Parechovirus infection in infants: Evidence-based parental counselling for paediatricians.

AIM: Human parechovirus (HPeV) is an increasingly recognised cause of severe illness and central nervous system infection in infants. Medium- to long-term neurodevelopmental outcomes post-HPeV infection remain unknown. This study aims to assess neurodevelopmental outcomes for children hospitalised as infants with HPeV infection in their second and third years of life. METHODS: This prospective cohort study followed children hospitalised with HPeV in Brisbane, Queensland during the 2017/2018 outbreak. Serial application of Ages and Stages Questionnaire (ASQ) was used to assess developmental progress in the second and third years of life. Data from clinical follow-up, audiology and neuroradiology were included. RESULTS: In the second year of life, 63% (n = 29) of children showed some or significant concerns for developmental delay. This had largely been ameliorated by the third year of life when only 30% (n = 14) reported developmental concerns. Prematurity and apnoeas were associated with developmental concerns at 27-36 months of age. Communication was the most common domain of concern. CONCLUSIONS: The majority of infants hospitalised with HPeV infection in 2017-2018 showed normalisation of developmental progress by 27-36 months of age. Further investigation into more subtle neurological impairments in later childhood is required. These results can help guide clinicians in counselling parents during the acute illness and in planning appropriate follow-up.

A systematic review and meta-analysis: tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils).

Asthma severity and control can be measured both subjectively and objectively. Traditionally asthma treatments have been individualised using symptoms and spirometry/peak flow. Increasingly treatment tailored in accordance with inflammatory markers (sputum eosinophil counts or fractional exhaled nitric oxide (FeNO) data) is advocated as an alternative strategy. The objective of this review was to evaluate the efficacy of tailoring asthma interventions based on inflammatory markers (sputum analysis and FeNO) in comparison with clinical symptoms (with or without spirometry/peak flow) for asthma-related outcomes in children and adults. Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles were searched. The last searches were in February 2009. All randomised controlled comparisons of adjustment of asthma treatment based on sputum analysis or FeNO compared with traditional methods (primarily clinical symptoms and spirometry/peak flow) were selected. Results of searches were reviewed against predetermined criteria for inclusion. Relevant studies were selected, assessed and data extracted independently by at least two people. The trial authors were contacted for further information. Data were analysed as 'intervention received' and sensitivity analyses performed. Six (2 adults and 4 children/adolescent) studies utilising FeNO and three adult studies utilising sputum eosinophils were included. These studies had a degree of clinical heterogeneity including definition of asthma exacerbations, duration of study and variations in cut-off levels for percentage of sputum eosinophils and FeNO to alter management in each study. Adults who had treatment adjusted according to sputum eosinophils had a reduced number of exacerbations compared with the control group (52 vs. 77 patients with ≥1 exacerbation in the study period; p=0.0006). There was no significant difference in exacerbations between groups for FeNO compared with controls. The daily dose of inhaled corticosteroids at the end of the study was decreased in adults whose treatment was based on FeNO in comparison with the control group (mean difference -450.03 µg, 95% CI -676.73 to -223.34; p<0.0001). However, children who had treatment adjusted according to FeNO had an increase in their mean daily dose of inhaled corticosteroids (mean difference 140.18 µg, 95% CI 28.94 to 251.42; p=0.014). It was concluded that tailoring of asthma treatment based on sputum eosinophils is effective in decreasing asthma exacerbations. However, tailoring of asthma treatment based on FeNO levels has not been shown to be effective in improving asthma outcomes in children and adults. At present, there is insufficient justification to advocate the routine use of either sputum analysis (due to technical expertise required) or FeNO in everyday clinical practice.

Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults.

BACKGROUND: The measurement of severity and control of asthma in both children and adults can be based on subjective or objective measures. It has been advocated that fractional exhaled nitric oxide (FeNO) can be used to monitor airway inflammation as it correlates with some markers of asthma. Interventions for asthma therapies have been traditionally based on symptoms and/or spirometry. OBJECTIVES: To evaluate the efficacy of tailoring asthma interventions based on exhaled nitric oxide in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was completed in December 2006. SELECTION CRITERIA: All randomised controlled comparisons of adjustment of asthma therapy based on exhaled nitric oxide compared to traditional methods (primarily clinical symptoms and spirometry/peak flow). DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. Relevant studies were independently selected in duplicate. Two authors independently assessed trial quality and extracted data. Authors were contacted for further information but none were received. Data was analysed as "intervention received" and sensitivity analyses performed. MAIN RESULTS: Four (2 adult and 2 paediatric) studies were included; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut off levels and duration of study. Of 356 participants randomised, 324 completed the trials. In the meta-analysis, there was no difference between groups for the primary outcome of asthma exacerbations or for other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose inhaled corticosteroid per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms; WMD -282.46 (95% CI -422.08 to -142.84). There was no difference in ICS dose between the groups in the overall daily dose in the adult studies or in the paediatric studies. AUTHORS' CONCLUSIONS: Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the four studies that were found, and the results show only modest differences. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids is currently uncertain.

Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults.

BACKGROUND: Asthma severity and control can be measured both subjectively and objectively. Sputum analysis for evaluation of percentage of sputum eosinophilia directly measures airway inflammation, and is one method of objectively monitoring asthma. Interventions for asthma therapies have been traditionally based on symptoms and spirometry. OBJECTIVES: To evaluate the efficacy of tailoring asthma interventions based on sputum analysis in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was on 31 October 2006. SELECTION CRITERIA: All randomised controlled comparisons of adjustment of asthma therapy based on sputum eosinophils compared to traditional methods (primarily clinical symptoms and spirometry/peak flow). DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. Three sets of reviewers selected relevant studies. Two review authors independently assessed trial quality extracted data. Authors were contacted for further information but none were received. Data was analysed as "treatment received" and sensitivity analyses performed. MAIN RESULTS: Three adult studies were included; these studies were clinically and methodologically heterogenous (use of medications, cut off for percentage of sputum eosinophils and definition of asthma exacerbation). There were no eligible paediatric studies. Of 246 participants randomised, 221 completed the trials. In the meta-analysis, a significant reduction in number of participants who had one or more asthma exacerbations occurred when treatment was based on sputum eosinophils in comparison to clinical symptoms; pooled odds ratio (OR) was 0.49 (95% CI 0.28 to 0.87); number needed to treat to benefit (NNTB) was 6 (95% CI 4 to 32). There were also differences between groups in the rate of exacerbation (any exacerbation per year) and severity of exacerbations defined by requirement for use of oral corticosteroids but the reduction in hospitalisations was not statistically significant. Data for clinical symptoms, quality of life and spirometry were not significantly different between groups. The mean dose of inhaled corticosteroids per day was similar in both groups and no adverse events were reported. However sputum induction was not always possible. AUTHORS' CONCLUSIONS: Tailored asthma interventions based on sputum eosinophils is beneficial in reducing the frequency of asthma exacerbations in adults with asthma. This review supports the use of sputum eosinophils to tailor asthma therapy for adults with frequent exacerbations and severe asthma. Further studies need to be undertaken to strengthen these results and no conclusion can be drawn for children with asthma.

Analysis of multiple sugar probes in urine and plasma by high-performance anion-exchange chromatography with pulsed electrochemical detection. Application in the assessment of intestinal permeability in human immunodeficiency virus infection.

Mannitol, 3-O-methylglucose and lactulose administered orally are used to investigate small intestinal absorption pathways and mucosal integrity. Current methods of analysis include thin-layer chromatography, gas chromatography (GC) and enzymatic analysis, which require separate estimation of mono- and disaccharides and for GC, prior derivatization. We describe a high-pressure anion-exchange chromatographic method coupled with pulsed electrochemical detection allowing simultaneous measurement of all three sugars and its clinical application in monitoring intestinal damage in human immunodeficiency virus (HIV) infection. Sample preparation is simple and fast. All sugars are resolved within 10 min. Mean recovery is 93.3% for all sugars and the overall relative standard deviation is 4.2%. Intestinal permeability (lactulose/mannitol ratio) rises with disease progression to AIDS, indicating mucosal damage. The greatest increase in permeability is associated with chronic diarrhoea. The method is an ideal non-invasive test to assess gut mucosal damage in HIV infection.

A regional experience of red cell aplasia.

The incidence and current management of red cell aplasia in children was determined from a retrospective survey of haematologists and paediatricians in the northern health region of England over a 7-year period. Thirty-three children were diagnosed: 4 had Diamond Blackfan anaemia, 22 transient erythroblastopenia of childhood, and 7 parvovirus B19 aplasia, with annual incidences of 1, 5 and 2 per 1,000,000 children respectively. Many were over-investigated. Three with Diamond Blackfan anaemia were steroid responsive. One with transient erythroblastopenia was retrospectively diagnosed because anaemia did not recur after steroids were stopped. Transient erythroblastopenia is the most common single cause of red cell aplasia in immunocompetent children. Time, observation and bone marrow examination before steroid therapy are the ways to distinguish transient erythroblastopenia from Diamond Blackfan anaemia or leukaemia. Interpretation of red cell indices using age-related percentiles may reduce the number of inappropriate investigations of the anaemia, but is often unhelpful in distinguishing the various causes of red cell aplasia.

Simultaneous quantification of mannitol, 3-O-methyl glucose, and lactulose in urine by HPLC with pulsed electrochemical detection, for use in studies of intestinal permeability.

The percentage of an oral dose of mannitol, 3-O-methyl glucose, and lactulose excreted in urine is used in noninvasive investigation of active and passive intestinal mucosal transport. We developed a high-pressure liquid-chromatographic method involving anion exchange and pulsed electrochemical detection that allows the simultaneous determination of all three sugar probes in urine. Sample preparation is simple: diluting, mixing with internal standard (melibiose), and desalting. With use of a Dionex 250 x 40 mm Carbopac PA-1 column and elution with an isocratic mixture of 120 mmol/L NaOH and 0.5 mmol/L zinc acetate, all sugars were resolved within 10 min. The standard curve of the method is linear to the following concentrations: mannitol 125 mg/L, 3-O-methyl glucose 300 mg/L, and lactulose 40 mg/L. The minimal detectable concentration of lactulose is 0.4 mg/L. Analytical recovery of the sugars is between 89.0% and 99.5%. The precision of estimation (CV) ranges from 1.76% to 5.6% overall. Reference intervals were established from results for 28 healthy children. The method is adaptable for the study of carbohydrates at low concentrations in other biological fluids.

Low dose continuous infusion doxorubicin in children and young adults.

Ten patients (age range 3.2-26.3 yrs) with relapsed or resistant malignancies received a total of 20 courses of low dose continuous infusion doxorubicin (3 mg/m2/day for 28 days) delivered by portable Graseby infusion pumps via central venous catheters. Each patient received a median dose of 144 mg/m2 (range 87-261). Four patients responded to treatment (1 complete response (CR) and 3 partial response (PR)) and performance status improved in seven patients. Overall toxicity was minimal: WHO Grade 4 anaemia in 2/18 courses, Grade 4 neutropenia in 1/18, Grade 3-4 thrombocytopenia in 3/18, nausea and vomiting of Grades 2 and 4 in 4/20 and 1/20 respectively, and mucositis of Grades 2 and 4 in 2/20 courses each. Cardiac toxicity was assessed using echocardiography, and fractional shortening remained within normal limits in all patients. Low dose continuous infusion doxorubicin is a feasible, well tolerated, ambulatory therapy in children and may be an effective way of delivering doxorubicin with less toxicity, thus enabling the development of more dose intensive regimens.

Chemotherapy in the management of infantile fibrosarcoma.

Infantile fibrosarcoma (IF) has traditionally been treated with surgery, which may have considerable morbidity. Chemotherapy has been suggested in order to reduce the need for extensive surgery. Nine children with histologically confirmed IF who received chemotherapy are described. Six children were treated with chemotherapy initially, two following conservative surgery, and one following recurrence after surgery. All received vincristine (V) and actinomycin D (A), and six received additional drugs including ifosfamide (I), cyclophosphamide (C), adriamycin (Ad), etoposide (E), and cisplatinum (CDDP). Objective responses were achieved in eight: three responded completely (CR), two responded partially (PR), which allowed conservative surgery, one had stable disease, one had an initial PR, but subsequently had tumour recurrence 1 month after cessation of treatment, necessitating further surgery and chemotherapy, and one had an initial PR but died following local and regional metastases. One child had no response to chemotherapy but is alive with stable residual disease. Thus, five of nine children achieved a CR--three with chemotherapy alone. With the inclusion of chemotherapy as part of their treatment, five children, for whom curative surgery may have resulted in amputation, remain alive with limbs intact. Chemotherapy including V and A should be given to infants with fibrosarcoma in whom curative surgery would be mutilating.

The hazards of automatic-dishwasher detergent.

Automatic-dishwasher detergent is a common household substance which is extremely corrosive and potentially fatal if ingested. In this report, we discuss the implications of the ingestion of automatic-dishwasher detergent in 18 children over a three-year period. Ten of the 18 children gained access to the automatic-dishwasher detergent from the dishwasher on the completion of a washing-cycle, while the remainder ingested the detergent directly from the packet. There was a poor correlation between the presenting signs and symptoms and the subsequent endoscopic findings in the 14 children who underwent endoscopy.