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The Journal of Pediatrics Jun 2024To demonstrate a high-yield molecular diagnostic workflow for lateralized overgrowth (LO), a congenital condition with abnormal enlargement of body parts, and to...
OBJECTIVE
To demonstrate a high-yield molecular diagnostic workflow for lateralized overgrowth (LO), a congenital condition with abnormal enlargement of body parts, and to classify it by molecular genetics. and STUDY DESIGN: We categorized 186 retrospective cases of LO diagnosed between 2003 and 2023 into suspected Beckwith-Wiedemann spectrum (BWSp), PIK3CA-Related Overgrowth Spectrum (PROS), vascular overgrowth (VO) , or isolated (ILO), based on initial clinical assessments, to determine the appropriate first-tier molecular tests and tissue for analysis. Patients underwent testing for 11p15 epigenetic abnormalities or somatic variants in genes related to PI3K/AKT/mTOR, vascular proliferation, and RAS-MAPK cascades using blood or skin DNA. For cases with negative initial tests, a sequential cascade molecular approach was employed to improve diagnostic yield.
RESULTS
This approach led to a molecular diagnosis in 54% of cases, 89% of cases consistent with initial clinical suspicions and 11% reclassified. BWSp was the most common cause, with 43% of cases exhibiting 11p15 abnormalities. PROS had the highest confirmation rate, with 74% of clinically diagnosed patients showing a PIK3CA variant. VO demonstrated significant clinical overlap with other syndromes. Molecular diagnosis of ILO proved challenging, with only 21% of cases classifiable into a specific condition.
CONCLUSION
Despite, LO is underdiagnosed from a molecular viewpoint and to date has had no diagnostic guidelines, which would be crucial for addressing potential cancer predisposition, enabling precision medicine treatments, or guiding management. This study sheds light on the molecular etiology of LO, highlighting the importance of tailored diagnostic approach and of selecting appropriate testing to achieve the highest diagnostic yield.
PubMed: 38945442
DOI: 10.1016/j.jpeds.2024.114177 -
Implementation and Performance of a Point-of-Care COVID-19 Test Program in 4,000 California Schools.The Journal of Pediatrics Jun 2024To evaluate the feasibility and accuracy of an unprecedented COVID-19 antigen testing program in schools, which required a healthcare provider order, laboratory...
OBJECTIVE
To evaluate the feasibility and accuracy of an unprecedented COVID-19 antigen testing program in schools, which required a healthcare provider order, laboratory director, a Clinical Laboratory Improvement Amendments (CLIA) certificate of waiver, as well as training of school personnel.
STUDY DESIGN
Descriptive report of a point-of-care, school-based antigen testing program in California from 8/1/2021 through 5/30/2022, in which participants grades K-12 self-swabbed and school personnel performed testing. Participants included 944,009 students, personnel, and community members from 4,022 California K-12 schools. Outcomes measured include sensitivity and specificity (with polymerase chain reaction [PCR] as comparator), of the Abbott BinaxNOW™ antigen test, number of tests performed, and active infections identified.
RESULTS
Of 102,022 paired PCR/antigen tests, the overall sensitivity and specificity for the antigen test was 81.2% (95%CI:80.5%-81.8%) and 99.6% (95%CI:99.5%-99.6%), respectively using cycle threshold (Ct) values <30. During January through March 2022, the highest prevalence period, the positive predictive value (PPV) of antigen testing was 94.7% and the negative predictive value was 94.2%. Overall, 4,022 school sites were enrolled and 3,987,840 million antigen tests were performed on 944,009 individuals. A total of 162,927 positive antigen tests were reported in 135,163 individuals (14.3% of persons tested).
CONCLUSIONS
Rapidly implementing a school-based testing program in thousands of schools is feasible. Self-swabbing and testing by school personnel can yield accurate results. On-site COVID-19 testing is no longer necessary in schools, but this model provides a framework for future infectious disease threats.
PubMed: 38945441
DOI: 10.1016/j.jpeds.2024.114178 -
International Journal of Infectious... Jun 2024This study sought to detect and characterize influenza A (IAV) and influenza D (IDV) viruses circulating among commercial birds and shop owners in Pakistan's live bird...
OBJECTIVE
This study sought to detect and characterize influenza A (IAV) and influenza D (IDV) viruses circulating among commercial birds and shop owners in Pakistan's live bird markets.
METHODS
Oropharyngeal swabs (n=600; n=300 pools) collected from poultry and nasopharyngeal swabs (n=240) collected from poultry workers were studied for molecular evidence of IAV and IDV using real-time and conventional RT-PCR protocols.
RESULTS
Nineteen (6.3%) poultry pools were positive for IAV and 73.9% of these were positive for H9N2 subtypes. Two (0.83%) poultry workers had evidence of IAV, and both were also H9N2 subtypes. The poultry and human influenza A-positive specimens all clustered phylogenetically by Sanger and next-generation sequencing with previously detected H9N2 poultry isolates. No field specimens were positive for IDV.
CONCLUSION
H9N2 IAV is likely enzootic in Punjab Province Pakistan's live bird markets and may be colonizing the noses of workers and market visitors. Regular monitoring for avian influenza-associated human illness in Punjab seems to be a needed public measure.
PubMed: 38945434
DOI: 10.1016/j.ijid.2024.107146 -
International Journal of Infectious... Jun 2024The emergence of new SARS-CoV-2 variants has led to the development of Omicron-targeting bivalent mRNA vaccines. It is crucial to understand how bivalent vaccines may...
OBJECTIVES
The emergence of new SARS-CoV-2 variants has led to the development of Omicron-targeting bivalent mRNA vaccines. It is crucial to understand how bivalent vaccines may improve antibody responses against new variants.
METHODS
A total of 107 participants, who had three COVID-19 WT mRNA vaccine doses, were recruited, and given either a monovalent (WT) or a bivalent mRNA vaccination (Pfizer/BioNTech Bivalent (WT and BA.4/BA.5) or Moderna Bivalent (WT and BA.1)). Blood samples were taken before booster and at 28 days post-booster.
RESULTS
We found significantly lower fold change in serum binding IgA responses against BA.1, BA.5 and EG.5.1 spike in the bivalent booster group, compared with the monovalent (WT) booster group, following vaccination. However, this was only observed in individuals with prior infection. The relative fold change in serum binding IgA response was more skewed towards WT over variant (BA.1, BA.5 or EG.5.1) spike in previously infected bivalent-booster-vaccinees, as compared with previously infected monovalent-(WT)-booster-vaccinees.
CONCLUSION
The findings suggest imprinting of antibody responses that is shaped by the first vaccination (WT spike). Previous infection also affects the boosting effect of follow-up vaccination. Studies are needed to understand how to induce a robust and long-lasting IgA immunity for protection against COVID-19 infection.
PubMed: 38945433
DOI: 10.1016/j.ijid.2024.107147 -
International Journal of Infectious... Jun 2024Hospitalised neonates are vulnerable to infection and have high rates of antibiotic utilisation.
Prospective antimicrobial stewardship interventions by multidisciplinary teams to reduce neonatal antibiotic use in South Africa: the Neonatal Antimicrobial Stewardship (NeoAMS) study.
BACKGROUND
Hospitalised neonates are vulnerable to infection and have high rates of antibiotic utilisation.
METHODS
Fourteen South African neonatal units (seven public, seven private sector) assembled multidisciplinary teams involving neonatologists, microbiologists, pharmacists, and nurses to implement prospective audit and feedback neonatal antimicrobial stewardship (NeoAMS) interventions. The teams attended seven online training sessions. Pharmacists conducted weekday antibiotic prescription reviews in the neonatal intensive care unit and/or neonatal wards providing feedback to the clinical teams. Anonymised demographic and NeoAMS interventions data were aggregated for descriptive purposes and statistical analysis.
FINDINGS
During the 20-week NeoAMS intervention in 2022, 565 neonates were enrolled. Pharmacists evaluated seven hundred antibiotic prescription episodes; rule-out sepsis (180; 26%) and culture-negative sepsis (138; 20%) were the most frequent indications for antibiotic prescription. For infection episodes with an identified pathogen, only 51% (116/229) of empiric treatments provided adequate antimicrobial coverage. Pharmacists recommended 437 NeoAMS interventions (0·6 per antibiotic prescription episode), with antibiotic discontinuation (42%), therapeutic drug monitoring (17%), and dosing (15%) recommendations most frequent. Neonatal clinicians' acceptance rates for AMS recommendations were high (338; 77%). Mean antibiotic length of therapy decreased by 24% from 9·1 to 6·9 days (0·1 day decrease per intervention week; p=0·001), with the greatest decline in length of therapy for culture-negative sepsis (8·2 days (95%CI 5·7-11·7) to 5·9 days (95% CI 4·6-7·5); p=0·032).
INTERPRETATION
This neonatal AMS programme was successfully implemented in heterogenous and resource-limited settings. Pharmacist-recommended AMS interventions had high rates of clinician acceptance. The NeoAMS intervention significantly reduced neonatal antibiotic use, particularly for culture-negative sepsis.
FUNDING
A grant from Merck provided partial support.
PubMed: 38945432
DOI: 10.1016/j.ijid.2024.107158 -
International Journal of Infectious... Jun 2024Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in young children. With substantial advances in RSV research, we aimed...
OBJECTIVES
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in young children. With substantial advances in RSV research, we aimed to conduct an updated systematic review of risk factors for RSV-ALRI in children under five years.
METHODS
We updated our previously published literature search to November 2022 among three English databases and additionally searched three Chinese databases (from January 1995) to identify all relevant publications. We performed random-effects meta-analyses to estimate the pooled odds ratio and 95% confidence interval (CI) for each risk factor and each outcome (RSV-ALRI in the community and RSV-ALRI hospitalisation).
RESULTS
A total of 47 studies were included (26 from the updated search). Indoor air pollution was identified as a possible risk factor for RSV-ALRI in the community (OR 1.45, 95% CI: 1.10-1.90). The identified risk factors for RSV-ALRI hospitalisation fall into four categories: demographic (male sex, Māori and Pacific ethnicities vs European or other ethnicities), pre- and post- neonatal (prematurity, low birth weight, small for gestational age, maternal smoking during pregnancy or lactation, maternal age <30 years vs 30-34 years, multiparity, caesarean section vs vaginal), household and environmental (having siblings, passive smoking, maternal asthma, daycare centre attendance), and health and medical conditions (any chronic diseases, bronchopulmonary dysplasia, HIV infections, congenital heart disease, Down syndrome, cystic fibrosis, previous asthma). The pooled ORs ranged from 1.14 to 4.55.
CONCLUSIONS
Our findings on the risk factors for RSV-ALRI help identify RSV high-risk groups, which has important implications for RSV prevention at both individual and population levels.
PubMed: 38945430
DOI: 10.1016/j.ijid.2024.107125 -
Acta Tropica Jun 2024Dengue fever is a viral illness, mainly transmitted by Aedes aegypti and Aedes albopictus. With climate change and urbanisation, more urbanised areas are becoming...
Dengue fever is a viral illness, mainly transmitted by Aedes aegypti and Aedes albopictus. With climate change and urbanisation, more urbanised areas are becoming suitable for the survival and reproduction of dengue vector, consequently are becoming suitable for dengue transmission in China. Chongqing, a metropolis in southwestern China, has recently been hit by imported and local dengue fever, experiencing its first local outbreak in 2019. However, the genetic evolution dynamics of dengue viruses and the spatiotemporal patterns of imported and local dengue cases have not yet been elucidated. Hence, this study implemented phylogenetic analyses using genomic data of dengue viruses in 2019 and 2023 and a spatiotemporal analysis of dengue cases collected from 2013 to 2022. We sequenced a total of 15 nucleotide sequences of E genes. The dengue viruses formed separate clusters and were genetically related to those from Guangdong Province, China, and countries in Southeast Asia, including Laos, Thailand, Myanmar and Cambodia. Chongqing experienced a dengue outbreak in 2019 when 168 imported and 1,243 local cases were reported, mainly in September and October. Few cases were reported in 2013-2018, and only six were imported from 2020 to 2022 due to the COVID-19 lockdowns. Our findings suggest that dengue prevention in Chongqing should focus on domestic and overseas population mobility, especially in the Yubei and Wanzhou districts, where airports and railway stations are located, and the period between August and October when dengue outbreaks occur in endemic regions. Moreover, continuous vector monitoring should be implemented, especially during August-October, which would be useful for controlling the Aedes mosquitoes. This study is significant for defining Chongqing's appropriate dengue prevention and control strategies.
PubMed: 38945422
DOI: 10.1016/j.actatropica.2024.107308 -
Neuroscience and Biobehavioral Reviews Jun 2024Research has indicated unique challenges in audiovisual integration of speech among autistic individuals, although methodological differences have led to divergent... (Review)
Review
Research has indicated unique challenges in audiovisual integration of speech among autistic individuals, although methodological differences have led to divergent findings. We conducted a systematic literature search to identify studies that measured audiovisual speech integration among both autistic and non-autistic individuals. Across the 18 identified studies (combined N = 952), autistic individuals showed impaired audiovisual integration compared to their non-autistic peers (g = 0.69, 95% CI [0.53, 0.85], p <.001). This difference was not found to be influenced by participants' mean ages, studies' sample sizes, risk-of-bias scores, or paradigms investigated. However, a subgroup analysis suggested that child studies may show larger between-group differences than adult ones. The prevailing pattern of impaired audiovisual speech integration in autism may have cascading effects on communicative and social behavior. However, small samples and inconsistency in design/analysis translated into considerable heterogeneity in findings and opacity regarding the influence of underlying unisensory and attentional factors. We recommend three key directions for future research: larger samples, more research with adults, and standardization of methodology and analytical approaches.
PubMed: 38945419
DOI: 10.1016/j.neubiorev.2024.105787 -
The Journal of Hospital Infection Jun 2024Continuous fluid infusions delivered between therapies by piggy-back systems avoid disconnection and reconnection of central venous catheters (CVC), thereby reducing...
BACKGROUND
Continuous fluid infusions delivered between therapies by piggy-back systems avoid disconnection and reconnection of central venous catheters (CVC), thereby reducing opportunities for line contamination. However, the impact of continuous versus intermittent infusions on central line-associated bloodstream infections (CLABSI) is unknown.
AIM
To investigate the effect of temporary infusion interruption and line disconnection, with or without use of a 70% isopropyl alcohol cap (IPA-C) use on CLABSI rates in haematology patients.
METHODS
Quasi-experimental study in two haemato-oncology units. At baseline (P1, September 2020 - August 2021), continuous intravenous piggy-back infusions were mandatory. In a first intervention phase (P2, September 2021 - August 2022), infusion disconnections were implemented with use of a 70% isopropyl alcohol cap (IPA-C) for passive decontamination. In a second intervention phase (P3, September 2022 - August 2023), infusion disconnections continued without the use of IPA-C. Rates of CLABSI were compared across the three intervention periods using segmented Poisson regression.
FINDINGS
A total of 11,039 catheter-days across 764 CVC and 16,226 patient-days were included. 21 CLABSI were recorded across all intervention periods. Compared with P1, incidence rate ratios (IRRs) for CLABSI did not significantly change in P2 (IRR 0.76 [95% CI 0.27-2.15]) and P3 (IRR 0.79 [CI 95% 0.28-2.22]). No CVCs were removed due to occlusion during the study period. Five of 21 CLABSI were polymicrobial, and coagulase-negative staphylococci were isolated in 19/21 cases (90%).
CONCLUSION
Interruption of continuous infusions in haemato-oncology patients with a CVC was not associated with a substantial change in CLABSI rates, whether or not an IPA-C was used.
PubMed: 38945400
DOI: 10.1016/j.jhin.2024.05.021 -
Kidney International Jun 2024Baseline kidney function following kidney transplantation is often used in research and clinical decision-making yet is not well defined. Here, a method to determine...
Baseline kidney function following kidney transplantation is often used in research and clinical decision-making yet is not well defined. Here, a method to determine baseline function was proposed and validated on three single-center retrospective cohorts consisting of 922 patients from Belgium (main cohort) and two validation cohorts of 987 patients from the Netherlands and 519 patients from Germany. For each transplant, a segmented regression model was fitted on the estimated glomerular filtration rate (eGFR) evolution during the first-year post-transplantation. This yielded estimates for change point timing, rate of eGFR change before and after change point and eGFR value at change point, now considered the "baseline function". Associations of eGFR evolution with recipient/donor characteristics and the graft failure rate were assessed with linear regression and Cox regression respectively. The change point occurred on average at an eGFR value of 43.7±14.6 mL/min/1.73m, at a median time of 6.5 days post-transplantation. Despite significant associations with several baseline donor-recipient characteristics (particularly, donor type; living vs deceased), the predictive value of these characteristics for eGFR value and timing of the change point was limited. This followed from a large heterogeneity within eGFR trajectories, which in turn indicated that favorable levels of kidney function could be reached despite a suboptimal initial evolution. Segmented regression consistently provided a good fit to early eGFR evolution, and its estimate of the change point can be a useful reference value in future analyses. Thus, our study shows that baseline kidney function after transplantation is heterogeneous and partly related to pretransplant donor characteristics.
PubMed: 38945395
DOI: 10.1016/j.kint.2024.05.030