METHODS: This was a randomized controlled trial at 2 centers. A total of 78 patients requiring DC were randomized in a 1:1:1 ratio into 3 groups: vacuum drains (VD), passive drains (PD), and no drains (ND). Complications studied were need for surgical revision, SGH amount, new remote hematomas, postcraniectomy hydrocephalus (PCH), functional outcomes, and mortality.
RESULTS: Only 1 VD patient required surgical revision to evacuate SGH. There was no difference in SGH thickness and volume among the 3 drain types (P = 0.171 and P = 0.320, respectively). Rate of new remote hematoma and PCH was not significantly different (P = 0.647 and P = 0.083, respectively), but the ND group did not have any patient with PCH. In the subgroup analysis of 49 patients with traumatic brain injury, the SGH amount of the PD and ND group was significantly higher than that of the VD group. However, these higher amounts did not translate as a significant risk factor for poor functional outcome or mortality. VD may have better functional outcome and mortality.
CONCLUSIONS: In terms of complication rates, VD, PD, and ND may be used safely in DC. A higher amount of SGH was not associated with poorer outcomes. Further studies are needed to clarify the advantage of VD regarding functional outcome and mortality, and if ND reduces PCH rates.
PATIENTS AND METHODS: FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129).
RESULTS: Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; P < .0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; P < .0001) and 0.02 (95% CI, < 0.01 to 0.05; P = .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively.
CONCLUSION: Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.
METHODS: A structured questionnaire was used to collect data on a child's current and previous illnesses, oral health behaviours, dietary habits, parental smoking behaviours and parents' dental history. The intraoral examination recorded dental caries (dmfs), enamel defects, gingival health, melanin pigmentation and soft tissue health. Stimulated saliva was collected. Total sIgA levels were quantified using indirect competitive ELISA with a SalimetricsTM kit.
RESULTS: The 44 children (aged 15-69 months) recruited were divided into two groups: ETS and non-ETS (control). There were 22 children in each: 16 who were exposed to ETS during and after gestation were identified as the ETSB subgroup. Participants exposed to ETS were more likely to have had upper respiratory tract and middle ear infections during the neonatal period and had higher mean dmft, mean dmfs, mean percent of surfaces with demarcated opacities and mean GI than the non-ETS participants. The children exposed to ETS before and after birth had the highest occurrence of enamel opacities showed a higher risk for dental caries even though more children in this group used the recommended fluoride toothpaste (1000 ppm fluoride). Mothers who smoked either never breastfed their children or breastfed their children for less than the recommended period of 6 months. Children exposed to ETS were shown to have higher mean total sIgA (μg/ml) than the children in the control group.
CONCLUSIONS: Associations between ETS exposure before and after gestation and oral health, including salivary changes in young children were shown in the present study. Dental health professionals should include a question about household smoking in children's dental histories, which would allow opportunities to discuss the impact of smoking on child oral health. Longitudinal oral health studies should include a history of maternal smoking during pregnancy and afterwards.
MATERIALS AND METHODS: A cross-sectional study was done among 253 children of 5-, 12-, and 15-year-olds living in various orphanage houses of Selangor, Kuala Lumpur, Malaysia. Demographic data, and dietary and oral hygiene practices were collected through a structured questionnaire. Clinical examinations of children were conducted to assess oral health status and recorded in the World Health Organization oral health assessment form (1997). Stimulated saliva was collected for S. mutans and Lactobacilli levels. The statistical software, namely, Statistical Package for the Social Sciences version 19.0 was used for the analysis of the data.
RESULTS: The final data analysis included 253 children of which 116 (45.8%) were boys and 137 (54.2%) were girls. Overall, 140 (55.33%) children were caries-free and 113 (44.66%) children presented with caries (decayed/missing/filled surface >0). High levels of salivary microbiological counts (S. mutans and Lactobacilli), i.e., ≥105, stress the importance of necessary preventive oral health services. Treatment needs among orphan children showed that most of the children, i.e., 58 (22.9%), need preventive or caries-arresting care followed by 49 (19.4%) who require two-surface filling as an immediate measure.
CONCLUSION: From the results of our study, orphan children have low utilization of preventive and therapeutic oral health services. Urgent attention is required to plan a comprehensive dental health-care program to improve their oral health status.
CLINICAL SIGNIFICANCE: Parents are the primary caretakers of children, but woefully some of them have to lead their lives without parents, the latter either being dead or incapable of bringing up their children. Such a group of children is known as orphans. As oral health is an integral part of general health, it is essential for health-care policy makers to address oral health needs of this underprivileged group of society. This article highlights the risk factors and treatment needs among orphan schoolchildren.
METHODS: Children aged 5-18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years.
FINDINGS: Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs.
INTERPRETATION: A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration.
TRIAL REGISTRATION: ClinicalTrials.gov No CTRI/2013/10/004121.
METHODS: A review of medical records of children who underwent adenotonsillectomy between January 2011 and December 2014 was performed. Association between demographic variables and post-operative complications were examined using chi-square and Mann-Whitney tests.
RESULTS: A total of 214 children were identified, and of these, 19 (8.8%) experienced post-operative complications. Six children (2.8%) had respiratory complications: hypoxaemia in four and laryngospasm requiring reintubation in a further two. Both of the latter patients were extubated upon arrival to PICU and required no escalation of therapy. A total of 13 (6.1%) children had non-respiratory complications: 8 (3.7%) had infection and 5 (2.3%) had haemorrhage. A total of 26 (12.1%) children were electively admitted to PICU and mean stay was 19.5 (SD ± 13) h. No association between demographic characteristics, comorbid conditions or polysomnographic parameters and post-operative complications were noted. A total of 194 (90.7%) children stayed only one night in hospital (median 1 day, range 1-5 days).
CONCLUSION: The previously identified risk factors and criteria for PICU admission need revision, and new recommendations are necessary.
METHODS: All-cause and cause-specific mortality estimates were obtained from the 2013 Global Burden of Disease Study. Data were extracted from 1990 to 2013 for the developmental age range from 1 to 24 years, for both sexes. Trends in all-cause and cause-specific mortality for the major epidemiological causes were estimated.
RESULTS: From 1990 to 2013, all-cause mortality decreased in all age groups. Reduction of all-cause mortality was greatest in 1- to 4-year-olds (2.4% per year reduction) and least in 20- to 24-year-olds (.9% per year reduction). Accordingly, in 2013, all-cause mortality was highest in 20- to 24-year-old males (129 per 100,000 per year). In 1990, the principal cause of death for 1- to 9-year boys and girls was vaccine preventable diseases. By 2013, neoplasms had become the major cause of death in 1-9 year olds of both sexes. The major cause of death in 10- to 24-year-old females was typhoid in 1990 and neoplasms in 2013, whereas the major cause of death in 10- to 24-year-old males remained road traffic injuries.
CONCLUSIONS: The reduction in mortality across the epidemiological transition in Malaysia has been much less pronounced for adolescents than younger children. The contribution of injuries and noncommunicable diseases to adolescent mortality suggests where public health strategies should focus.
DATA SOURCES: A PubMed search was completed in Clinical Queries using the key terms "Staphylococcal scalded skin syndrome" and "Ritter disease".
RESULTS: SSSS is caused by toxigenic strains of Staphylococcus aureus. Hydrolysis of the amino-terminal extracellular domain of desmoglein 1 by staphylococcal exfoliative toxins results in disruption of keratinocytes adhesion and cleavage within the stratum granulosum which leads to bulla formation. The diagnosis is mainly clinical, based on the findings of tender erythroderma, bullae, and desquamation with a scalded appearance especially in friction zones, periorificial scabs/crusting, positive Nikolsky sign, and absence of mucosal involvement. Prompt empiric treatment with intravenous anti-staphylococcal antibiotic such as nafcillin, oxacillin, or flucloxacillin is essential until cultures are available to guide therapy. Clarithromycin or cefuroxime may be used should the patient have penicillin allergy. If the patient is not improving, critically ill, or in communities where the prevalence of methicillin-resistant S. aureus is high, vancomycin should be used.
CONCLUSION: A high index of suspicion is essential for an accurate diagnosis to be made and treatment promptly initiated.
METHODS: A case-control study was performed to detect HLA loci involved in aromatic antiepileptic drug-induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes.
RESULTS: HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome (p = 5.63 × 10(-15)). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group (p = 1.02 × 10(-5)) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls (p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association.
CONCLUSIONS: HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China.
METHODS: We performed trio-based whole-exome sequencing (WES) in 210 families and case-only WES in 489 individuals with epileptic encephalopathies. The functional effect of CYFIP2 variants on WAVE signaling was evaluated by computational structural analysis and in vitro transfection experiments.
RESULTS: We identified three de novo CYFIP2 variants at the Arg87 residue in 4 unrelated individuals with early-onset epileptic encephalopathy. Structural analysis indicated that the Arg87 residue is buried at an interface between CYFIP2 and WAVE1, and the Arg87 variant may disrupt hydrogen bonding, leading to structural instability and aberrant activation of the WAVE regulatory complex. All mutant CYFIP2 showed comparatively weaker interactions to the VCA domain than wild-type CYFIP2. Immunofluorescence revealed that ectopic speckled accumulation of actin and CYFIP2 was significantly increased in cells transfected with mutant CYFIP2.
INTERPRETATION: Our findings suggest that de novo Arg87 variants in CYFIP2 have gain-of-function effects on the WAVE signaling pathway and are associated with severe neurological disorders. Ann Neurol 2018;83:794-806.
METHODS: A randomized controlled trial was conducted in 3 district hospitals in Sabah, Malaysia to compare the efficacy of AL against chloroquine (CQ) for uncomplicated knowlesi malaria. Participants were included if they weighed >10 kg, had a parasitemia count <20000/μL, and had a negative rapid diagnostic test result for Plasmodium falciparum histidine-rich protein 2. Diagnosis was confirmed by means of polymerase chain reaction. Patients were block randomized to AL (total target dose, 12 mg/kg for artemether and 60 mg/kg for lumefantrine) or CQ (25 mg/kg). The primary outcome was parasite clearance at 24 hours in a modified intention-to-treat analysis.
RESULTS: From November 2014 to January 2016, a total of 123 patients (including 18 children) were enrolled. At 24 hours after treatment 76% of patients administered AL (95% confidence interval [CI], 63%-86%; 44 of 58) were aparasitemic, compared with 60% administered CQ (47%-72%; 39 of 65; risk ratio, 1.3 [95% CI, 1.0-1.6]; P = .06). Overall parasite clearance was shorter after AL than after CQ (median, 18 vs 24 hours, respectively; P = .02), with all patients aparasitemic by 48 hours. By day 42 there were no treatment failures. The risk of anemia during follow-up was similar between arms. Patients treated with AL would require lower bed occupancy than those treated with CQ (2414 vs 2800 days per 1000 patients; incidence rate ratio, 0.86 [95% CI, .82-.91]; P < .001). There were no serious adverse events.
CONCLUSIONS: AL is highly efficacious for treating uncomplicated knowlesi malaria; its excellent tolerability and rapid therapeutic response allow earlier hospital discharge, and support its use as a first-line artemisinin-combination treatment policy for all Plasmodium species in Malaysia.
CLINICAL TRIALS REGISTRATION: NCT02001012.