Primary prevention of acute respiratory tract infections in children using a bacterial immunostimulant: a double-masked, placebo-controlled clinical trial. Safety and efficacy of two courses of OM-85 BV in the prevention of respiratory tract infections in children during 12 months. A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study). Stimulation of nonspecific immunity to reduce the risk of recurrent infections in children attending day-care centers. The Epicrèche Research Group. A randomized controlled trial of home injury hazard reduction: the HOME injury study. Management for the children with otitis media with effusion in the tertiary hospital. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract: a double-blind, placebo-controlled multicenter study. Intranasal flunisolide treatment in children with adenoidal hypertrophy. Prevention of otitis media by adenoidectomy in children younger than 2 years. Abstracts of randomized controlled trials presented at the society for pediatric research meeting: an example of publication bias. Preventing injuries in children: cluster randomised controlled trial in primary care. Evaluation of exposure with response-prevention for obsessive compulsive disorder in childhood and adolescence. Enhancing ventilation in homes of children with asthma: pragmatic randomised controlled trial. Bacterial lysate (I.R.S. 19) applied intranasally in the prevention of acute respiratory diseases in children: a randomized double-blind study. Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment. Randomized controlled trials in pediatric surgery: could we do better? Medication diaries do not improve outcomes with highly active antiretroviral therapy in Kenyan children: a randomized clinical trial. Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group. Providing child safety equipment to prevent injuries: randomised controlled trial. A prospective, single-blind, randomized controlled trial of antiseptic cream for recurrent epistaxis in childhood. Three-year follow-up of clinical and inflammation parameters in children monosensitized to mites undergoing sub-lingual immunotherapy. Behavioral counseling for reducing children's ETS exposure: implementation in community clinics. Can parents who smoke socialise their children against smoking? Results from the Smoke-free Kids intervention trial. A randomized, double-blind, placebo-controlled noninferiority trial of amoxicillin for clinically diagnosed acute otitis media in children 6 months to 5 years of age. Echinacea purpurea and osteopathic manipulative treatment in children with recurrent otitis media: a randomized controlled trial. Effectiveness of a single-session early psychological intervention for children after road traffic accidents: a randomised controlled trial. Evaluating the effectiveness of exposure and acceptance strategies to improve functioning and quality of life in longstanding pediatric pain--a randomized controlled trial. A randomized trial on effectiveness of artemether-lumefantrine versus artesunate plus amodiaquine for unsupervised treatment of uncomplicated Plasmodium falciparum malaria in Ghanaian children. Ribosomal immunostimulation: assessment of studies evaluating its clinical relevance in the prevention of upper and lower respiratory tract infections in children and adults. Evaluation of an inter-organizational prevention program against injuries among the elderly in a WHO Safe Community. A new social communication intervention for children with autism: pilot randomised controlled treatment study suggesting effectiveness. Early virological suppression with three-class antiretroviral therapy in HIV-infected African infants. Prophylaxis for recurrent acute otitis media: a Brazilian study. Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial. [Interventions to prevent accidental injuries in children between 7 and 13 years of age]. Anticholinergic prophylaxis does not prevent emesis following strabismus surgery in children. Treatment of childhood encopresis: a randomized trial comparing three treatment protocols. 4A randomized trial of prolonged prone positioning in children with acute respiratory failure. Iron supplementation improves iron status and reduces morbidity in children with or without upper respiratory tract infections: a randomized controlled study in Colombo, Sri Lanka. Generalizability of trial results based on randomized versus nonrandomized allocation of OME infants to ventilation tubes or watchful waiting. EPA supplementation improves teacher-rated behaviour and oppositional symptoms in children with ADHD.
Acute respiratory tract infections (ARTIs) are among the main causes of morbidity and mortality in children. The bacterial extract OM-85 BV has shown some protective effect for ARTIs in preschool children and a reduction in exacerbations of chronic bronchitis in adults.
                This trial reports results of a double-masked, placebo-controlled, parallel-group clinical study that assessed the efficacy and tolerability of OM-85 BV in the prevention of ARTIs in school girls living in an orphanage.
                Two hundred girls (age range, 6 to 13 years) living in an orphanage entered the trial. Participants were randomly allocated to receive either OM-85 BV or placebo for 10 consecutive days a month for 3 consecutive months. Patients were followed up for 6 months, including the administration period. The trial began in September 1996 and finished in March 1997. Primary end points were the type and number of infections. Secondary end points included when an infection occurred, time to clinical cure, severity of infection, absenteeism from school due to an ARTI, number of antibiotics or other drugs prescribed, and duration of concomitant drug treatment.
                During the trial, patients in the OM-85 BV group experienced 143 ARTIs (135 upper ARTIs and 8 otitis episodes) and patients in the placebo group experienced 299 ARTIs (273 upper ARTIs, 1 lower ARTI, and 25 otitis episodes). The median number of ARTIs was 1.0 (0.0, 3.0; 5th percentile, 95th percentile) in the OM-85 BV group compared with 3.0 (2.0, 4.0; 5th percentile, 95th percentile) in the placebo group. This difference was statistically significant (P < 0.001). Participants who received OM-85 BV also showed significantly better results (P < 0.001) than participants who received placebo in terms of median duration of illness, median number of missed school days due to an ARTI, median number of antibiotic and drug courses, and median duration of concomitant treatment. There were significant differences (P < 0.05) in severity of ARTIs during month 4 of the trial, with patients receiving OM-85 BV showing less severe ARTIs than patients receiving placebo and shorter mean time to clinical cure from the second month to the fourth month. No adverse events related to the trial medications were reported. Conclusions: OM-85 BV had a preventive effect on ARTIs in the school girls, with a reduction in the antibiotic requirements and the duration of ARTIs. Future studies are needed to further explore the role of OM-85 BV in the prevention of ARTIs. Acute respiratory tract infections (ARTIs) are among the main causes of morbidity and mortality in children. The bacterial extract OM-85 BV (bronchovaxom) has shown protective effect for ARTIs on children. We report a double-blind, placebo-controlled, parallel, prospective clinical trial to assess the safety and efficacy of two courses of OM-85 BV in the prevention of ARTIs in susceptible children during 12 months.
                Fifty-four susceptible children from 1 to 12 years of age living in the metropolitan area of Chihuahua City were selected. They were randomized to receive either OM-85 BV or placebo (one capsule a day for 10 days a month for 3 consecutive months) at the beginning of the trial and 6 months later with the same schedule. Patients were followed up for 12 months, including the administration period. The trial began in July 1997 and ended in April 1999.
                The number (mean +/- SD) of ARTIs was 5.04 +/- 1.99 (median, 5.0) in the OM-85 BV group vs 8.0 +/- 2.55 (median, 8.0) in the placebo group, with a mean difference of - 2.96 (95% confidence interval [CI], - 4.22 to - 1.7). The number of antibiotic courses was 2.46 +/- 2.08 (median, 1.5) in the treatment group vs 4.46 +/- 2.08 (median, 4.0) in the control group, a difference of - 2.0 (95% CI, - 3.14 to - 0.86). The total duration of ARTIs was 35.23 +/- 17.64 days (median, 30.5 days) in the OM-85 BV group vs 60.75 +/- 25.44 days (median, 55.0 days) in the placebo group, ie, a difference of - 25.52 days (95% CI, - 37.56 to - 13.47 days), p < 0.001 by Student's t test and Mann-Whitney U test for all the items. Four patients in the OM-85 BV group had five adverse events. Only one episode of skin rash was related to the medication intake. Six patients in the control group had six adverse events.
                OM-85 BV had a preventive effect on ARTI in the susceptible children for 12 months with an important reduction on the antibiotic requirements and the number of days of suffering ARTIs. Prevention of arthropathy is a major goal of hemophilia treatment. While studies in adults have demonstrated an impact of prophylaxis on the incidence of joint bleeds and patients' well-being in terms of improved quality of life (QoL), it is unclear whether or not prophylaxis influences the outcome and perception of well- of children with hemophilia.
                This randomized controlled study compared the efficacy of prophylaxis with episodic therapy in preventing hemarthroses and image-proven joint damage in children with severe hemophilia A (factor VIII <1%) over a 10-year time period.
                Forty-five children with severe hemophilia A, aged 1-7 years (median 4), with negative clinical-radiologic joint score at entry and at least one bleed during the previous 6 months, were consecutively randomized to prophylaxis with recombinant factor VIII (25 IU kg(-1) 3 × week) or episodic therapy with ≥25 IU kg(-1) every 12-24 h until complete clinical bleeding resolution. Safety, feasibility, direct costs and QoL were also evaluated.
                Twenty-one children were assigned to prophylaxis, 19 to episodic treatment. Children on prophylaxis had fewer hemarthroses than children on episodic therapy: 0.20 vs. 0.52 events per patient per month (P < 0.02). Plain-film radiology showed signs of arthropathy in six patients on prophylaxis (29%) vs. 14 on episodic treatment (74%) (P < 0.05). Prophylaxis was more effective when started early (≤36 months), with patients having fewer joint bleeds (0.12 joint bleeds per patient per month) and no radiologic signs of arthropathy.
                This randomized trial confirms the efficacy of prophylaxis in preventing bleeds and arthropathy in children with hemophilia, particularly when it is initiated early in life.
                © 2011 International Society on Thrombosis and Haemostasis. A randomized, double blind, placebo-controlled clinical trial was performed in 423 children attending day-care centers to assess whether stimulating nonspecific immunity would reduce the incidence of recurrent infections. The drug used for the trial (Imocur) is an extract obtained from eight different species of bacteria. At the end of the total follow-up period (3 months with treatment and 4.5 months without), the risk for > or = 4 episodes of upper respiratory infections was not significantly lower in the treated group than in the placebo group (26.7% vs. 33.8%, relative risk, 0.79; 95% confidence interval, 0.59 to 1.06). In an exploratory analysis limited to the 3-month treatment period, however, we observed a 48% reduction in the risk of presenting > or = 3 episodes of upper respiratory infections: 9.5% vs. 18.3%, respectively, in the treatment group and the placebo group (relative risk, 0.52; 95% confidence interval, 0.31 to 0.86). Similar results were found for the risk of > or = 1 episode of gastroenteritis. We also observed a strong correlation between the drug efficacy and age; this observation is coherent with the underlying pathophysiologic model in which the immune system matures with age. To test the efficacy of installing safety devices in the homes of young children on total injury rates and on injuries deemed a priori modifiable by the installation of these devices.
                A nested, prospective, randomized controlled trial.
                Indoor environment of housing units.
                Mothers and their children from birth to 3 years old participating in the Home Observation and Measures of the Environment study. Among 8878 prenatal patients, 1263 (14.2%) were eligible, 413 (32.7%) agreed to participate, and 355 were randomly assigned to the intervention (n = 181) or control (n = 174) groups.
                Installation of multiple passive measures (eg, stair gates, cabinet locks, and smoke detectors) to reduce exposure to injury hazards. Injury hazards were assessed at home visits by teams of trained research assistants using a validated survey.
                Modifiable and medically attended injury (ie, telephone calls, office visits, and emergency visits for injury).
                The mean age of children at intervention was 6.3 months. Injury hazards were reduced in the intervention homes but not in the control homes at 1 and 2 years (P < .004). There was no difference in the rate for all medically attended injuries in intervention children compared with controls: 14.3 injuries (95% confidence interval [CI], 9.7-21.1 injuries) vs 20.8 injuries (95% CI, 14.4-29.9 injuries) per 100 child-years (P = .17); but there was a significant reduction in the rate of modifiable medically attended injuries in intervention children compared with controls: 2.3 injuries (95% CI, 1.0-5.5 injuries) vs 7.7 injuries (95% CI, 4.2-14.2 injuries) per 100 child-years (P = .03).
                An intervention to reduce exposure to hazards in homes led to a 70% reduction in the rate of modifiable medically attended injury.
                clinicaltrials.gov Identifier: NCT00129324. Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.
                Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.
                Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).
                In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals. Effective ways to prevent arthropathy in severe hemophilia are unknown.
                We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI).
                Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P=0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups.
                Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597 [ClinicalTrials.gov].).
                Copyright 2007 Massachusetts Medical Society. Recurrent upper respiratory tract infections (URTIs) are common illnesses in young children. As the immunoactive bacterial extract OM-85 has been shown to prevent these infections in both adults and children, the aim of the present trial was to investigate further its efficacy and safety in infection-prone children.
                This is a randomized, double-blind, placebo-controlled, multicenter study with OM-85 in 232 patients aged 36 to 96 months with recurrent URTIs. Treatment was one capsule daily during month 1 and during 10 days in months 3 to 5. URTI was defined by the presence of at least two of the following: rhinitis, pharyngitis, cough, hoarseness, temperature > or = 38.5 degrees C, or URTI-related prescription of an antibiotic.
                OM-85-treated patients had a lower rate of URTIs (p < 0.05). The cumulated difference in URTIs between the two groups reached - 0.40 URTIs per patient in 6 months, corresponding to a 16% reduction in the active-treatment group with respect to placebo. The largest difference was observed in the patients having had three or more URTIs during the study period; odds ratios for three or more URTIs were 0.51 (95% confidence interval, 0.29 to 0.91) and 0.65 (95% confidence interval, 0.37 to 1.11) after 5 months and 6 months, respectively. The difference between OM-85 and placebo was independent of age but was more important in patients reporting a larger number of URTIs in the previous year. Patients' global assessment showed improvement in comparison to the previous season in the majority of the cases (OM-85, 78.4% of cases; placebo, 75.5%); however, there were more cases reporting worsening with placebo (6.4% vs 0.9%; p = 0.05).
                OM-85 treatment significantly reduced the rate of URTIs, particularly in children with a history of frequent URTIs. Safety and tolerance of test medication were good, comparable to placebo. Adenoidal hypertrophy (AH) represents one of the most frequent indications for surgery in children and it has been proposed that treatment with intranasal corticosteroids can decrease the size of AH. Therefore, the aim of the study is to evaluate the effect of the use of intranasal flunisolide among children affected by AH. 178 children with AH were evaluated in this randomised and controlled study. Inclusion criteria for the study required that each patient had to have a III or IV degree of AH on the initial endoscopic examination. Children were treated with intranasal flunisolide or isotonic saline solution for 8 weeks. After treatment, endoscopy was performed to re-evaluate AH degree. Flunisolide treatment was associated with significant (p less than 0.04) reduction of AH degree. There was moreover a consistent reduction of children (46 out of 58) proposed to adenoidectomy. No clinically important adverse events were reported. In conclusion, this preliminary study demonstrates that an 8-week treatment with intranasal flunisolide is significantly associated with reduction of AH, thus preventing the recurrence to adenoidectomy, and is safe. To test the effect of adenoidectomy in connection with tympanostomy compared with tympanostomy only in preventing otitis media in children younger than 2 years.
                Prospective trial with randomized and nonrandomized arms.
                Primary care study clinics.
                The study participants were selected from 2497 children who had been enrolled in the Finnish Otitis Media Vaccine Trial at the age of 2 months. A total of 306 children, aged 1 to 2 years, who had experienced recurrent episodes of otitis media were randomized into 2 treatment groups: tympanostomy with or without adenoidectomy. Of the 306 children, 137 were operated on according to random basis (randomized trial). The 169 children whose parents declined participation in the randomized trial were operated on according to the parents' preferences (nonrandomized trial). All children were followed up until 2 years of age. The mean follow-up time was 7 months.
                The rate of acute otitis media episodes.
                The average reduction in the rate of all acute otitis media episodes in the adenoidectomy group was 19% (95% confidence interval [CI], -14% to 43%) among children enrolled in the randomized trial and 25% (95% CI, -13% to 50%) in the nonrandomized trial. The reduction in the randomized trial was mainly due to reduction in the rate of pneumococcal otitis media (58%, 95% CI, 16%-79%).
                In children younger than 2 years, concurrent adenoidectomy during the insertion of tympanostomy tubes does not seem to have a major advantage over the insertion of tympanostomy tubes alone in preventing otitis media. Publication bias toward studies that favor new therapies has been known to occur for the past 40 years, yet its implications are not well studied in child health. The increased interest in meta-analyses has highlighted the need to identify the totality of evidence when addressing treatment questions.
                To measure the percentage of randomized controlled trials (RCTs) presented at a major pediatric scientific meeting that were subsequently published as full-length articles, to investigate factors associated with publication, and to describe the variables that change from abstract to manuscript form.
                The scientific proceedings from the Society for Pediatric Research were hand searched for RCTs (1992-1995). Subsequent publication was ascertained through a search of various electronic databases. Quality of abstracts and manuscripts was measured, and data were extracted using a structured form.
                A total of 264 (59.1%) of 447 abstracts were subsequently published. Almost 64% of RCTs that were subsequently published favored new therapy compared with 43.5% of studies that were never published (P<.001). Mean effect size for published vs unpublished RCTs was 0.74 vs 0.05 (P<.001). Median sample size was larger in published (n = 45) vs unpublished (n = 34) RCTs (P =.02). Quality was significantly lower for abstracts vs published RCTs (P<.001). For 5% of abstracts that were subsequently published, the conclusion regarding treatment efficacy changed.
                Publication bias is a serious threat to assessing the effectiveness of interventions in child health, as little more than half of RCTs presented at a major scientific meeting are subsequently published. There is a need to institute an international registry of RCTs in children so that the totality of evidence can be accessed when assessing treatment effectiveness. To assess the effectiveness of safety advice at child health surveillance consultations, provision of low cost safety equipment to families receiving means tested state benefits, home safety checks, and first aid training on frequency and severity of unintentional injuries in children at home.
                Cluster randomised controlled trial.
                36 general practices in Nottingham.
                All children aged 3-12 months registered with participating practices.
                A package of safety advice at child health surveillance consultations at 6-9, 12-15, and 18-24 months; provision of low cost safety equipment to families on means tested state benefits; and home safety checks and first aid training by health visitors.
                Primary outcomes measures were frequency and severity of medically attended injuries. Secondary outcome measures were self reported safety practices, possession and use of safety equipment, knowledge and confidence in dealing with first aid, and perceptions of risk of injury and risk of hazards assessed by postal questionnaire at baseline and follow up at 25 months.
                At baseline, both groups had similar risk factors for injury, sociodemographic characteristics, safety practices, possession and use of safety equipment, knowledge and confidence in dealing with first aid, and perceptions of risk. No significant difference was found in frequency of at least one medically attended injury (odds ratio 0.97, 95% confidence interval 0.72 to 1.30), at least one attendance at an accident and emergency department for injury (1.02, 0.76 to 1.37), at least one primary care attendance for injury (0.75, 0.48 to 1.17), or at least one hospital admission for injury (0.69, 0.42 to 1.12). No significant difference in the secondary outcome measures was found between the intervention and control groups.
                The intervention package was not effective in reducing the frequency of minor unintentional injuries in children at home, and larger trials are required to assess the effect on more severe injuries. The present study was undertaken to estimate the effect of exposure plus response-prevention (E/RP), delivered alone intensively over 5-weeks and without concomitant pharmacotherapy, for children and adolescents with OCD. Twenty children and adolescents with OCD, not receiving medication for this condition, were randomized to E/RP or a wait-list condition. Statistically and clinically significant symptomatic improvement was found in the E/RP group compared with controls, with improvement maintained at follow-up an average of 14 weeks later. Effect size in the main intention-to-treat analysis was 1.23 and in the secondary per protocol analysis was 1.64. This study lends further support to the view that E/RP is an effective treatment for childhood OCD. Few robust studies have tested whether enhancing housing also improves health.
                To evaluate the effectiveness of installing ventilation systems, and central heating where necessary, in the homes of children with moderate or severe asthma.
                Pragmatic randomised controlled trial (RCT) in homes within Wrexham County Borough, Wales, UK.
                A pragmatic RCT was carried out, of a tailored package of housing improvements providing adequate ventilation and temperature, following inspection by a housing officer. One hundred and ninety-two children with asthma aged 5 to 14 years, identified from general practice registers, were randomised to receive this package, either immediately or a year after recruitment. At baseline, and after 4 and 12 months, parents reported their child's asthma-specific and generic quality of life, and days off school.
                The package improved parent-reported asthma-specific quality of life significantly at both 4 and 12 months. At 12 months, this showed an adjusted mean difference between groups of 7.1 points (95% confidence interval [CI] = 2.8 to 11.4, P= 0.001): a moderate standardised effect size of 0.42. The generic quality-of-life scale showed reported physical problems were significantly reduced at 4 months, but not quite at 12 months, when the mean difference was 4.5 (95% CI = -0.2 to 9.1, P= 0.061). The improvement in psychosocial quality of life at 12 months was not significant, with a mean difference of 2.2 (95% CI = -1.9 to 6.4, P= 0.292). Parent-reported school attendance improved, but not significantly.
                This novel and pragmatic trial, with integrated economic evaluation, found that tailored improvement of the housing of children with moderate to severe asthma significantly increases parent-reported asthma-related quality of life and reduces physical problems. Collaborative housing initiatives have potential to improve health. A controlled trial was undertaken to test I.R.S. 19 (a commercial intranasal spray) versus placebo in the prevention of acute respiratory diseases (ARD) in 825 maternity-school children in three cities; another control group of 327 children received neither I.R.S. 19 nor placebo. The spraying was done twice a day for a total of 20 spraying days in each child; sprayings were interrupted on weekends and during absence, the mean spraying period being 34 calendar days. During the 6-month study (1 November to 30 April) the children were monitored for ARD morbidity causing absence from school. A total of 1,585 such ARD cases occurred; their etiology was not investigated. The indices evaluated were: total duration of ARD-associated absence, ARD incidence, and mean duration of one illness. With the administration schedule used, I.R.S. 19 did not, in an overall evaluation, surpass placebo in any of these indices in either normal children or a subgroup of children with presumed enhanced ARD susceptibility. The widespread use of antibiotics for treatment of acute otitis media (AOM) has resulted in the emergence of multidrug-resistant pathogens that are difficult to treat. However, it has been shown that most children with nonsevere AOM recover without ABX. The objective of this study was to evaluate the safety, efficacy, acceptability, and costs of a non-ABX intervention for children with nonsevere AOM.
                Children 6 months to 12 years old with AOM were screened by using a novel AOM-severity screening index. Parents of children with nonsevere AOM received an educational intervention, and their children were randomized to receive either immediate antibiotics (ABX; amoxicillin plus symptom medication) or watchful waiting (WW; symptom medication only). The investigators, but not the parents, were blinded to enrollment status. Primary outcomes included parent satisfaction with AOM care, resolution of symptoms, AOM failure/recurrence, and nasopharyngeal carriage of Streptococcus pneumoniae strains resistant to ABX. Secondary outcomes included medication-related adverse events, serious adverse events, unanticipated AOM-related office and emergency department visits and telephone calls, the child's absence from day care or school resulting from AOM, the parent's absence from school or work because of their child's AOM, and costs of treatment. Subjects were defined as failing (days 0-12) or recurring (days 13-30) if they experienced a higher AOM-severity score on reexamination.
                A total of 223 subjects were recruited: 73% were nonwhite, 57% were <2 years old, 47% attended day care, 82% had experienced prior AOM, and 83% had not been fully immunized with heptavalent pneumococcal vaccine. One hundred twelve were randomized to ABX, and 111 were randomized to WW. Ninety-four percent of the subjects were followed to the 30-day end point. Parent satisfaction with AOM care was not different between the 2 treatment groups at either day 12 or 30. Compared with WW, symptom scores on days 1 to 10 resolved faster in subjects treated with immediate ABX. At day 12, among the immediate-ABX group, 69% of tympanic membranes and 25% of tympanograms were normal, compared with 51% of normal tympanic membranes and 10% of normal tympanograms in the WW group. Parents of children in the ABX group gave their children fewer doses of pain medication than did parents of children in the WW group. Subjects in the ABX group experienced 16% fewer failures than subjects in the WW group. Of the children in the WW group, 66% completed the study without needing ABX. Immediate ABX resulted in eradication of S pneumoniae carriage in the majority of children, but S pneumoniae strains cultured from children in the ABX group at day 12 were more likely to be multidrug-resistant than strains from children in the WW group. More ABX-related adverse events were noted in the ABX group, compared with the WW group. No serious AOM-related adverse events were observed in either group. Office and emergency department visits, phone calls, and days of work/school missed were not different between groups. Prescriptions for ABX were reduced by 73% in the WW group compared with the ABX group. Costs of ABX averaged $47.41 per subject in the ABX group and $11.43 in the WW group.
                Sixty-six percent of subjects in the WW group completed the study without ABX. Parent satisfaction was the same between groups regardless of treatment. Compared with WW, immediate ABX treatment was associated with decreased numbers of treatment failures and improved symptom control but increased ABX-related adverse events and a higher percent carriage of multidrug-resistant S pneumoniae strains in the nasopharynx at the day-12 visit. Key factors in implementing a WW strategy were (a) a method to classify AOM severity; (b) parent education; (c) management of AOM symptoms; (d) access to follow-up care; and (e) use of an effective ABX regimen, when needed. When these caveats are observed, WW may be an acceptable alternative to immediate ABX for some children with nonsevere AOM. Randomized controlled trials (RCTs) are accepted as the gold standard for assessing the effectiveness of clinical interventions but are rarely reported in pediatric surgery. Have RCTs submitted to the British Association of Paediatric Surgeons (BAPS) Annual Congress during the last 5 years been adequately designed and large enough to produce a valid result?
                Abstracts accepted by the Annual BAPS Congress meetings between 1996 and 2000 were examined in collaboration with a senior health services researcher. The quality of the design, methodology, statistical analysis and conclusions, and the adequacy of the sample size were assessed for all identifiable clinical RCTs.
                From 760 accepted abstracts, there were only 9 RCTs (1%) of clinical interventions. In only 4 trials was the relevant primary end-point specified at the outset of the study, and none documented the method of randomization. Only one abstract mentioned blinding with respect to the intervention or outcome measure. Sample sizes were inadequate to detect even large clinical differences. To date, only one of these RCTs has been published in an English-language, peer-reviewed journal.
                Clear guidelines exist for the conduct of RCTs, yet compliance with these standards was rarely documented in abstracts of pediatric surgical RCTs presented at BAPS. Sample sizes were inadequate. RCTs in pediatric surgery are difficult to perform, but the specialty would benefit from well-designed, carefully conducted, multicentre, clinical RCTs to advance evidence-based practice.
                Copyright 2003, Elsevier Science (USA). All rights reserved. As highly active antiretroviral therapy (HAART) becomes increasingly available to African children, it is important to evaluate simple and feasible methods of improving adherence in order to maximize benefits of therapy.
                HIV-1-infected children initiating World Health Organization non-nucleoside reverse transcriptase-inhibitor-containing first-line HAART regimens were randomized to use medication diaries plus counselling, or counselling only (the control arm of the study). The diaries were completed daily by caregivers of children randomized to the diary and counselling arm for nine months. HIV-1 RNA, CD4+ T cell count, and z-scores for weight-for-age, height-for-age and weight-for-height were measured at a baseline and every three to six months. Self-reported adherence was assessed by questionnaires for nine months.
                Ninety HIV-1-infected children initiated HAART, and were followed for a median of 15 months (interquartile range: 2-21). Mean CD4 percentage was 17.2% in the diary arm versus 16.3% in the control arm at six months (p = 0.92), and 17.6% versus 18.9% at 15 months (p = 0.36). Virologic response with HIV-1 RNA of <100 copies/ml at nine months was similar between the two arms (50% for the diary arm and 36% for the control, p = 0.83). The weight-for-age, height-for-age and weight-for-height at three, nine and 15 months after HAART initiation were similar between arms. A trend towards lower self-reported adherence was observed in the diary versus the control arm (85% versus 92%, p = 0.08).
                Medication diaries did not improve clinical and virologic response to HAART over a 15-month period. Children had good adherence and clinical response without additional interventions. This suggests that paediatric HAART with conventional counselling can be a successful approach. Further studies on targeted approaches for non-adherent children will be important. The antimetabolite methotrexate has been shown in placebo-controlled trials to be effective in adults with rheumatoid arthritis. Methotrexate may also be effective in children with resistant juvenile rheumatoid arthritis, but the supporting data are from uncontrolled trials.
                Centers in the United States and the Soviet Union participated in this randomized, controlled, double-blind trial designed to evaluate the effectiveness and safety of orally administered methotrexate. Patients received one of the following treatments each week for six months: 10 mg of methotrexate per square meter of body-surface area (low dose), 5 mg of methotrexate per square meter (very low dose), or placebo. The use of prednisone (less than or equal to 10 mg per day) and two nonsteroidal antiinflammatory drugs was also allowed.
                The 127 children (mean age, 10.1 years) had a mean duration of disease of 5.1 years; 114 qualified for the analysis of efficacy. According to a composite index of several response variables, 63 percent of the children who received low-dose methotrexate improved, as compared with 32 percent of those in the very-low-dose group and 36 percent of those in the placebo group (P = 0.013). As compared with the placebo group, the low-dose group also had significantly larger mean reductions from base line in the number of joints with pain on motion (-11.0 vs. -7.1), the pain-severity score (-19 vs. -11.5), the number of joints with limited motion (-5.4 vs. -0.7), and the erythrocyte sedimentation rate (-19.0 vs. -6 mm per hour). In the methotrexate groups only three children had the drug discontinued because of mild-to-moderate side effects; none had severe toxicity.
                Methotrexate given weekly in low doses is an effective treatment for children with resistant juvenile rheumatoid arthritis, and at least in the short term this regimen is safe. To assess the effectiveness of safety advice and safety equipment in reducing unintentional injuries for families with children aged under 5 years and living in deprived areas.
                Randomised controlled trial.
                47 general practices in Nottingham.
                3428 families with children under 5.
                A standardised safety consultation and provision of free and fitted stair gates, fire guards, smoke alarms, cupboard locks, and window locks.
                Primary outcome measures were whether a child in the family had at least one injury that required medical attendance and rates of attendance in primary and secondary care and of hospital admission for injury over a two year period. Secondary outcome measures included possession of safety equipment and safety practices.
                No significant difference was found in the proportion of families in which a child had a medically attended injury (odds ratio 1.14, 95% confidence interval 0.98 to 1.50) or in the rates of attendance in secondary care (incidence rate ratio 1.02, 0.90 to 1.13) or admission to hospital (1.02, 0.70 to 1.48). However, children in the intervention arm had a significantly higher attendance rate for injuries in primary care (1.37, 1.11 to 1.70, P = 0.003). At both one and two years' follow up, families in the intervention arm were significantly more likely to have a range of safety practices, but absolute differences in the percentages were relatively small.
                The intervention resulted in significant improvements in safety practices for up to two years but did not reduce injuries that necessitated medical attendance. Although equipment was provided and fitted free of charge, the observed changes in safety practices may not have been large enough to affect injury rates. Epistaxis is common in children. Trials show antiseptic cream is as effective as cautery, but it is not known whether either is better than no treatment. We wished to know the efficacy of cream in children with recurrent epistaxis. The design was a single-blind, prospective, randomized controlled trial set in the Otolaryngology clinic in a children's hospital. The participants were 103 children referred by their general practitioner for recurrent epistaxis. Excluded were those with suspected tumours, bleeding disorders or allergies to constituents of the cream. Referral letters were randomized to treatment and no treatment groups. Treatment was antiseptic cream to the nose twice daily for 4 weeks, which was prescribed by the general practitioner before clinic attendance. All children were given an appointment for 8 weeks after randomization. The main outcome measures were the proportion of children in each group with no epistaxis in the 4 weeks preceding clinic review. Complete data were available for 88 (85%) of the children. Of the treatment group, 26/47 (55%) had no epistaxis in the 4 weeks before the clinic appointment. Of the controls, 12/41 (29%) had no epistaxis over the 4 weeks. This is a relative risk reduction of 47% for persistent bleeding (95% CI 9-69%) and an absolute risk reduction of 26% (95% CI 12-40%), giving a number needed to treat of 3.8 (95% CI 2.5-8.5). We conclude that antiseptic cream is an effective treatment for recurrent epistaxis in children. Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy (SLIT) is highly beneficial. Twenty-four children (age 4-16) monosensitized to house dust mite were randomized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design (Marcucci et al., Allergy 2003: 58: 657-62). Thereafter, for 2 yr they all received active treatment. Symptom scores for rhinitis, asthma, and drug usage were daily recorded. Eosinophil cationic protein (ECP) and tryptase in sputum and nasal secretions, serum and nasal mite-specific immunoglobulin E (IgE) were recorded before treatment and at 10-12 months intervals. Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values (p = 0.0043 and 0.0195, respectively) in the third year of active treatment. None of the other inflammatory parameters was increased. In placebo treated patients all these parameters tended to decrease only after switching to active treatment. Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study. In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline. A significant difference was reached in patients treated for 2 yr for rhinitis and asthma (p = 0.0009 and 0.0019, respectively) but not for drug usage and in patients treated for 3 yr for rhinitis, asthma, and drug usage (p = 0.0105, 0.0048, and 0.02, respectively). SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation. These outcomes were followed by a consolidated clinical improvement in the second and third year of treatment. The present randomized controlled trial tested the effectiveness of a behavioral counseling program for reducing children's exposure to environmental tobacco smoke (ETS). Counseling was delivered by clinic staff as part of well-child health care services in a community clinic setting. A total of 150 mothers with children aged 4 years or younger were recruited. Parent-reported and children's urinary cotinine measures of ETS exposure were obtained at baseline, 3 months, 6 months (post-test), and 12 months (follow-up). Saliva samples were obtained from mothers who reported quitting smoking, for objective verification by thiocyanate analysis. After baseline, mothers were randomly assigned to a measures-only control condition or an intervention consisting of seven behavioral counseling sessions over 6 months. Counseling included behavioral contracting, self-monitoring, problem solving, and positive reinforcement. Results indicated acceptable test-retest reliability and validity of measures. Parent-reported measures indicated that, in both groups, children's exposure to their mothers' tobacco smoke in the home and to all tobacco smoke declined steeply from baseline to 6 months post-test, and remained essentially level during follow-up. Mothers' smoking rates followed the same pattern. Children's urinary cotinine concentrations did not show significant change over time in either group. Findings on the fidelity of treatment implementation suggest that the structure and funding of the community clinic health care system and associated staff turnover and training issues resulted in participants receiving a less efficacious intervention than in our past efficacy trials. Implications for future effectiveness trials are discussed. To evaluate Smoke-free Kids, a new home based programme to assist parents who smoke in socializing their children against smoking.
                Two year randomised controlled trial.
                At baseline, 887 adult smokers who had an abstinent child in the third grade (ages 7-8 years); 671 adults and children were retained through the 24 month follow up.
                Programme modules, newsletters, incentives, support calls.
                Anti-smoking socialisation; susceptibility to smoking.
                Of 327 parents randomised to treatment, 210 obtained adequate treatment by using at least three of five core modules. Programme efficacy analyses, which compared these parents with controls (n = 344), showed that exposure to adequate treatment predicted significantly higher levels in nearly all categories of anti-smoking socialisation three months post-intervention. Two years post-baseline, children of parents who reported adequate treatment scored significantly higher than controls on attributes that reduce susceptibility to smoking, and they scored significantly lower than controls on attributes that raise susceptibility to smoking. Programme effectiveness analyses compared all parents randomised to treatment (n = 327) with controls (n = 344). Treatment effects were evident for several socialisation outcomes; however, these effects were smaller and less consistent than those from the efficacy analyses. Similarly, although treated children scored higher than controls on attributes that reduce susceptibility and lower than controls on attributes that raise susceptibility, several of these between-group differences were not significant.
                Given adequate exposure to the Smoke-free Kids programme, significant beneficial effects were observed on anti-smoking socialisation in households where parents smoke cigarettes, and significant beneficial effects were observed on children's susceptibility to smoking after two years. Improving programme acceptance and utilisation is necessary before programme effectiveness can be demonstrated. Debate continues with respect to a "watch and wait" approach versus immediate antibiotic treatment for the initial treatment of acute otitis media. In this double-blind noninferiority trial, we compared clinical improvement rates at 14 days for children (6 months to 5 years of age) with acute otitis media who were randomly assigned to receive amoxicillin or placebo.
                We enrolled healthy children who presented to clinics or the emergency department with a new episode of acute otitis media during the fall and winter months in Ottawa (from December 1999 to the end of March 2002). The children were randomly assigned to receive amoxicillin (60 mg/kg daily) or placebo for 10 days. Telephone follow-up was performed on each of days 1, 2 and 3 and once between day 10 and day 14. The primary outcome was clinical resolution of symptoms, defined as absence of receipt of an antimicrobial (other than the amoxicillin in the treatment group) at any time during the 14-day period. Secondary outcomes were the presence of pain and fever and the activity level in the first 3 days, recurrence rates, and the presence of middle ear effusion at 1 and 3 months.
                According to clinical scoring, 415 of the 512 children who could be evaluated had moderate disease. At 14 days 84.2% of the children receiving placebo and 92.8% of those receiving amoxicillin had clinical resolution of symptoms (absolute difference -8.6%, 95% confidence interval -14.4% to -3.0%). Children who received placebo had more pain and fever in the first 2 days. There were no statistical differences in adverse events between the 2 groups, nor were there any significant differences in recurrence rates or middle ear effusion at 1 and 3 months.
                Our results did not support the hypothesis that placebo was noninferior to amoxicillin (i.e., that the 14-day cure rates among children with clinically diagnosed acute otitis media would not be substantially worse in the placebo group than the treatment group). Nevertheless, delaying treatment was associated with resolution of clinical signs and symptoms in most of the children. Recurrent otitis media is a common problem in young children. Echinacea and osteopathic manipulative treatment have been proposed as preventive measures, but have been inadequately studied. This study was designed to assess the efficacy of Echinacea purpurea and/or osteopathic manipulative treatment (OMT) for prevention of acute otitis media in otitis-prone children.
                A randomized, placebo-controlled, two-by-two factorial trial with 6-month follow-up, conducted 1999 - 2002 in Tucson, Arizona. Patients were aged 12-60 months with recurrent otitis media, defined as three or more separate episodes of acute otitis media within six months, or at least four episodes in one year. Ninety children (44% white non-Hispanic, 39% Hispanic, 57% male) were enrolled, of which 84 had follow-up for at least 3 months. Children were randomly assigned to one of four protocol groups: double placebo, echinacea plus sham OMT, true OMT (including cranial manipulation) plus placebo echinacea, or true echinacea plus OMT. An alcohol extract of Echinacea purpurea roots and seeds (or placebo) was administered for 10 days at the first sign of each common cold. Five OMT visits (or sham treatments) were offered over 3 months.
                No interaction was found between echinacea and OMT. Echinacea was associated with a borderline increased risk of having at least one episode of acute otitis media during 6-month follow-up compared to placebo (65% versus 41%; relative risk, 1.59, 95% CI 1.04, 2.42). OMT did not significantly affect risk compared to sham (44% versus 61%; relative risk, 0.72, 95% CI 0.48, 1.10).
                In otitis-prone young children, treating colds with this form of echinacea does not decrease the risk of acute otitis media, and may in fact increase risk. A regimen of up to five osteopathic manipulative treatments does not significantly decrease the risk of acute otitis media.
                ClinicalTrials.gov Identifier: NCT00010465. Road traffic accidents (RTAs) are the leading health threat to children in Europe, resulting in 355,000 injuries annually. Because children can suffer significant and long-term mental health problems following RTAs, there is considerable interest in the development of early psychological interventions. To date, the research in this field is scarce, and currently no evidence-based recommendations can be made.
                To evaluate the effectiveness of a single-session early psychological intervention, 99 children age 7-16 were randomly assigned to an intervention or control group. The manualised intervention was provided to the child and at least one parent around 10 days after the child's involvement in an RTA. It included reconstruction of the accident using drawings and accident-related toys, and psychoeducation. All of the children were interviewed at 10 days, 2 months and 6 months after the accident. Parents filled in questionnaires. Standardised instruments were used to assess acute stress disorder (ASD), posttraumatic stress disorder (PTSD), depressive symptoms and behavioural problems.
                The children of the two study groups showed no significant differences concerning posttraumatic symptoms and other outcome variables at 2 or at 6 months. Interestingly, analyses showed a significant intervention x age-group effect, indicating that for preadolescent children the intervention was effective in decreasing depressive symptoms and behavioural problems.
                This study is the first to show a beneficial effect of a single-session early psychological intervention after RTA in preadolescent children. Therefore, an age-specific approach in an early stage after RTAs may be a promising way for further research. Younger children can benefit from the intervention evaluated here. However, these results have to be interpreted with caution, because of small subgroup sizes. Future studies are needed to examine specific approaches for children and adolescents. Also, the intervention evaluated here needs to be studied in other groups of traumatised children.
                Clinical Trial Registry: ClinicalTrials.gov: NCT00296842. Although several studies have illustrated the effectiveness of cognitive behavior therapy (CBT) on adult pain patients, there are few randomized controlled trials on children and adolescents. There is particularly a need for studies on pediatric patients who are severely disabled by longstanding pain syndromes. Acceptance and Commitment Therapy, as an extension of traditional CBT, focuses on improving functioning and quality of life by increasing the patient's ability to act effectively in concordance with personal values also in the presence of pain and distress. Following a pilot study, we sought to evaluate the effectiveness of an ACT-oriented intervention based on exposure and acceptance strategies and to compare this with a multidisciplinary treatment approach including amitriptyline (n=32). The ACT condition underwent a relatively brief treatment protocol of approximately 10 weekly sessions. Assessments were made before and immediately after treatment, as well as at 3.5 and 6.5 months follow-up. Prolonged treatment in the MDT group complicated comparisons between groups at follow-up assessments. Results showed substantial and sustained improvements for the ACT group. When follow-up assessments were included, ACT performed significantly better than MDT on perceived functional ability in relation to pain, pain intensity and to pain-related discomfort (intent-to-treat analyses). At post-treatment, significant differences in favor of the ACT condition were also seen in fear of re/injury or kinesiophobia, pain interference and in quality of life. Thus, results from the present study support previous findings and suggest the effectiveness of this ACT-oriented intervention for pediatric longstanding pain syndromes. Numerous trials have demonstrated high efficacy and safety of artemisinin-based combination therapy (ACT) under supervised treatment. In contrast, effectiveness studies comparing different types of ACT applied unsupervised are scarce. The aim of this study was to compare effectiveness, tolerability and acceptance of artesunate plus amodiaquine (ASAQ) against that of artemether-lumefantrine (AL) in Ghanaian children with uncomplicated Plasmodium falciparum malaria.
                A randomized open-label trial was conducted at two district hospitals in the Ashanti region, Ghana, an area of intense malaria transmission. A total of 246 children under five years of age were randomly assigned to either ASAQ (Arsucam) or AL (Coartem). Study participants received their first weight-adjusted dose under supervision. After the parent/guardian was advised of times and mode of administration the respective three-day treatment course was completed unobserved at home. Follow-up visits were performed on days 3, 7, 14 and 28 to evaluate clinical and parasitological outcomes, adverse events, and haematological recovery. Length polymorphisms of variable regions of msp1 and msp2 were determined to differentiate recrudescences from reinfections. Acceptance levels of both treatment regimens were assessed by means of standardized interviews.
                Adequate clinical and parasitological responses after AL and ASAQ treatment were similar (88.3% and 91.7%, respectively). Interestingly, more late clinical failures until day 28 occurred in AL-treated children than in those who received ASAQ (17.5% and 7.3%, respectively; Hazard Ratio 2.41, 95% CI 1.00-5.79, p < 0.05).Haematological recovery and drug tolerability were not found to be significantly different in both study arms. The acceptance of treatment with ASAQ was higher than that with AL (rank-scores 10.6 and 10.3, respectively; p < 0.05).
                Unobserved AL and ASAQ treatment showed high adequate clinical and parasitological responses, though AL was inferior in preventing late clinical failures. To review the efficacy of the ribosomal immunostimulant Ribomunyl in preventing upper and lower respiratory tract infections.
                Review of studies of 3 and 6 months' duration comprising part of the international registration file.
                Data from 2117 patients (1215 children and 902 adults); ribosomal immunostimulant n = 1062, placebo n = 1055.
                Nineteen randomised, double-blind, placebo-controlled clinical trials were performed between 1983 and 1994 in Europe. In children with ear-nose-throat (ENT) infections, 3 months' ribosomal immunostimulant treatment significantly decreased the mean number of recurrences (27-68% reduction), and reduced the duration of infection (28-66% reduction) and antibacterial requirement (29-60% reduction). Ribosomal immunostimulant was similarly effective in children with ENT and bronchopulmonary infections, reducing the mean number of recurrences by 32-61% compared with placebo. In children with otitis media, ribosomal immunostimulant reduced recurrences by 10-53% and also reduced the duration of infection, antibacterial use and local surgery requirement. Results obtained from studies of 6 months' duration confirmed or extended these results. In adult patients with ENT or mixed respiratory infections, ribosomal immunostimulant produced similar reductions to those seen in children for recurrent infections (54-78% reduction), duration of infection (42-79% reduction) and antibacterial use (38% reduction).
                These results clearly demonstrate that ribosomal immunostimulant is effective in preventing and in reducing upper and lower respiratory tract infections in children and adults. The aim of the study was to evaluate the outcome of a participatory community-based prevention program against injuries among the elderly. A population-based quasi-experimental design was used with pre- and post-implementation measurements in an intervention and a control area. The program was based on cross-sectoral participation in detecting and taking action against injuries among the elderly. Change in the relative risk of injury was estimated by the odds ratio. Morbidity in moderately (AIS 2) severe injury in the study area was reduced from 46 per 1000 population years to 25 per 1000 population years (odds ratio 0.55; 95% confidence interval 0.46-0.65), while the minor (AIS 1) injuries increased (odds ratio 1.55; 95% confidence interval 1.21-1.91). The risk of severe or fatal (AIS 3-6) injuries remained constant. In the study area, only a slight decrease in the total morbidity rate was observed (odds ratio 0.87; 95% confidence interval 0.77-0.99). In the control area, there was no evident change in the total morbidity rates. Falls decreased or showed a tendency to decrease in the age groups 65 to 79-y-old in the study area, while they increased in the older age group. The results indicate that no sharp boundaries should be drawn between safety education, physical conditioning, environmental adjustments and secondary prevention measures when planning safety promotion among the elderly. Future studies should address these issues along with the methodological complexity associated with assessment of participatory community-based safety promotion programs. Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness. Randomised controlled trial (RCT) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder. We aimed to test a new theoretically based social communication intervention targeting parental communication in a randomised design against routine care alone.
                The intervention was given in addition to existing care and involved regular monthly therapist contact for 6 months with a further 6 months of 2-monthly consolidation sessions. It aimed to educate parents and train them in adapted communication tailored to their child's individual competencies. Twenty-eight children with autism were randomised between this treatment and routine care alone, stratified for age and baseline severity. Outcome was measured at 12 months from commencement of intervention, using standardised instruments.
                All cases studied met full Autism Diagnostic Interview (ADI) criteria for classical autism. Treatment and controls had similar routine care during the study period and there were no study dropouts after treatment had started. The active treatment group showed significant improvement compared with controls on the primary outcome measure--Autism Diagnostic Observation Schedule (ADOS) total score, particularly in reciprocal social interaction--and on secondary measures of expressive language, communicative initiation and parent-child interaction. Suggestive but non-significant results were found in Vineland Adaptive Behaviour Scales (Communication Sub-domain) and ADOS stereotyped and restricted behaviour domain.
                A Randomised Treatment Trial design of this kind in classical autism is feasible and acceptable to patients. This pilot study suggests significant additional treatment benefits following a targeted (but relatively non-intensive) dyadic social communication treatment, when compared with routine care. The study needs replication on larger and independent samples. It should encourage further RCT designs in this area. Infants infected with HIV-1 perinatally despite single-dose nevirapine progress rapidly. Data on treatment outcome in sub-Saharan African infants exposed to single-dose nevirapine are urgently required. This feasibility study addresses efficacy of infant antiretroviral therapy in this setting.
                HIV-infected infants in Durban, South Africa, received randomized immediate or deferred (when CD4 cell count reached <20%) four-drug antiretroviral therapy (zidovudine/lamivudine/nelfinavir/nevirapine). Genotyping for non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was undertaken pre-antiretroviral therapy. Monthly follow-up to 1-year post-antiretroviral therapy included viral load, CD4 cell count and verbal/measured adherence monitoring.
                All 63 infants were exposed to single-dose nevirapine. Twenty-one out of 51 (39%) infants with baseline genotyping results had NNRTI resistance (most frequently Y181C; 20%). Forty-three infants were randomized to immediate antiretroviral therapy (ART): three withdrew pre-antiretroviral therapy; 36 out of 40 completed 1-year of ART. Twenty infants received deferred ART: 17 reached CD4 cell counts less than 20% (median d99) and 13 out of 17 started antiretroviral therapy in year 1. Verbal and measured adherence was 99% and 95%, respectively. One-year post-ART, 49 out of 49 (100%) infants had a viral load less than 400 copies/ml; 46 out of 49 (94%) had viral load less than 50 copies/ml. Ten infants (20%) required second-line ART due to virological failure or tuberculosis treatment, therefore 39 out of 49 (80%) achieved viral load less than 400 copies/ml by intention-to-treat. Time to viral load less than 50 copies/ml correlated with maternal CD4 cell count (r = -0.42; P = 0.005) and infant pre-ART viral load (r = 0.64; P < 0.001). NNRTI mutations had no significant effect on virological suppression. Infants starting immediate compared with deferred ART had fewer illness episodes (P = 0.003), but no significant difference in virological suppression.
                Excellent adherence and virological suppression are achievable in infants, despite high-frequency NNRTI mutations and rapid disease progression. Infants remain relatively neglected in roll-out programmes and ART provision must be expanded. We enrolled 60 children with recurrent acute otitis media (AOM) in a study of the effectiveness of antimicrobial prophylaxis. All children were entered into the study following an acute episode of infection treated with amoxicillin (AMX) for 10 days. Following therapy, the children were re-examined, and then randomly assigned to receive either trimethoprim-sulfamethoxazole (TMP-SMX), amoxicillin (AMX) or a placebo (PLA). Twenty children were included in each group. Each drug was administered once a day at bedtime, at 1/3 the therapeutic dose, for 3 months. Children were re-evaluated with pneumootoscopy during episodes of acute illness and with pneumootoscopy and impedance tympanometry (TYMP) at monthly intervals. We observed a significantly increased rate of recurrent AOM in children receiving placebo compared with those who received antibiotics (50% vs. 17% P < 0.005). Both prophylactic antibiotics were equally effective in preventing recurrent AOM (recurrence rate 20% TMP-SMX, 15% AMX). We also observed that recurrences in children receiving placebo occurred earlier in the study period than in those receiving antibiotics. These results suggest that antimicrobial prophylaxis in children with recurrent acute otitis media is effective in reducing subsequent disease. The similar efficacy of both antibiotics tested suggests that the less expensive agent should be used. Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by approximately 50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab.
                This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged <or=6 months at enrollment or children aged <or=24 months with chronic lung disease of prematurity who received 15 mg/kg palivizumab or motavizumab monthly. Secondary end points included outpatient medically attended lower respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and motavizumab serum concentrations.
                Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with palivizumab recipients, achieving noninferiority. Motavizumab was superior to palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events.
                Children receiving prophylaxis with motavizumab or palivizumab had low rates of RSV hospitalization; motavizumab recipients experienced 50% fewer RSV MALRIs than palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk. Accidents are an important cause of childhood injury. It is hypothesized that safety education programs can reduce accidents in primary school-aged children. This study aimed to determine whether child and parent safety education programs can decrease the incidence of accidental injury in children when compared with controls.
                The study population (aged 7-13 years) were recruited from four local primary schools, and randomly assigned into an Intervention or a Control group. The Intervention group received child and parent safety education and was taught injury prevention strategies. The Control group received no injury prevention education or intervention. The incidence of accidental injury was compared between the two groups.
                In the first year after intervention the incidence of accidental injury was 262 cases in the Intervention group (8.26%) and 234 cases (8.67%) in the Control group (P > 0.05). In the second year after intervention, however, the incidence of accidental injury was significantly less in the Intervention group (211 cases, 6.54%) compared with the Control group (229 cases, 8.63%) (P < 0.01).
                Injury prevention strategies and child and parent safety education can reduce risks of accidental injury in children. One hundred and twenty-one children were studied in this prospective, randomized double-blind, placebo-controlled comparison of the effectiveness of anticholinergic prophylaxis for the prevention of emetic symptoms following strabismus surgery. The children were allocated to three groups, to receive placebo (n = 40), glycopyrrolate (n = 40) or atropine (n = 41). The incidence of intraoperative oculocardiac reflex (OCR) and of postoperative emetic symptoms for 24 h was recorded. The incidence of OCR was 55% in the placebo group compared with 5% and 2% in the glycopyrrolate and atropine groups respectively (P < 0.05). Thirty percent (12/40) of patients in the placebo group, 25% (10/40) in the glycopyrrolate group, and 22% (9/41) in the atropine group experienced nausea and/or vomiting (difference not significant). It is concluded that prophylactic administration of anticholinergic agents during strabismus surgery in children despite being effective against the occurrence of the oculocardiac reflex, does not reduce the incidence of emetic symptoms. To compare short- and long-term effectiveness of three additive treatment protocols in children experiencing chronic encopresis.
                Children, 6 to 15 years of age, who experienced at least weekly fecal soiling for 6 months or longer were eligible for the study. Children were randomly assigned to a group that received intensive medical therapy (IMT), a group that received intensive medical therapy plus a behavior management program called enhanced toilet training (ETT), or a group that received intensive medical therapy with enhanced toilet training and external anal sphincter electromyographic biofeedback (BF). Data concerning toileting habits were collected for 14 consecutive days before an initial visit, and at 3, 6, and 12 months after initiation of therapy. All data were collected using a computerized voice-mail system that telephoned the families each day. At 12 months, children were classified as significantly improved (reduction in soiling, P < 0.001) or cured (<one fecal accident in 2 weeks).
                Eighty-seven children participated in the study, 72 boys and 15 girls. Mean age at enrollment was 8.6 +/- 2.0 years, and mean duration of symptoms was 58.2 +/- 38.5 months. At 12 months, the cure rates for the IMM, ETT, and BF groups were 36, 48, and 39, respectively (not significant). The improvement rates for these three groups were 45, 78, and 54, respectively (P < 0.05). These results were very stable over time (r > 0.90, P < 0.001 in each case). Response to treatment during the first 2 weeks of therapy was highly predictive of outcome at 3, 6, and 12 months (P < 0.0001). Children in the ETT group used less laxative medication (P < 0.04) and required fewer treatment contacts (P = 0.08) than children in the IMM group. All three treatments resulted in significant increases in daily bowel movements passed in the toilet and self-initiated toileting, and resulted in decreases in average daily soiling at 3, 6, and 12 months (P < 0.05).
                Enhanced toilet training is somewhat more effective in treating childhood encopresis than either intensive medical therapy or anal sphincter biofeedback therapy. Although similar total cure rates at 1 year can be expected with these three forms of therapy, enhanced toilet training results in statistically significant decreases in the daily frequency of soiling for the greatest number of children. To compare the effect of the prone position (PP) vs supine position (SP) on oxygenation in children with acute respiratory failure (ARF).
                Prospective, randomized controlled trial.
                A 36-bed pediatric critical-care unit in a tertiary-care, university-based children's hospital.
                Ten children (mean [SD] age, 5 +/- 3.6 years) with ARF with a baseline oxygenation index (OI) of 22 +/- 8.5.
                Following a period of stabilization in the SP, baseline data were collected and patients were randomized to one of two groups in a two-crossover study design: group 1, supine/prone sequence; group 2, prone/supine sequence. Each position was maintained for 12 h. Lung mechanics and acute response to inhaled nitric oxide were examined in each position.
                OI was significantly better in the PP compared to the SP over the 12-h period (analysis of variance, p = 0.0016). When patients were prone, a significant improvement in OI was detected (7.9 +/- 5.3; p = 0.002); this improvement occurred early (within 2 h in 9 of 10 patients) and was sustained over the 12-h study period. Static respiratory system compliance and resistance were not significantly affected by the position change. Inhaled nitric oxide had no effect on oxygenation in either position. Urine output increased while prone, resulting in a significantly improved fluid balance (+ 6.6 +/- 15.2 mL/kg/12 h in PP vs + 18.9 +/- 13.6 mL/kg/12 h in SP; p = 0.041). No serious adverse effects were detected in the PP.
                In children with ARF, oxygenation is significantly superior in the PP than in the SP. This improvement occurs early, remains sustained for a 12-h period, and is independent of changes in lung mechanics. Iron deficiency anemia and recurrent infections are common among children of low socioeconomic status.
                The objective was to evaluate the effects of iron supplementation on iron status and morbidity in children with or without infection.
                Children aged 5-10 y were recruited for a randomized, controlled, double-blind study from outpatients attending the Children's Hospital, Colombo, Sri Lanka. Clinical, inflammatory, nutritional, and iron statuses were determined at baseline and after the intervention. Children with a history of recurrent upper respiratory tract infections (URTIs) and with laboratory and clinical evidence of a current URTI constituted the infection group (n = 179), and children without infection constituted the control group (n = 184). Subjects in both groups were supplemented with ferrous sulfate (60 mg Fe) or placebo once daily for 8 wk. Morbidity from URTIs, the number of gastrointestinal infections, and compliance were recorded every 2 wk.
                The overall prevalence of anemia was 52.6%. Iron supplementation significantly improved iron status by increasing hemoglobin (P < 0.001) and serum ferritin (P < 0.001) concentrations from baseline values in the children with or without infection. There was no significant improvement in iron status in the children who received placebo. In both the infection group and the control group, the mean number of URTI episodes and the total number of days sick with an URTI during the period of intervention were significantly lower (P < 0.005 and P < 0.001, respectively) in the children who received iron supplements than in those who received placebo.
                Iron supplementation significantly improves iron status and reduces morbidity from URTIs in children with or without infection. The objective was to study the generalizability of trial results by comparing randomized patients to eligible but nonrandomized patients who received the same management. Implementation of trial results is only justifiable when the results can be generalized to the total domain population. The design was a multicentre randomized controlled trial on the effect of early screening and treatment with ventilation tubes on infants with otitis media with effusion. Randomized (n = 187) and nonrandomized eligible patients (n = 133) were followed up. The study population comprised children who were detected by auditory screening at the age of 9-12 months and who were subsequently diagnosed with persistent bilateral otitis media with effusion for 4-6 months. A significant difference was found in the distribution of some prognostic factors: more randomized children had older siblings, did not attend day care and had mothers with a lower educational level than the nonrandomized children. These factors, however, did not modify the outcome. No differences were found in mean hearing levels between the randomized and nonrandomized children: in both the randomized and nonrandomized children ventilation tubes improved the hearing level, especially after 6 months. However, in the long term (12 months), the hearing levels were equal again. The results of the randomized and nonrandomized patients were comparable. The results of this trial appear to be generalizable to the total domain population. The procedure of following up both randomized and nonrandomized patients is recommended when there is concern about selective participation and reduced generalizability. Measure efficacy of eicosapentaenoic acid (EPA) in children with attention deficit hyperactivity disorder (ADHD).
                Randomized controlled trial (RCT) of 0.5 g EPA or placebo (15 weeks) in 92 children (7-12 years) with ADHD. Efficacy measure was Conners' Parent/Teacher Rating Scales (CPRS/CTRS). Fatty acids were analysed in serum phospholipids and red blood cell membranes (RBC) at baseline and endpoint with gas chromatography.
                EPA improved CTRS inattention/cognitive subscale (p = 0.04), but not Conners' total score. In oppositional children (n = 48), CTRS total score improved ≥25% in 48% of the children receiving EPA vs. 9% for placebo [effect size (ES) 0.63, p = 0.01]. In less hyperactive/impulsive children (n = 44), ≥25% improvement was seen in 36% vs. 18% (ES 0.41, n.s.), and with both these types of symptoms 8/13 with EPA vs. 1/9 for placebo improved ≥25% (p = 0.03). Children responding to treatment had lower EPA concentrations (p = 0.02), higher AA/EPA (p = 0.005) and higher AA/DHA ratios (p = 0.03) in serum at baseline. Similarly, AA/EPA (p = 0.01), AA/DHA (p = 0.038) and total omega-6/omega-3 ratios (p = 0.028) were higher in RBC, probably because of higher AA (p = 0.011).
                Two ADHD subgroups (oppositional and less hyperactive/impulsive children) improved after 15-week EPA treatment. Increasing EPA and decreasing omega-6 fatty acid concentrations in phospholipids were related to clinical improvement.
                © 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.
This review shows that IS reduce the incidence of ARTIs by 40% on average in susceptible children. Studies in healthy children are not available. Although the safety profile in the studies was good, some IS may be unsafe. ARTI-susceptible children may benefit from IS treatment. Further high-quality trials are needed and we encourage national health authorities to conduct large, multicentre, double-blind, placebo-controlled RCTs on the role of IS in preventing ARTIs in children.