Aim To describe and test a new technique to obtain midstream urine samples in newborns. Design and methods This was a prospective feasibility and safety study conducted in the neonatal unit of ...University Infanta Sofía Hospital, Madrid. A new technique based on bladder and lumbar stimulation manoeuvres was tested over a period of 4 months in 80 admitted patients aged less than 30 days. The main variable was the success rate in obtaining a midstream urine sample within 5 min. Secondary variables were time to obtain the sample and complications. Results This technique was successful in 86.3% of infants. Median time to sample collection was 45 s (IQR 30). No complications other than controlled crying were observed. Conclusions A new, quick and safe technique with a high success rate is described, whereby the discomfort and waste of time usually associated with bag collection methods can be avoided.
Logistic regression (LR) is the most common prediction model in medicine. In recent years, supervised machine learning (ML) methods have gained popularity. However, there are many concerns about ML ...utility for small sample sizes. In this study, we aim to compare the performance of 7 algorithms in the prediction of 1-year mortality and clinical progression to AIDS in a small cohort of infants living with HIV from South Africa and Mozambique. The data set (n = 100) was randomly split into 70% training and 30% validation set. Seven algorithms (LR, Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Naïve Bayes (NB), Artificial Neural Network (ANN), and Elastic Net) were compared. The variables included as predictors were the same across the models including sociodemographic, virologic, immunologic, and maternal status features. For each of the models, a parameter tuning was performed to select the best-performing hyperparameters using 5 times repeated 10-fold cross-validation. A confusion-matrix was built to assess their accuracy, sensitivity, and specificity. RF ranked as the best algorithm in terms of accuracy (82,8%), sensitivity (78%), and AUC (0,73). Regarding specificity and sensitivity, RF showed better performance than the other algorithms in the external validation and the highest AUC. LR showed lower performance compared with RF, SVM, or KNN. The outcome of children living with perinatally acquired HIV can be predicted with considerable accuracy using ML algorithms. Better models would benefit less specialized staff in limited resources countries to improve prompt referral in case of high-risk clinical progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fever without source (FWS) in infants is a frequent cause of consultation at the emergency department, and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this ...study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection. This is a cross-sectional study of infants under 90 days of age with FWS and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1 to June 26, 2020. Three hundred and thirty-three children with COVID-19 were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a
Streptococcus mitis
bacteremia. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the pediatric intensive care unit because of apnea episodes. No patients died.
Conclusion
: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection. Standardized markers to rule out bacterial infections remain useful in this population, and the outcome is generally good.
What is Known:
• Fever without source (FWS) in infants is a common cause of consultation at the emergency department, and young infants have a higher risk of serious bacterial infections (SBI).
• The emergence of the new coronavirus SARS-CoV-2 could affect the approach to young infants with FWS in the emergency department. management of those children is a challenge because information about bacterial coinfection and prognosis is scarce.
What is New:
• SARS-CoV-2 infection should be ruled out in young infants (< 90 days of age) with FWS in areas with community transmission.
• Bacterial coinfection rarely coexists in those infants.
• Inflammatory markers were not increased in children without bacterial coinfection.
• Outcome is good in most patients.
Although super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice, many different ...LPV/r dosing strategies are applied due to poor availability of pediatric separate ritonavir formulations needed to superboost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB) treatment.
This was a 2-arm pharmacokinetic substudy nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB treatment; during rifampicin cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r.
In total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) had LPV Ctrough <1.0 mg/L compared with 1/5 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin.
Double-dosed or semisuperboosted LPV/r for infants aged 1-12 months receiving rifampicin resulted in substantial proportions of subtherapeutic LPV levels. There is an urgent need for data on alternative antiretroviral regimens in infants with HIV/TB coinfection, including twice-daily dolutegravir.
This study provides practical recommendations on infection screening in pediatric patients with immune-mediated rheumatic diseases and immunosuppressive therapies. For this reason, a qualitative ...approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using Mesh and free texts to identify articles that analyzed data on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases and immunosuppressive therapies. The results were presented and discussed in a nominal group meeting, comprising a committee of 12 pediatric rheumatologists from the infections prevention and treatment working group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process that was extended to members of the Spanish Society of Pediatric Rheumatology and Vaccine Advisory Committee of the Spanish Association of Pediatrics. Participants to the process produced a score ranging from 0 = totally disagree to 10 = totally agree. Agreement was considered if at least 70% of participants voted ≥ 7. The literature review included more than 400 articles. Overall, 63 recommendations were generated (21 on infection screening) voted by 59 pediatric rheumatologists and other pediatric specialists, all of them achieving the pre-established agreement level. The recommendations on screening cover all the procedures (serology, assessment of risk factors, and other clinical activities) connected with the screening for infections including tuberculosis; hepatitis A, B, and C viruses; measles; mumps; rubella; diphtheria; and other infections.
Conclusion
: Screening for infections is an essential part of risk management in pediatric patients with immune-mediated rheumatic diseases and immunosuppressive therapies.
What is Known:
•
Infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases.
•
At present, practical information on infectious prophylaxis in children with rheumatic diseases is limited, and often extrapolated from children with cancer.
What is New:
•
In the absence of evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that would be useful in clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists.
Objective To assess whether dexamethasone (DXM) decreases the time to recovery in patients with parapneumonic pleural effusion. Study design This was a multicenter, randomized, double blind, ...parallel-group, placebo-controlled clinical trial of 60 children, ranging in age from 1 month to 14 years, with community-acquired pneumonia (CAP) and pleural effusion. Patients received either intravenous DXM (0.25 mg/kg/dose) or placebo every 6 hours over a period of 48 hours, along with antibiotics. The primary endpoint was the time to recovery in hours, defined objectively. We also evaluated complications and adverse events. Results Among the 60 randomized patients (mean age, 4.7 years; 58% female), 57 (95%) completed the study. Compared with placebo recipients, the patients receiving DXM had a shorter time to recovery, after adjustment by severity group and stratification by center (hazard ratio, 1.95; 95% CI, 1.10-3.45; P = .021). The median time to recovery for patients receiving DXM was 68 hours (2.8 days) shorter than patients receiving placebo (109 hours vs 177 hours; P = .037). In exploratory subgroup analysis, the median time to recovery for patients with simple effusion receiving DXM was 76 hours (3.1 days) shorter than for patients with simple effusion receiving placebo ( P = .017). The median time to recovery for patients with complicated effusion receiving DXM was 14 hours (0.5 days) shorter than for patients with complicated effusion receiving placebo ( P = .66). The difference in the effect of DXM in the 2 severity groups was not statistically significant ( P = .138 for interaction). There were no significant differences in complications or adverse events attributable to the study drugs, except for hyperglycemia. Conclusion In this trial, DXM seemed to be a safe and effective adjunctive therapy for parapneumonic pleural effusion. Trial registration ClinicalTrials.gov : NCT01261546.
Initiation of antiretroviral treatment (ART) in patients early after HIV-infection and long-term suppression leads to low or undetectable levels of HIV RNA and cell-associated (CA) HIV DNA and RNA. ...Both CA-DNA and CA-RNA, overestimate the size of the HIV reservoir but CA-RNA as well as p24/cell-free viral RNA can be indicators of residual viral replication. This study describes HIV RNA amounts and levels of cytokines/soluble markers in 40 well-suppressed adolescents who initiated ART early in life and investigated which viral markers may be informative as endpoints in cure clinical trials within this population.
Forty adolescents perinatally infected with HIV on suppressive ART for >5 years were enrolled in the CARMA study. HIV DNA and total or unspliced CA-RNA in PBMCs were analyzed by qPCR/RT-qPCR and dPCR/RT-dPCR. Cell-free HIV was determined using an ultrasensitive viral load (US-VL) assay. Plasma markers and p24 were analyzed by digital ELISA and correlations between total and unspliced HIV RNA and clinical markers, including age at ART, Western Blot score, levels of cytokines/inflammation markers or HIV CA-DNA, were tested.
CA-RNA was detected in two thirds of the participants and was comparable in RT-qPCR and RT-dPCR. Adolescents with undetectable CA-RNA showed significantly lower HIV DNA compared to individuals with detectable CA-RNA. Undetectable unspliced CA-RNA was positively associated with age at ART initiation and Western Blot score. We found that a higher concentration of TNF-α was predictive of higher CA-DNA and CA-RNA. Other clinical characteristics like US-VL, time to suppression, or percent CD4+ T-lymphocytes were not predictive of the CA-RNA in this cross-sectional study.
Low CA-DNA after long-term suppressive ART is associated with lower CA-RNA, in concordance with other reports. Patients with low CA-RNA levels in combination with low CA-DNA and low Western Blot scores should be further investigated to characterize candidates for treatment interruption trials. Unspliced CA-RNA warrants further investigation as a marker that can be prioritized in paediatric clinical trials where the sample volume can be a significant limitation.
Background
Identifying subphenotypes within heterogeneous diseases may have an impact in terms of therapeutic options. In this study, we aim to assess different subphenotypes in children living with ...human immunodeficiency virus (HIV-1), according to the clinical, virological, and immunological characteristics.
Methods
We collected clinical and sociodemographic data, baseline viral load (VL), CD4 and CD8 count and percentage, age at initiation of ART, HIV DNA reservoir size in peripheral blood mononuclear cells (PBMCs), cell-associated RNA (CA-RNA), ultrasensitive VL, CD4 subsets (T effector CD25+, activated memory cells, Treg cells), humoral-specific HIV response (T-bet B cells), innate response (CD56dim natural killer (NK) cells, NKp46+, perforin), exhaustion markers (PD-1, PD-L1, DNAM), CD8 senescence, and biomarkers for T-lymphocyte thymic output (TREC) and endothelial activation (VCAM). The most informative variables were selected using an unsupervised lasso-type penalty selection for sparse clustering. Hierarchical clustering was performed using Pearson correlation as the distance metric and WARD.D2 as the clustering method. Internal validation was applied to select the best number of clusters. To compare the characteristics among clusters, boxplot and Kruskal Wallis test were assessed.
Results
Three subphenotypes were discovered (cluster1: n=18, 45%; cluster2: n=11, 27.5%; cluster3: n=11, 27.5%). Patients in cluster1 were treated earlier, had higher baseline %CD4, low HIV reservoir size, low western blot score, higher TREC values, and lower VCAM values than the patients in the other clusters. In contrast, cluster3 was the less favorable. Patients were treated later and presented poorer outcomes with lower %CD4, and higher reservoir size, along with a higher percentage of CD8 immunosenescent cells, lower TREC, higher VCAM cytokine, and a higher %CD4 PD-1. Cluster2 was intermediate. Patients were like those of cluster1, but had lower levels of t-bet expression and higher HIV DNA reservoir size.
Conclusions
Three HIV pediatric subphenotypes with different virological and immunological features were identified. The most favorable cluster was characterized by a higher rate of immune reconstitution and a slower disease progression, and the less favorable with more senescence and high reservoir size. In the near future therapeutic interventions for a path of a cure might be guided or supported by the different subphenotypes.
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