This study aimed to investigate the trend and seasonality of infection due to respiratory syncytial virus (RSV) at KK Women's and Children's Hospital (KKH) in Singapore and to examine the risk ...factors for mortality among children with RSV infection requiring admission to the paediatric intensive care unit (PICU).
A retrospective study was conducted at KKH on children with RSV infections who were admitted to the PICU between January 2004 and December 2010. The medical records of children who died from RSV infections were reviewed. Linear regression was performed to determine the risk factors for RSV mortality.
RSV infection was documented in 5,785 children during the study period; the infection was noted to be occurring throughout the year, with a small increase in prevalence between the months of June and August every year. Among 85 (1.5%) out of 5,785 children who were admitted to the PICU for RSV infection, 74 (1.3%) survived and 11 (0.2%) died. Multivariate logistic regression analysis showed that haemodynamically significant cardiac disease (odds ratio OR 12.2, 95% confidence interval CI 0.9-16.7, p = 0.05), immunodeficiency (OR 71.4, 95% CI 8.2-500, p < 0.001) and metabolic disease (OR 71.4, 95% CI 4.3-1,000, p = 0.003) were independent risk factors for mortality in RSV infections. Prematurity increased the risk of admission to the PICU but was not significantly associated with mortality.
Children with haemodynamically significant cardiac disease, immunodeficiency and metabolic disease were at higher risk of death after hospitalisation for RSV-related illnesses. These children should be considered for palivizumab prophylaxis.
The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled ...study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD.
As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome.
This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development.
The study was registered in the Dutch Trial Register (Number: 2838 ) on 4th April 2011.
•Growing evidence associates inflammation during pregnancy with behavioural and cognitive outcomes of the offspring.•Asthma during pregnancy may trigger maternal immune activation (MIA).•Maternal ...asthma symptoms during pregnancy were associated with internalising behaviours and executive functioning at age 7.•Paternal asthma symptoms in the perinatal period was not linked to child outcomes.
Maternal history of inflammatory conditions has been linked to offspring developmental and behavioural outcomes. This phenomenon may be explained by the maternal immune activation (MIA) hypothesis, which posits that dysregulation of the gestational immune environment affects foetal neurodevelopment. The timing of inflammation is critical. We aimed to understand maternal asthma symptoms during pregnancy, in contrast with paternal asthma symptoms during the same period, on child behaviour problems and executive function in a population-based cohort.
Data were obtained from 844 families from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort. Parent asthma symptoms during the prenatal period were reported. Asthma symptoms in children were reported longitudinally from two to five years old, while behavioural problems and executive functioning were obtained at seven years old. Parent and child measures were compared between mothers with and without prenatal asthma symptoms. Generalized linear and Bayesian phenomics models were used to determine the relation between parent or child asthma symptoms and child outcomes.
Children of mothers with prenatal asthma symptoms had greater behavioural and executive problems than controls (Cohen’s d: 0.43–0.75; all p < 0.05). This association remained after adjustments for emerging asthma symptoms during the preschool years and fathers’ asthma symptoms during the prenatal period. After adjusting for dependence between child outcomes, the Bayesian phenomics model showed that maternal prenatal asthma symptoms were associated with child internalising symptoms and higher-order executive function, while child asthma symptoms were associated with executive function skills. Paternal asthma symptoms during the prenatal period were not associated with child outcomes.
Associations between child outcomes and maternal but not paternal asthma symptoms during the prenatal period suggests a role for MIA. These findings need to be validated in larger samples, and further research may identify behavioural and cognitive profiles of children with exposure to MIA.
This randomized clinical trial (Registration: NCT03085134) assessed if an extensively hydrolyzed formula (EHF) supplemented with two human milk oligosaccharides (HMO) and reduced protein content ...(2.20 g/100 kcal) supports normal growth in infants with cow’s milk protein allergy (CMPA). Secondary outcomes were gastrointestinal tolerability, safety, and effect on infections. Nonbreastfed infants aged 0−6 months with CMPA were enrolled. Body weight, length, and head circumference were measured monthly for 4 months (primary study endpoint), after 6 months, and at the age of 12 months. Of 200 infants screened, 194 (mean age 3.2 months) were randomized. At the 4-month follow-up, daily weight gain for the test formula was noninferior to the control formula; p < 0.005. There were no significant group differences in anthropometric parameters. Both formulas were safe and well tolerated. Infants in the HMO group had a statistically significant reduction in the frequency of upper respiratory tract infections and a lower incidence of ear infections at 12 months (per protocol analysis). The relative risk of lower respiratory tract and gastrointestinal infections was reduced by 30−40%, but this was not statistically significant due to sample size limitations. In summary, the HMO-supplemented formula supports normal growth in infants with CMPA and suggests a protective effect against respiratory and ear infections in the first year of life.
Making a diagnosis of perioperative anaphylaxis and identifying culprit drugs are diagnostic challenges. The aim of this study is to describe the perioperative presentation of anaphylaxis and results ...of patients who underwent allergy evaluation. This is a retrospective review of perioperative anaphylaxis of severity Grade 2 and above based on the Australian and New Zealand Anaesthetic Allergy Group criteria from 2015 to 2019 in a tertiary paediatric hospital. Data collected were demographics, clinical features, investigations and management. Of the 35,361 cases of paediatric anaesthesia, there were 15 cases of perioperative anaphylaxis, giving an incidence of four in 10,000. The median age was seven years (interquartile range four-15 years) with a male predominance of 86.7% (13/15). The severity of anaphylaxis was Grade 2 in 33.3% (5/15) and Grade 3 in 66.7% (10/15). The commonest presenting feature was hypotension (13/15, 86.7%) while the earliest symptom was respiratory change (9/15, 60.0%). Dynamic tryptase was raised in 75% (6/8) of the patients with adequate tryptase samples. Eight patients (53.3%) completed allergy testing, of whom five patients (62.5%) had IgEmediated anaphylaxis with skin test positive to cefazolin (n1/43), atracurium (n1/41) and rocuronium (n1/41). Three patients (25.0%) had non-IgE-mediated reactions with negative skin tests. Although only half the patients completed allergy evaluation, a culprit drug could be identified in 62.5%, with antibiotics being the commonest. This emphasises the need for appropriate evaluation in cases of suspected perioperative anaphylaxis.
The optimal coronary revascularization strategy (coronary artery bypass grafting CABG or percutaneous coronary intervention PCI) in patients with end-stage renal disease (ESRD) remains uncertain. We ...performed an updated systematic review and meta-analysis of observational studies comparing CABG and PCI in patients with ESRD using a random-effects model for the primary outcome of long-term all-cause mortality. Our review registered through PROSPERO included observational studies published after 2011 to ensure overlap with previous studies and identified 7 new studies for a total of 23. We found that the median sample size in the selected studies was 125 patients (25 to 15,784) with a large variation in the covariate risk adjustment and only 3 studies reporting the indications for the revascularization strategy. CABG was associated with a small reduction in mortality (relative risk 0.92, 95% CI 0.89 to 0.96) with significant heterogeneity demonstrated (p = 0.005, I2 = 48.6%). Subgroup analysis by categorized “year of study initiation” (<1990, 1991 to 2003, >2004) further confirmed the summary estimate trending toward survival benefit of CABG along with a substantial decrease in heterogeneity after 2004 (p = 0.64, I2 = 0%). In conclusion, our updated systematic review and meta-analysis demonstrated that in patients with ESRD referred for coronary revascularization, CABG was associated with a small decrease in the relative risk of long-term mortality compared with PCI. The generalizability of the finding to all patients with ESRD referred for coronary revascularization is limited because of a lack of known indications for coronary revascularization, substantial variation in covariate risk adjustment, and lack of randomized clinical trial data.
MALDI-MSI is a powerful technology for localizing drug and metabolite distributions in biological tissues. To enhance our understanding of tuberculosis (TB) drug efficacy and how efficiently certain ...drugs reach their site of action, MALDI-MSI was applied to image the distribution of the second-line TB drug moxifloxacin at a range of time points after dosing. The ability to perform multiple monitoring of selected ion transitions in the same experiment enabled extremely sensitive imaging of moxifloxacin within tuberculosis-infected rabbit lung biopsies in less than 15 min per tissue section. Homogeneous application of a reference standard during the matrix spraying process enabled the ion-suppressing effects of the inhomogeneous lung tissue to be normalized. The drug was observed to accumulate in granulomatous lesions at levels higher than that in the surrounding lung tissue from 1.5 h postdose until the final time point. MALDI-MSI moxifloxacin distribution data were validated by quantitative LC/MS/MS analysis of lung and granuloma extracts from adjacent biopsies taken from the same animals. Drug distribution within the granulomas was observed to be inhomogeneous, and very low levels were observed in the caseum in comparison to the cellular granuloma regions. In this experiment the MALDI-MRM-MSI method was shown to be a rapid and sensitive method for analyzing the distribution of anti-TB compounds and will be applied to distribution studies of additional drugs in the future.
Enzyme replacement therapy significantly reduces morbidity and mortality in patients with Pompe disease. Development of hypersensitivity reactions to enzyme replacement therapy is common and can ...adversely affect disease outcomes when treatment is halted or delayed.
Our institution reports a case of successful alglucosidase alfa enzyme replacement therapy desensitisation in a 9-year-old girl with infantile onset Pompe disease.
A desensitisation protocol was tailored to our patient with the help of a multidisciplinary team including the allergist, geneticist, nurses and pharmacists.
For our patient, desensitisation was successful using a multi-step three-fold dose escalation protocol.
Desensitisation is possible in individuals with hypersensitivity reactions to enzyme replacement. Desensitisation protocols need to be tailored according to the patient's needs and responses to find a protocol that is safe, effective and simple.
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