Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis.

PURPOSE: Emerging studies suggest that low-pass genome sequencing (GS) provides additional diagnostic yield of clinically significant copy-number variants (CNVs) compared with chromosomal microarray analysis (CMA). However, a prospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of low-pass GS compared with CMA is warranted. METHODS: A total of 1023 women undergoing prenatal diagnosis were enrolled. Each sample was subjected to low-pass GS and CMA for CNV analysis in parallel. CNVs were classified according to guidelines of the American College of Medical Genetics and Genomics. RESULTS: Low-pass GS not only identified all 124 numerical disorders or pathogenic or likely pathogenic (P/LP) CNVs detected by CMA in 121 cases (11.8%, 121/1023), but also defined 17 additional and clinically relevant P/LP CNVs in 17 cases (1.7%, 17/1023). In addition, low-pass GS significantly reduced the technical repeat rate from 4.6% (47/1023) for CMA to 0.5% (5/1023) and required less DNA (50 ng) as input. CONCLUSION: In the context of prenatal diagnosis, low-pass GS identified additional and clinically significant information with enhanced resolution and increased sensitivity of detecting mosaicism as compared with the CMA platform used. This study provides strong evidence for applying low-pass GS as an alternative prenatal diagnostic test.

Steroid phobia, Chinese medicine and asthma control.

BACKGROUND: Inhaled corticosteroids (ICS) are the mainstay of treatment for asthma. Corticosteroid (CS) phobia and fears are prevalent, and these may influence therapeutic efficacy and asthma control. AIM: The aim of this study was to evaluate if CS fear is associated with asthma control in children. METHODS: Patients aged >4 years with asthma at a pediatric outpatient clinic were surveyed, and the Asthma Control Test (ACT) was used for the assessment of asthma control. RESULTS: Ninety-eight patients and their parents were interviewed. Thirty-four (35%) parents reported moderate or significant CS fear. They were more likely than those with no or little fear to have poorer asthma control (mean ACT scores 21.3 ± 4.0 vs 23.1 ± 3.3, P = 0.02), discuss their fears with their doctors (P < 0.001), request CS sparing medications (P = 0.044) and resort to Chinese medicine (CM) usage (P < 0.001). Backward binomial logistic regression showed parents with moderate/significant fears were more likely to discuss their fears with their doctors (OR: 5.21; 95% CI: 1.86-14.59; P = 0.002) and have used CM (OR: 4.28; 95% CI: 1.61-11.41; P = 0.004). CS fear was not translated to reduced self-reported compliance in the prescribed ICS. About 40% of the respondents had ever used Chinese Medicine (CM) with 82% of the users reported having used Chinese herbal medicine and 49% had used cold moxibustion. CONCLUSIONS: CS fear and CM usage are prevalent. Parents with CS fear were more likely to have children with poorer asthma control and have used Chinese medicine. Physicians caring for children with asthma should be aware of parents with CS fear, prepared to address the fear or concerns and offer evidence-based alternative treatment.

Do we need another symptom score for childhood eczema?

AIM: It is important to objectively measure the severity of atopic dermatitis (AD). This study aims to investigate correlations among various clinical severity scores and determine how a severity score based on symptoms alone performs. METHODS: A Chinese-translated symptom score based on Patient-Oriented Eczema Measure (POEM, a short-term subjective-symptom score), Scoring Atopic Dermatitis (SCORAD, a short-term subjective-symptom and objective-sign score), Nottingham Eczema Severity Score (NESS, a long-term subjective symptoms + objective signs), Children Dermatology Life Quality Index (CDLQI, a short-term subjective-symptom score), skin hydration (SH) and transepidermal water loss (TEWL) were compared and Spearman's rho correlations was evaluated. RESULTS: 126 sets of clinical scores from eczema patients (mean age: 11.4 ± 5.6 years; 34.7% male) were evaluated. The modified-POEM, objective SCORAD, NESS and CDLQI correlated well with each other. All round, best correlations were obtained with POEM: Objective SCORAD (rho = 0.7, p < 0.001), NESS (rho = 0.69, p < 0.001), SCORAD symptom of itch (rho = 0.75, p < 0.01), SCORAD symptom of sleep loss (rho = 0.64, p < 0.01), CDLQI (rho = 0.77, p < 0.001) and SH (rho= -0.043, p < 0.05). Linear stepwise-backward regression demonstrated that POEM was independently associated with CDLQI parameters of pruritus (B: 2.16; p = 0.018), activities (B: 1.80; p = 0.009), sleep disturbance (B: 2.78; p < 0.001) and NESS parameter of sleep disturbance (B: 1.02; p = 0.003). CONCLUSION: Clinical scores for acute, chronic, subjective symptoms and objective signs correlated well with each other. The symptom measures by modified POEM is easy to perform by parents or patients and correlated better with most other clinical scores, making it an all-round ideal symptom-based severity score for research.

Testing the Actions of a Multi-action Emollient: Patient's Acceptability Determines Product Efficacy.

AIM: Eczema or Atopic Dermatitis (AD) is associated with itch, sleep disturbance, impaired life quality, reduced skin hydration, impaired epidermal barrier function and colonization by Staphylococcus aureus (SA). We investigated an emollient with claimed multi-actions on barrier repair, antihistaminergic and antimicrobial effects. METHODS: Consecutive AD patients were recruited. Swabs and cultures from eczematous areas, disease severity (SCOring Atopic Dermatitis score: SCORAD), quality-of-life (Children Dermatology Life Quality Index, CDLQI), Skin Hydration (SH), and Transepidermal Water Loss (TEWL) were obtained before and 4-week following usage of the emollient. Global or General Acceptability of Treatment (GAT) was obtained (as very good, good, fair or poor). RESULTS: 30 AD patients were recruited. 73% reported "very good" or "good", whereas 27% reported "fair" or "poor" GAT of the emollient. Following the use of the multi-action emollient, area affected, disease intensity and severity significantly improved, especially in the very good/good group (p=0.006-0.035). There was no significant improvement of itch or sleep scores, quality of life, SH, TEWL, S. aureus colonization status, or use of topical treatments. When compared with the historical data of another product, there was no statistical difference between the two creams. CONCLUSION: The emollient is acceptable in nearly three-quarter of AD patients. Patients that accept the moisturizer have less area affected, disease intensity and severity than the non-accepting counterparts following its usage. Despite claim for multi-action, there were no appreciable quality-oflife, anti-itch, skin barrier, and anti-microbial effects.

Relevance of Cat and Dog Sensitization by Skin Prick Testing in Childhood Eczema and Asthma.

BACKGROUND: Household animal dander has been implicated as aeroallergen in childhood atopic diseases. Many parents seek healthcare advice if household pet keeping may be detrimental in atopic eczema (AE), allergic rhinitis and asthma. AIM: We investigated if skin sensitization by cat/dog dander was associated with disease severity and quality of life in children with AE. METHODS: Demographics, skin prick test (SPT) results, disease severity (Nottingham eczema severity score NESS), Children Dermatology Life Quality Index (CDLQI), blood IgE and eosinophil counts of a cohort of AE patients were reviewed. RESULTS: 325 AE patients followed at a pediatric dermatology clinic were evaluated. Personal history of asthma was lowest (20%) in the dog-dander-positive-group but highest (61%) in bothcat- and-dog-dander-positive group (p=0.007). Binomial logistic regression ascertained that catdander sensitization was associated with increasing age (adjusted odds ratio [aOR], 1.056; 95% Confidence Interval [CI], 1.006 to 1.109; p=0.029), dust-mite sensitization (aOR, 4.625; 95% CI, 1.444 to 14.815; p=0.010), food-allergen sensitization (aOR, 2.330; 95% CI, 1.259 to 4.310; p=0.007) and keeping-cat-ever (aOR, 7.325; 95% CI, 1.193 to 44.971; p=0.032); whereas dogdander sensitization was associated with dust-mite sensitization (aOR, 9.091; 95% CI, 1.148 to 71.980; p=0.037), food-allergen sensitization (aOR, 3.568; 95% CI, 1.341 to 9.492; p=0.011) and keeping-dog-ever (aOR, 6.809; 95% CI, 2.179 to 21.281; p=0.001). However, neither cat nor dog sensitization were associated with asthma, allergic rhinitis, parental or sibling atopic status, disease severity or quality of life. CONCLUSION: Physicians should advise parents that there is no direct correlation between AE severity, quality of life, asthma or allergic rhinitis with cutaneous sensitization to cats or dogs. Sensitized patients especially those with concomitant asthma and severe symptoms may consider non-furry alternatives if they plan to have a pet. Highly sensitized individuals, especially those with asthma co-morbidity, may have to remove their pet for a trial period to determine if symptoms improve.

Clinical Signs, Staphylococcus and Atopic Eczema-Related Seromarkers.

Childhood eczema or atopic dermatitis (AD) is a distressing disease associated with pruritus, sleep disturbance, impaired quality of life and Staphylococcus aureus isolation. The pathophysiology of AD is complex and various seromarkers of immunity are involved. We investigated if anti-staphylococcal enterotoxin IgE (anti-SE), selected seromarkers of T regulatory (Treg), T helper (Th) and antigen-presenting cells (APC) are associated with clinical signs of disease severity and quality of life. Disease severity was assessed with the Scoring Atopic Dermatitis (SCORAD) index, and quality of life with the Children's Dermatology Life Quality Index (CDLQI) in AD patients ≤18 years old. Concentrations of anti-staphylococcus enterotoxin A and B immunoglobulin E (anti-SEA and anti-SEB), selected Treg/Th/APC chemokines, skin hydration and transepidermal water loss (TEWL) were measured in these patients. Forty patients with AD [median (interquartile range) age of 13.1 (7.9) years) were recruited. Backward stepwise linear regression (controlling for age, personal allergic rhinitis and asthma, and other blood markers) showed the serum anti-SEB level was positively associated with S. aureus and S. epidermidis isolations, objective SCORAD, clinical signs and CDLQI. TNF-α (a Th1 cytokine) was positively associated with objective SCORAD (B = 4.935, p = 0.010), TGF-ß (a Treg cytokine) negatively with disease extent (B = -0.015, p = 0.001), IL-18 (an APC cytokine) positively with disease extent (B = 0.438, p = 0.001) and with TEWL (B = 0.040, p = 0.010), and IL-23 (an APC cytokine) negatively with disease extent (B = -2.812, p = 0.006) and positively with pruritus (B = 0.387, p = 0.007). CONCLUSIONS: Blood levels of anti-SEB, Th1, Treg and APC cytokines are correlated with various clinical signs of AD. AD is a systemic immunologic disease involving Staphylococcus aureus, cellular, humoral, cytokine and chemokine pathophysiology.

Mortality, length of stay, bloodstream and respiratory viral infections in a pediatric intensive care unit.

OBJECTIVES: We investigated whether diagnostic categories and presence of infections were associated with increased mortality or length of stay (LOS) in patients admitted to a pediatric intensive care unit (PICU). METHODS: A retrospective study of all PICU admissions between October 2002 and April 2016 was performed. Oncologic vs nononcologic, trauma/injuries vs nontraumatic, infectious (gram-positive, gram-negative, fungal bloodstream infections, common respiratory viruses) vs noninfectious diagnoses were evaluated for survival and LOS. RESULTS: Pediatric intensive care unit admissions (n = 2211) were associated with a mortality of 5.3%. Backward binary logistic regression showed that nonsurvival was associated with leukemia (odds ratio [OR], 4.81; 95% confidence interval [CI], 2.2-10.10; P < .0005), lymphoma (OR, 21.34; 95% CI, 3.89-117.16; P < .0005), carditis/myocarditis (OR, 7.91; 95% CI, 1.98-31.54; P = .003), encephalitis (OR, 6.93; 95% CI, 3.27-14.67; P < .0005), bloodstream infections with gram-positive organisms (OR, 5.32; 95% CI, 2.67-10.60; P < .0005), gram-negative organisms (OR, 8.23; 95% CI, 4.10-16.53; P < .0005), fungi (OR, 3.93; 95% CI, 1.07-14.42; P = .039), and pneumococcal disease (OR, 3.26; 95% CI, 1.21-8.75; P = .019). Stepwise linear regression revealed that LOS of survivors was associated with bloodstream gram-positive infection (B = 98.2; 95% CI, 75.7-120.7; P < .0005). CONCLUSIONS: Patients with diagnoses of leukemia, lymphoma, cardiomyopathy/myocarditits, encephalitis, and comorbidity of bloodstream infections and pneumococcal disease were significantly at risk of PICU mortality. Length of stay of survivors was associated with bloodstream gram-positive infection. The highest odds for death were among patients with leukemia/lymphoma and bloodstream coinfection. As early diagnosis of these childhood malignancies is desirable but not always possible, adequate and early antimicrobial coverage for gram-positive and gram-negative bacteria might be the only feasible option to reduce PICU mortality in these patients. In Hong Kong, a subtropical Asian city, none of the common respiratory viruses were associated with increased mortality or LOS in PICU.