAPELLA number, NCT04150068.).

Association Between a Policy to Subsidize Supermarkets in Underserved Areas and Childhood Obesity Risk.

JAMA Pediatrics

The establishment and renovation of supermarkets may promote healthy diet practices among youth by increasing retail infrastructure for fresh foods.

To estimate the association between the Food Retail Expansion to Support Health (FRESH) program and the weight status of children and adolescents.

Using a difference-in-differences (DiD) design and including 12 months before and after a FRESH supermarket opened, data were analyzed for residentially stable public school students in kindergarten through 12th grade with objectively measured height and weight data from the academic years 2009 through 2016. Of the 8 FRESH-subsidized supermarkets in residential neighborhoods in New York City, New York, 5 were new and 3 were renovation projects between December 2011 and June 2014. Data were analyzed from June 2021 to January 2022.

The treatment group included students who resided within 0.50 miles of a FRESH-subsidized supermarket and had at least 1 body mass index (BMI) measurement within 12 months before and 3 to 12 months after the month a FRESH supermarket opened (n = 22 712 student-year observations). A 2-stage matching-weighting approach was used to construct a control group of students who resided more than 0.50 miles from a FRESH supermarket in a FRESH-eligible area (n = 86 744 student-year observations).

BMI z score was calculated using objectively measured height and weight data from FITNESSGRAM, an annual, school-based, standardized fitness assessment of every New York City public school student. Obesity was defined as 95th percentile or greater of the BMI z score using Centers for Disease Control and Prevention growth charts.

The treatment group in the analytic sample had 11 356 students (22 712 student-year observations), and the control group had 43 372 students (86 744 student-year observations). The students were predominately Black (18.8%) and Hispanic and Latino (68.5%) and eligible for free or reduced-priced lunch (84.6%). There was a significant decrease in BMI z score among students who resided within 0.50 miles of a FRESH supermarket (vs control group students) in the 3- to 12-month follow-up period (DiD, -0.04; 95% CI, -0.06 to -0.02). This was true for those exposed to supermarkets that were either new (DiD, -0.07; 95% CI, -0.11 to -0.03) or renovated (DiD, -0.03; 95% CI, -0.06 to -0.01). A statistically significant decrease was also observed in the likelihood of obesity (DiD, -0.01; 95% CI, -0.02 to -0.002).

Government-subsidized supermarkets may contribute to a small decrease in obesity risk among children residing near those supermarkets, if part of a comprehensive policy approach.

Developmental Outcomes for Children After Elective Birth at 39 Weeks' Gestation.

JAMA Pediatrics

Elective births at 39 weeks' gestation are increasing. While this option may improve maternal and perinatal outcomes compared with expectant management, longer-term childhood developmental outcomes are uncertain.

To investigate the association between elective birth at 39 weeks' gestation and the risk of childhood developmental vulnerability.

For this cohort study, 2 causal inference analyses were conducted using Australian statewide, population-based data. Perinatal data from births between January 1, 2005, and December 31, 2013, were linked to childhood developmental outcomes at age 4 to 6 years (assessed using multiple imputation via inverse probability-weighted regression adjustment). Data analyses were conducted between September 7 and November 9, 2021.

Two exposure groups were considered: (1) elective birth between 39 weeks and 0 days' and 39 weeks and 6 days' gestation vs expectant management and (2) birth via induction of labor vs planned cesarean delivery among those born electively at 39 weeks' gestation.

Childhood developmental vulnerability at school entry, defined as scoring below the 10th percentile in at least 2 of 5 developmental domains (physical health and well-being, social competence, emotional maturity, school-based language and cognitive skills, and communication skills and general knowledge).

Of 176 236 births with linked outcome data, 88 165 met the inclusion criteria. Among these, 15 927 (18.1%) were elective births at 39 weeks' gestation (induction of labor or planned cesarean delivery), and 72 238 (81.9%) were expectantly managed with subsequent birth between 40 and 43 weeks' gestation. Compared with expectant management, elective birth at 39 weeks' gestation was not associated with an altered risk of childhood global developmental vulnerability (adjusted relative risk [aRR], 1.03; 95% CI, 0.96-1.12) or with developmental vulnerability in any of the individual domains. In an analysis restricted to elective births at 39 weeks' gestation, induction of labor (n = 7928) compared with planned cesarean delivery (n = 7999) was not associated with childhood developmental vulnerability (aRR, 0.96; 95% CI, 0.82-1.12) or with vulnerability in any individual domains.

In this cohort study, elective birth at 39 weeks' gestation was not associated with childhood developmental vulnerability. For those born electively at 39 weeks' gestation, birth after induction of labor or by elective cesarean delivery had similar developmental outcomes.

Association of Food and Nonalcoholic Beverage Marketing With Children and Adolescents' Eating Behaviors and Health: A Systematic Review and Meta-analysis.

JAMA Pediatrics

There is widespread interest in the effect of food marketing on children; however, the comprehensive global evidence reviews are now dated.

To quantify the association of food and nonalcoholic beverage marketing with behavioral and health outcomes in children and adolescents to inform updated World Health Organization guidelines.

Twenty-two databases were searched (including MEDLINE, CINAHL, Web of Science, Embase, and The Cochrane Library) with a publication date limit from January 2009 through March 2020.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed. Inclusion criteria were primary studies assessing the association of food marketing with specified outcomes in children and adolescents (aged 0-19 years). Exclusion criteria were qualitative studies or those on advertising of infant formula. Of 31 063 articles identified, 96 articles were eligible for inclusion in the systematic review, and 80 articles in the meta-analysis (19 372 participants).

Two reviewers independently extracted data. Random-effects models were used for meta-analyses; meta-regressions, sensitivity analyses, and P curve analyses were also performed. Where appropriate, pooling was conducted using combining P values and vote counting by direction of effect. Grading of Recommendations Assessment, Development, and Evaluation was used to judge certainty of evidence.

Critical outcomes were intake, choice, preference, and purchasing. Important outcomes were purchase requests, dental caries, body weight, and diet-related noncommunicable diseases.

Participants totaled 19 372 from 80 included articles. Food marketing was associated with significant increases in intake (standardized mean difference [SMD], 0.25; 95% CI, 0.15-0.35; P < .001), choice (odds ratio, 1.77; 95% CI, 1.26-2.50; P < .001), and preference (SMD, 0.30; 95% CI, 0.12-0.49; P = .001). Substantial heterogeneity (all >76%) was unexplained by sensitivity or moderator analyses. The combination of P values for purchase requests was significant but no clear evidence was found for an association of marketing with purchasing. Data on dental health and body weight outcomes were scarce. The certainty of evidence was graded as very low to moderate for intake and choice, and very low for preference and purchasing.

In this systematic review and meta-analysis, food marketing was associated with increased intake, choice, preference, and purchase requests in children and adolescents. Implementation of policies to restrict children's exposure is expected to benefit child health.

Association of Diagnostic Stewardship for Blood Cultures in Critically Ill Children With Culture Rates, Antibiotic Use, and Patient Outcomes: Results of the Bright STAR Collaborative.

JAMA Pediatrics

Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics.

To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes.

This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children's Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes.

A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative).

The primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics ≥3 days after PICU admission) and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock.

Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation.

Multidisciplinary diagnostic stewardship interventions can reduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.

Prefusion F Protein-Based Respiratory Syncytial Virus Immunization in Pregnancy.

N Engl J

Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in pregnant women and their infants are uncertain.

In a phase 2b trial, we randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 μg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety end points and immunogenicity end points that, in this interim analysis, included 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical-cord blood, as well as maternal-to-infant transplacental transfer ratios.

This planned interim analysis included 406 women and 403 infants; 327 women (80.5%) received RSVpreF vaccine. Most postvaccination reactions were mild to moderate; the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide. The incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants. The geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies. Transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations. Across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios.

RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. (Funded by Pfizer; number, NCT04032093.).