Pneumococcal haemolytic uraemic syndrome in the postvaccine era – BMJ Archives of disease in childhood


Objective Pneumococcal infection is a leading cause of haemolytic uraemic syndrome (HUS) and is potentially vaccine preventable. Published data suggest high mortality and poor renal outcomes. The introduction of the 7-valent pneumococcal conjugate vaccine (PCV) has seen the emergence of disease caused by non-vaccine strains, particularly 19A. We sought to describe serotype prevalence and outcomes, particularly after the introduction of the 13-valent PCV.

Design and setting We performed a retrospective chart review, using hospital medical records to identify cases of HUS in a tertiary paediatric hospital in Australia over a 20-year period (January 1997–December 2016). Associated pneumococcal infection was identified, and serotype data were categorised according to vaccine era: prevaccine (January 1997–December 2004), PCV7 (January 2005–June 2011) and PCV13 (July 2011–December 2016).

Results We identified 66 cases of HUS. Pneumococcal infection was proven in 11 cases, representing 4% (1/26) of cases prior to the introduction of PCV7, 20% (3/15) in the PCV7 era and 28% (7/25) in the PCV13 era. Subtype 19A was the most prevalent pneumococcal serotype (6/11). All four patients who received PCV7 were infected with a non-vaccine serotype. Four of the five patients who received PCV13 were classed as vaccine failures. Median follow-up was 14 (range 1–108) months. Chronic kidney disease was the most common complication (4/7). We observed no mortality, neurological sequelae or progression to end-stage kidney disease.

Conclusions Serotype 19A is most commonly associated with pneumococcal HUS, despite the introduction of the 13-valent vaccine. Chronic kidney disease is a significant complication of pneumococcal HUS.

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Characteristics of children admitted to intensive care with acute bronchiolitis – European Journal or Pediatrics


To assess factors associated with outcome in children admitted to paediatric intensive care (PIC) with bronchiolitis. A retrospective study of children admitted to the PICU at St Mary’s Hospital, London with bronchiolitis over a 6-year period (2011–2016). All bronchiolitis admissions < 2 years were included. Data collected particularly noted risk factors for severity, demographics, microbiology and outcome. We compared respiratory syncytial virus (RSV) with non-RSV status. Multivariate analysis was performed. Two hundred seventy-four patients were identified. Median age was 60 days (IQR 28–150 days), 63% were male, 90% were invasively ventilated and 42% were previously healthy. Pre-existing co-morbidities were present in 38%. The most frequently isolated pathogens were RSV (60%) and rhinovirus (26%). Co-infection was present in 45%, most commonly with RSV, rhinovirus and bacterial pathogens. Median length of stay (LOS) was 6 days (IQR 4.75–10). Younger age, prematurity, RSV, co-infection and co-morbidity were identified as significant risk factors for prolonged LOS. Six children died. Five of these had documented co-morbidities.

Conclusion: RSV causes more severe bronchiolitis than other viruses. Nearly half of children admitted to PICU with RSV were previously healthy. Current guidelines for immunoprophylaxis of RSV bronchiolitis should be re-considered.
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Local anaesthetics and regional anaesthesia versus conventional analgesia for preventing persistent postoperative pain in adults and children – Cochrane review



Regional anaesthesia may reduce the rate of persistent postoperative pain (PPP), a frequent and debilitating condition. This review was originally published in 2012 and updated in 2017.


To compare local anaesthetics and regional anaesthesia versus conventional analgesia for the prevention of PPP beyond three months in adults and children undergoing elective surgery.

Authors’ conclusions

We conclude that there is moderate-quality evidence that regional anaesthesia may reduce the risk of developing PPP after three to 18 months after thoracotomy and three to 12 months after caesarean section. There is low-quality evidence that regional anaesthesia may reduce the risk of developing PPP three to 12 months after breast cancer surgery. There is moderate evidence that intravenous infusion of local anaesthetics may reduce the risk of developing PPP three to six months after breast cancer surgery.

Our conclusions are considerably weakened by the small size and number of studies, by performance bias, null bias, attrition and missing data. Larger, high-quality studies, including children, are needed. We caution that except for breast surgery, our evidence synthesis is based on only a few small studies. On a cautionary note, we cannot extend our conclusions to other surgical interventions or regional anaesthesia techniques, for example we cannot conclude that paravertebral block reduces the risk of PPP after thoracotomy. There are seven ongoing studies and 12 studies awaiting classification that may change the conclusions of the current review once they are published and incorporated.

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Pharmacological interventions for recurrent abdominal pain in childhood – Cochrane review




Between 4% and 25% of school-aged children at some stage complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with their daily lives. When no clear organic cause is found, the children are managed with reassurance and simple measures; a large range of pharmacological interventions have been recommended for use in these children.

Authors’ conclusions

There is currently no convincing evidence to support the use of drugs to treat RAP in children. Well-conducted clinical trials are needed to evaluate any possible benefits and risks of pharmacological interventions. In practice, if a clinician chooses to use a drug as a ‘therapeutic trial’, they and the patient need to be aware that RAP is a fluctuating condition and any ‘response’ may reflect the natural history of the condition or a placebo effect, rather than drug efficacy.

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Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia – NEJM



Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent β-thalassemia. After previously establishing that lentiviral transfer of a marked β-globin (βA-T87Q) gene could substitute for long-term red-cell transfusions in a patient with β-thalassemia, we wanted to evaluate the safety and efficacy of such gene therapy in patients with transfusion-dependent β-thalassemia.


In two phase 1–2 studies, we obtained mobilized autologous CD34+ cells from 22 patients (12 to 35 years of age) with transfusion-dependent β-thalassemia and transduced the cells ex vivo with LentiGlobin BB305 vector, which encodes adult hemoglobin (HbA) with a T87Q amino acid substitution (HbAT87Q). The cells were then reinfused after the patients had undergone myeloablative busulfan conditioning. We subsequently monitored adverse events, vector integration, and levels of replication-competent lentivirus. Efficacy assessments included levels of total hemoglobin and HbAT87Q, transfusion requirements, and average vector copy number.


At a median of 26 months (range, 15 to 42) after infusion of the gene-modified cells, all but 1 of the 13 patients who had a non–β0/β0 genotype had stopped receiving red-cell transfusions; the levels of HbAT87Q ranged from 3.4 to 10.0 g per deciliter, and the levels of total hemoglobin ranged from 8.2 to 13.7 g per deciliter. Correction of biologic markers of dyserythropoiesis was achieved in evaluated patients with hemoglobin levels near normal ranges. In 9 patients with a β0/β0 genotype or two copies of the IVS1-110 mutation, the median annualized transfusion volume was decreased by 73%, and red-cell transfusions were discontinued in 3 patients. Treatment-related adverse events were typical of those associated with autologous stem-cell transplantation. No clonal dominance related to vector integration was observed.


Gene therapy with autologous CD34+ cells transduced with the BB305 vector reduced or eliminated the need for long-term red-cell transfusions in 22 patients with severe β-thalassemia without serious adverse events related to the drug product. (Funded by Bluebird Bio and others; HGB-204 and HGB-205 numbers, NCT01745120 and NCT02151526.)

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Effect of childhood BMI on asthma: a systematic review and meta-analysis of case-control studies – BMC Pediatrics



Asthma is a multifactorial syndrome that threatens the health of children. Body mass index (BMI) might be one of the potential factors but the evidence is controversial. The aim of this study is to perform a comprehensive meta-analysis to investigate the association between asthma and BMI.


Electronic databases including, Web of Science, Pubmed, Scopus, Science Direct, ProQuest, up to April 2017, were searched by two researchers independently. The keywords “asthma, body mass index, obesity, overweight, childhood and adolescence” were used. Random and fixed effects models were applied to obtain the overall odds ratios (ORs) and standardized mean difference (SMD). Heterogeneity between the studies was examined using I2 and Cochrane Q statistics.


After reviewing 2511 articles, 16 studies were eligible for meta-analysis according to inclusion/exclusion criteria. A meta-analysis from 11 case-control studies revealed OR of asthma and overweight as OR = 1.64; (95% Confidence Interval (CI): 1.13–2.38) and from 14 case-control studies, OR for asthma and obesity was OR = 1.92 (95% CI: 1.39–2.65), which indicated that risk of asthma in overweight and obese children and adolescence was significantly higher (1.64 and 1.92 times) than that of individuals with (p-value < 0.01 for underweight/normal weight in both cases). Furthermore, there was a significant relationship between asthma and BMI > 85 percentile according to SMD SMD = 0.21; (95%CI: 0.03–0.38; p-value = 0.021).


The results showed a significant relationship between BMI (obesity/overweight) and asthma among children and adolescents. It is important to study the confounding factors that affect the relationship between asthma and BMI in future epidemiological researches.

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Macrolides in Children With Community-Acquired Pneumonia: Panacea or Placebo? Journal of the Pediatric Infectious Diseases Society

Image: Google Images, copyright free


Pneumonia, most often caused by a respiratory virus, is common in childhood. Mycoplasma pneumoniae also is detected frequently, particularly in older children in the era of pneumococcal conjugate vaccination. Despite recommendations for β-lactam antibiotics, macrolide antibiotics, including erythromycin, clarithromycin, and azithromycin, are prescribed frequently to children with acute lower respiratory infection. However, the significance of detecting “atypical” pathogens, including M pneumoniae, in children remains contentious. Considering the potential for antibacterial and anti-inflammatory activities of macrolides, our understanding of the role of these drugs in acute and chronic infections and in inflammatory conditions is changing. Some observational data have revealed improved outcomes in adults and children with pneumonia who are prescribed macrolides, although its widespread use has led to increases in macrolide resistance in Streptococcus pneumoniae and M pneumoniae. Clinical trials to define the role of macrolides in pediatric acute respiratory infection must be prioritized.

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