Recent Advances in Pediatric Use of Oral Paracetamol in Fever and Pain Management

Paracetamol is a common analgesic and antipyretic drug for management of fever and mild-to-moderate pain in infants and children, and it is considered as first-line therapy for the treatment of both according to international guidelines and recommendations. The mechanism of action of paracetamol is complex and multifactorial, and several aspects of the pharmacology impact its clinical use, especially in the selection of the correct analgesic and antipyretic dose. A systematic literature search was performed by following procedures for transparent reporting of systematic reviews and meta-analyses. To maximize efficacy and avoid delays in effect, use of the appropriate dose of paracetamol is paramount. Older clinical studies using paracetamol at subtherapeutic doses of ≤10 mg/kg generally show that it is less effective than non-steroidal anti-inflammatory drugs (NSAIDs). However, recent evidence shows that when used at dose of 15 mg/kg for fever and pain management, paracetamol is significantly more effective than placebo, and at least as effective as NSAIDs. Paracetamol 15 mg/kg has a tolerability profile similar to that of placebo and NSAIDs such as ibuprofen and ketoprofen used for short-term treatment of fever. However, when used at repetitive doses for consecutive days, paracetamol shows lower risk of adverse events compared to NSAIDs. Also, unlike NSAIDs, paracetamol is indicated for use in children of all ages. Overall, clinical evidence qualifies paracetamol 15 mg/kg a safe and effective option for treatment of pain and fever in children

Vaccine against tuberculosis: what's new?

BACKGROUND: one of the World Health Organization Millennium Development Goal is to reduce tuberculosis incidence by 2015. However, more of 8.5 million tuberculosis cases have been reported in 2011, with an increase of multidrug-resistant strains. Therefore, the World Health Organization target cannot be reach without the help of a vaccine able to limit the spread of tuberculosis. Nowadays, bacille Calmette-Guérin is the only vaccine available against tuberculosis. It prevents against meningeal and disseminated tuberculosis in children, but its effectiveness against pulmonary form in adolescents and adults is argued. METHOD: a systematic review was performed by searches of Pubmed, references of the relevant articles and Aeras and ClinicalTrial.gov websites. RESULTS: 100 articles were included in this review. Three viral vectored booster vaccines, five protein adjuvant booster vaccines, two priming vaccines and two therapeutic vaccines have been analyzed. CONCLUSIONS: Several vaccines are in the pipeline, but further studies on basic research, clinical trial and mass vaccination campaigns are needed to achieve the TB eradication target by 2050

Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis infection in children: A 2013 update

BACKGROUND: Previous meta-analyses regarding the performance of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting results, probably due to different inclusion/exclusion criteria. METHODS: We systematically searched PubMed, EMBASE and Cochrane databases and calculated pooled estimates of sensitivities and specificities of QuantiFERON-TB Gold In Tube (QFT-G-IT), T-SPOT.TB, and tuberculin skin test (TST). Several sub-analysis were performed: stratification by background (low income vs. high income countries); including only microbiological confirmed TB cases; including only studies performing a simultaneous three-way comparison of the three tests, and including immunocompromised children. RESULTS: Overall, 31 studies (6183 children) for QFT-G-IT, 14 studies (2518 children) for T-SPOT.TB and 34 studies (6439 children) for TST were included in the analyses. In high income countries QFT-G-IT sensitivity was 0.79 (95%IC: 0.75-0.82) considering all the studies, 0.78 (95%CI:0.70-0.84) including only studies performing a simultaneous three-way comparison and 0.86 (95%IC 0.81-0.90) considering only microbiologically confirmed studies. In the same analyses T-SPOT.TB sensitivity was 0.67 (95%IC 0.62-0.73); 0.76 (95%CI: 0.68 to 0.83); and 0.79 (95%IC 0.69-0.87), respectively. In low income countries QFT-G-IT pooled sensitivity was significantly lower: 0.57 (95%IC:0.52-0.61), considering all the studies, and 0.66 (95%IC 0.55-0.76) considering only microbiologically confirmed cases; while T-SPOT.TB sensitivity was 0.61 (95%IC 0.57-0.65) overall, but reached 0.80 (95%IC 0.73-0.86) in microbiologically confirmed cases. In microbiologically confirmed cases TST sensitivity was similar: 0.86 (95%IC 0.79-0.91) in high income countries, and 0.74 (95%IC 0.68-0.80) in low income countries. Higher IGRAs specificity with respect to TST was observed in high income countries (97-98% vs. 92%) but not in low income countries (85-93% vs. 90%). CONCLUSIONS: Both IGRAs showed no better performance than TST in low income countries

Intimal Sarcoma of the Descending Aorta Mimicking Aortitis

We describe a 74-year-old male patient with an intimal sarcoma of the descending aorta mimicking aortitis. The patient presented with lower back pain, fever, and increased C-reactive protein, erythrocyte sedimentation rate, and immunoglobulin G4 (IgG4) serum levels, together with Staphylococcus epidermidis-positive blood cultures. These findings, together with evidence of a 49-mm pseudoaneurysm of the descending thoracic aorta, caused us to suspect aortitis. However, postoperative histology and immunohistochemistry demonstrated the presence of an intimal aortic sarcoma. At the 8-month follow-up, local recurrence of the neoplasm and lung metastases were noted

Vitamin D status and predictors of hypovitaminosis D in internationally adopted children

To evaluate vitamin D status in internationally adopted children at first medical evaluation in Italy and to identify possible risk factors for hypovitaminosis D in this population.25-hydroxyvitamin D [25(OH)D] levels were analyzed in internationally adopted children consecutively recruited at one Italian Center between 2010 and 2014 as part of the first screening protocol. Demographic, clinical and laboratory data were prospectively collected. Serum 25(OH)D levels <10 ng/mL, <20 ng/mL, and <30 ng/mL were used to define severe vitamin D deficiency, vitamin D deficiency and hypovitaminosis D, respectively.962 internationally adopted children (median age: 5.47 years; IQR:3.14-7.93) were included in the study. Median 25(OH)D level was 22.0 ng/mL (IQR:15.0-30.0 ng/mL); 710/962 (73.8%) children showed hypovitaminosis D (<30 ng/mL), 388/962 (40.3%) had vitamin D deficiency (<20 ng/dL), and 92/962 (9.6%) had severe vitamin D deficiency (<10ng/mL). No case of clinical rickets was observed. Hypovitaminosis D was particularly frequent (>90%) in children adopted from Ethiopia, Peru, India, Bulgaria and Lithuania. At multivariate analysis an increased risk of hypovitaminosis D was found to be associated with: age ≥ 6 years, time spent in Italy ≥ 3 months, blood sample taken in winter, spring or fall, compared to summer. Gender, ethnicity/continent of origin, tubercular infection, intestinal parassitosis and BMI-z-score < -2 were not associated with vitamin D status.Hypovitaminosis D is common in internationally adopted children, from all ethnic group. The evaluation of serum 25(OH)D level could be useful early after the adoption to promptly start vitamin D supplementation/treatment if needed

Kawasaki disease in a girl with turner syndrome: A remarkable association

We describe a girl with Turner syndrome, a genetic disorder of the X chromosome in a phenotypic female at increased risk of autoimmune and immunological diseases, who developed Kawasaki disease at the age of four years. Given the possible relationship between these two disorders, we recommend suspecting Kawasaki disease in patients with Turner syndrome who present with persistent fever of unknown origin and who are not responsive to antibiotic therapy. Attention should be given to this phenomenon, as patients with Turner syndrome are themselves at higher risk of cardiovascular defects. Further studies are needed to better clarify this issue

Clinical peculiarities of tuberculosis

The ongoing spread of tuberculosis (TB) in poor resource countries and the recently increasing incidence in high resource countries lead to the need of updated knowledge for clinicians, particularly for pediatricians. The purpose of this article is to provide an overview on the most important peculiarities of TB in children. Children are less contagious than adults, but the risk of progression to active disease is higher in infants and children as compared to the subsequent ages. Diagnosis of TB in children is more difficult than in adults, because few signs are associated with primary infection, interferon-gamma release assays and tuberculin skin test are less reliable in younger children, M. tuberculosis is more rarely detected in gastric aspirates than in smears in adults and radiological findings are often not specific. Treatment of latent TB is always necessary in young children, whereas it is recommended in older children, as well as in adults, only in particular conditions. Antimycobacterial drugs are generally better tolerated in children as compared to adults, but off-label use of second-line antimycobacterial drugs is increasing, because of spreading of multidrug resistant TB worldwide. Given that TB is a disease which often involves more than one member in a family, a closer collaboration is needed between pediatricians and clinicians who take care of adults