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Background Central venous catheters (CVCs) facilitate the administration of intravenous drugs, fluids, blood products and parenteral nutrition to patients with either chronic disease or critical illness. Despite a pivotal role within medical management, a common complication associated with CVC use is occlusion of the CVC lumen(s). CVC occlusion can interrupt and cause serious delays in administration of treatment interventions. Objectives The primary objective of this review was to assess the efficacy and safety of different interventions used to restore patency of occluded CVC lumens, in adults and children. Search methods We identified trials by searching the Cochrane Central Register of Clinical Trials (CENTRAL) ( The Cochrane Library 2011, Issue 9); OvidSP MEDLINE (1950 to September 2011); OvidSP EMBASE (1980 to September 2011) and NHS Evidence CINAHL (1982 to September 2011). We also searched clinical trial registers, handsearched reference lists, contacted pharmaceutical companies and authors of publications that met the inclusion criteria to identify trials. Selection criteria We selected randomized controlled trials which investigated the efficacy of an intervention (chemical, surgical or drug) used to restore patency to an occluded CVC lumen, in either adults or children. Data collection and analysis Three authors independently assessed those studies that met the inclusion criteria for quality and extracted the relevant data using a standardized form. Main results No studies were found that investigated the efficacy and safety of either chemical or surgical interventions. Seven studies (eight papers) with a total of 632 participants were identified from the search. They investigated different comparisons, strengths of thrombolytic or anticoagulant drug interventions for treating CVC lumen occlusion thought to be caused by a thrombus. There was low quality evidence from a meta-analysis of two studies suggesting that urokinase (various strengths) was more effective than placebo for restoring patency to occluded CVC lumens in adults and children with underlying medical conditions (relative risk (RR) 2.09, 95% confidence interval (CI) 1.47 to 2.95), with a number needed to treat of 4 (95% CI 2 to 8). There was insufficient evidence to draw conclusions on the safety of urokinase. The overall quality of the evidence provided by these studies was low to very low due to one or more domains being assessed as either at 'unclear risk of bias' or 'high risk of bias'. Furthermore, the total number of participants in these studies was small and consequently may lead to spurious results. Authors' conclusions There is inadequate evidence to draw strong conclusions on the efficacy or safety of the drug interventions included in this review. There is some low quality evidence from a meta-analysis of two studies investigating urokinase (various strengths) and some very low evidence from two single studies investigating alteplase 2 mg/2 mL that suggest that these two drug interventions may be effective in treating withdrawal or total occlusion of CVC lumens caused by thrombosis. Further high quality, sufficiently powered research is still required to look at the efficacy and safety of urokinase, alteplase and other chemical, surgical and drug interventions for treating CVC lumen occlusion. Research studies which exclusively include child participants are especially warranted. Plain Language Summary Interventions for restoring patency of occluded central venous catheter lumens A central venous catheter is a small, hollow tube that is inserted into a large vein in either the chest, neck or groin. Central venous catheters enable healthcare professionals to administer drugs and other fluids directly into the blood stream, in order to treat critically ill patients or those patients with a long-term condition. In certain chronic conditions, patients or their carers may also be involved with the administration of treatment interventions via the central venous catheter. Occasionally, the catheter lumens can become blocked with either a blood clot or a treatment intervention solidifying in the tube, or due to the position of the tube inside the vein. If the catheter does become blocked it may mean that the patient has to undergo further surgery to remove and replace the blocked catheter. No studies were found investigating the efficacy and safety of surgical interventions (brush, snare or guidewire exchange) or chemical interventions (hydrochloric acid, sodium bicarbonate, 70% ethanol solution) to unblock the catheter. Our search identified seven studies (eight papers), with a total of 632 participants, that investigated different drug comparisons or compared different strengths of drug therapies for treating catheters that were either completely or partially blocked with a blood clot. This review has found low to very low quality evidence suggesting that thrombolytic drugs (urokinase and alteplase) could be effective in unblocking central venous catheter lumens blocked by blood clots. However, the total number of participants included in these trials was small and consequently the results of the analysis may well be over exaggerated. There were also issues with the way the studies were conducted that could possibly have introduced bias. In conclusion, more research is required to establish the efficacy and safety of different treatment interventions used to unblock occluded central venous catheter lumens. Particularly, there is a need for studies exclusively in children. [ABSTRACT FROM AUTHOR]

Background Since autism was first described, major difficulties in social interaction have been a defining feature of individuals with autism spectrum disorders (ASD). Social skills groups are a common intervention for individuals with ASD. Although a frequently recommended practice, the few studies that have addressed the efficacy of social skills groups have shown mixed results. Objectives To determine the effectiveness of social skills groups for improving social competence, social communication, and quality of life for people with ASD who are six to 21 years of age. Search methods We searched the following databases in December 2011: CENTRAL (2011 Issue 4), MEDLINE (1948 to November Week 3, 2011), EMBASE (1980 to Week 50, 2011), PsycINFO (1887 to December Week 2, 2011), CINAHL (1937 to current), ERIC (1966 to current), Sociological Abstracts (1952 to current), OCLC WorldCat (12 December 2011), Social Science Citation Index (1970 to 16 December 2011), and the metaRegister of Controlled Trials (20 December 2011). We also searched the reference lists of published papers. Selection criteria Randomized control trials (RCTs) comparing treatment (social skills groups) with a control group who were not receiving the treatment for participants aged six to 21 years with ASD. The control group could be no intervention, wait list, or treatment as usual. Outcomes sought were standardized measures of social competence, social communication, quality of life, emotion recognition, and any other specific behaviors. Data collection and analysis Two review authors independently selected and appraised studies for inclusion and assessed the risk of bias in each included study. All outcome data were continuous and standardized mean difference effect sizes (ES) with small sample correction were calculated. We conducted random-effects meta-analysis where possible. Main results We included five RCTs evaluating the effects of social skills groups in 196 participants with ASD aged 6 to 21 years old. The results show there is some evidence that social skills groups improve overall social competence (ES = 0.47, 95% confidence interval (CI) 0.16 to 0.78, P = 0.003) and friendship quality (ES = 0.41, 95% CI 0.02 to 0.81, P = 0.04) for this population. No differences were found between treatment and control groups in relation to emotional recognition (ES = 0.34, 95% CI -0.20 to 0.88, P = 0.21) assessed in two studies or social communication as related to the understanding of idioms (ES = 0.05, 95% CI -0.63 to 0.72, P = 0.89), which was assessed in only one study. Two additional quality of life outcomes were evaluated, with results of single studies suggesting decreases in loneliness (ES = -0.66, 95% CI -1.15 to -0.17) but no effect on child or parental depression. No adverse events were reported. Given the nature of the intervention and the selected outcome measures, the risk of performance and detection bias are high. There is limited generalizability from the studies as they were all conducted in the US; they focused mainly on children aged 7 to 12, and the participants were all of average or above average intelligence. Authors' conclusions There is some evidence that social skills groups can improve social competence for some children and adolescents with ASD. More research is needed to draw more robust conclusions, especially with respect to improvements in quality of life. Plain Language Summary Social skills groups for people aged 6 to 21 years with autism spectrum disorders (ASD) Social deficits remain one of the most difficult areas for individuals with autism spectrum disorders, especially for those with average or above average cognitive skills. An intervention often used to treat social deficits for these individuals is social skills groups. This review synthesized the results of five randomized controlled trials of social skills groups including 196 individuals with autism spectrum disorders (aged 6 to 21 years). We found individuals receiving treatment showed some indications of improved social competence and better friendships when compared with those not receiving treatment. Participants receiving treatment also showed indications of less loneliness. The ability to recognize different emotions was measured in two studies and there was no evidence that it was improved by taking part in a social skills group. Social communication as it relates to idiomatic expressions was only reported in one study and no significant differences between treatment and control group were found. Nor was there evidence of a beneficial effect of social skills groups on parental or child depression. No adverse effects were reported in the studies. Limitations of this review include a small number of studies and participants, and a high risk of bias due to parents knowing whether their child was in the intervention group or not. The studies focused mainly on children with ASD aged 7 to 12 with average or above average intelligence, and they were all carried out in the US. [ABSTRACT FROM AUTHOR]

Background Treatment guidelines for asthma recommend inhaled corticosteroids (ICS) as first-line therapy for children with persistent asthma. Although ICS treatment is generally considered safe in children, the potential systemic adverse effects related to regular use of these drugs have been and continue to be a matter of concern, especially the effects on linear growth. Objectives To assess the impact of ICS on the linear growth of children with persistent asthma and to explore potential effect modifiers such as characteristics of available treatments (molecule, dose, length of exposure, inhalation device) and of treated children (age, disease severity, compliance with treatment). Search methods We searched the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO; we handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases to look for potential relevant unpublished studies. The literature search was conducted in January 2014. Selection criteria Parallel-group randomised controlled trials comparing daily use of ICS, delivered by any type of inhalation device for at least three months, versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma. Data collection and analysis Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We conducted meta-analyses using the Cochrane statistical package RevMan 5.2 and Stata version 11.0. We used the random-effects model for meta-analyses. We used mean differences (MDs) and 95% CIs as the metrics for treatment effects. A negative value for MD indicates that ICS have suppressive effects on linear growth compared with controls. We performed a priori planned subgroup analyses to explore potential effect modifiers, such as ICS molecule, daily dose, inhalation device and age of the treated child. Main results We included 25 trials involving 8471 (5128 ICS-treated and 3343 control) children with mild to moderate persistent asthma. Six molecules (beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone propionate and mometasone furoate) given at low or medium daily doses were used during a period of three months to four to six years. Most trials were blinded and over half of the trials had drop out rates of over 20%. Compared with placebo or non-steroidal drugs, ICS produced a statistically significant reduction in linear growth velocity (14 trials with 5717 participants, MD -0.48 cm/y, 95% CI -0.65 to -0.30, moderate quality evidence) and in the change from baseline in height (15 trials with 3275 participants; MD -0.61 cm/y, 95% CI -0.83 to -0.38, moderate quality evidence) during a one-year treatment period. Subgroup analysis showed a statistically significant group difference between six molecules in the mean reduction of linear growth velocity during one-year treatment (Chi2 = 26.1, degrees of freedom (df) = 5, P value < 0.0001). The group difference persisted even when analysis was restricted to the trials using doses equivalent to 200 μg/d hydrofluoroalkane (HFA)-beclomethasone. Subgroup analyses did not show a statistically significant impact of daily dose (low vs medium), inhalation device or participant age on the magnitude of ICS-induced suppression of linear growth velocity during a one-year treatment period. However, head-to-head comparisons are needed to assess the effects of different drug molecules, dose, inhalation device or patient age. No statistically significant difference in linear growth velocity was found between participants treated with ICS and controls during the second year of treatment (five trials with 3174 participants; MD -0.19 cm/y, 95% CI -0.48 to 0.11, P value 0.22). Of two trials that reported linear growth velocity in the third year of treatment, one trial involving 667 participants showed similar growth velocity between the budesonide and placebo groups (5.34 cm/y vs 5.34 cm/y), and another trial involving 1974 participants showed lower growth velocity in the budesonide group compared with the placebo group (MD -0.33 cm/y, 95% CI -0.52 to -0.14, P value 0.0005). Among four trials reporting data on linear growth after treatment cessation, three did not describe statistically significant catch-up growth in the ICS group two to four months after treatment cessation. One trial showed accelerated linear growth velocity in the fluticasone group at 12 months after treatment cessation, but there remained a statistically significant difference of 0.7 cm in height between the fluticasone and placebo groups at the end of the three-year trial. One trial with follow-up into adulthood showed that participants of prepubertal age treated with budesonide 400 μg/d for a mean duration of 4.3 years had a mean reduction of 1.20 cm (95% CI -1.90 to -0.50) in adult height compared with those treated with placebo. Authors' conclusions Regular use of ICS at low or medium daily doses is associated with a mean reduction of 0.48 cm/y in linear growth velocity and a 0.61-cm change from baseline in height during a one-year treatment period in children with mild to moderate persistent asthma. The effect size of ICS on linear growth velocity appears to be associated more strongly with the ICS molecule than with the device or dose (low to medium dose range). ICS-induced growth suppression seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment. However, additional studies are needed to better characterise the molecule dependency of growth suppression, particularly with newer molecules (mometasone, ciclesonide), to specify the respective role of molecule, daily dose, inhalation device and patient age on the effect size of ICS, and to define the growth suppression effect of ICS treatment over a period of several years in children with persistent asthma. PLAIN LANGUAGE SUMMARY Do inhaled corticosteroids reduce growth in children with persistent asthma? Review question: We reviewed the evidence on whether inhaled corticosteroids (ICS) could affect growth in children with persistent asthma, that is, a more severe asthma that requires regular use of medications for control of symptoms. Background: Treatment guidelines for asthma recommend ICS as first-line therapy for children with persistent asthma. Although ICS treatment is generally considered safe in children, parents and physicians always remain concerned about the potential negative effect of ICS on growth. Search date: We searched trials published until January 2014. Study characteristics: We included in this review trials comparing daily use of corticosteroids, delivered by any type of inhalation device for at least three months, versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma. Key results: Twenty-five trials involving 8471 children with mild to moderate persistent asthma (5128 treated with ICS and 3343 treated with placebo or non-steroidal drugs) were included in this review. Eighty percent of these trials were conducted in more than two different centres and were called multi-centre studies; five were international multi-centre studies conducted in high-income and low-income countries across Africa, Asia-Pacifica, Europe and the Americas. Sixty-eight percent were financially supported by pharmaceutical companies. Meta-analysis (a statistical technique that combines the results of several studies and provides a high level of evidence) suggests that children treated daily with ICS may grow approximately half a centimeter per year less than those not treated with these medications during the first year of treatment. The magnitude of ICS-related growth reduction may depend on the type of drug. Growth reduction seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment. Evidence provided by this review allows us to conclude that daily use of ICS can cause a small reduction in height in children up to 18 years of age with persistent asthma; this effect seems minor compared with the known benefit of these medications for asthma control. Quality of evidence: Eleven of 25 trials did not report how they guaranteed that participants had an equal chance of receiving ICS or placebo or non-steroidal drugs. All but six trials did not report how researchers were kept unaware of the treatment assignment list. However, this methodological limitation may not significantly affect the quality of evidence because the results remained almost unchanged when we excluded these trials from the analysis. [ABSTRACT FROM AUTHOR]

Background Inhaled corticosteroids (ICS) are the first-line treatment for children with persistent asthma. Their potential for growth suppression remains a matter of concern for parents and physicians. Objectives To assess whether increasing the dose of ICS is associated with slower linear growth, weight gain and skeletal maturation in children with asthma. Search methods We searched the Cochrane Airways Group Specialised Register of trials (CAGR) and the ClinicalTrials.gov website up to March 2014. Selection criteria Studies were eligible if they were parallel-group randomised trials evaluating the impact of different doses of the same ICS using the same device in both groups for a minimum of three months in children one to 17 years of age with persistent asthma. Data collection and analysis Two review authors ascertained methodological quality independently using the Cochrane Risk of bias tool. The primary outcome was linear growth velocity. Secondary outcomes included change over time in growth velocity, height, weight, body mass index and skeletal maturation. Main results Among 22 eligible trials, 17 group comparisons were derived from 10 trials (3394 children with mild to moderate asthma), measured growth and contributed data to the meta-analysis. Trials used ICS (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting beta2-agonist and generally compared low (50 to 100 μg) versus low to medium (200 μg) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks. In the four comparisons reporting linear growth over 12 months, a significant group difference was observed, clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS (N = 728 school-aged children; mean difference (MD)0.20 cm/y, 95% confidence interval (CI) 0.02 to 0.39; high-quality evidence): No statistically significant heterogeneity was noted between trials contributing data. The ICS molecules (ciclesonide, fluticasone, mometasone) used in these four comparisons did not significantly influence the magnitude of effect (X2 = 2.19 (2 df), P value 0.33). Subgroup analyses on age, baseline severity of airway obstruction, ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed because of similarity across trials or inadequate reporting. A statistically significant group difference was noted in unadjusted change in height from zero to three months (nine comparisons; N = 944 children; MD 0.15, 95% CI -0.28 to -0.02; moderate-quality evidence) in favour of a higher ICS dose. No statistically significant group differences in change in height were observed at other time points, nor were such differences in weight, bone mass index and skeletal maturation reported with low quality of evidence due to imprecision. Authors' conclusions In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of ICS and low to medium doses of HFA-beclomethasone equivalent, favouring the use of low-dose ICS. No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents' and physicians' concerns about the growth suppressive effect of ICS, lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern. All future paediatric trials comparing different doses of ICS with or without placebo should systematically document growth. Findings support use of the minimal effective ICS dose in children with asthma. PLAIN LANGUAGE SUMMARY Does altering the dose of inhaled corticosteroids make a difference in growth among children with asthma? Background Asthma guidelines recommend inhaled corticosteroids (ICS) as the first choice of treatment for children with persistent asthma that is not well controlled when only a reliever inhaler is used to treat symptoms. Steroids work by reducing inflammation in the lungs and are known to control underlying symptoms of asthma. However, parents and physicians remain concerned about the potential negative effect of ICS on growth. Review question Does altering the dose of inhaled corticosteroids make a difference in the growth of children with asthma? What evidence did we find? We studied whether a difference could be seen in the growth of children with persistent asthma who were using different doses of the same ICS molecule and the same delivery device. We found 22 eligible trials, but only 10 of them measured growth or other measures of interest. Overall, 3394 children included in the review combined 17 group comparisons (i.e. 17 groups of children with mild to moderate asthma using a particular dose and type of steroid in 10 trials). Trials used different ICS molecules (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) either on their own or in combination with a long-acting beta2-agonist (a drug used to open up the airways) and generally compared low doses of corticosteroids (50 to 100 μg) with low to medium (200 μg) doses of corticosteroids (converted in μg HFA-beclomethasone equivalent) over 12 to 52 weeks. Results We found a small but statistically significant group difference in growth over 12 months between these different doses clearly favouring the lower dose of ICS. The type of corticosteroid among newer molecules (ciclesonide, fluticasone, mometasone) did not seem to influence the impact on growth over one year. Differences in corticosteroid doses did not seem to affect the change in height, the gain in weight, the gain in bone mass index and the maturation of bones. Quality of the evidence This review is based on a small number of trials that reported data and were conducted on children with mild to moderate asthma. Only 10 of 22 studies measured the few outcomes of interest for this review, and only four comparisons reported growth over 12 months. Our confidence in the quality of evidence is high for this outcome, however it is low to moderate for several other outcomes, depending on the number of trials reporting these outcomes. Moreover, a few outcomes were reported only by a single trial; as these findings have not been confirmed by other trials, we downgraded the evidence for these outcomes to low quality. An insufficient number of trials have compared the effect of a larger difference in dose, for example, between a high dose and a low dose of ICS and of other popular molecules such as budesonide and beclomethasone over a year or longer of treatment. Conclusions We report an evidence-based ICS dose-dependent reduction in growth velocity in prepubescent school-aged children with mild to moderate persistent asthma. The choice of ICS molecule (mometasone, ciclesonide or fluticasone) was not found to affect the level of growth velocity response over a year. The effect of corticosteroids on growth was not consistently reported: among 22 eligible trials, only four comparisons reported the effects of corticosteroids on growth over one year. In view of parents' and clinicians' concerns, lack of or incomplete reporting of growth is a matter of concern given the importance of the topic. We recommend that growth be systematically reported in all trials involving children taking ICS for three months or longer. Until further data comparing low versus high ICS dose and trials of longer duration are available, we recommend that the minimal effective ICS dose be used in all children with asthma. [ABSTRACT FROM AUTHOR]

Background Necrotizing enterocolitis (NEC) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants. Through prevention of bacterial migration across the mucosa, competitive exclusion of pathogenic bacteria, and enhancing the immune responses of the host, prophylactic enteral probiotics (live microbial supplements) may play a role in reducing NEC and the associated morbidity. Objectives To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC or sepsis, or both, in preterm infants. Search methods For this update, searches were made of MEDLINE (1966 to October 2013), EMBASE (1980 to October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 10), and abstracts of annual meetings of the Society for Pediatric Research (1995 to 2013). Selection criteria Only randomized or quasi-randomized controlled trials that enrolled preterm infants < 37 weeks gestational age or < 2500 g birth weight, or both, were considered. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one prespecified clinical outcome. Data collection and analysis Standard methods of The Cochrane Collaboration and its Neonatal Group were used to assess the methodologic quality of the trials and for data collection and analysis. Main results Twenty-four eligible trials were included. Included trials were highly variable with regard to enrolment criteria (that is birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical relative risk (RR) 0.43, 95% confidence interval (CI) 0.33 to 0.56; 20 studies, 5529 infants) and mortality (typical RR 0.65, 95% CI 0.52 to 0.81; 17 studies, 5112 infants). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.91, 95% CI 0.80 to 1.03; 19 studies, 5338 infants). The included trials reported no systemic infection with the supplemental probiotics organism. Probiotics preparations containing either lactobacillus alone or in combination with bifidobacterium were found to be effective. Authors' conclusions Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence strongly supports a change in practice. Head to head comparative studies are required to assess the most effective preparations, timing, and length of therapy to be utilized. [ABSTRACT FROM AUTHOR]

Background Policies for timing of cord clamping vary, with early cord clamping generally carried out in the first 60 seconds after birth, whereas later cord clamping usually involves clamping the umbilical cord more than one minute after the birth or when cord pulsation has ceased. The benefits and potential harms of each policy are debated. Objectives To determine the effects of early cord clamping compared with late cord clamping after birth on maternal and neonatal outcomes Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (13 February 2013). Selection criteria Randomised controlled trials comparing early and late cord clamping. Data collection and analysis Two review authors independently assessed trial eligibility and quality and extracted data. Main results We included 15 trials involving a total of 3911 women and infant pairs. We judged the trials to have an overall moderate risk of bias. Maternal outcomes: No studies in this review reported on maternal death or on severe maternal morbidity. There were no significant differences between early versus late cord clamping groups for the primary outcome of severe postpartum haemorrhage (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.65 to 1.65; five trials with data for 2066 women with a late clamping event rate (LCER) of ˜3.5%, I2 0%) or for postpartum haemorrhage of 500 mL or more (RR 1.17 95% CI 0.94 to 1.44; five trials, 2260 women with a LCER of ˜12%, I2 0%). There were no significant differences between subgroups depending on the use of uterotonic drugs. Mean blood loss was reported in only two trials with data for 1345 women, with no significant differences seen between groups; or for maternal haemoglobin values (mean difference (MD) -0.12 g/dL; 95% CI -0.30 to 0.06, I2 0%) at 24 to 72 hours after the birth in three trials. Neonatal outcomes: There were no significant differences between early and late clamping for the primary outcome of neonatal mortality (RR 0.37, 95% CI 0.04 to 3.41, two trials, 381 infants with a LCER of ˜1%), or for most other neonatal morbidity outcomes, such as Apgar score less than seven at five minutes or admission to the special care nursery or neonatal intensive care unit. Mean birthweight was significantly higher in the late, compared with early, cord clamping (101 g increase 95% CI 45 to 157, random-effects model, 12 trials, 3139 infants, I2 62%). Fewer infants in the early cord clamping group required phototherapy for jaundice than in the late cord clamping group (RR 0.62, 95% CI 0.41 to 0.96, data from seven trials, 2324 infants with a LCER of 4.36%, I2 0%). Haemoglobin concentration in infants at 24 to 48 hours was significantly lower in the early cord clamping group (MD -1.49 g/dL, 95% CI -1.78 to -1.21; 884 infants, I2 59%). This difference in haemoglobin concentration was not seen at subsequent assessments. However, improvement in iron stores appeared to persist, with infants in the early cord clamping over twice as likely to be iron deficient at three to six months compared with infants whose cord clamping was delayed (RR 2.65 95% CI 1.04 to 6.73, five trials, 1152 infants, I2 82%). In the only trial to report longer-term neurodevelopmental outcomes so far, no overall differences between early and late clamping were seen for Ages and Stages Questionnaire scores. Authors' conclusions A more liberal approach to delaying clamping of the umbilical cord in healthy term infants appears to be warranted, particularly in light of growing evidence that delayed cord clamping increases early haemoglobin concentrations and iron stores in infants. Delayed cord clamping is likely to be beneficial as long as access to treatment for jaundice requiring phototherapy is available. Plain Language Summary Effect of timing of umbilical cord clamping of term infants on mother and baby outcomes At the time of birth, the infant is still attached to the mother via the umbilical cord, which is part of the placenta. The infant is usually separated from the placenta by clamping the cord. This clamping is one part of the third stage of labour (the time from birth of the baby until delivery of the placenta) and the timing can vary according to clinical policy and practice. Although early cord clamping has been thought to reduce the risk of bleeding after birth (postpartum haemorrhage), this review of 15 randomised trials involving a total of 3911 women and infant pairs showed no significant difference in postpartum haemorrhage rates when early and late cord clamping (generally between one and three minutes) were compared. There were, however, some potentially important advantages of delayed cord clamping in healthy term infants, such as higher birthweight, early haemoglobin concentration, and increased iron reserves up to six months after birth. These need to be balanced against a small additional risk of jaundice in newborns that requires phototherapy. [ABSTRACT FROM AUTHOR]

Background Cough causes concern for parents and is a major cause of outpatient visits. It can impact on quality of life, cause anxiety and affect sleep in parents and children. Several remedies, including honey, have been used to alleviate cough symptoms. Objectives To evaluate the effectiveness of honey for acute cough in children in ambulatory settings. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library Issue 4, 2011) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1950 to December week 4, 2011); EMBASE (1990 to January 2012); CINAHL (1981 to January 2012); Web of Science (2000 to January 2012); AMED (1985 to January 2012); LILACS (1982 to January 2012); and CAB abstracts (2009 to January 2012). Selection criteria Randomised controlled trials (RCTs) comparing honey given alone, or in combination with antibiotics, versus nothing, placebo or other over-the-counter (OTC) cough medications to participants aged from two to 18 years for acute cough in ambulatory settings. Data collection and analysis Two review authors independently screened search results for eligible studies and extracted data on reported outcomes. Main results We included two RCTs of high risk of bias involving 265 children. The studies compared the effect of honey with dextromethorphan, diphenhydramine and 'no treatment' on symptomatic relief of cough using the 7-point Likert scale. Honey was better than 'no treatment' in reducing frequency of cough (mean difference (MD) -1.07; 95% confidence interval (CI) -1.53 to -0.60; two studies; 154 participants). Moderate quality evidence suggests honey did not differ significantly from dextromethorphan in reducing cough frequency (MD -0.07; 95% CI -1.07 to 0.94; two studies; 149 participants). Low quality evidence suggests honey may be slightly better than diphenhydramine in reducing cough frequency (MD -0.57; 95% CI -0.90 to -0.24; one study; 80 participants). Adverse events included mild reactions (nervousness, insomnia and hyperactivity) experienced by seven children (9.3%) from the honey group and two (2.7%) from the dextromethorphan group; the difference was not significant (risk ratio (RR) 2.94; 95% Cl 0.74 to 11.71; two studies; 149 participants). Three children (7.5%) in the diphenhydramine group experienced somnolence (RR 0.14; 95% Cl 0.01 to 2.68; one study; 80 participants) but there was no significant difference between honey versus dextromethorphan or honey versus diphenhydramine. No adverse event was reported in the 'no treatment' group. Authors' conclusions Honey may be better than 'no treatment' and diphenhydramine in the symptomatic relief of cough but not better than dextromethorphan. There is no strong evidence for or against the use of honey. Plain Language Summary Honey for acute cough in children Cough is a cause for concern for parents and a major cause of outpatient visits in most settings for both children and adults. Cough can impact on quality of life, cause anxiety and affect sleep for parents and children. For this reason an immediate remedy is usually sought by both the caregiver and the recipient. Cochrane reviews have assessed the effectiveness of over-the-counter (OTC) cough medications, but none have studied honey as a cough relief. A systematic review evaluating the effectiveness of honey for reducing acute cough symptoms due to upper respiratory tract infections (URTIs) in children would be useful. A review of two small randomised controlled trials (RCTs) showed that honey was moderately better than 'no treatment' for the relief of cough, reducing bothersome cough, improving quality of sleep for children and parents and reducing the severity of cough. This review included two small trials involving 265 children, aged two to 18 years. The effects of honey and dextromethorphan on symptomatic relief of cough, bothersome cough, and quality of sleep for both child and parent did not differ. Honey may be better than diphenhydramine for symptomatic relief of cough, reducing the severity of cough, and improving sleep quality for both parent and child. Dextromethorphan and diphenhydramine are both common ingredients in cough medications. Parents of seven children given honey and two given dextromethorphan reported their children suffered mild reactions from insomnia, hyperactivity and nervousness. Parents of three children in the diphenhydramine group reported somnolence. However, as with other medications, its benefit should be considered alongside the adverse effects. The limitation of this review update is that only two small studies with high risk of bias were included. [ABSTRACT FROM AUTHOR]

Background Young children with autism spectrum disorders (ASD) have impairments in the areas of communication and social interaction and often display repetitive or non-compliant behaviour. This early pattern of difficulties is a challenge for parents. Therefore, approaches that help parents develop strategies for interaction and management of behaviour are an obvious route for early intervention in ASD. This review updates a Cochrane review first published in 2002 but is based on a new protocol. Objectives To assess the effectiveness of parent-mediated early interventions in terms of the benefits for both children with ASD and their parents and to explore some potential moderators of treatment effect. Search methods We searched a range of psychological, educational and biomedical databases including CENTRAL, MEDLINE, Embase, PsycINFO and ERIC in August 2012. As this is an update of a previous review, we limited the search to the period following the original searches in 2002. Bibliographies and reference lists of key articles were searched, field experts were contacted and key journals were handsearched. Selection criteria We included only randomised controlled trials of early intervention for children with ASD. The interventions in the experimental condition were mediated by parents; the control conditions included no treatment, treatment as usual, waiting list, alternative child-centred intervention not mediated by parents, or alternative parent-mediated intervention of hypothesised lesser effect than the experimental condition. Data collection and analysis Two review authors (HM and IPO) independently screened articles identified in the search and decided which articles should be retrieved in full. For each included study, two review authors (IPO and EH) extracted and recorded data, using a piloted data collection form. Two review authors (IPO and HM) assessed the risk of bias in each study. We performed data synthesis and analysis using The Cochrane Collaboration's Review Manager 5.1 software. Main results The review includes 17 studies from six countries (USA, UK, Australia, Canada, Thailand and China), which recruited 919 children with ASD. Not all 17 studies could be compared directly or combined in meta-analyses due to differences in the theoretical basis underpinning interventions, the duration and intensity of interventions, and the outcome measurement tools used. Data from subsets of 10 studies that evaluated interventions to enhance parent interaction style and thereby facilitate children's communication were included in meta-analyses. The largest meta-analysis combined data from 316 participants in six studies and the smallest combined data from 55 participants in two studies. Findings from the remaining seven studies were reported narratively. High risk of bias was evident in the studies in relation to allocation concealment and incomplete outcome data; blinding of participants was not possible. Overall, we did not find statistical evidence of gains from parent-mediated approaches in most of the primary outcomes assessed (most aspects of language and communication - whether directly assessed or reported; frequency of child initiations in observed parent-child interaction; child adaptive behaviour; parents' stress), with findings largely inconclusive and inconsistent across studies. However, the evidence for positive change in patterns of parent-child interaction was strong and statistically significant (shared attention: standardised mean difference (SMD) 0.41; 95% confidence interval (CI) 0.14 to 0.68, P value < 0.05; parent synchrony: SMD 0.90; 95% CI 0.56 to 1.23, P value < 0.05). Furthermore, there is some evidence suggestive of improvement in child language comprehension, reported by parents (vocabulary comprehension: mean difference (MD 36.26; 95% CI 1.31 to 71.20, P value < 0.05). In addition, there was evidence suggesting a reduction in the severity of children's autism characteristics (SMD -0.30, 95% CI -0.52 to -0.08, P value < 0.05). However, this evidence of change in children's skills and difficulties as a consequence of parent-mediated intervention is uncertain, with small effect sizes and wide CIs, and the conclusions are likely to change with future publication of high-quality RCTs. Authors' conclusions The review finds some evidence for the effectiveness of parent-mediated interventions, most particularly in proximal indicators within parent-child interaction, but also in more distal indicators of child language comprehension and reduction in autism severity. Evidence of whether such interventions may reduce parent stress is inconclusive. The review reinforces the need for attention to be given to early intervention service models that enable parents to contribute skilfully to the treatment of their child with autism. However, practitioners supporting parent-mediated intervention require to monitor levels of parent stress. The ability to draw conclusions from studies would be improved by researchers adopting a common set of outcome measures as the quality of the current evidence is low. Plain Language Summary Early intervention delivered by parents for young children with autism spectrum disorders Autism spectrum disorders (ASD) affect more than 1% of children and is usually evident in behaviour before the age of three years. A child with ASD lacks understanding of how to interact with another person, may not have developed language or understand other people's communication, and may insist on routines and repetitive behaviours. This early pattern of difficulties is a challenge for parents. Therefore, helping parents to develop strategies for interaction and management of behaviour is an obvious route for early intervention. The present review brings up to date one published in 2003, which found only two well-designed studies. This review, based on a new protocol, includes 17 randomised controlled trials, most published since 2010, in which interventions delivered by parents were compared with no treatment or local services, or alternative child-centred intervention such as nursery attendance, or another parent-delivered intervention that differed in some way from the main condition. We were able to combine outcome information and so increase confidence in the results. All the studies were rated on the quality of their evidence, which was then taken into account in judging how firmly conclusions could be drawn. The studies varied in the content of what parents were trained to do, and over what length of time parents had contact with professionals. Parents received training either individually with their child or in groups with other parents. In the majority of the studies, the interventions aimed to help parents be more observant and responsive during interactions with their child in order to help their child develop communication skills. In summary, the review finds sufficient evidence that the ways in which parents interacted with their children did change as intended. The review also suggests improvement in child outcomes such as understanding of language and severity of autism characteristics as a result of interventions delivered by parents. However, important outcomes such as other aspects of children's language, children's adaptive skills and parent stress did not show change. The evidence is not yet strong for any outcome and would benefit from researchers measuring effects in the same ways. [ABSTRACT FROM AUTHOR]

Background Bronchopulmonary dysplasia (BPD) is an important complication associated with considerable morbidity in preterm infants. Corticosteroids in various regimens have been tried out to prevent BPD. Objective To examine the evidence from Cochrane systematic reviews regarding the effectiveness and associated complications of corticosteroids used to prevent BPD in preterm infants. Methods The Cochrane Database of Systematic Reviews was searched to identify reviews of corticosteroids for BPD in preterm infants. Data were extracted by one investigator, and checked by a second investigator for accuracy. Results are presented as risk ratios (RR) with 95% confidence intervals (CI). We considered <8 days as early and >7 days as late administration. Main results Six reviews (67 trials and 6535 patients) were included and covered three main comparisons: inhaled corticosteroids versus placebo, inhaled versus systemic corticosteroids and systemic corticosteroids versus placebo. Systemic corticosteroids compared with placebo significantly reduced the incidence of BPD (early: RR 0.79, 95% CI 0.71-0.88; late: RR 0.72, 95% CI 0.63-0.82), and BPD or mortality (early: RR 0.89, 95% CI 0.84-0.95; late: RR 0.72, 95% CI 0.63-0.82) at 36 weeks post-menstrual age. Similar results were observed for these outcomes assessed at 28 days of life at which time there was additionally a reduction in mortality (late: RR 0.49, 95% CI 0.28-0.85). There was a higher incidence of cerebral palsy associated with systemic corticosteroids compared with placebo when initiated early (RR 1.45, 95% CI 1.06-1.98). No differences in neurodisability based on Bayley Mental or Psychomotor Developmental Index scores were observed for inhaled or systemic corticosteroids compared with placebo. Hypertension was significantly increased in association with systemic corticosteroids versus placebo (early: RR 1.85, 95% CI 1.55-2.22; late: RR 2.66, 95% CI 1.58-4.49) as were gastrointestinal (GI) perforations when treatment was initiated early (RR 1.81, 95% CI 1.33-2.48). Author's Conclusion Systemic corticosteroids decrease BPD and early mortality in premature infants but have a risk of complications, particularly when initiated in the first week of life. Owing to the wide range of dosing protocols, timing of initiation, doses and duration of therapy in the included reviews, it is difficult to determine, based on the evidence examined in this overview, a protocol that is both safe and effective. Further research should focus on determining the most effective dose and timing of corticosteroid administration beyond the first week of life to maximize benefit in decreasing BPD and mortality while avoiding short- and long-term harms. [ABSTRACT FROM AUTHOR]

Background Mumps, measles and rubella (MMR) are serious diseases that can lead to potentially fatal illness, disability and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. Objectives To assess the effectiveness and adverse effects associated with the MMR vaccine in children up to 15 years of age. Search methods For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, PubMed (July 2004 to May week 2, 2011) and Embase.com (July 2004 to May 2011). Selection criteria We used comparative prospective or retrospective trials assessing the effects of the MMR vaccine compared to placebo, do nothing or a combination of measles, mumps and rubella antigens on healthy individuals up to 15 years of age. Data collection and analysis Two review authors independently extracted data and assessed methodological quality of the included studies. One review author arbitrated in case of disagreement. Main results We included five randomised controlled trials (RCTs), one controlled clinical trial (CCT), 27 cohort studies, 17 case-control studies, five time-series trials, one case cross-over trial, two ecological studies, six self controlled case series studies involving in all about 14,700,000 children and assessing effectiveness and safety of MMR vaccine. Based on the available evidence, one MMR vaccine dose is at least 95% effective in preventing clinical measles and 92% effective in preventing secondary cases among household contacts. Effectiveness of at least one dose of MMR in preventing clinical mumps in children is estimated to be between 69% and 81% for the vaccine prepared with Jeryl Lynn mumps strain and between 70% and 75% for the vaccine containing the Urabe strain. Vaccination with MMR containing the Urabe strain has demonstrated to be 73% effective in preventing secondary mumps cases. Effectiveness of Jeryl Lynn containing MMR in preventing laboratory-confirmed mumps cases in children and adolescents was estimated to be between 64% to 66% for one dose and 83% to 88% for two vaccine doses. We did not identify any studies assessing the effectiveness of MMR in preventing rubella. The highest risk of association with aseptic meningitis was observed within the third week after immunisation with Urabe-containing MMR (risk ratio (RR) 14.28; 95% confidence interval (CI) from 7.93 to 25.71) and within the third (RR 22.5; 95% CI 11.8 to 42.9) or fifth (RR 15.6; 95% CI 10.3 to 24.2) weeks after immunisation with the vaccine prepared with the Leningrad-Zagreb strain. A significant risk of association with febrile seizures and MMR exposure during the two previous weeks (RR 1.10; 95% CI 1.05 to 1.15) was assessed in one large person-time cohort study involving 537,171 children aged between three months and five year of age. Increased risk of febrile seizure has also been observed in children aged between 12 to 23 months (relative incidence (RI) 4.09; 95% CI 3.1 to 5.33) and children aged 12 to 35 months (RI 5.68; 95% CI 2.31 to 13.97) within six to 11 days after exposure to MMR vaccine. An increased risk of thrombocytopenic purpura within six weeks after MMR immunisation in children aged 12 to 23 months was assessed in one case-control study (RR 6.3; 95% CI 1.3 to 30.1) and in one small self controlled case series (incidence rate ratio (IRR) 5.38; 95% CI 2.72 to 10.62). Increased risk of thrombocytopenic purpura within six weeks after MMR exposure was also assessed in one other case-control study involving 2311 children and adolescents between one month and 18 years (odds ratio (OR) 2.4; 95% CI 1.2 to 4.7). Exposure to the MMR vaccine was unlikely to be associated with autism, asthma, leukaemia, hay fever, type 1 diabetes, gait disturbance, Crohn's disease, demyelinating diseases, bacterial or viral infections. Authors' conclusions The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunisation with the MMR vaccine cannot be separated from its role in preventing the target diseases. Plain language summary Using the combined vaccine for protection of children against measles, mumps and rubella Measles, mumps and rubella (MMR) are three very dangerous infectious diseases which cause severe morbidity, disability and death in low-income countries. Based on the evidence provided by three cohort studies (3104 participants), vaccination with one dose of MMR vaccine is at least 95% effective in preventing clinical measles among preschool children; in schoolchildren and adolescents at least one dose of MMR vaccine was 98% effective in preventing laboratory-confirmed measles cases; one or two MMR doses were respectively 92% and 95% effective in preventing secondary measles cases. At least one dose of MMR vaccine is effective in preventing clinical mumps among children and adolescents when prepared with Jeryl Lynn strains (vaccine effectiveness = 69% to 81%, one cohort and one case-control study, 1656 participants), as well as when prepared with Urabe strain (vaccine effectiveness = 70% to 75%, one cohort and one case-control study, 1964 participants). Effectiveness against laboratory-confirmed mumps in children and adolescents was estimated to be between 64% to 66% for one and 83% to 88% for two doses of Jeryl Lynn MMR (two case-control studies, 1664 participants) and 87% for Urabe-containing MMR (one cohort study, 48 participants). Vaccination with Urabe MMR confers protection against secondary mumps infection (vaccine effectiveness = 73%, one cohort study, 147 participants). We identified no studies assessing the effectiveness of MMR vaccine against clinical or laboratory-confirmed rubella. Results from two very large case series studies involving about 1,500,000 children who were given the MMR vaccine containing Urabe or Leningrad-Zagreb strains show this vaccine to be associated with aseptic meningitis; whereas administration of the vaccine containing Moraten, Jeryl Lynn, Wistar RA, RIT 4385 strains is associated with febrile convulsion in children aged below five years (one person-time cohort study, 537,171 participants; two self controlled case series studies, 1001 participants). The MMR vaccine could also be associated with idiopathic thrombocytopaenic purpura (two case-controls, 2450 participants, one self controlled case series, 63 participants). We could assess no significant association between MMR immunisation and the following conditions: autism, asthma, leukaemia, hay fever, type 1 diabetes, gait disturbance, Crohn's disease, demyelinating diseases, or bacterial or viral infections. The methodological quality of many of the included studies made it difficult to generalise their results. The glossary of study designs is available in the full-text review. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing acute respiratory infections, resulting in about 3.4 million hospitalisations annually in children under five. Palivizumab is the only product approved for prevention of serious RSV disease, as motavizumab is no longer being developed for this condition. The efficacy and safety of palivizumab has been evaluated in randomized controlled trials (RCTs) and a large number of economic evaluations (EEs) have tested its cost-effectiveness. Objectives To assess the effectiveness and safety of palivizumab prophylaxis in reducing the risk of complications (hospitalization due to RSV infection) in high-risk infants and children. To assess the cost-effectiveness (or cost-utility) of palivizumab prophylaxis in infants and children in different risk groups. Search methods We searched CENTRAL (2012, Issue 7), MEDLINE (1996 to July week 4, 2012), EMBASE (1996 to August 2012), CINAHL (1996 to August 2012) and LILACS (1996 to August 2012) for RCTs. We searched the NHS Economic Evaluations Database (NHS EED 2012, Issue 4), Health Economics Evaluations Database (HEED, 9 August 2012), Paediatric Economic Database Evaluations (PEDE, 1980 to 2009), MEDLINE (1996 to July week 4, 2012) and EMBASE (1996 to August 2012) for EEs. Selection criteria We included RCTs comparing palivizumab prophylaxis with a placebo or another type of prophylaxis in preventing serious lower respiratory tract disease caused by RSV in paediatric patients at high risk. We included cost-effectiveness analyses and cost-utility analyses comparing palivizumab prophylaxis with no prophylaxis. Data collection and analysis Two review authors independently assessed risk of bias for the included studies and extracted data for both the RCTs and EEs. We calculated risk ratios (RRs) and their associated 95% confidence intervals (CIs) for dichotomous outcomes and for adverse events (AEs). For continuous outcomes, we provided a narrative summary of results due to missing data on standard deviations. We performed fixed-effect meta-analyses for the estimation of pooled effects whenever there was no indication of heterogeneity between included RCTs. We summarised the results reported in included EEs, such as incremental costs, incremental effectiveness, and incremental cost-effectiveness and/or cost-utility ratios (ICERs), and we calculated ICER present values in 2011 Euros for all studies. Main results Of the seven available RCTs, three compared palivizumab with a placebo in a total of 2831 patients, and four compared palivizumab with motavizumab in a total of 8265 patients. All RCTs were sponsored by the drug manufacturing company. The overall quality of RCTs was good, but most of the outcomes assessed relied on data from only two studies. Palivizumab prophylaxis was associated with a statistically significant reduction in RSV hospitalisations (RR 0.49, 95% CI 0.37 to 0.64) and a statistically non-significant reduction in all-cause mortality (RR 0.69, 95% CI 0.42 to 1.15) when compared to placebo. When compared to motavizumab, palivizumab recipients showed a non-significant increase in the risk of RSV hospitalisations (RR 1.36, 95% CI 0.97 to 1.90) and a non-significant risk reduction in all-cause mortality (RR 0.74, 95% CI 0.38 to 1.43). In both cases, the proportion of children with any AE or any AE related to the study drug was similar between the two groups. We included 34 studies that reported cost-effectiveness and/or cost-utility data for palivizumab prophylaxis in high-risk children with different underlying medical conditions. The overall quality of EEs was good, but the variations in modelling approaches were considerable across the studies, leading to large differences in the results. The cost-effectiveness of palivizumab prophylaxis depends on the consumption of resources taken into account by the study authors, and on the cost-effectiveness threshold set by the healthcare sector in each country. Authors' conclusions There is evidence that palivizumab prophylaxis is effective in reducing the frequency of hospitalisations due to RSV infection, i.e. in reducing the incidence of serious lower respiratory tract RSV disease in children with chronic lung disease, congenital heart disease, or those born preterm. Results from economic evaluations of palivizumab prophylaxis are inconsistent across studies, ranging from highly cost-effective to not cost-effective, implying that economic findings must be interpreted with caution. The availability of low-cost palivizumab would reduce its inequitable distribution, so that RSV prophylaxis would be available to the poorest countries where children are at greatest risk. Plain Language Summary Palivizumab for reducing the risk of severe RSV infection in children Respiratory syncytial virus (RSV) infection is a major cause of acute respiratory infections in children. RSV infection can lead to morbidity and mortality in children, resulting in hospitalization, admission to an intensive care unit, the need for intensive medical therapies and death. Most infected children suffer little consequence. However, children who have other serious health problems are known to be at higher risk of complications from RSV infection. This review examined the use of a passive immunisation - palivizumab - to prevent and modify the severity of RSV infection in these children and to determine if it is cost-effective. The results from this review are based on data from seven studies (all sponsored by the drug manufacturing company) involving 11,096 participants reporting on efficacy and safety of palivizumab, and 34 studies reporting on its cost-effectiveness. Our findings suggest a favorable effect of preventive use of palivizumab in children who are at higher risk of acquiring severe RSV infection, when compared to placebo. Children treated with palivizumab were less often hospitalised, spent fewer days in the hospital, were admitted to an intensive care unit less often, and had fewer days of oxygen therapy than children who received a placebo. Considering the underlying health problems in this population of infants and children, high rates of adverse events are quite expected. Our findings showed that children treated with palivizumab experienced adverse events similarly as often as children treated with placebo. Palivizumab was shown to be effective in reducing the hospitalisations, but whether it is also cost-effective is not easy to determine. This review found large differences in cost-effectiveness results across the studies. Due to the high costs of the drug, in many countries palivizumab prophylaxis might not be available as a standard treatment. [ABSTRACT FROM AUTHOR]

Background Febrile seizures occurring in a child older than one month during an episode of fever affect 2% to 4% of children in Great Britain and the United States and recur in 30%. Rapid-acting antiepileptics and antipyretics given during subsequent fever episodes have been used to avoid the adverse effects of continuous antiepileptic drugs. Objectives To evaluate the effectiveness and safety of antiepileptic and antipyretic drugs used prophylactically to treat children with febrile seizures. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011. Issue 3); MEDLINE (1966 to May 2011); EMBASE (1966 to May 2011); Database of Abstracts of Reviews of Effectiveness (DARE) (May 2011). No language restrictions were imposed. We also contacted researchers in the field to identify continuing or unpublished studies. Selection criteria Trials using randomised or quasi-randomised patient allocation that compared the use of antiepileptic or antipyretic agents with each other, placebo or no treatment. Data collection and analysis Two review authors (RN and MO) independently applied pre-defined criteria to select trials for inclusion and extracted the pre-defined relevant data, recording methods for randomisation, blinding and exclusions. Outcomes assessed were seizure recurrence at 6, 12, 18, 24, 36 months and at age 5 to 6 years in the intervention and non-intervention groups, and adverse medication effects. The presence of publication bias was assessed using funnel plots. Main results Thirty-six articles describing 26 randomised trials with 2740 randomised participants were included. Thirteen interventions of continuous or intermittent prophylaxis and their control treatments were analysed. Methodological quality was moderate to poor in most studies. We could not do a meta-analysis for eight of the 13 comparisons due to insufficient numbers of trials. No significant benefit for valproate, pyridoxine, intermittent phenobarbitone or ibuprofen versus placebo or no treatment was found; nor for diclofenac versus placebo followed by ibuprofen, acetominophen or placebo; nor for intermittent rectal diazepam versus intermittent valproate, nor phenobarbitone versus intermittent rectal diazepam. There was a significant reduction of recurrent febrile seizures with intermittent oral diazepam versus placebo with a relative risk (RR) of 0.67 (95% confidence interval (CI) 0.48 to 0.94) at 24 months), RR of 0.61 (95% CI 0.15 to 0.89) at 48 months, with no benefit at 6, 12 or 72 months. Phenobarbitone versus placebo or no treatment reduced seizures at 6, 12 and 24 months but not at 18 or 72 month follow up (RR 0.60, 95% CI 0.42 to 0.84 at 6 months; RR 0.59, 95% CI 0.46 to 0.75 at 12 months; and RR 0.65, 95% CI 0.49 to 0.88 at 24 months). Intermittent rectal diazepam versus no treatment or placebo also reduced seizures (RR 0.60, 95% CI 0.41 to 0.86 at 6 months; RR 0.65, 95% CI 0.49 to 0.87 at 12 months; RR 0.2, 95% CI 0.1 to 0.39 at 18 months; RR 0.36, 95% CI 0.18 to 0.71 at 36 months), with no benefit at 24 months. Intermittent clobazam compared to placebo at 6 months resulted in a RR of 0.09 (95% CI 0.02 to 0.30), an effect found against an extremely high (83.3%) recurrence rate in the controls and which is a result that needs replication. The recording of adverse effects was variable. Lower comprehension scores in phenobarbitone treated children were found in two studies. In general, adverse effects were recorded in up to some 30% of children in the phenobarbitone treated group and in up to 36% in benzodiazepine treated groups. Evidence of publication bias was found in the meta analyses of comparisons for phenobarbitone versus placebo (8 studies) at 12 months but not at 6 months (6 studies); and valproate versus placebo (4 studies) at 12 months; with too few studies to identify publication bias for the other comparisons. Authors' conclusions No clinically important benefits for children with febrile seizures were found for intermittent oral diazepam, phenytoin, phenobarbitone, intermittent rectal diazepam, valproate, pyridoxine, intermittent phenobarbitone or intermittent ibuprofen, nor for diclofenac versus placebo followed by ibuprofen, acetominophen or placebo. Adverse effects were reported in up to 30% of children. Apparent benefit for clobazam treatment in one recent trial needs to be replicated to be judged reliable. Given the benign nature of recurrent febrile seizures, and the high prevalence of adverse effects of these drugs, parents and families should be supported with adequate contact details of medical services and information on recurrence, first aid management and, most importantly, the benign nature of the phenomenon. Plain Language Summary Prophylactic drug management for febrile seizures in children Seizures occurring in association with fever are the most common neurologic disorder in children, affecting two to four per cent of all children. On average, one out of three children with febrile seizures have recurrent seizures. In this review the effects of antiepileptic and antipyretic medications to prevent recurrent seizures was examined. No significant or important benefits of these medications were found for children with febrile seizures. Adverse effects of the medications were common. The benefit found for treatment with clobazam in one 2011 study needs to be repeated to show that this finding is reliable. Meanwhile, parents and families should be supported with the adequate contact details of medical services and information on recurrence, first aid management and, most importantly, the benign nature of the phenomenon. [ABSTRACT FROM AUTHOR]

Background Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. Objectives To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. Search methods We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). Selection criteria All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Data collection and analysis Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. Main results One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. Authors' conclusions There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. There is a need for large, randomised controlled trials for this serious condition. Plain Language Summary Propofol versus thiopental sodium for the treatment of refractory status epilepticus Persistent convulsions are a major medical emergency associated with significant morbidity and mortality. At times, these convulsions fail to respond to first- and second-line drug therapy and may be observed in up to 31% of patients suffering from persistent seizure or convulsive activities. Persistent seizure activity may become refractory to antiepileptic drugs. Anaesthetics such as thiopental sodium and propofol are frequently given for control of seizures in such situations. Both agents have inherent side effects and complications. This review appraises the evidence for the these anaesthetic drugs in controlling seizure activity in patients with RSE. There is a lack of good-quality evidence to support the choice of anaesthetic drug for the treatment of patients with RSE. Only one trial could be identified, which was terminated early due to recruitment problems. The two drugs did not show any difference among each other. The only difference noted was the requirement of prolonged mechanical ventilation for patients in the thiopental group. This could be due to the long half-life of the drug. There is a clear need for a large randomised controlled trial to study the efficacy of anaesthetic agents in the treatment of RSE. [ABSTRACT FROM AUTHOR]

Background Acute respiratory infections (ARIs) comprise a large and heterogeneous group of infections including bacterial, viral and other aetiologies. In recent years, procalcitonin - the prohormone of calcitonin - has emerged as a promising marker for the diagnosis of bacterial infections and for improving decisions about antibiotic therapy. Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with acute respiratory infections and different settings ranging from primary care to emergency departments (EDs), hospital wards and intensive care units (ICUs). Objectives The aim of this systematic review based on individual patient data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 2) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May 2011) and EMBASE (1974 to May 2011) to identify suitable trials. Selection criteria We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm or usual care/guidelines. Trials were excluded if they exclusively focused on paediatric patients or if they used procalcitonin for another purpose than to guide initiation and duration of antibiotic treatment. Data collection and analysis Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days. For the primary care setting, treatment failure was defined as death, hospitalisation, ARI-specific complications, recurrent or worsening infection, and patients reporting any symptoms of an ongoing respiratory infection at follow-up. For the ED setting, treatment failure was defined as death, ICU admission, re-hospitalisation after index hospital discharge, ARI-associated complications, and recurrent or worsening infection within 30 days of follow-up. For the ICU setting, treatment failure was defined as death within 30 days of follow-up. Secondary endpoints were antibiotic use (initiation of antibiotics, duration of antibiotics and total exposure to antibiotics (total amount of antibiotic days divided by total number of patients)), length of hospital stay for hospitalised patients, length of ICU stay for critically ill patients, and number of days with restricted activities within 14 days after randomisation for primary care patients. For the two co-primary endpoints of all-cause mortality and treatment failure, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression. The hierarchical regression model was adjusted for age and clinical diagnosis as fixed-effect. The different trials were added as random-effects into the model. We fitted corresponding linear regression models for antibiotic use. We conducted sensitivity analyses stratified by clinical setting and ARI diagnosis to assess the consistency of our results. Main results We included 14 trials with 4221 participants. There were 118 deaths in 2085 patients (5.7%) assigned to procalcitonin groups compared to 134 deaths in 2126 control patients (6.3%) (adjusted OR 0.94, 95% CI 0.71 to 1.23). Treatment failure occurred in 398 procalcitonin group patients (19.1%) and in 466 control patients (21.9%). Procalcitonin guidance was not associated with increased mortality or treatment failure in any clinical setting, or ARI diagnosis. These results proved robust in various sensitivity analyses. Total antibiotic exposure was significantly reduced overall (median (interquartile range) from 8 (5 to 12) to 4 (0 to 8) days; adjusted difference in days, -3.47, 95% CI -3.78 to -3.17, and across all the different clinical settings and diagnoses. Authors' conclusions Use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARI was not associated with higher mortality rates or treatment failure. Antibiotic consumption was significantly reduced across different clinical settings and ARI diagnoses. Further high-quality research is needed to confirm the safety of this approach for non-European countries and patients in intensive care. Moreover, future studies should also establish cost-effectiveness by considering country-specific costs of procalcitonin measurement and potential savings in consumption of antibiotics and other healthcare resources, as well as secondary cost savings due to lower risk of side effects and reduced antimicrobial resistance. Procalcitonin testing to initiate or discontinue antibiotics in acute respiratory tract infections Unnecessary antibiotic use significantly contributes to increasing bacterial resistance, medical costs and the risk of drug-related adverse events. The blood marker procalcitonin increases in bacterial infections and decreases when patients recover from the infection. Hence, procalcitonin may be used to support clinical decision making for the initiation and discontinuation of antibiotic therapy in patients with a clinical suspicion of infection. Randomised controlled trials have demonstrated that such a strategy works, particularly in patients with an infection of the respiratory tract. However, most of these individual studies did not include enough patients to allow for a conclusive assessment about safety (low statistical power). Thus, the risk for mortality and severe complications associated with procalcitonin-guided decision making remained unclear. This systematic review included individual patient data from 14 randomised controlled trials with a total of 4211 participants. When looking at these combined data, we found no increased risk for all-cause mortality or treatment failure when procalcitonin was used to guide initiation and duration of antibiotic treatment in participants with acute respiratory infections compared to control participants. However, we found a consistent reduction of antibiotic use, mainly due to lower prescription rates in primary care and lower duration of antibiotic courses in emergency department and intensive care unit patients. This analysis is limited to adult patients with respiratory infections excluding patients who were immuno-compromised (i.e. HIV positive, those receiving immuno-suppressive therapies or chemotherapy). Most trials were conducted in Europe and China and similar studies in other countries including the United States are warranted. [ABSTRACT FROM AUTHOR]

Background Dampness and mould in buildings have been associated with adverse respiratory symptoms, asthma and respiratory infections of inhabitants. Moisture damage is a very common problem in private houses, workplaces and public buildings such as schools. Objectives To determine the effectiveness of remediating buildings damaged by dampness and mould in order to reduce or prevent respiratory tract symptoms, infections and symptoms of asthma. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 2), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1951 to June week 1, 2011), EMBASE (1974 to June 2011), CINAHL (1982 to June 2011), Science Citation Index (1973 to June 2011), Biosis Previews (1989 to June 2011), NIOSHTIC (1930 to November 2010) and CISDOC (1974 to November 2010). Selection criteria Randomised controlled trials (RCTs), cluster-RCTs (cRCTs), interrupted time series studies and controlled before-after (CBA) studies of the effects of remediating dampness and mould in a building on respiratory symptoms, infections and asthma. Data collection and analysis Two authors independently extracted data and assessed the risk of bias in the included studies. Main results We included eight studies (6538 participants); two RCTs (294 participants), one cRCT (4407 participants) and five CBA studies (1837 participants). The interventions varied from thorough renovation to cleaning only. We found moderate-quality evidence in adults that repairing houses decreased asthma-related symptoms (among others, wheezing (odds ratio (OR) 0.64; 95% confidence interval (CI) 0.55 to 0.75) and respiratory infections (among others, rhinitis (OR 0.57; 95% CI 0.49 to 0.66)). For children, we found moderate-quality evidence that the number of acute care visits (among others mean difference (MD) -0.45; 95% CI -0.76 to -0.14)) decreased in the group receiving thorough remediation. One CBA study showed very low-quality evidence that after repairing a mould-damaged office building, asthma-related and other respiratory symptoms decreased. For children and staff in schools, there was very low-quality evidence that asthma-related and other respiratory symptoms in mould-damaged schools were similar to those of children and staff in non-damaged schools, both before and after intervention. For children, respiratory infections might have decreased after the intervention. Authors' conclusions We found moderate to very low-quality evidence that repairing mould-damaged houses and offices decreases asthma-related symptoms and respiratory infections compared to no intervention in adults. There is very low-quality evidence that although repairing schools did not significantly change respiratory symptoms in staff or children, pupils' visits to physicians due to a common cold were less frequent after remediation of the school. Better research, preferably with a cRCT design and with more validated outcome measures, is needed. Plain Language Summary Interventions for preventing or reducing symptoms of asthma, other respiratory symptoms and respiratory infections in mould-damaged buildings Moisture damage is a very common problem in private houses, workplaces and public buildings around the world and has been associated with adverse respiratory symptoms, asthma and respiratory infections of inhabitants. Our aim was to determine the effectiveness of remediating buildings damaged by dampness and mould in reducing or preventing the occurrence of respiratory tract symptoms, infections and symptoms of asthma. We included eight studies with 6538 participants; three randomised controlled trials (RCTs) and five non-RCTs. The interventions aimed to remove mould and dampness from family houses, schools or, in one study, an office building. When remediation of houses was compared to no intervention at all, we found evidence that mould remediation reduced asthma-related symptoms and respiratory infections. It also decreased the use of asthma medication in asthmatics. We found very low-quality evidence that after repairing a mould-damaged office that asthma-related and other respiratory symptoms decreased. For extensive remediation compared with information only, there was moderate-quality evidence that the number of asthma symptom days among asthmatic children did not decrease significantly. However, the number of emergency and inpatient visits decreased after the repair of the building. Pupil visits to physicians due to a common cold were less frequent after the building was repaired but respiratory symptoms (stuffy nose, runny nose, dry throat, hoarseness, eye irritation) were similar before and after the intervention both among pupils and adults working in the schools. Due to a wide range of outcome measures and variation in study designs, it was difficult to draw hard conclusions. Better research is needed, preferably with a cluster-RCT (cRCT) design and with more validated outcome measures. [ABSTRACT FROM AUTHOR]

Background In industrialised countries injuries (including burns, poisoning or drowning) are the leading cause of childhood death and steep social gradients exist in child injury mortality and morbidity. The majority of injuries in pre-school children occur at home but there is little meta-analytic evidence that child home safety interventions reduce injury rates or improve a range of safety practices, and little evidence on their effect by social group. Objectives We evaluated the effectiveness of home safety education, with or without the provision of low cost, discounted or free equipment (hereafter referred to as home safety interventions), in reducing child injury rates or increasing home safety practices and whether the effect varied by social group. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2009, Issue 2) in The Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Social Sciences Citation Index (SSCI), ISI Web of Science: Conference Proceedings Citation Index- Science (CPCI-S), CINAHL (EBSCO) and DARE (2009, Issue 2) in The Cochrane Library. We also searched websites and conference proceedings and searched the bibliographies of relevant studies and previously published reviews. We contacted authors of included studies as well as relevant organisations. The most recent search for trials was May 2009. Selection criteria Randomised controlled trials (RCTs), non-randomised controlled trials and controlled before and after (CBA) studies where home safety education with or without the provision of safety equipment was provided to those aged 19 years and under, and which reported injury, safety practices or possession of safety equipment. Data collection and analysis Two authors independently assessed study quality and extracted data. We attempted to obtain individual participant level data (IPD) for all included studies and summary data and IPD were simultaneously combined in meta-regressions by social and demographic variables. Pooled incidence rate ratios (IRR) were calculated for injuries which occurred during the studies, and pooled odds ratios were calculated for the uptake of safety equipment or safety practices, with 95% confidence intervals. Main results Ninety-eight studies, involving 2,605,044 people, are included in this review. Fifty-four studies involving 812,705 people were comparable enough to be included in at least one meta-analysis. Thirty-five (65%) studies were RCTs. Nineteen (35%) of the studies included in the meta-analysis provided IPD. There was a lack of evidence that home safety interventions reduced rates of thermal injuries or poisoning. There was some evidence that interventions may reduce injury rates after adjusting CBA studies for baseline injury rates (IRR 0.89, 95% CI 0.78 to 1.01). Greater reductions in injury rates were found for interventions delivered in the home (IRR 0.75, 95% CI 0.62 to 0.91), and for those interventions not providing safety equipment (IRR 0.78, 95% CI 0.66 to 0.92). Home safety interventions were effective in increasing the proportion of families with safe hot tap water temperatures (OR 1.41, 95% CI 1.07 to 1.86), functional smoke alarms (OR 1.81, 95% CI 1.30 to 2.52), a fire escape plan (OR 2.01, 95% CI 1.45 to 2.77), storing medicines (OR 1.53, 95% CI 1.27 to 1.84) and cleaning products (OR 1.55, 95% CI 1.22 to 1.96) out of reach, having syrup of ipecac (OR 3.34, 95% CI 1.50 to 7.44) or poison control centre numbers accessible (OR 3.30, 95% CI 1.70 to 6.39), having fitted stair gates (OR 1.61, 95% CI 1.19 to 2.17), and having socket covers on unused sockets (OR 2.69, 95% CI 1.46 to 4.96). Interventions providing free, low cost or discounted safety equipment appeared to be more effective in improving some safety practices than those interventions not doing so. There was no consistent evidence that interventions were less effective in families whose children were at greater risk of injury. Authors' conclusions Home safety interventions most commonly provided as one-to-one, face-to-face education, especially with the provision of safety equipment, are effective in increasing a range of safety practices. There is some evidence that such interventions may reduce injury rates, particularly where interventions are provided at home. Conflicting findings regarding interventions providing safety equipment on safety practices and injury outcomes are likely to be explained by two large studies; one clinic-based study provided equipment but did not reduce injury rates and one school-based study did not provide equipment but did demonstrate a significant reduction in injury rates. There was no consistent evidence that home safety education, with or without the provision of safety equipment, was less effective in those participants at greater risk of injury. Further studies are still required to confirm these findings with respect to injury rates. Plain Language Summary Home safety education and providing safety equipment for injury prevention Injuries are the leading cause of childhood death in industrialised countries. People living in disadvantaged circumstances are at greater risk of injury than those who are more advantaged. This review examined whether home safety education and providing safety equipment reduced injuries and increased safety behaviours and safety equipment use. It also looked at whether home safety education was more or less effective in disadvantaged families. The review authors found 98 studies involving 2,605,044 participants which reported many different safety behaviours, but relatively few studies included information on injuries. The authors found that home safety interventions provided in the home may reduce injury rates, but more research is needed to confirm this finding. The results often varied between studies but, overall, families who received home safety interventions were more likely to have a safe hot tap water temperature, a working smoke alarm, a fire escape plan, fitted stair gates, socket covers on unused sockets, syrup of ipecac, poison control centre numbers accessible, and to store medicines and cleaning products out of reach of children. The authors found that home safety education was equally effective in the families whose children were at greater risk of injury. [ABSTRACT FROM AUTHOR]

Background Infant acute pain and distress is commonplace. Infancy is a period of exponential development. Unrelieved pain and distress can have implications across the lifespan. Objectives To assess the efficacy of non-pharmacological interventions for infant and child (up to three years) acute pain, excluding breastmilk, sucrose, and music. Analyses accounted for infant age (preterm, neonate, older) and pain response (pain reactivity, pain-related regulation). Search methods We searched CENTRAL in The Cochrane Library (2011, Issue 1), MEDLINE (1966 to April 2011), EMBASE (1980 to April 2011), PsycINFO (1967 to April 2011), Cumulative Index to Nursing and Allied Health Literature (1982 to 2011), Dissertation Abstracts International (1980 to 2011) and www.clinicaltrials.gov. We also searched reference lists and contacted researchers via electronic list-serves. Selection criteria Participants included infants from birth to three years. Only randomized controlled trials (RCTs) or RCT cross-overs that had a no-treatment control comparison were eligible for inclusion in the analyses. We examined studies that met all inclusion criteria except for study design (e.g. had an active control) to qualitatively contextualize results. Data collection and analysis We refined search strategies with three Cochrane-affiliated librarians. At least two review authors extracted and rated 51 articles. Study quality ratings were based on a scale by Yates and colleagues. We analyzed the standardized mean difference (SMD) using the generic inverse variance method. We also provided qualitative descriptions of 20 relevant but excluded studies. Main results Fifty-one studies, with 3396 participants, were analyzed. The most commonly studied acute procedures were heel-sticks (29 studies) and needles (n = 10 studies). The largest SMD for treatment improvement over control conditions on pain reactivity were: non-nutritive sucking-related interventions (preterm: SMD -0.42; 95% CI -0.68 to -0.15; neonate: SMD -1.45, 95% CI -2.34 to -0.57), kangaroo care (preterm: SMD -1.12, 95% CI -2.04 to -0.21), and swaddling/facilitated tucking (preterm: SMD -0.97; 95% CI -1.63 to -0.31). For immediate pain-related regulation, the largest SMDs were: non-nutritive sucking-related interventions (preterm: SMD -0.38; 95% CI -0.59 to -0.17; neonate: SMD -0.90, 95% CI -1.54 to -0.25), kangaroo care (SMD -0.77, 95% CI -1.50 to -0.03), swaddling/facilitated tucking (preterm: SMD -0.75; 95% CI -1.14 to -0.36), and rocking/holding (neonate: SMD -0.75; 95% CI -1.20 to -0.30).The presence of significant heterogeneity limited our confidence in the lack of findings for certain analyses. Authors' conclusions There is evidence that different non-pharmacological interventions can be used with preterms, neonates, and older infants to significantly manage pain behaviors associated with acutely painful procedures. Plain Language Summary Non-pharmacological interventions for acute pain in infants We examined 13 different types of commonly investigated non-pharmacological treatments (excluding breastmilk, sucrose, and music) to determine their efficacy for pain reactions after an acutely painful procedure (right after the needle ('pain reactivity') and less immediate pain reactions ('immediate pain-related regulation').Fifty-one randomized controlled trials were included involving 3396 participants. For preterm infants, there was sufficient evidence to recommend kangaroo care, sucking-related interventions, and swaddling/facilitated tucking interventions for both pain reactivity and immediate pain-related regulation. For neonates, there was sufficient evidence to recommend sucking-related interventions as an effective treatment for pain reactivity and immediate pain-related regulation.Rocking/holding was also found to be efficacious for neonatal immediate pain-related regulation.For older infants, there were no treatments reviewed that demonstrated sufficient evidence. Due to significant differences in the magnitude of treatment effects among studies (heterogeneity), some analyses that found a lack of treatment effect need to be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical interventions in adults with symptomatic or asymptomatic cardiac dysfunction due to other causes are beneficial, it is not known if the same treatments are effective for childhood cancer patients and survivors with anthracycline-induced cardiotoxicity. Objectives To compare the effect of medical interventions on anthracycline-induced cardiotoxicity in childhood cancer patients or survivors with the effect of placebo, other medical interventions or no treatment. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library, 2011, issue 1), MEDLINE/PubMed (1949 to May 2011) and EMBASE/Ovid (1980 to May 2011) for potentially relevant articles. We additionally searched reference lists of relevant articles, conference proceedings and ongoing trial databases. Selection criteria Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing the effectiveness of medical interventions to treat anthracycline-induced cardiotoxicity with either placebo, other medical interventions or no treatment. Data collection and analysis Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessments which were checked by another review author. Main results We identified two RCTs. One trial (135 patients) compared enalapril with placebo in childhood cancer survivors with asymptomatic anthracycline induced cardiac dysfunction. The other trial (68 patients) compared a two-week treatment of phosphocreatine with a control treatment (vitamin C, ATP, vitamin E, oral coenzyme Q10) in leukaemia patients with anthracycline-induced cardiotoxicity. Both studies had methodological limitations. The RCT on enalapril showed no (statistically) significant differences in overall survival, mortality due to heart failure, development of clinical heart failure and quality of life between treatment and control group. A post-hoc analysis showed a decrease (i.e. improvement) in one measure of cardiac function (left ventricular end systolic wall stress (LVESWS): -8.62% change) compared with placebo (+1.66% change) in the first year of treatment (P = 0.036), but not afterwards. Patients treated with enalapril had a higher risk of dizziness or hypotension (RR 7.17, 95% CI 1.71 to 30.17) and fatigue (Fisher's exact test, P = 0.013). The RCT on phosphocreatine found no differences in overall survival, mortality due to heart failure, echocardiographic cardiac function and adverse events between treatment and control group. Authors' conclusions For the effect of enalapril in childhood cancer survivors with asymptomatic cardiac dysfunction, only one RCT is available. Although there is some evidence that enalapril temporarily improves one parameter of cardiac function (LVESWS), it is unclear whether it improves clinical outcomes. Enalapril was associated with a higher risk of dizziness or hypotension and fatigue. Clinicians should weigh the possible benefits with the known side-effects of enalapril in childhood cancer survivors with asymptomatic anthracycline-induced cardiotoxicity. For the effect of phosphocreatine in childhood cancer patients with anthracycline-induced cardiotoxicity, only one RCT is available. Limited data with a high risk of bias showed no significant difference between phosphocreatine and control treatment on echocardiographic function and clinical outcomes. We did not identify any RCTs or CCTs studying other medical interventions for symptomatic or asymptomatic cardiotoxicity in childhood cancer patients or survivors. High-quality studies should be performed. Plain Language Summary Treatment for cardiac problems caused by anthracycline chemotherapy for childhood cancer Anthracyclines are anti-cancer drugs that are used in the treatment of different types of childhood cancer. An important adverse effect of anthracyclines is damage to the heart that can lead to asymptomatic (without complaints) or symptomatic (with complaints) cardiac problems during and after cancer treatment. There are several drugs available to treat other types of cardiac problems in adults, but it is not known if these drugs are beneficial in treating cardiac problems caused by anthracyclines in childhood cancer patients and survivors. If a physician is confronted with a childhood cancer patient or survivor with anthracycline-induced cardiac problems, he or she should be able to make an informed decision to treat this patient based on high-quality evidence about the beneficial and adverse effects of the treatment options. We searched for and summarised studies that evaluated drugs for treating anthracycline-induced cardiac problems in childhood cancer patients and survivors. We identified two randomised studies evaluating two different drugs in two different types of patients. One of these drugs, an ACE-inhibitor (enalapril), had a short-term beneficial effect on heart function in survivors of childhood cancer with asymptomatic cardiac problems caused by anthracyclines compared with placebo. However, the drug had no significant beneficial effect on other important outcomes and was associated with side effects such as dizziness and fatigue. This study was of reasonable/good quality. The other study was of low quality and found no effect of a short treatment with phosphocreatine in childhood leukaemia patients with symptomatic or asymptomatic cardiac problems compared with a control treatment with vitamin C, ATP, vitamin E, and oral coenzyme Q10. No definitive conclusions can be made about treatment options for anthracycline-induced cardiac problems in childhood cancer patients and survivors. High-quality studies are necessary to show if there are drugs that improve heart function in these patients. [ABSTRACT FROM AUTHOR]

Background Necrotizing enterocolitis (NEC) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants. Through prevention of bacterial migration across the mucosa, competitive exclusion of pathogenic bacteria, and enhancing the immune responses of the host, prophylactic enteral probiotics (live microbial supplements) may play a role in reducing NEC and associated morbidity. Objectives To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC and/or sepsis in preterm infants. Search methods For this update, searches were made of MEDLINE (1966 to October 2010), EMBASE (1980 to October 2010), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2010), and abstracts of annual meetings of the Society for Pediatric Research (1995 to 2010). Selection criteria Only randomized or quasi-randomized controlled trials that enrolled preterm infants < 37 weeks gestational age and/or < 2500 g birth weight were considered. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one prespecified clinical outcome. Data collection and analysis Standard methods of the Cochrane Collaboration and its Neonatal Group were used to assess the methodologic quality of the trials, data collection and analysis. Main results Sixteen eligible trials randomizing 2842 infants were included. Included trials were highly variable with regard to enrollment criteria (i.e. birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. Data regarding extremely low birth weight infants (ELBW) could not be extrapolated. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical RR 0.35, 95% CI 0.24 to 0.52) and mortality (typical RR 0.40, 95% CI 0.27 to 0.60). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.90, 95% CI 0.76 to 1.07). The included trials reported no systemic infection with the probiotics supplemental organism. The statistical test of heterogeneity for NEC, mortality and sepsis was insignificant. Authors' conclusions Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence supports a change in practice. More studies are needed to assess efficacy in ELBW infants and assess the most effective formulation and dose to be utilized. Plain Language Summary Probiotics for prevention of necrotizing enterocolitis in preterm infants Necrotizing enterocolitis (NEC) is a serious disease that affects the bowel of premature infants in the first few weeks of life. Although the cause of NEC is not entirely known, milk feeding and bacterial growth play a role. Probiotics (dietary supplements containing potentially beneficial bacteria or yeast) have been used to prevent NEC. Our review of studies found that the use of probiotics reduces the occurrence of NEC and death in premature infants born less than 1500 grams. There is insufficient data with regard to the benefits and potential adverse effects in the most at risk infants less than 1000 grams at birth. [ABSTRACT FROM AUTHOR]

Background: Fractures are a manifestation of physical abuse and common accidental injuries. Distinguishing which fractures are indicative of abuse and optimizing the identification of occult fractures are the challenges. Objectives: To identify additional studies published since our original systematic reviews to address these two issues. Methods: An all-language literature search of 14 databases was conducted for the years 2005-2013, using revised keywords. All studies underwent standardized critical appraisal by two independent reviewers, applying quality criteria relating to the confirmation of child abuse, exclusion of abuse and quality of skeletal survey conducted. A meta-analysis, stratified by age, was conducted to determine the predictive value for abuse of specific fractures by fitting a random effects model. Results: Twenty-three studies addressed 'radiological investigations', and nine studies 'fractures indicative of abuse'. Radiological studies reiterated that a single investigation (skeletal survey or radionuclide imaging ) will miss some abusive fractures; in 8.4-37.6% of children, the repeat skeletal survey added new information that influenced the child protection procedures. Debate continues as to the optimal images to include in the repeat skeletal survey. A meta-analysis of femoral and humeral fractures by age highlighted that children younger than 18 months are significantly more likely to have sustained their fracture as a consequence of abuse, than those aged 1-4 years. Authors' Conclusions: Recent literature validates the original conclusions that repeat skeletal imaging adds important information on fractures. Comparative studies of femoral, humeral, rib and skull fractures enabled a meta-analysis by age, however further comparative studies are needed. [ABSTRACT FROM AUTHOR]