Search

Purpose Neurosurgery (NS) is an essential modality for large brain metastases (BM). Postoperative stereotactic radiosurgery (SRS) is the standard of care adjuvant treatment. Pachymeningeal failure (PMF) is a newly described entity, distinct from classical leptomeningeal failure (LMF), that is uniquely observed in postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS + SRS. Methods From a prospective registry (2009 to 2021), we identified all patients treated with NS + SRS. Clinical, imaging, pathological, and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model. Results 144 Patients were identified. The median age was 62 (23–90). PMF occurred in 21.5% (31/144). Female gender [Hazard Ratio (HR) 2.65, p = 0.013], higher Graded Prognostic Assessment (GPA) index (HR 2.4, p

The purpose of this study is to compare the clinical effectiveness of dopamine (DA) versus norepinephrine (NE) as first-line therapy for sepsis-related hypotension in preterm infants. This is a retrospective cohort study over 10 years at two tertiary neonatal units. Preterm infants born 35 weeks post-menstrual age (PMA), who received DA or NE as primary therapy for hypotension during sepsis, defined as culture-positive or culture-negative infections or necrotizing enterocolitis (NEC), were included. Episode-related mortality ( 7 days from treatment), pre-discharge mortality, and major morbidities among survivors were compared between two groups. Analyses were adjusted using the inverse probability of treatment weighting estimated by propensity score (PS). A total of 156 infants were included, 113 received DA and 43 NE. The mean ± SD PMA at birth and at treatment for the DA and NE groups were 25.8 ± 2.3 vs. 25.2 ± 2.0 weeks and 27.7 ± 3.0 vs. 27.1 ± 2.6 weeks, respectively (p 0.05). Pre-treatment, the NE group had higher mean airway pressure (14 ± 4 vs. 12 ± 4 cmHNE may be more effective than DA for management of sepsis-related hypotension among preterm infants. These data provide a rationale for prospective evaluation of these commonly used agents.•Dopamine is the commonest vasoactive agent used to support blood pressure among preterm infants. •For adult patients, norepinephrine is recommended as the preferred therapy over dopamine for septic shock.•This is the first study examining the relative clinical effectiveness of dopamine and norepinephrine as first-line pharmacotherapy for sepsis-related hypotension among preterm infants. •Norepinephrine use may be associated with lower mortality and morbidity than dopamine in preterm infants with sepsis.

A large vertical incision is recommended when performing front-of-neck access in patients with impalpable neck landmarks during a cannot intubate-cannot oxygenate (CICO) scenario. We investigated the impact of ultrasonography on vertical incision size of a front-of-neck access on an ultrasound-compatible impalpable porcine larynx model.Emergency medicine and anesthesia trainees were randomized to the Ultrasound (US, n = 21) and Non-Ultrasound (NUS, n = 21) groups. Within 1 week after a teaching session on airway ultrasound and Scalpel-Bougie-Tube (SBT) technique, participants were instructed to perform cricothyroidotomy on the model during a simulated cannot intubate-cannot oxygenate scenario. The primary outcome was a vertical size incision. Secondary outcomes were procedural completion time, horizontal size incision, tissue injury severity, and correct tube placement.The ultrasound group performed a significantly smaller vertical incision [median (IQR), 35.0 (15, 40) vs 65.0 (52, 100) mm (95% CI) - 30.0 (- 55.1, - 4.9), p = 0.02] and took longer total time to complete the procedure [median (IQR), 200.5 (126, 267) vs 93.5 (71.0, 167.5) secs (95% CI) 91.0 (3.73, 178.3), p = 0.04]. Tissue injury severity and correct tube placement were similar between groups.Ultrasound-guided identification of the cricothyroid membrane significantly reduced the recommended vertical incision size with similar success rates. However, there was an increased time when performing a Scalpel-Bougie-Tube cricothyroidotomy on an impalpable porcine larynx model by physicians in training. Ultrasonography should not be used in an emergency scenario of airway rescue. Its potential use to pre-mark the cricothyroid membrane should be considered in difficult airway management of impalpable neck.RéSUMé: OBJECTIF: Il est recommandé de pratiquer une grande incision verticale lors de l'accès à l'avant du cou chez les patients dont les repères du cou sont impalpables, dans le cadre d'un scénario d'intubation impossible à oxygéner (CICO). Nous avons étudié l'impact de l'échographie sur la taille de l'incision verticale d'un accès à la face avant du cou sur un modèle de larynx porcin impalpable compatible avec l'échographie. MéTHODES: Des stagiaires en médecine d'urgence et en anesthésie ont été répartis de manière aléatoire entre les groupes "échographie" (US, n = 21) et "non-échographie" (NUS, n = 21). Une semaine après une session d'enseignement sur l'échographie des voies aériennes et la technique Scalpel-Bougie-Tube (SBT), les participants ont reçu l'instruction de réaliser une cricothyroïdotomie sur le modèle lors d'un scénario simulé d'impossibilité d'intubation et d'oxygénation. Le résultat primaire était une incision de taille verticale. Les résultats secondaires étaient le temps de réalisation de la procédure, la taille horizontale de l'incision, la gravité de la lésion tissulaire et le placement correct du tube. RéSULTATS: Le groupe échographie a réalisé une incision verticale significativement plus petite [médiane (IQR), 35,0 (15,40) vs 65,0 (52,100) mm (IC à 95 %) -30,0 (-55,1, -4,9), p = 0,02] et a pris un temps total plus long pour terminer la procédure [médiane (IQR), 200,5 (126, 267) vs 93,5 (71,0, 167,5) secondes (IC à 95 %) 91,0 (3,73, 178,3), p = 0,04]. La gravité des lésions tissulaires et le placement correct du tube étaient similaires entre les groupes. CONCLUSIONS: L'identification échoguidée de la membrane cricothyroïdienne a réduit de manière significative la taille de l'incision verticale recommandée avec des taux de réussite similaires. Cependant, il y avait une augmentation du temps lors de la réalisation d'une cricothyroïdotomie Scalpel-Bougie-Tube sur un modèle de larynx porcin impalpable par des médecins en formation. L'échographie ne doit pas être utilisée dans un scénario d'urgence de sauvetage des voies respiratoires. Son utilisation potentielle pour pré-marquer la membrane cricothyroïdienne devrait être envisagée dans la gestion des voies aériennes difficiles du cou impalpable.

Examine the real-world clinical impact of adopting less invasive surfactant administration (LISA) as the primary surfactant administration method in extremely preterm infants.Single-center pre-post cohort study conducted over a 4-year period comparing outcomes of spontaneously breathing inborn infants 24GA and birth weight were 27.1 (26, 28.1) weeks and 914 (230) g, and 27.1 (26.1, 28.1) weeks and 920 (236) g for pre- and post-cohorts, respectively. Pre-cohort had higher C-section rates, (67% vs. 51%, p = 0.03). After adjustment for covariates, LISA was associated with reduced IMV exposure [AOR (95% CI) 0.07 (0.04, 0.11)], lower odds of the composite clinical outcome [0.49 (0.33, 0.73)], and most of its individual components.Real-world experience favors LISA as the primary method in extremely preterm infants with established spontaneous respiration.Less invasive surfactant administration (LISA) is associated with a reduction in respiratory morbidity, but real-world data of routine use among extremely preterm infants are limited. LISA is associated with reduced frequency of exposure to and duration of IMV in both ≤72 h after birth and during hospital stay. LISA is associated with a reduction in mortality, and most other major morbidities including bronchopulmonary dysplasia, and interventricular hemorrhage. Data from a large North American center providing real-world clinical outcomes following LISA as the primary method of surfactant administration.

Assessment of sensory block level during labour epidural analgesia is an essential component of clinical practice and patient safety. Nevertheless, the methods and direction of testing are not standardized. In our hospital, sensory block testing to ice is routinely used, but while some anesthesiologists test the block from a nonanesthetized to an anesthetized area, some do it in the opposite direction. It is unknown how these two different practices affect identification of the sensory block level. The objective of this study was to determine the agreement between these two practices.We enrolled 31 patients admitted to the labour and delivery unit in a prospective cohort study. At their request, labour epidural analgesia was performed as per institutional routine. Sensory block level to ice was assessed using opposite directions by two randomly assigned independent investigators, one and two hours after the loading dose was administered.Sensory block levels to ice assessed from an anesthetized area to a nonanesthetized area were lower than those when assessed with the stimulus applied in the opposite direction, typically one segment lower.Given the small difference detected with both methods, it may be acceptable to use either in clinical practice. Nevertheless, the lack of standardization may have a significant impact when comparing studies involving assessment of sensory block to ice.www.gov (NCT03572439); registered 28 June 2018.RéSUMé: OBJECTIF: L’évaluation du niveau de bloc sensoriel pendant l’analgésie péridurale obstétricale est une composante essentielle de la pratique clinique et de la sécurité des patientes. Néanmoins, les méthodes et l’orientation des tests ne sont pas standardisées. Dans notre hôpital, les tests à la glace des blocs sensoriels sont couramment utilisés, mais alors que certains anesthésiologistes testent le bloc d’une zone non anesthésiée à une zone anesthésiée, certains le font dans la direction opposée. Nous ne savons pas dans quelle mesure ces deux pratiques différentes affectent l’identification du niveau du bloc sensoriel. L’objectif de cette étude était de déterminer la concordance entre ces deux pratiques. MéTHODE: Nous avons recruté 31 patientes admises à l’unité obstétricale dans une étude de cohorte prospective. À leur demande, l’analgésie péridurale obstétricale a été réalisée conformément à la routine institutionnelle. Le niveau du bloc sensoriel tel que mesuré par un test à la glace a été évalué dans les deux directions par deux chercheurs indépendants assignés au hasard, une et deux heures après l’administration de la dose de charge. RéSULTATS: Les niveaux de blocs sensoriels tels que mesurés par un test à la glace évalués d’une zone anesthésiée à une zone non anesthésiée étaient inférieurs à ceux évalués lorsque le stimulus était appliqué dans la direction opposée, habituellement un segment plus bas. DISCUSSION: Compte tenu de la petite différence détectée entre les deux méthodes, il peut être acceptable d’utiliser l’une ou l’autre dans la pratique clinique. Néanmoins, le manque de standardisation peut avoir un impact significatif lors de la comparaison d’études impliquant l’évaluation du bloc sensoriel à l’aide d’un test à la glace. ENREGISTREMENT DE L’éTUDE: www.ClinicalTrials.gov (NCT03572439); enregistrée le 28 juin 2018.

Introduction: Recent studies reported decreased incidence of late onset sepsis in the neonatal intensive care unit (NICU), but it is unclear whether this is also true for late onset meningitis. Recent reports that both meningitis and intraventricular hemorrhage (IVH) are associated with systemic inflammation also raise questions about an association between the 2. Methods: All preterm infants Results: Of 36,573 infants included, 32,198 had no infection, 3,977 had only late onset CPBSI and 398 had late onset meningitis. There was significant decrease in incidence of late onset CPBSI (14%–10%; adjusted odds ratio (AOR) = 0.93; 95% confidence interval [CI] 0.92, 0.95) but not late onset meningitis (1.6%–1.2%; AOR = 0.98; 95% CI 0.94, 1.01). Compared to infants with no IVH grade 3 or above, infants with IVH grade 3, or above had higher odds of late onset meningitis versus no infection (AOR 4.16; 95% CI 3.17, 5.44), and higher odds of late onset meningitis versus late onset CPBSI (AOR 4.11; 95% CI 3.08, 5.50). Conclusions: There was a decreasing trend of late onset CPBSI but not late onset meningitis. An association between late onset meningitis and IVH grade 3 or above was observed. Late onset CPBSI and meningitis may have different risk factors and require different prevention strategies.

Multiple pregnancy is associated with higher risk of uterine atony, postpartum hemorrhage (PPH), blood transfusion, hysterectomy, and death. The optimal dose of oxytocin at cesarean delivery in people with twin pregnancy is unknown. We sought to determine the effective bolus dose of oxytocin required to initiate adequate uterine tone in 90% of people (ED90) with twin pregnancy undergoing elective cesarean delivery. Our hypothesis was that the dose of oxytocin would be higher than 0.5 international units (IU) but lower than 5 IU.A double-blind dose-finding study using the biased coin up-down method was undertaken in people with twin pregnancy ≥36 weeks gestational age undergoing elective cesarean delivery under neuraxial anesthesia. Those with additional risk factors for PPH, apart from twin pregnancy, were excluded. Oxytocin was administered as an intravenous bolus over 1 minute on delivery of the second fetus. The first patient received 0.5 IU, and subsequent oxytocin doses were administered according to a sequential allocation scheme. The actual doses administered were 0.5, 1, 2, 3, 4, and 5 IU of oxytocin. The primary outcome was the response defined as the satisfactory uterine tone at 2 minutes after completion of administration of the oxytocin bolus, as assessed by the operating obstetrician. Secondary outcomes included need for rescue uterotonic drugs, adverse effects, and estimated blood loss. The ED90 was estimated using the Dixon-Mood and the isotonic regression methods.Thirty patients were included in study. The estimated ED90 of oxytocin was 4.38 IU (95% confidence interval [CI], 3.68-4.86 IU) and 3.41 IU (95% CI, 2.83-3.98 IU) by the isotonic regression and Dixon-Mood methods, respectively. Seven patients had inadequate tone at the 2-minute evaluation point and required rescue uterotonic drugs. The median (interquartile range [IQR]) estimated blood loss was 1031 mL (732-1462 mL) calculated by the change in 24-hour hematocrit. Incidence of hypotension after oxytocin administration was 27%, nausea 30%, and vomiting 17%.Our results demonstrated that people with twin pregnancy require a much higher dose of oxytocin than those with singleton pregnancies. We recommended people with twin pregnancies should receive an initial 5 IU bolus over at least 1 minute when undergoing elective cesarean delivery under neuraxial anesthesia.

BACKGROUND The objective of this study was to investigate the association between systolic, diastolic, and mean blood pressures (SBP, DBP, and MBP) and adverse outcomes in preterm neonates with late-onset sepsis (LOS). METHODS This is a two-center retrospective study over 6 years. Neonates 72 h age were included. Outcome measures were organ dysfunction (ODF) using the predefined criteria and post-ODF mortality (≤7 days from LOS onset). The lowest noninvasive blood pressures (BPs) recorded at baseline (24-48 h pre-LOS) and 0-12, 13-24, 25-36, and 37-48 h post LOS were analyzed. RESULTS Of 147 neonates, ODF occurred in 70 (48%), of which 20 (29%) died. ODF was associated with a drop in all BP components, starting 0-12 h post-LOS onset (p

Approximately one in five women will experience severe postoperative pain after Cesarean delivery (CD). Previously, a bedside three-item questionnaire (3-IQ) has shown to predict women experiencing higher evoked pain intensity after CD, with an area under the receiver operator characteristics (ROC) curve of 0.72. We hypothesized that the addition of psychophysical pain tests to the existing 3-IQ would improve the ability to predict severe pain in women undergoing elective CD under spinal anesthesia This was a prospective cohort study on women undergoing elective CD under spinal anesthesia. Women were assessed preoperatively using the 3-IQ, pressure algometry (PA) and mechanical temporal summation (TS) response. All women received standard perioperative care, including a multimodal analgesia regimen that included intrathecal fentanyl and morphine. A 0–100 mm visual analogue scale (VAS) was used to assess the severity of pain at rest (VASr) and on movement (VASm) at 24 and 48 hr after surgery. Patient satisfaction and opioid consumption were also recorded. We performed ROC curve analyses to assess whether we could improve the ability to predict our primary outcome of severe pain on movement at 24 hr (VASm24 ≥ 70). We studied 195 women. Median [interquartile range] VASm24 was 53 [32–72] and 28% of patients experienced a VASm24 ≥ 70. The ability to predict a VASm24 ≥ 70 assessed by the area under the ROC curve was 0.64 using the 3-IQ and 0.67 using the 3-IQ combined with TS and PA. The addition of PA and TS to the 3-IQ model resulted in a predictive model that performed similarly to the 3-IQ model alone. Further research is warranted in this area to better predict women at risk of severe pain post CD.

To assess the association between time of birth and mortality among preterm infants. Population-based study of infants born 22–36 weeks gestation (GA) in Canada from 2010 to 2015 (n = 173 789). Multivariable logistic regression models assessed associations between timing of birth and mortality. Among infants 22–27 weeks GA, evening birth was associated with higher mortality than daytime birth (adjusted odds ratio [AOR] 1.14, 95% CI 1.01–1.29). Among infants 28–32 weeks GA and 33–36 weeks GA, night birth was associated with lower mortality than daytime birth (AOR 0.75, 95% CI 0.59–0.95; AOR 0.78, 95% CI 0.62–0.99, respectively). Sensitivity analysis excluding infants with major congenital anomaly revealed that associations between hour of birth and mortality among infants born 28–32 and 33–36 weeks GA decreased or were not statistically significant. Higher mortality among extremely preterm infants during off-peak hours may suggest variations in available resources based on time of day.

OBJECTIVE To evaluate inter-rater agreement for sonographic classification of stomach position (as a surrogate for liver herniation) in fetal left congenital diaphragmatic hernia (LCDH) among: (i) fetal medicine specialists from the North American Fetal Therapy Network (NAFTNet) centers within and without the fetal endoscopic tracheal occlusion (FETO) consortium and in comparison to an expert external reviewer (ER1); and (iii) among two expert ERs (ER1 and ER2). METHODS Forty-eight physicians from 26 NAFTNet centers and 2 ERs were asked to assess 13 sonographic clips of isolated LCDH and classify stomach position as "intra-abdominal," "anterior left chest," "mid to posterior left chest," or "retro-cardiac" based on the classification published by Basta et al.8 Interrater agreement was assessed by determining proportion of stomach position ratings concordant amongst NAFTNet participants and ER1. Agreement for stomach position between ERs was calculated using kappa statistics. RESULTS Agreement for stomach position was 69% (39%-85%; n = 19) and 54% (23%-92%; n = 29) among FETO and non-FETO NAFTNet participants, respectively, when compared to ER1. Most disagreement in stomach position was related to a discrepancy of one position. ERs were in agreement for stomach position in 5 of 13 cases (38.5%) and inter-rater agreement was highest for "anterior" stomach position. CONCLUSION Interrater agreement for stomach position assessment in CDH was poor across NAFTNet and indeed amongst expert reviewers.

BACKGROUND Decision-making deficits in airway emergencies have led to adverse patient outcomes. A cognitive aid would assist clinicians through critical decision-making steps, preventing key action omission. OBJECTIVE We aimed to investigate the effects of a visual airway cognitive aid on decision-making in a simulated airway emergency scenario. DESIGN Randomised controlled study. SETTING Single-institution, tertiary-level hospital in Toronto, Canada from September 2017 to March 2019. PARTICIPANTS Teams consisting of a participant anaesthesia resident, nurse and respiratory therapist were randomised to intervention (N = 20 teams) and control groups (N = 20 teams). INTERVENTION Participants in both groups received a 15-min didactic session on crisis resource management which included teamwork communication and the concepts of cognitive aids for the management of nonairway and airway critical events. Only participants in the intervention group were familiarised, oriented and instructed on a visual airway cognitive aid that was developed for this study. Within 1 to 4 weeks after the teaching session, teams were video-recorded managing a simulated 'cannot intubate-cannot oxygenate' scenario with the aid displayed in the simulation centre. MAIN OUTCOME MEASURES Decision-making time to perform a front-of-neck access (FONA), airway checklist actions, teamwork performances and a postscenario questionnaire. RESULTS Both groups performed similar key airway actions; however, the intervention group took a shorter decision-making time than the control group to perform a FONA after a last action [mean ± SD, 80.9 ± 54.5 vs. 122.2 ± 55.7 s; difference (95% CI) -41.2 (-76.5 to -6.0) s, P = 0.023]. Furthermore, the intervention group used the aid more than the control group (63.0 vs. 28.1%, P

OBJECTIVES To assess short- and long-term outcome in a cohort of fetuses diagnosed with hydrothorax (FHT) which underwent thoracoamniotic shunting in utero, and to examine the antenatal predictors of survival and of survival with normal neurodevelopmental outcome. METHODS This was a retrospective analysis of 132 fetuses that underwent thoracoamniotic shunting at our center between 1991 and 2014. Data were extracted from hospital obstetric and relevant neonatal intensive care and neonatal developmental follow-up databases. Outcomes included survival to discharge and survival with normal neurodevelopmental outcome beyond 18 months. Information on malformations, syndromes and genetic abnormalities were obtained from antenatal, postnatal and pediatric hospital records or by parent report. We compared pregnancy characteristics among those who survived vs non-survivors and among those with normal neurodevelopmental outcome vs those who were abnormal or died. We explored whether there was a trend in survival over the study period. RESULTS The mean gestational age at diagnosis of FHT was 25.6 weeks. The fetus was hydropic at diagnosis in 61% of cases, 69% had bilateral effusions and 55% had bilateral shunts inserted. Other diagnoses were present in 24% of cases, two-thirds of which were discovered only postnatally. There were 16 intrauterine and 30 neonatal deaths, with a 65% survival rate overall. The mean gestational age at delivery of liveborns was 35.4 (range, 26.9-41.6) weeks, and 88/116 (76%) were preterm (

BACKGROUND: Conflicting reports have emerged for rates of preterm births and stillbirths during the COVID-19 pandemic. Most of these reports did not account for natural variation in these rates. We aimed to evaluate variations in preterm birth and stillbirth rates before and during the COVID-19 pandemic in Ontario, Canada. METHODS: We conducted a retrospective cohort study using linked population health administrative databases of pregnant people giving birth in any hospital in Ontario between July 2002 and December 2020. We calculated preterm birth and stillbirth rates. We assessed preterm birth at 22-28, 29-32 and 33-36 weeks' gestation, and stillbirths at term and preterm gestation. We used Laney control P' charts for the 18-year study period (6-mo observation periods) and interrupted time-series analyses for monthly rates for the most recent 4 years. RESULTS: We evaluated 2 465 387 pregnancies, including 13 781 that resulted in stillbirth. The mean preterm birth rate for our cohort was 7.96% (range 7.32%-8.59%). From January to December 2020, we determined that the preterm birth rate in Ontario was 7.87%, with no special cause variation. The mean stillbirth rate for the cohort was 0.56% (range 0.48%-0.70%). From January to December 2020, the stillbirth rate was 0.53%, with no special cause variation. We did not find any special cause variation for preterm birth or stillbirth subgroups. We found no changes in slope or gap between prepandemic and pandemic periods using interrupted time-series analyses. INTERPRETATION: In Ontario, Canada, we found no special cause variation (unusual change) in preterm birth or stillbirth rates, overall or by subgroups, during the first 12 months of the COVID-19 pandemic compared with the previous 17.5 years.

Purpose Conventional palpation techniques for cricothyroid membrane (CTM) identification are inaccurate and unreliable. Ultrasound plays a multi-faceted role in airway management, however there is limited literature around its use for CTM identification prior to cricothyrotomies. This review sought to compare ultrasound to palpation in the general population, identify its indications in subjects with ill-defined neck anatomy, and determine its role in defining neck anatomy. Methods Two reviewers independently assessed titles, abstracts and full-text English articles through the Ovid Medline and EMBASE databases. Studies related to ultrasound for CTM assessment and/or cricothyrotomy in subjects older than 12 years were included. Results Fourteen studies were selected. Compared to palpation, ultrasound has greater accuracy, but longer CTM identification times in those with normal airway anatomy. Interestingly, ultrasound offers comparable times to palpation in patients with difficult airways. Ultrasound also helps define anatomical parameters in the neutral and extended neck positions thereby underscoring the importance of neck positioning during cricothyrotomies and confirming consensus-based incision recommendations set by the Difficult Airway Society. Conclusion Ultrasound appears to be superior to palpation for CTM localization especially in those with difficult airway anatomy and objectively defines neck anatomy. Its pre-emptive use should be incorporated during difficult airway management.

For patients with recurrent implantation failure in IVF, histologic or transcriptomic testing of the endometrium during the mid-secretory phase is often considered. Histological dating of endometrial biopsies (Noyes criteria) can determine if endometrial morphology is consistent with the period of receptivity. Alternatively, endometrial tissue can be sent for a commercial Endometrial Receptivity Array (ERA) test which characterizes the gene expression of the endometrium using a panel of 238 genes that have been implicated in endometrial receptivity. This study aimed to compare the two tests to assess their concordance and to examine the ability of the ERA to successfully predict implantation and pregnancy in a subsequent personalized embryo transfer. A retrospective review was done of 97 patients with a history of implantation failure who underwent an ERA, 35 of whom had histologic dating on the same sample. ERA and histology were classified as 'concordant' when samples were receptive by both tests or non-receptive by both tests. The ERA result was then used to personalize the embryo transfer day, and pregnancy rates from the first subsequent frozen transfer cycle were analyzed. The results indicated that there is poor concordance between ERA and histological dating with only 40.0% agreement and a kappa (95%CI) = -0.18 (-0.50, 0.14). According to the ERA, 48.5% of biopsies were receptive, 47.4% were non-receptive and 2.01% were insufficient tissue for analysis. The clinical pregnancy rate in patients shown to be receptive by ERA was 26.7% and non-receptive was 22.5% following the subsequent personalized ET (p = 0.66). This study concludes that there is a high degree of discordance between histological dating of the endometrium and molecular analysis by ERA. There was no evidence of clinical benefit when embryo transfer was personalized according to ERA in patients with a history of implantation failure.

Background and ObjectivesNo evidence of disease activity (NEDA)-4 has been suggested as a treatment target for disease-modifying therapy (DMT) in relapsing-remitting multiple sclerosis (RRMS). However, the ability of NEDA-4 to discriminate long-term outcomes in MS and how its performance compares with NEDA-3 remain uncertain. We conducted a systematic review and meta-analysis to evaluate (1) the association between NEDA-4 and no long-term disability progression in MS and (2) the comparative performance of NEDA-3 and NEDA-4 in predicting no long-term disability progression.MethodsEnglish-language abstracts and manuscripts were systematically searched in MEDLINE, Embase, and the Cochrane databases from January 2006 to November 2021 and reviewed independently by 2 investigators. We selected studies that assessed NEDA-4 at 1 or 2 years after DMT start and had at least 4 years of follow-up for determination of no confirmed disability progression. We conducted a meta-analysis using random-effects model to determine the pooled odds ratio (OR) for no disability progression with NEDA-4 vs EDA-4. For the comparative analysis, we selected studies that evaluated both NEDA-3 and NEDA-4 with at least 4 years of follow-up and examined the difference in the association of NEDA-3 and NEDA-4 with no disability progression.ResultsFive studies of 1,000 patients (3 interferon beta and 2 fingolimod) met inclusion criteria for both objectives. The median duration of follow-up was 6 years (interquartile range: 4–6 years). The prevalence of NEDA-4 ranged from 4.2% to 13.9% on interferon beta therapy and 24.9% to 25.1% on fingolimod therapy. The pooled OR for no long-term confirmed disability progression with NEDA-4 vs EDA-4 was 2.14 (95% confidence interval: 1.36–3.37; I2= 0). We did not observe any significant difference between NEDA-4 and NEDA-3 in the comparative analyses.DiscussionIn patients with RRMS, NEDA-4 at 1–2 years was associated with 2 times higher odds of no long-term disability progression, at 6 years compared with EDA-4, but offered no advantage over NEDA-3.

The aim of this retrospective cohort study was to study the clinical burden associated with cardio-pulmonary critical decompensations (CPCDs) in preterm neonates and factors associated with mortality. Through the Canadian Neonatal Network (30 tertiary NICUs, 2010-2017), we identified infants 32-week gestational age with CPCDs, defined by "significant exposure" to cardiotropes and/or inhaled nitric oxide (iNO): (1) either therapy for ≥ 3 consecutive days, (2) both for ≥ 2 consecutive days, or (3) any exposure within 2 days of death. Early CPCDs (≤ 3 days of age) and late CPCDs ( 3 days) were examined separately. Outcomes included CPCD-incidence, mortality, and inter-site variability using standardized ratios (observed/adjusted expected rate) and network funnel plots. Mixed-effects analysis was used to quantify unit-level variability in mortality. Overall, 10% of admissions experienced CPCDs (n = 2915). Late CPCDs decreased by ~ 5%/year, while early CPCDs were unchanged during the study period. Incidence and CPCD-associated mortality varied between sites, for both early (0.6-7.5% and 0-100%, respectively) and late CPCDs (2.5-15% and 14-83%, respectively), all p 0.01. Units' late-CPCD incidence and mortality demonstrated an inverse relationship (slope = -2.5, p 0.01). Mixed-effects analysis demonstrated clustering effect, with 6.4% and 8.6% of variability in mortality after early and late CPCDs respectively being site-related, unexplained by available patient-level characteristics or unit volume. Mortality was higher with combined exposure than with only-cardiotropes or only-iNO (41.3%, 24.8%, 21.5%, respectively; p 0.01).Clustering effects exist in CPCD-associated mortality among Canadian NICUs, with higher incidence units showing lower mortality. These data may aid network-level benchmarking, patient-level risk stratification, parental counseling, and further research and quality improvement work.• Preterm neonates remain at high risk of acute and chronic complications; the most critically unwell require therapies such as cardiotropic drugs and inhaled nitric oxide. • Infants requiring these therapies are known to be at high risk for adverse neonatal outcomes and for mortality.• This study helps illuminate the national burden of acute cardio-pulmonary critical decompensation (CPCD), defined as the need for cardiotropic drugs or inhaled nitric oxide, and highlights the high risk of morbidity and mortality associated with this disease state. • Significant nationwide variability exists in both CPCD incidence and associated mortality; a clustering effect was observed with higher incidence sites showing lower CPCD-associated mortality.

To describe the incidence, trends, management's variability and short-term outcomes of preterm infants with severe post-hemorrhagic ventricular dilatation (sPHVD).We reviewed infantslt;33 weeks' gestation who had PHVD and were admitted to the Canadian Neonatal Network between 2010 and 2018. We compared perinatal characteristics and short-term outcomes between those with sPHVD and those with mild/moderate PHVD and those with and without ventriculo-peritoneal (VP) shunt.Of 29,417 infants, 2439 (8%) had PHVD; rate increased from 7.3% in 2010 to 9.6% in 2018 (P = 0.005). Among infants with PHVD, sPHVD (19%) and VP shunt (29%) rates varied significantly across Canadian centers and between geographic regions (P lt; 0.01 and P = 0.0002). On multivariable analysis, sPHVD was associated with greater mortality, seizures and meningitis compared to mild/moderate PHVD.Significant variability in sPHVD and VP shunt rates exists between centers and regions in Canada. sPHVD was associated with increased mortality and morbidities.

Objective: This study aimed to determine the range of weight loss, at 3 days postnatal age, associated with the lowest risk of mortality/short-term morbidity in preterm infants

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To conduct a network meta‐analysis to evaluate the benefits and adverse effects of various NRS modes when used as primary support modes for preterm infants.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and adverse effects of various NRS modes when used as post‐extubation support for preterm infants.

Background and ObjectivesWe conducted a systematic review and meta-analysis to evaluate the relationship between no evidence of disease activity (NEDA) and no long-term disability progression on low- and high-efficacy therapy in relapsing-remitting multiple sclerosis (RRMS).MethodsMEDLINE, Embase, and the Cochrane Database were searched from January 1, 2006, to January 26, 2021. We selected studies that evaluated NEDA-3 (no relapse, new MRI lesion, or confirmed disability progression) at 1 or 2 years and had a minimum of 4 years of follow-up for determination of disability progression. Data were extracted by 2 independent reviewers and were meta-analyzed with a random-effects model. Primary outcome of no disability progression was defined as no confirmed progression on the Expanded Disability Status Scale during follow-up. We assessed the odds ratio (OR) for no disability progression with NEDA vs evidence of disease activity (EDA). Positive predictive value (PPV) of NEDA for no disability progression was summarized for studies with prevalence of no progression >80% vs ≤80% separately.ResultsWe included 29 studies in our qualitative synthesis, of which 27 (16 low efficacy, 11 high efficacy) were included in the meta-analysis (N = 10,935 participants). Median follow-up was 5.6 years (interquartile range 4.3–8.0 years). The pooled ORs for no progression with NEDA-3 vs EDA were 2.32 (95% CI 1.58–3.42; I2 = 73%) for low-efficacy therapy and 3.19 (95% CI 1.86–5.47; I2 = 86%) for high-efficacy therapy. Among studies with prevalence of no progression at follow-up >80%, the pooled PPV for low efficacy therapy was 91% (95% CI 89%–93%) and for high-efficacy therapy was 92% (95% CI 88%–94%). Among studies with prevalence of no progression ≤80%, the pooled PPV for low-efficacy therapy was 81% (95% CI 75%–86%) and for high-efficacy therapy was 86% (95% CI 80%–90%).DiscussionNEDA-3 is associated with no long-term disability progression in RRMS on both low- and high-efficacy therapies. Further studies of early composite outcome measures incorporating easily measurable biomarkers and longer follow-up may help to improve the prognostic value of NEDA-3 in RRMS.Trial Registration InformationInternational Prospective Register of Systematic Reviews Identifier: CRD42020189316.

To compare short term respiratory outcomes in preterm infants treated with bovine lipid extract surfactant or poractant alfa.Prospective comparative effectiveness cohort study of infants32 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.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.In this pragmatic study, we did not identify any difference in short term outcomes between the groups based on the type of surfactant received.

BackgroundNecrotizing enterocolitis (NEC) is the leading cause of death among preterm infants born at MethodsOur prospective multicenter, double-blinded, randomized, controlled trial will include infants born at n = 1549) will receive at least two feeds of fresh human milk (i.e., within 4 h of expression) per day from the time of enrollment until 32 weeks’ corrected age or discharge to home. Infants in the control group (n = 1549) will receive previously frozen human milk following the current standard protocols. Following informed consent, enrolled infants will be randomly allocated to the control or fresh human milk groups. The primary outcome is the composite outcome mortality or NEC ≥ stage 2 at 32 weeks’ corrected age, and the secondary outcomes are mortality, NEC ≥ stage 2, NEC needing surgery, late-onset sepsis, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), weight gain, change in weight, increase in length, increase in head circumference, time to full enteral feeds, and finally, the number and type of critical incident reports, including feeding errors.DiscussionOur double-blinded, randomized, controlled trial aims to examine whether fresh human milk can improve infant outcomes. The results of this study will impact both Chinese and international medical practice and feeding policy for preterm infants. In addition, data from our study will inform changes in health policy in NICUs across China, such that mothers are encouraged to enter the NICU and express fresh milk for their infants.Trial registrationChinese Clinical Trial Registry; #ChiCTR1900020577; registered January 1, 2019;http://www.chictr.org.cn/showprojen.aspx?proj=34276

Context No head-to-head clinical trials compare contemporary first-line therapies for metastatic renal cell carcinoma (mRCC). A network meta-analysis provides an approach for quantitative analysis. Objective To indirectly compare the efficacy and safety of first-line treatments for mRCC in the intention-to-treat (ITT) population and by clinical risk group. Evidence acquisition An updated systematic review from database inception to February 17, 2019 identified all parallel-group randomized controlled trials assessing first-line therapy for mRCC. “Clinically relevant” studies were selected for a network meta-analysis. Progression-free survival (PFS) was the primary outcome. Overall survival (OS), overall response rate (ORR), and grade 3 and 4 adverse events (AEs) were secondary outcomes. Evidence synthesis We identified 12 relevant trials: 12 reported outcomes for PFS, nine for OS, 10 for ORR, and nine for AEs. In the ITT population, cabozantinib (surface under the cumulative ranking curves [SUCRA] 84%), avelumab plus axitinib (SUCRA 68%), and pembrolizumab plus axitinib (SUCRA 82%) were superior to the other agents for PFS; pembrolizumab plus axitinib appeared superior for OS (SUCRA 95%); and atezolizumab demonstrated the lowest likelihood of AEs (SUCRA 100%). Findings were similar in the intermediate/poor-risk subgroup. Based on the limited data available, avelumab plus axitinib may be preferred in patients with favorable-risk disease. Conclusions The optimal first-line treatment for mRCC appears to differ by efficacy endpoint, toxicity, and clinical risk group. Direct comparative studies remain important in guiding treatment choice. Patient summary Head-to-head comparisons do not exist for the newest treatments of metastatic renal cell carcinoma (mRCC). In an indirect comparison, we found that pembrolizumab plus axitinib and cabozantinib are good options for most patients with mRCC.

Phenylephrine (PE) is currently the vasopressor of choice to prevent and treat spinal-induced hypotension at cesarean delivery (CD). However, its use is often associated with reflex bradycardia. Norepinephrine (NE) has been put forward as an alternative vasopressor during CD due to its ability to treat hypotension while maintaining heart rate (HR). Recent studies have focused on the role of NE used as an infusion with favorable results compared to PE. No studies have compared equipotent bolus doses of PE and NE at CD. We hypothesized that when used in equipotent doses as an intermittent bolus regimen to prevent and treat spinal-induced hypotension, NE would result in a reduction in the incidence of bradycardia compared to PE.This was a double-blind, randomized clinical trial of women undergoing elective CD under spinal anesthesia. Women were randomized to receive either PE 100 µg or NE 6 µg when the systolic blood pressure (SBP) was below baseline. In addition to the randomized treatment, ephedrine was given intravenously to both groups if the SBP was below baseline and the HR60 bpm or if the SBP was80% of baseline for 2 consecutive readings. The primary outcome was bradycardia (HR50 bpm) in the predelivery period. Secondary outcomes included hypotension (SBP80% of baseline), hypertension (SBP120% of baseline), tachycardia (HR120% of baseline), ≥2 episodes of bradycardia, nausea, vomiting, umbilical artery and vein blood gases, and Apgar scores.One hundred twelve patients were randomized. The incidence of bradycardia was lower in the NE group compared to the PE group (10.7% vs 37.5%; P.001; difference [95% confidence interval {CI}], -26.8% [-41.8% to -11.7%]), implying an estimated 71% relative reduction (95% CI, 35%-88%). The distribution of the number of bradycardia episodes was also different between the 2 groups (P = .007). Further testing showed that the patients in the PE group had a higher risk of multiple bradycardia episodes (≥2 episodes) compared to the NE group (19.6% for PE versus 3.6% for NE; P = .008). The proportion of patients requiring rescue boluses of ephedrine was lower in the NE group compared to the PE group (7.2% for NE versus 21.4% for PE; P.03; difference [95% CI], -14.3% [-27.0% to -1.6%]). No differences were observed between the 2 groups in the incidence of other secondary outcomes.When used as an intermittent bolus regimen to prevent and treat spinal-induced hypotension during CD, NE resulted in a significant reduction in the incidence of bradycardia as compared to an equipotent bolus regimen of PE. We conclude that the hemodynamic profile offered by NE during CD is superior to that of PE due to less fluctuations in HR and possibly cardiac output.

Objective: To identify how Family Integrated Care (FICare) affected maternal stress and anxiety. Study Design: This secondary analysis of the FICare cluster randomised controlled trial included infants born between 1 April 2013 and 31 August 2015 at ≤33 weeks’ gestation. Mothers completed the PSS:NICU and STAI questionnaires at enrolment and study day 21. Results: 1383 mothers completed the surveys at one or both time-points. The mean PSS:NICU and STAI scores at day 21 were significantly lower in the FICare mothers than controls (PSS:NICU mean [standard deviation] FICare 2.32 [0.75], control 2.48 [0.78], p = 0.0005; STAI FICare 70.8 [20.0], control 74.2 [19.6], p = 0.0004). The sights and sounds, looks and behaviour, and parental role PSS:NICU subscales and the state and trait STAI subscales were all significantly different between FIC are and controls at day 21. The magnitude of change in all stress and anxiety subscales was greater in the FICare group than controls. These differences remained significant after adjustment for confounders with the greatest change in the parental role (least-squares mean [95% confidence interval] FICare −0.65 [−0.72, 0.57], control −0.31 [−0.38, −0.24], p < 0.0001) and state anxiety subscales. Conclusion: FICare is effective at reducing NICU-related maternal stress and anxiety.

Background The Acute Care of at-Risk Newborns (ACoRN) program was developed in Canada to train health care providers in the identification and management of newborns who are at-risk and/or become unwell after birth. The ACoRN process follows a stepwise framework that enables evaluation, decision, and action irrespective of caregiver experience. This study examined the hypothesis that the ACoRN educational program improved clinical practices and outcomes in China. Methods In a before-and-after study, ACoRN training was provided to physicians, neonatal nurses, and administrators in 16 county hospitals in Zhejiang, PRC. Demographic and clinical data were collected on babies admitted to neonatal units before (May 1, 2008 to March 31, 2009) and after (June 1, 2010 to April 30, 2012) training. Results A total of 4,310 babies (1,865 pre- and 2,445 post-training) from 14 sites were included. There were more in-hospital births (97.8% versus 95.6%, P Conclusions ACoRN training significantly increased patient evaluations and changed clinical practices. However, we were unable to ascertain improvement in morbidity or mortality.

Quality improvement initiatives in neonatology have yielded positive results; however, few programs have demonstrated sustainability. We evaluated an ongoing, national quality improvement initiative (Evidence-based Practice for Improving Quality Phase 3 (EPIQ-3)) on outcomes of preterm neonates with a gestational age (GA) of 220–286weeks (i.e., from 22 weeks and 0 days of gestation to 28 weeks and 6 days of gestation). Data from 7459 neonates admitted to 25 Canadian centers between 2013 and 2017 were studied. Trends in mortality and major morbidities were evaluated. The number of neonates with a GA of 220–236weeks increased from 90 in 2013 to 139 in 2017 without a significant change in any other GA categories. In the entire cohort, the odds of composite outcome of mortality or any major morbidity (adjusted odds ratio (AOR) 0.72, 95% confidence interval (CI) 0.61–0.84) and of necrotizing enterocolitis (AOR 0.66, 95% CI 0.49–0.89) were lower in 2017 than in 2013. When calculated per year, the odds of composite outcome (AOR 0.93, 95% CI 0.89–0.97) and odds of necrotizing enterocolitis (AOR 0.89, 95% CI 0.82–0.96) decreased significantly. Among the subgroup of neonates with a GA of 260–286weeks, the odds of composite outcome (AOR 0.63, 95% CI 0.51–0.79), necrotizing enterocolitis (AOR 0.44, 95% CI 0.26–0.73), and nosocomial infection (AOR 0.64, 95% CI 0.49–0.84) were reduced. The collaborative, multidisciplinary, nationwide EPIQ-3 program improved outcomes of preterm neonates, and the improvement was sustainable over 5 years.

Objective: To evaluate the association of a combined exposure to antenatal steroids and prophylactic indomethacin with the outcome of spontaneous intestinal perforation (SIP) among neonates born at 7 days before birth) exposures. The co-exposure was prophylactic indomethacin. The primary outcome was SIP. Multivariable logistic regression analysis was used to calculate aORs. Results: Among 4720 eligible infants, 4121 (87%) received antenatal steroids and 1045 (22.1%) received prophylactic indomethacin. Among infants exposed to antenatal steroids, those who received prophylactic indomethacin had higher odds of SIP (aOR 1.61, 95% CI 1.14-2.28) compared with no prophylactic indomethacin. Subgroup analyses revealed recent antenatal steroids exposure with prophylactic indomethacin had higher odds of SIP (aOR 1.67, 95% CI 1.15-2.43), but latent antenatal steroids exposure with prophylactic indomethacin did not (aOR 1.24, 95% CI 0.48-3.21), compared with the respective groups with no prophylactic indomethacin. Among those not exposed to antenatal steroids, mortality was lower among those who received prophylactic indomethacin (aOR 0.45, 95% CI 0.28-0.73) compared with no prophylactic indomethacin. Conclusions: In preterm neonates of

Early antibiotic administration is an important modifiable factor in reducing mortality from late-onset bloodstream infections in preterm infants. In a cohort study including 142 infants with non-coagulase negative staphylococcus bloodstream infection at two tertiary neonatal intensive care units, we identified typical practice-related factors that may be targeted to prevent delays in antibiotic administration. Collection of cerebrospinal fluid or urine sample before administering antibiotics, a longer time taken to site a peripheral intravenous catheter among those without pre-existing access, and a longer time taken to administer fluid boluses were associated with a longer than median time to antibiotic administration.

The objective of this study was to investigate the association between systolic, diastolic, and mean blood pressures (SBP, DBP, and MBP) and adverse outcomes in preterm neonates with late-onset sepsis (LOS).This is a two-center retrospective study over 6 years. Neonates35 weeks gestational age (GA) with blood ± cerebrospinal fluid culture positive for organisms other than coagulase-negative Staphylococcus at72 h age were included. Outcome measures were organ dysfunction (ODF) using the predefined criteria and post-ODF mortality (≤7 days from LOS onset). The lowest noninvasive blood pressures (BPs) recorded at baseline (24-48 h pre-LOS) and 0-12, 13-24, 25-36, and 37-48 h post LOS were analyzed.Of 147 neonates, ODF occurred in 70 (48%), of which 20 (29%) died. ODF was associated with a drop in all BP components, starting 0-12 h post-LOS onset (p 0.01 for all); BPs remained unchanged in the non-ODF group. Mortality was associated with a greater reduction in SBP [-13 (-19, -8) vs. -4 (-8, 0); p 0.01] and MBP [-9 (-13, -5) vs. +1 (-1, +4); p = 0.03] 0-12 h post-LOS onset. SBP had a higher area under the curve for mortality than MBP and DBP (0.83, 0.81, and 0.78, respectively). An inverse relation may exist between corrected GA and percentage reduction in SBP from baseline for equivalent risk of death.Reduction in BPs early in illness may identify preterm neonates at the highest risk of ODF and mortality from LOS.Drop in BPs from baseline starting in the immediate post-illness onset period may identify preterm neonates at the highest risk of developing ODF and mortality in LOS. Lowest systolic followed by mean BP measured during the first 12 h of illness provided the highest discriminating ability for LOS-related mortality. Absolute BPs recorded during the first 12 h of illness performed better than relative change from baseline for identifying neonates at risk of LOS-related mortality. The specific BP thresholds identified in this study may inform future therapeutic trials.

IntroductionPatent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants and evidence regarding the best treatment approach is lacking. Currently available medical options to treat a PDA include indomethacin, ibuprofen or acetaminophen. Wide variation exists in PDA treatment practices across Canada. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we plan to conduct a comparative effectiveness study of the different pharmacotherapeutic agents used to treat the PDA in preterm infants.Methods and analysisA multicentre prospective observational comparative-effectiveness research study of extremely preterm infants born Standard dose ibuprofen (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals) irrespective of postnatal age (oral/intravenous).Adjustable dose ibuprofen (oral/intravenous) (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by two doses of 10 mg/kg at 24 hours intervals if treated after the postnatal age cut-off for lower dose as per the local centre policy).Acetaminophen (oral/intravenous) (15 mg/kg every 6 hours) for 3–7 days.Intravenous indomethacin (0.1–0.3 mg/kg intravenous every 12–24 hours for a total of three doses).OutcomesThe primary outcome is failure of primary pharmacotherapy (defined as need for further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy). The secondary outcomes include components of the primary outcome as well as clinical outcomes related to response to treatment or adverse effects of treatment.Sites and sample sizeThe study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years.AnalysisTo examine the relative effectiveness of the four treatment strategies, the primary outcome will be compared pairwise between the treatment groups using χ2 test. Secondary outcomes will be compared pairwise between the treatment groups using χ2 test, Student’s t-test or Wilcoxon rank sum test as appropriate. To further examine differences in the primary and secondary outcomes between the four groups, multiple logistic or linear regression models will be applied for each outcome on the treatment groups, adjusted for potential confounders using generalised estimating equations to account for within-unit-clustering. As a sensitivity analysis, the difference in the primary and secondary outcomes between the treatment groups will also be examined using propensity score method with inverse probability weighting approach.Ethics and disseminationThe study has been approved by the IWK Research Ethics Board (#1025627) as well as the respective institutional review boards of the participating centres.Trial registration numberNCT04347720.

Programmed intermittent epidural bolus (PIEB) provides better analgesia for labour pain than continuous epidural infusion does. Nevertheless, commonly used PIEB regimens are associated with high sensory block. We hypothesized that a PIEB technique with slower bolus delivery speed would produce lower sensory levels.We recruited term nulliparous women with singleton pregnancies during the first stage of labour. All participants had an American Society of Anesthesiologists Physical Status score of II-III, had epidural catheters placed at L3/4, and had epidural analgesia maintained with PIEB 10 mL every 40 min using 0.0625% bupivacaine with fentanyl 2 µg·mLWe analyzed data from 90 women. The proportion of women presenting sensory block ≥ T6 at any time was not different between G125 and G250 groups (60.0% vs 64.4%; difference, -4.4%; 95% confidence interval [CI], -24.5 to 15.6; P = 0.66). The median [interquartile range] highest sensory block level was also not different between G125 and G250 groups (T6 [T7-T5] vs T5 [T7-T5], P = 0.39). Women in the G125 group had a lower incidence of hypotension than women in the G250 group did (11.1% vs 33.3%; difference, -22.2%; 95% CI, -38.8 to -5.67; P = 0.01). Quality of analgesia and patient satisfaction were not different between groups.The maintenance of epidural analgesia with a PIEB delivery speed of 125 mL·hrwww.ClinicalTrials.gov (NCT03236298); registered 1 August 2017.RéSUMé: OBJECTIF: L’administration programmée intermittente de bolus périduraux (PIEB, pour programmed intermittent epidural bolus) fournit une meilleure analgésie pour la douleur du travail que l’analgésie péridurale par perfusion continue. Néanmoins, les régimes de PIEB couramment utilisés sont associés à un bloc sensoriel élevé. Nous avons émis l’hypothèse qu’une technique de PIEB avec une vitesse d’administration plus lente du bolus produirait des niveaux sensoriels inférieurs. MéTHODE: Nous avons recruté des femmes nullipares à terme ayant des grossesses uniques au cours de la première étape du travail obstétrical. Toutes les participantes avaient un score de statut physique II-III de l’American Society of Anesthesiologists, des cathéters périduraux placés au niveau L3/4 et une analgésie péridurale maintenue avec des PIEB de 10 mL de bupivacaïne 0,0625 % et de 2 μg·mL