Less-invasive surfactant administration (LISA) is increasingly used. We investigated the feasibility of a new LISA-device (Neofact®) in neonates.
Prospective observational pilot study with open-label ...LISA in two tertiary neonatal intensive care units.
20 infants with a gestational age of ≥26+0/7 weeks and an indication for LISA (Respiratory Severity Score (RSS)≥5 or fraction of inspired oxygen (FiO
) ≥0.30). Infants with respiratory tract malformations or unavailability of an instructed neonatologist were excluded.
Success of LISA, defined as laryngoscopy-confirmed intratracheal catheter position or a decrease in FiO
by ≥0.05 or to 0.21, accompanied by an RSS decrease of ≥2; number of attempts needed for tracheal catheterisation.
20/57 screened infants were enrolled. Successful application occurred in 19/20 (95%). One application failed after three attempts. No device-related adverse events occurred. The median number of attempts was 2, success rate per attempt 19/31 (61%).
LISA via Neofact® appears feasible.
Less-invasive surfactant administration (LISA) under continuous positive airway pressure is increasingly used for the treatment of neonatal respiratory distress. Different procedures are described, ...but data on the optimal catheter insertion depth are sparse.
To generate data for recommending an optimal catheter insertion depth in LISA.
We examined 112 anterior-posterior chest X-rays from intubated infants and determined the carina's vertebral projection, whenever possible. After that, distances between the middle of cervical vertebra 4 (C4) and thoracic vertebra 2 and the middle of C4 to thoracic vertebra 3, respectively, were measured. Results were plotted against infant's weight.
A weight-based chart and recommendations for the optimal intratracheal catheter position in infants with a body weight between 350 and 4000 g were created.
Generated data offer standardisation and may thus help to find a balance between risk of surfactant reflux and unilateral surfactant administration.
Clinical studies on cognitive behavioral therapy (CBT) that include schizophrenia patients primarily on the basis of negative symptoms are uncommon. However, those studies are necessary to assess the ...efficacy of CBT on negative symptoms. This article first gives an overview of CBT on negative symptoms and discusses the methodological problems of selecting an adequate control group. Furthermore, the article describes a clinical study (the TONES-Study, ISRCTN 25455020), which aims to investigate whether CBT is specifically efficacious for the reduction of negative symptoms. This multicenter randomized clinical trial comparing CBT with cognitive remediation (CR) for control of nonspecific effects is depicted in detail. In our trial, schizophrenia patients (n = 198) participated in manualized individual outpatient treatments. Primary outcome is the negative syndrome assessed with the positive and negative syndrome scale, analyzed with multilevel linear mixed models. Patients in both groups moderately improved regarding the primary endpoint. However, against expectation, there was no difference between the groups after treatment in the intention to treat as well as in the per-protocol analysis. In conclusion, psychotherapeutic intervention may be useful for the reduction of negative symptoms. However, there is no indication for specific effects of CBT compared with CR.
There is an ongoing controversy regarding management of ureteropelvic junction obstruction in infants, with a shift towards a non-operative approach. However, precise predictors of outcome are ...lacking. Recent studies postulated a high prognostic value of Technetium-99m-mercaptoacetyltriglycine tissue tracer transit with regard to the development of an impaired differential renal function and its potential improvement following pyeloplasty.
To evaluate the prognostic value of Technetium-99m-mercaptoacetyltriglycine tissue tracer transit for the occurrence of changes in differential renal function in infants with suspected unilateral ureteropelvic junction obstruction in a prospective observational multicenter study.
Infants below 3 months of age with a unilateral isolated hydronephrosis ≥ grade 3 received ultrasound and Technetium-99m-mercaptoacetyltriglycine diuretic renography at two different time points (timepoint 1 and timepoint 2). Data were analyzed at local centers and at the study center and were collected in an internet-based database system. Tissue tracer transit was determined for each diuretic renography, inter-observer variation for tissue tracer transit and standard parameters for judgement of differential renal function development were assessed.
Thirty-seven patients were analyzed. Median age was 11 weeks (7-15) at timepoint 1 and 26 weeks (19-33) at timepoint 2. A delayed tissue tracer transit at timepoint 1 was not associated with deterioration of differential renal function at timepoint 2 in both, locally (10/37 cases) and centrally (4/37) analyzed cases. However, sensitivity and specificity were poor. The intraclass correlation coefficient comparing local and central findings of tissue tracer transit and renal drainage demonstrated poor or fair agreement. Analysis of standard parameters for differential renal function development revealed a prognostic value only for the dichotomized anteroposterior renal pelvic diameter (APD, p = 0.03, 95%-CI 1.2-22.2).
Regarding the primary endpoint of our study, we could not confirm the hypothesis that delayed tissue tracer transit reliably predicts a subsequent decline in differential renal function in the cohort of patients studied. Whether the low age of the patients, technical problems in the correct assessment of tissue tracer transit by the investigator in early infancy, the study design, or the parameter itself played a role is debated.
In the presented setting tissue tracer transit was not useful as a predictive parameter for deterioration of differential renal function in infants with suspected unilateral ureteropelvic junction obstruction. Sensitivity and specificity of tissue tracer transit were not sufficient for risk stratification. Improved utility of tissue tracer transit as a marker might be achieved using a different study setting.
The rapid emergence of the Omicron variant and its large number of mutations led to its classification as a variant of concern (VOC) by the World Health Organization. Subsequently, Omicron evolved ...into distinct sublineages (eg, BA.1 and BA.2), which currently represent the majority of global infections. Initial studies of the neutralizing response toward BA.1 in convalescent and vaccinated individuals showed a substantial reduction.
We assessed antibody (immunoglobulin G IgG) binding, ACE2 (angiotensin-converting enzyme 2) binding inhibition, and IgG binding dynamics for the Omicron BA.1 and BA.2 variants compared to a panel of VOCs/variants of interest, in a large cohort (N = 352) of convalescent, vaccinated, and infected and subsequently vaccinated individuals.
While Omicron was capable of efficiently binding to ACE2, antibodies elicited by infection or immunization showed reduced binding capacities and ACE2 binding inhibition compared to wild type. Whereas BA.1 exhibited less IgG binding compared to BA.2, BA.2 showed reduced inhibition of ACE2 binding. Among vaccinated samples, antibody binding to Omicron only improved after administration of a third dose.
Omicron BA.1 and BA.2 can still efficiently bind to ACE2, while vaccine/infection-derived antibodies can bind to Omicron. The extent of the mutations within both variants prevents a strong inhibitory binding response. As a result, both Omicron variants are able to evade control by preexisting antibodies.
Importance Red blood cell transfusions are commonly administered to infants weighing less than 1000 g at birth. Evidence-based transfusion thresholds have not been established. Previous studies have ...suggested higher rates of cognitive impairment with restrictive transfusion thresholds. Objective To compare the effect of liberal vs restrictive red blood cell transfusion strategies on death or disability. Design, Setting, and Participants Randomized clinical trial conducted in 36 level III/IV neonatal intensive care units in Europe among 1013 infants with birth weights of 400 g to 999 g at less than 72 hours after birth; enrollment took place between July 14, 2011, and November 14, 2014, and follow-up was completed by January 15, 2018. Interventions Infants were randomly assigned to liberal (n = 492) or restrictive (n = 521) red blood cell transfusion thresholds based on infants’ postnatal age and current health state. Main Outcome and Measures The primary outcome, measured at 24 months of corrected age, was death or disability, defined as any of cognitive deficit, cerebral palsy, or severe visual or hearing impairment. Secondary outcome measures included individual components of the primary outcome, complications of prematurity, and growth. Results Among 1013 patients randomized (median gestational age at birth, 26.3 interquartile range {IQR}, 24.9-27.6 weeks; 509 50.2% females), 928 (91.6%) completed the trial. Among infants in the liberal vs restrictive transfusion thresholds groups, respectively, incidence of any transfusion was 400/492 (81.3%) vs 315/521 (60.5%); median volume transfused was 40 mL (IQR, 16-73 mL) vs 19 mL (IQR, 0-46 mL); and weekly mean hematocrit was 3 percentage points higher with liberal thresholds. Among infants in the liberal vs restrictive thresholds groups, the primary outcome occurred in 200/450 (44.4%) vs 205/478 (42.9%), respectively, for a difference of 1.6% (95% CI, −4.8% to 7.9%; P = .72). Death by 24 months occurred in 38/460 (8.3%) vs 44/491 (9.0%), for a difference of −0.7% (95% CI, −4.3% to 2.9%; P = .70), cognitive deficit was observed in 154/410 (37.6%) vs 148/430 (34.4%), for a difference of 3.2% (95% CI, −3.3% to 9.6%; P = .47), and cerebral palsy occurred in 18/419 (4.3%) vs 25/443 (5.6%), for a difference of −1.3% (95% CI, −4.2% to 1.5%; P = .37), in the liberal vs the restrictive thresholds groups, respectively. In the liberal vs restrictive thresholds groups, necrotizing enterocolitis requiring surgical intervention occurred in 20/492 (4.1%) vs 28/518 (5.4%); bronchopulmonary dysplasia occurred in 130/458 (28.4%) vs 126/485 (26.0%); and treatment for retinopathy of prematurity was required in 41/472 (8.7%) vs 38/492 (7.7%). Growth at follow-up was also not significantly different between groups. Conclusions and Relevance Among infants with birth weights of less than 1000 g, a strategy of liberal blood transfusions compared with restrictive transfusions did not reduce the likelihood of death or disability at 24 months of corrected age.
Purpose
To investigate, whether capsulorhexis training on the EYESi surgical simulator improves wet-lab operating performance of surgical novices.
Methods
Randomized, masked experimental study. ...Thirty-one medical students and 32 ophthalmological residents were randomized to either virtual reality (VR) training, or control. Initially and after 3 weeks each participant performed three capsulorhexis tasks in a porcine wet-lab. In between, participants from the VR training groups completed two training trials on the EYESi surgical simulator (VRmagic, Mannheim, Germany). VR training consisted of basic skill tasks and capsulorhexis tasks of increasing difficulty, and preset performance goals had to be reached for each task. All wet-lab procedures (
n
= 372) were recorded on DVD, and assessed by a masked observer. Each wet-lab capsulorhexis was evaluated with regard to five criteria (circularity, size, centering, time, tissue protection) using a predefined scoring system with a maximum overall score of 10 points (2 per criterion). The primary outcome measure was the intra-individual difference in the average overall performance score between the first and second wet-lab capsulorhexis procedures. Ten operation videos were additionally assessed by three further investigators to determine interobserver agreement.
Results
Inter-observer agreement regarding the overall performance score was high (ICC = 0.91). Compared to control groups, VR-trained students and residents showed significant improvement in their median wet-lab capsulorhexis overall performance score compared to controls (+3.67 vs +0.33 points,
P
= 0.001 and +3.33 vs ±0.00 points,
P
< 0.0001). The capsulorhexis performance of VR-trained students and residents was also more consistent with a lower standard deviation of scores compared to controls (SD 1.3 vs 2.1 and 1.2 vs 1.7 points respectively).
Conclusions
Structured capsulorhexis training on the EYESi to reach specific target criteria significantly improved wet-lab capsulorhexis performance.
ABSTRACTThis study examined the frequency and extent of detrimental effects of cognitive behavioral therapy (CBT) for psychosis. In a randomized clinical trial, we investigated the efficacy of CBT ...for the reduction of negative symptoms as compared with cognitive remediation (CR) in schizophrenia patients (n = 198). Safety was addressed through assessment of severe adverse events (SAEs), which were defined as suicides, suicide attempts, suicidal crises, and severe symptom exacerbations over a period of 12 months after inclusion in the study. Monthly assessments with Positive and Negative Syndrome Scale and Scale for the Assessment of Negative Symptoms allowed for the analysis of symptom increases during the treatment. There were no suicides in the trial. SAEs were observed in 10 CBT and 5 CR patients. Increases in negative symptoms occurred in 64 CBT and 58 CR patients. These differences were not significant. The maximum increase in negative symptoms under treatment, as compared with the baseline, was equal to an effect size of −0.66 in CBT patients and −0.77 in CR patients. Thus, the SAE rate was comparable between both interventions and was relatively low, given the severity of the psychotic disorder. Therapists should be aware of a subgroup of patients who show symptom increases with large effect sizes and might require more intensive care.
Introduction: Standardization of data items collected in paediatric clinical trials is an important but challenging issue. The Clinical Data Interchange Standards Consortium (CDISC) data standards ...are well understood by the pharmaceutical industry but lack the implementation of some paediatric specific concepts. When a paediatric concept is absent within CDISC standards, companies and research institutions take multiple approaches in the collection of paediatric data, leading to different implementations of standards and potentially limited utility for reuse. Objective: To overcome these challenges, the conect4children consortium has developed a cross-cutting paediatric data dictionary (CCPDD). Methods: The dictionary was built over three phases – scoping (including a survey sent out to ten industrial and 34 academic partners to gauge interest), creation of a longlist and consensus building for the final set of terms. The dictionary was finalized during a workshop with attendees from academia, hospitals, industry and CDISC. The attendees held detailed discussions on each data item and participated in the final vote on the inclusion of the item in the CCPDD.Results: Nine industrial and 34 academic partners responded to the survey, which showed overall interest in the development of the CCPDD. Following the final vote on 27 data items, three were rejected, six were deferred to the next version and a final opinion was sought from CDISC. The first version of the CCPDD with 25 data items was released in August 2019.Discussion and Conclusion: The continued use of the dictionary has the potential to ensure the collection of standardized data that is interoperable and can later be pooled and reused for other applications. The dictionary is already being used for case report form creation in three clinical trials. The CCPDD will also serve as one of the inputs to the Paediatric User Guide, which is being developed by CDISC.
Iron deficiency (ID) contributes to anaemia of prematurity, and hence the reliable assessment of iron nutrition status appears to be mandatory.
To establish gestational age (GA)-specific reference ...ranges for hepcidin concentrations in cord blood Hep(CB) of preterm and term infants and to identify pre- and perinatal confounding factors.
This is a prospective observational study including 221 infants (GA at birth: 24-42 weeks). Hep(CB) along with complete blood counts, ferritin and parameters of inflammation and clinical data were recorded. Data are presented as medians (IQR).
The Hep(CB) of very preterm infants (GA <30 weeks, n = 40) was 26.9 ng/ml (13.5-63.1), for moderately preterm infants (GA 30-36 weeks, n = 81) it was 45.9 ng/ml (24.7-74.5) and for term infants (GA ≥37 weeks, n = 100) it was 103.9 ng/ml (61.4-149.2). The Hep(CB) of infants with ID was lower 36.9 ng/ml (18.0-58.3) than that of iron-replete infants 86.6 ng/ml (51.9-143.8). The Hep(CB) of infants delivered by elective caesarean section was lower 38.3 ng/ml (15.5-73.7) than that of infants after spontaneous vaginal delivery or secondary caesarean section 80.3 ng/ml (48.5-137.6). Infants with a standard deviation score for birth weight (SDSBW) <-2 had a lower Hep(CB) 23.1 ng/ml (11.7-61.5) compared to infants with SDSBW ≥-2 71.1 ng/ml (34.0-121.7). The highest Hep(CB) (437.6 ng/ml) was recorded in an infant with Enterococcus faecalis sepsis. Multiple logistic regression analysis confirmed ferritin, GA and mode of delivery as important factors associated with Hep(CB).
This is the first report on GA-specific reference ranges for Hep(CB) in preterm infants. Whereas iron stores, GA and mode of delivery were associated with Hep(CB), the association with inflammation and intra-uterine growth retardation was less clear.
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