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Follow-up studies have demonstrated that bronchiolitis caused by respiratory syncytial virus (RSV) is strongly associated with wheezing in the ensuing years. During the acute infection the immune response may induce long-lasting detrimental effects, thereby contributing to post-bronchiolitis wheezing (PBW). Therefore, immune-modulating drugs like corticosteroids, administered in the acute phase of RSV bronchiolitis, may prevent PBW and asthma. To evaluate this, we performed a controlled prospective follow-up study after a randomized double-blind placebo-controlled intervention in the acute phase with oral prednisolone. Fifty-four patients under 2 years of age and hospitalized for RSV bronchiolitis between 1992 and 1995 were randomly assigned to prednisolone 1 mg/kg/day for 7 days or placebo. At the mean age of 5 years, 47 patients had completed their follow-up. Patients were divided into four groups: no wheezing, transient wheezing (wheezing during the first year of life); persistent wheezing (wheezing during the first year of life and asthma at the age of 5); and late-onset wheezing (no wheezing during the first year of life but asthma at the age of 5). Prevalence of wheezing and asthma were investigated through an interview by telephone, using a standardized questionnaire. We found no significant differences between the prednisolone- and the placebo-treated group in the number of patients with transient wheezing (8% vs. 17%), persistent wheezing (42% vs. 31%), or late-onset wheezing (17% vs. 13%). We conclude that oral prednisolone during the acute phase of RSV bronchiolitis is not effective in preventing PBW or asthma at the mean age of 5 years. Pediatr Pulmonol. 2000; 30: 92-96.

High plasma C-reactive protein (CRP) levels are associated with favorable outcome in adults with acute lung injury (ALI). The association between CRP levels and outcome has not been studied in ALI in children. We performed a historical cohort study in 93 mechanically ventilated children (0–18 years) with ALI. The CRP level within 48 h of disease onset was tested for association with 28-day mortality and ventilator-free days (VFD). Clinical parameters and ventilator settings were evaluated for possible confounding. Fourteen patients died within 28 days. The median (interquartile range) CRP level in nonsurvivors was 126 mg/L (64; 187) compared with 56 mg/L (20; 105) in survivors (p = 0.01). For every 10-mg/L rise in CRP level, the unadjusted odds (95 % confidence interval (95 % CI)) for mortality increased 8.7 % (2.1–15.8 %). Cardiovascular organ failure at onset of ALI was the strongest predictor for mortality (odds ratio, 30.5 (6.2–152.5)). After adjustment for cardiovascular organ failure, for every 10-mg/L rise in CRP level, the OR (95 % CI) for mortality increased 4.7 % (−2.7–12.6 %; p = 0.22). Increased CRP levels were associated with a decrease in VFD (ρ = −0.26, p = 0.01). Conclusion: increased plasma CRP levels are not associated with favorable outcome in ALI in children. This is in contrast with findings in adults with ALI.

Acute bronchiolitis in infants and young children is associated with long-term airway disease also known as post-bronchiolitic wheezing. Two major hypotheses have been proposed to explain the association between bronchiolitis and PBW. The first hypothesis considers bronchiolitis to be the first manifestation of recurrent wheezing in infants and children who are susceptible to obstructive airway disease. The second hypothesis suggests that the infection and concomitant inflammatory reaction in the acute phase leads to airway epithelium injury resulting in long-term obstructive airway disease. In line with the latter hypothesis, corticosteroids may have a beneficial effect on the prevention of post-bronchiolitic wheezing.The objective of this review was to evaluate the effect of inhaled corticosteroids, started during the acute phase of bronchiolitis, on the prevention of post-bronchiolitic wheezing.We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2006) which contains the Cochrane Acute Respiratory Infections Group's trials register, MEDLINE (1966 to September 2006), EMBASE (1980 to September 2006) and Current Contents (September 2006). Abstracts and reports of congresses (ERS 1999 to September 2005, ATS 1999 to September 2005) were obtained. We contacted experts in the field and pharmaceutical companies for ongoing or unpublished studies.Randomised placebo-controlled trials studying the effect of inhaled corticosteroids in children younger than two years of age with the clinical diagnosis of acute bronchiolitis were included.Two authors independently extracted data and assessed trial quality using the Jadad 5-point scale.Five studies matched the inclusion criteria, with a median Jadad score of 4 (Inter Quartile Range 3 to 4), involving 374 infants. Pooling of the data was limited, due to the clinical diversity of the studies. However, no effect of inhaled corticosteroids in the prevention of wheezing (diary records or GP diagnosed), hospital re-admissions or use of corticosteroids or bronchodilators could be demonstrated. Duration of therapy, length of follow up or causative agent (respiratory syncytial virus or not) did not influence the pooled effect. In the three studies that also evaluated the adverse events, none were reported.This review does not demonstrate an effect of inhaled corticosteroids given during the acute phase of bronchiolitis in the prevention of post-bronchiolitic wheezing. The small number of included participants and the inability to pool all clinical outcomes precludes us from making strong recommendations.

BACKGROUND: This is an updated version of the review which was first published in the Cochrane Database of Systematic Reviews in 2006. Long‐term central venous catheters (CVCs), including tunnelled CVCs (TCVCs) and totally implanted devices or ports (TIDs), are increasingly used when treating oncology patients. Despite international guidelines on sterile insertion and appropriate CVC maintenance and use, infection remains a common complication. These infections are mainly caused by Gram positive bacteria. Antimicrobial prevention strategies aimed at these micro‐organisms could potentially decrease the majority of CVC infections. The aim of this review was to evaluate the efficacy of antibiotics in the prevention of Gram positive infections in long‐term CVCs. OBJECTIVES: To determine the efficacy of administering antibiotics prior to the insertion of long‐term CVCs, or flushing or locking long‐term CVCs with a combined antibiotic and heparin solution, or both, to prevent Gram positive catheter‐related infections in adults and children receiving treatment for cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to June 2013) and the MEDLINE and EMBASE databases (1966 to 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing prophylactic antibiotics given prior to long‐term CVC insertion with no antibiotics, RCTs comparing a combined antibiotic and heparin solution with a heparin‐only solution to flush or lock newly inserted long‐term CVCs, and RCTs comparing a combination of these interventions in adults and children receiving treatment for cancer. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, classified them and extracted data on to a pre‐designed data collection form. We pooled data using the RevMan software version 5.2 and used random‐effects (RE) model methods for meta‐analyses. MAIN RESULTS: We included 11 trials with a total of 828 oncology patients (adults and children). We assessed most included studies to be at a low or unclear risk of bias. Five trials compared the use of antibiotics (vancomycin, teicoplanin or ceftazidime) given before the insertion of the long‐term CVC with no antibiotics, and six trials compared antibiotics (vancomycin, amikacin or taurolidine) and heparin with a heparin‐only solution for flushing or locking the long‐term CVC after use. Administering an antibiotic prior to insertion of the CVC did not significantly reduce Gram positive catheter‐related sepsis (CRS) (five trials, 360 adults; risk ratio (RR) 0.72, 95% confidence interval (CI) 0.33 to 1.58; I² = 5 2%; P = 0.41). Flushing and locking long‐term CVCs with a combined antibiotic and heparin solution significantly reduced the risk of Gram positive catheter‐related sepsis compared with a heparin‐only solution (468 participants, mostly children; RR 0.47, 95% CI 0.28 to 0.80; I² = 0%; P = 0.005). For a baseline infection rate of 15%, this reduction translated into a number needed to treat (NNT) of 12 (95% CI 9 to 33) to prevent one catheter‐related infection. We considered this evidence to be of a moderate quality. AUTHORS' CONCLUSIONS: There was no benefit to administering antibiotics before the insertion of long‐term CVCs to prevent Gram positive catheter‐related infections. Flushing or locking long‐term CVCs with a combined antibiotic and heparin solution appeared to reduce Gram positive catheter‐related sepsis experienced in people at risk of neutropenia through chemotherapy or disease. Due to insufficient data it was not clear whether this applied equally to TCVCs and totally implanted devices (TIDs), or equally to adults and children. The use of a combined antibiotic and heparin solution may increase microbial antibiotic resistance, therefore it should be reserved for high risk people or where baseline CVC infection rates are high (> 15%). Further research is needed to identify high risk groups most likely to benefit.

In 1991 and 1992, a prospective randomized trial was conducted on the northern Thai-Cambodian border. That trial compared the efficacy and tolerance of two mefloquine regimens for the treatment of uncomplicated Plasmodium falciparum malaria in an area with multi-drug-resistant P. falciparum. The resolution of fever and other symptoms was faster with high-dose mefloquine (25 mg/kg of body weight [M25 group; n = 68]) than with the conventional 15-mg/kg dose (M15 group; n = 71). There were no early treatment failures (days 7 to 9) in the M25 group, but there were 5 (7%) treatment failures in the M15 group (P = 0.03). The incidences of treatment failures by day 28 were 40% with the M15 group and 11% with the M25 group (P = 0.0004). By day 42, these values had risen to 50 and 27%, respectively (P = 0.01). The risk of treatment failure was highest in children (relative risk, 2.1; 95% confidence interval, 1.3 to 3.4) and patients with posttreatment diarrhea (relative risk, 2.0; 95% confidence interval, 1.3 to 3.1). Over half of the recrudescences in the M25 group occurred between days 28 and 42, whereas 17% of the recrudescences in the M15 group occurred between days 28 and 42 (P = 0.02). Thus, the sensitivity of assessment was significantly increased with longer follow-up. Treatment failure was associated with a delayed parasite clearance and an inadequate hematological recovery. Upper gastrointestinal side effects and dizziness were significantly more common in the M25 group, but overall, the high dose was relatively well tolerated, in particular by children. An increase in the dose to 25 mg/kg can prolong the therapeutic use of mefloquine in areas with multi-drug-resistant P.falciparum malaria where high-grade resistance to mefloquine is still rare.