槐杞黄颗粒辅助治疗儿童哮喘的随机对照多中心临床研究

目的：比较全球哮喘防治创议(The Global Initiative for Asthma,GINA)方案与 GINA 方案联合口服槐杞黄颗粒治疗哮喘患儿的临床疗效和安全性。方法采用随机、多中心平行对照临床试验方法。共收集1128例哮喘患儿,随机分为两组。观察组患儿采用 GINA 方案联合口服槐杞黄颗粒治疗,GINA 方案治疗组患儿按 GINA 方案治疗。分别于用药后的第1个月、3个月、6个月进行临床评价及 C-ACT 评分。临床评价指标为上呼吸道感染次数、支气管炎和肺炎发生次数、喘息发作次数、应用急救药次数、因喘息住院次数。比较两组的药物不良反应发生情况。结果用药后的第1个月、3个月、6个月,观察组较 GINA方案治疗组上呼吸道感染发生次数、支气管炎和肺炎发生次数及喘息发作次数均明显减少(P ＜0.05),C-ACT 评分均明显升高(P ＜0.05)。与药物相关的不良反应16例(轻度腹泻),其中观察组7例(1.15％), GINA 方案治疗组9例(1.73％),组间差异无统计学意义(P ＞0.05)。结论 GINA 方案联合口服槐杞黄颗粒治疗哮喘患儿,能明显减少其呼吸道感染及喘息发作的次数,可显著改善临床疗效,更好地达到哮喘控制的目标,且安全性好。     

Bronchial asthma and the short-term quality of life: follow-up study of childhood bronchial asthma in Hungary

The aim of our study is to determine and describe the current short-term health-related quality of life of recent adult patients who had bronchial asthma in childhood. Our objective was to investigate if symptom control in bronchial asthma could be in conflict with general quality of life. We made a follow-up study of 152 patients (105 male, 47 female) over the age of 30 (31-55 yr) who were allergic asthmatics in childhood. The patients' current symptoms and short-term quality of life were evaluated by a questionnaire. The patients developed asthmatic symptoms by age 4.4 (0.5-13) years on the average. Now 60% (91 persons) have no symptoms. They became symptom-free between 3 and 41 yr of age (mean = 14.2 +/- 8.2). Amongst the currently asthmatic patients (58 patients, 38%), 34 patients (22%) belong to the Global Initiative for Asthma (GINA) I, nine patients (6%) to the GINA II, five patients (3.3%) to the GINA III, and five patients (3.3%) to the GINA IV classification. Five patients (3.3%) did not specify their own symptoms. Three persons (2%) did not answer this question. Symptomatic patients reached 5.28 on the Juniper Asthma Quality of Life Questionnaire, while their asymptomatic peers scored statistically higher with 6.8 on the scale. Amongst the symptomatic patients, the most limited areas were: 'bothered by heavy breathing', 'had to avoid a situation or environment because of dust', 'experienced difficulty breathing out as a result of asthma', 'experienced asthma symptoms as a result of the weather or air pollution outside'. They were least 'concerned about medication', 'frustrated as a result of their asthma', they were least limited in 'going outside because of the weather or air pollution'. The most problematic areas for the symptom-free patients were 'had to avoid a situation or environment because of dust', 'had to avoid a situation or environment because of cigarette smoke', 'experiencing asthma symptoms as a result of being exposed to dust and the 'need to clear throat'. It seems that having no asthma symptoms is not equal to having a good quality of life for asthmatic patients. Moreover, symptom control in bronchial asthma is in conflict with quality of life, as many prophylactic measures to prevent exposure to allergens also restrict the patient's life.     

Azithromycin for Indigenous children with bronchiectasis: study protocol for a multi-centre randomized controlled trial

ABSTRACT: BACKGROUND: The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis.Methods/designWe are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12--24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV1; for children [GREATER-THAN OR EQUAL TO]6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4 months for up to 24 months from study entry are recorded on standardised forms. DISCUSSION: Should this trial demonstrate that azithromycin is efficacious in reducing the number of pulmonary exacerbations, it will provide a much-needed rationale for the use of long-term antibiotics in the medical management of bronchiectasis in Indigenous children.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12610000383066.     

Homeopathy for childhood diarrhea: combined results and metaanalysis from three randomized,controlled clinical trials

BACKGROUND: Previous studies have shown a positive treatment effect of individualized homeopathic treatment for acute childhood diarrhea, but sample sizes were small and results were just at or near the level of statistical significance. Because all three studies followed the same basic study design, the combined data from these three studies were analyzed to obtain greater statistical power. METHODS: Three double blind clinical trials of diarrhea in 242 children ages 6 months to 5 years were analyzed as 1 group. Children were randomized to receive either an individualized homeopathic medicine or placebo to be taken as a single dose after each unformed stool for 5 days. Parents recorded daily stools on diary cards, and health workers made home visits daily to monitor children. The duration of diarrhea was defined as the time until there were less than 3 unformed stools per day for 2 consecutive days. A metaanalysis of the effect-size difference of the three studies was also conducted. RESULTS: Combined analysis shows a duration of diarrhea of 3.3 days in the homeopathy group compared with 4.1 in the placebo group (P = 0.008). The metaanalysis shows a consistent effect-size difference of approximately 0.66 day (P = 0.008). CONCLUSIONS: The results from these studies confirm that individualized homeopathic treatment decreases the duration of acute childhood diarrhea and suggest that larger sample sizes be used in future homeopathic research to ensure adequate statistical power. Homeopathy should be considered for use as an adjunct to oral rehydration for this illness.     

The impact of childhood acute rotavirus gastroenteritis on the parents' quality of life: prospective observational study in European primary care medical practices

ABSTRACT: BACKGROUND: Rotavirus (RV) is the commonest cause of acute gastroenteritis in infants and young children worldwide. A Quality of Life study was conducted in primary care in three European countries as part of a larger epidemiological study (SPRIK) to investigate the impact of paediatric rotavirus gastroenteritis (RVGE) on affected children and their parents. METHODS: A self-administered questionnaire was linguistically validated in Spanish, Italian and Polish. The questionnaire was included in an observational multicentre prospective study of 302 children aged <5 years presenting to a general practitioner or paediatrician for RVGE at centres in Spain, Italy or Poland. RV infection was confirmed by polymerase chain reaction (PCR) testing (n = 264). The questionnaire was validated and used to assess the emotional impact of paediatric RVGE on the parents. RESULTS: Questionnaire responses showed that acute RVGE in a child adversely affects the parents' daily life as well as the child. Parents of children with RVGE experience worry, distress and impact on their daily activities. RVGE of greater clinical severity (assessed by the Vesikari scale) was associated with higher parental worries due to symptoms and greater changes in the child's behaviour, and a trend to higher impact on parents' daily activities and higher parental distress, together with a higher score on the symptom severity scale of the questionnaire. CONCLUSIONS: Parents of a child with acute RVGE presenting to primary care experience worry, distress and disruptions to daily life as a result of the child's illness. Prevention of this disease through prophylactic vaccination will improve the daily lives of parents and children.     

The prevalence of ibuprofen-sensitive asthma in children: a randomized controlled bronchoprovocation challenge study

OBJECTIVE: To determine the prevalence of ibuprofen-sensitive asthma in school-aged children with mild or moderate persistent asthma. STUDY DESIGN: A randomized, double-blind, placebo-controlled, crossover bronchoprovocation challenge study in children 6 to 18 years of age with mild or moderate persistent asthma. Patients received a single dose of ibuprofen or placebo, per randomization, and then returned 2 to 7 days later to repeat the procedures after taking that study drug not received at the first visit. At each visit, patients performed spirometry before and (1/2), 1, 2, and 4 hours after administration of study drug. We defined bronchospasm as a > or =20% decrease from baseline in the forced expired volume in the first second (FEV1) and ibuprofen sensitivity as bronchospasm following administration of ibuprofen but not placebo. RESULTS: Of the 127 patients screened, 100 (mean age, 11 years) completed the study. Two patients met criteria for ibuprofen-sensitive asthma, resulting in a prevalence of 2% (95% CI: 0.2%-7%). Neither patient was known to have had any exposure to ibuprofen before the study. CONCLUSION: The prevalence of ibuprofen-sensitive asthma was low but non-zero in this group of children with mild or moderate asthma. The possibility of ibuprofen-induced bronchospasm should be considered before administering ibuprofen to children with asthma.     

A randomized controlled study on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants

BACKGROUND: The prevalence of asthma has increased in developed countries in the past 2 decades. The effectiveness of intervention measures on the primary prevention of asthma has not been well studied. OBJECTIVE: To assess the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants (in this study, infants are defined as persons from birth to the age of 1 year). DESIGN: Prospective, prenatally randomized, controlled study with follow-up through the age of 1 year. SETTING: University hospital-based settings at 2 Canadian centers: Vancouver, British Columbia, and Winnipeg, Manitoba. PARTICIPANTS: A total of 545 high-risk infants (at least 1 first-degree relative with asthma or 2 first-degree relatives with other IgE-mediated allergic diseases) identified before birth. INTERVENTIONS: Avoidance of house dust mite and pet allergens and environmental tobacco smoke, encouragement of breastfeeding, and supplementation with a partially hydrolyzed formula. MAIN OUTCOME MEASURES: Probable or possible asthma, rhinitis without apparent colds, and a prick skin test result positive for common inhalant allergens. RESULTS: Thirty-eight (15.1%) of the 251 infants available for assessment in the intervention group and 49 (20.2%) of the 242 infants available for assessment in the control group fulfilled the criteria for possible or probable asthma (adjusted relative risk, 0.66; 90% confidence interval, 0.44-0.98). Also, 16.7% of the infants in the intervention group and 27.3% of the infants in the control group developed rhinitis without colds (adjusted relative risk, 0.51; 90% confidence interval, 0.35-0.74). The incidence of positive skin test results to 1 or more inhalant allergens was similar in both groups (4.4% in the intervention group and 4.6% in the control group). CONCLUSIONS: Our multifaceted intervention program resulted in a modest but significant (P= .04) reduction in the risk of possible or probable asthma and rhinitis without apparent colds at the age of 12 months in high-risk infants. In the absence of a validated definition of asthma at the age of 12 months, follow-up studies are needed to determine the effectiveness of the intervention program in the primary prevention of asthma in high-risk infants.     

福松治疗儿童便秘的多中心 随机对照临床研究

目的：儿童便秘的药物治疗至今尚未形成方案，该研究拟通过观察福松（聚乙二醇4000）治疗8岁以上儿童便秘的疗效及安全性，为儿科临床医师提供儿童便秘治疗的药物选择依据。方法：采用多中心、随机、开放、阳性药物（乳果糖）对照方法研究，在国内7家医院按入选标准纳入患儿216例，福松组105例（男43，女62，年龄11.29±2.80岁），乳果糖组111例（男47，女64，年龄11.20±2.75岁）。设福松组（口服福松）及乳果糖组（口服乳果糖）分别按20 g/d及15 mL/d口服，疗程2周。观察主要疗效指标（每周排便次数、每周主要大便性状、大便性状正常率）、次要疗效指标（临床完全缓解率、腹痛情况）及安全性评价（不良事件、实验室检查、体格检查）。结果：①福松组及乳果糖组服药第1、2周后每周排便次数分别增加4次、5次（中位数）和3次、4次，差异有统计学意义。②两组患儿治疗后大便性状均有明显改善，1周后大便性状评分分别为3.41±1.11及3.64±1.33；2周后为4.26±0.89及3.63±1.33，差异有统计学意义。③两组临床完全缓解率分别为第1周70％及40％，第2周为72％及41％；在123例治疗前伴有腹痛患儿中，治疗14 d时福松组75％腹痛消失，乳果糖组为57％，差异有统计学意义。④两组患儿均未发生严重不良事件，实验室及体格检查均未发现异常。结论：福松治疗8岁以上儿童便秘安全有效。［中国当代儿科杂志，2007，9（5）：429-432］     

模拟随机对照试验——一种新的用于疗效比较研究的统计分析方法

目的 本研究旨在通过探索处理混杂因素的手段,创造一种新的用于观察性数据疗效比较研究的统计分析方法。方法 本方法基于以下原理：针对诊断为同种疾病接受不同治疗的一组患者,采用反复多次模拟随机化分组并根据RCT的统计分析策略进行疗效比较,以拒绝H0的试验频率和不拒绝H0的试验频率之比（odds值）及其95%CI作为判断不同治疗方法间疗效差异的依据。采用计算机模拟的方法获得统计量odds值的分布。对包含结局变量和混杂因素变量的模拟数据库进行随机化分组,对根据符合方案集分析(PP)策略保留下来的样本进行结局变量比较。重复100次随机化分组,并对每次随机化分组后结局变量进行比较,同时也对混杂因素变量的组间均衡性进行分析。计算100次结局变量比较分析结果中拒绝H0与不拒绝H0的比值,即odds值,重复100次odds值的计算过程得到odds值的点估计值及其95%CI。根据样本量（n1=n2=50,100,500和1 000）、组间差异的把握度和效应量产生多个模拟数据库,观察分析得到的odds值及其95%CI的一致性和稳定性。同时验证混杂因素在根据PP策略保留下来的样本的组间均衡性。结果 ①对不同样本量下疗效有差异数据库分析得到的odds值均>1,odds值及其95%CI均随把握度的增加呈上升趋势;②对不同样本量下疗效无差异数据库分析得到的odds值均<1,odds值及其95%CI均随把握度的增加呈下降趋势,二者变化均呈现良好的线性关系;③同时验证样本量相等和不相等的情况下,混杂因素组间均衡的概率均>95%。结论 将本文发明的方法命名为模拟随机对照试验方法,简称sRCT。运用sRCT对模拟数据库分析得到结果的一致性和稳定性高,实现了在均衡混杂因素的基础上,创建了一种用于观察性数据疗效比较研究的新方法。     

Computerised paediatric asthma quality of life questionnaires in routine care

Background

Asthma quality of life questionnaires are not readily incorporated into clinical care. We therefore computerised the Paediatric Asthma Quality of Life Questionnaire (standardised) (PAQLQ(S)) and the Paediatric Asthma Caregivers Quality of Life Questionnaire (PACQLQ), with a colour‐coded printed graphical report.

Objectives

To (a) assess the feasibility of the electronic questionnaires in clinical care and (b) compare the child''s PAQLQ scores with the parent''s score, physician''s clinical score and spirometry.

Methods

Children with asthma were given a clinical severity score of 1–4 (increasing severity) and then completed the PAQLQ(S) electronically (scores 1–7 for increasing quality of life in emotional, symptoms and activity limitation domains) followed by spirometry and physician review. Parents completed the PACQLQ. Inclusion criteria required fluent Hebrew and reliable performance of spirometry. Children with additional chronic diseases were excluded.

Results

147 children with asthma aged 7–17 years completed PAQLQs and 115 accompanying parents completed PACQLQs, taking 8.3 (4.3–15) and 4.4 (1.5–12.7) min, respectively (mean (range)). Graphical reports enabled physicians to address quality of life during even brief visits. Children''s (PAQLQ) and parents'' (PACQLQ) total scores correlated (r = 0.61, p<0.001), although the children''s median emotional score of 6.3 was higher than their parents'' 5.7 (p<0.001), whereas median activity limitation score was lower than their parents'': 5.0 and 6.8, respectively (p<0.001). No correlation was found with physician''s clinical score or spirometry.

Conclusions

Electronic PAQLQs are easy to use, providing additional insight to spirometry and physician''s assessment, in routine asthma care. Future studies must assess impact on asthma management.     

Educational intervention by computer in childhood asthma: a randomized clinical trial testing the use of a new teaching intervention in childhood asthma

To affect asthma-related knowledge, behavior, and morbidity, researchers tested a new educational intervention for children with asthma: an asthma-specific computer game called Asthma Command, which was specifically designed for this study. Sixty-five children with moderately severe asthma were randomly assigned to one of two groups, and 54 completed the study. Both groups were seen approximately six times during the 1 year of the study. Control subjects (n = 29) played routine computer games. Experimental subjects (n = 25) played Asthma Command. Compared with children in the control group, experimental subjects showed improvement in knowledge about asthma (P less than .001), behavior related to the management of asthma (P less than .008), and a trend toward the reduction of acute visits due to asthma (P less than .13). Children in the experimental group also scored higher on the assessment of behaviors related to the management of asthma that were specifically addressed by the intervention provided by Asthma Command (P less than .01). Differences between the control and experimental groups showed a greater improvement in the experimental group in 21 (84%) of the 25 outcome variables in the study (P = .004, Sign test). The study indicates that an asthma-specific computer game can significantly affect knowledge and behavior and may potentially affect morbidity in childhood asthma.     

Computerised paediatric asthma quality of life questionnaires in routine care.

BACKGROUND: Asthma quality of life questionnaires are not readily incorporated into clinical care. We therefore computerised the Paediatric Asthma Quality of Life Questionnaire (standardised) (PAQLQ(S)) and the Paediatric Asthma Caregivers Quality of Life Questionnaire (PACQLQ), with a colour-coded printed graphical report. OBJECTIVES: To (a) assess the feasibility of the electronic questionnaires in clinical care and (b) compare the child's PAQLQ scores with the parent's score, physician's clinical score and spirometry. METHODS: Children with asthma were given a clinical severity score of 1-4 (increasing severity) and then completed the PAQLQ(S) electronically (scores 1-7 for increasing quality of life in emotional, symptoms and activity limitation domains) followed by spirometry and physician review. Parents completed the PACQLQ. Inclusion criteria required fluent Hebrew and reliable performance of spirometry. Children with additional chronic diseases were excluded. RESULTS: 147 children with asthma aged 7-17 years completed PAQLQs and 115 accompanying parents completed PACQLQs, taking 8.3 (4.3-15) and 4.4 (1.5-12.7) min, respectively (mean (range)). Graphical reports enabled physicians to address quality of life during even brief visits. Children's (PAQLQ) and parents' (PACQLQ) total scores correlated (r = 0.61, p<0.001), although the children's median emotional score of 6.3 was higher than their parents' 5.7 (p<0.001), whereas median activity limitation score was lower than their parents': 5.0 and 6.8, respectively (p<0.001). No correlation was found with physician's clinical score or spirometry. CONCLUSIONS: Electronic PAQLQs are easy to use, providing additional insight to spirometry and physician's assessment, in routine asthma care. Future studies must assess impact on asthma management.