How to analyze an observational study

This paper outlines the common statistical methods used to analyze four types of observational study: ecological studies, cross-sectional studies, case–control studies and cohort studies. Three statistical methods are considered in detail: correlation coefficients, t-tests for the difference between two means from independent samples and odds ratios. For each method, the need for the same four key outputs is highlighted: the measure of effect, its precision (95% confidence interval), its statistical significance (p-value) and its clinical significance (comparison to the minimum important difference). Where possible, this paper explains the derivation of measures of effect and statistical significance to help readers understand where the numbers come from. The paper also highlights other important aspects of analyzing the quantitative data collected in an observational study, potential biases to consider, and good practice in reporting. Examples from relevant pediatric studies are used where appropriate.     

Analysis of factors that influence body mass index from ages 3 to 6 years: A study based on the Toyama cohort study

BACKGROUND: The aim of the present study was to elucidate both environmental and behavioral factors that influence body mass index (BMI, kg/m2) among Japanese children from ages 3-6. METHODS: In 1992 (at age 3) and 1995 (at age 6), 8170 6-year-old children (4176 boys and 3994 girls) were surveyed using a questionnaire on both body build (height and weight) and lifestyle. The correlation between BMI for 3-year-olds and for 6-year-olds were analyzed. From the temporal changes of body build between age 3 and 6 years, we categorized children into four groups: group 1, normal at both age 3 years and 6 years (normal/normal); group 2, overweight at age 3 years and normal at age 6 years (overweight/normal); group 3, normal at age 3 years and overweight at age 6 years (normal/overweight); and group 4, overweight at both age 3 years and 6 years (overweight/overweight). The authors compared the four groups with each other according to sex, concerning frequencies of children who matched the categories of environmental and behavioral factors. Each factor was tested using the chi2 test. Overweight children were defined as those whose BMI value was age-sex specific in the 90th percentile or more. RESULTS: A significant correlation was found between body builds for children aged 3 and 6 years in both genders (boys, r = 0.559, P < 0.01; girls, r = 0.584, P < 0.01). Significant factors associated with overweight children were diet (eating rice, green tea, eggs, meat, but less breads and juice), rapid eating, short sleep duration, early bedtime, long periods of television viewing, avoidance of physical activity, and frequent bowel movement. DISCUSSION: Temporal changes in BMI from age 3 years to 6 years are significantly associated with both environmental and behavioral factors at age 6 years. The results of this study may be useful for health promotion programs designed to prevent obesity during the early stages of childhood.     

Prediction of academic and behavioural limitations in school-age survivors of bacterial meningitis

AIM: To develop a prediction rule to identify postmeningitic children at high risk of academic and behavioural limitations. METHODS: 182 children (mean age 10 y; range 5-14) were selected from a cohort of 674 school-age survivors of bacterial meningitis. These children had neither meningitis with "complex onset", nor prior cognitive or behavioural problems, nor severe disease sequelae. On average, 7 y after the meningitis, they were evaluated using an "Academic Achievement Test", and their parents filled in the "Child Behaviour Checklist". By reviewing the medical records, potential risk factors for academic and/or behavioural limitations were collected. Independent predictors were identified using multivariate logistic regression analysis, leading to the formulation of a prediction rule. RESULTS: The cumulative incidence of academic and/or behavioural limitations among children who survived bacterial meningitis without severe disease sequelae was 32%. The prediction rule was based on nine independent risk factors: gender, birthweight, educational level of the father, S. pneumoniae, cerebrospinal fluid leukocyte count, delay between admission and start of antibiotics, dexamethasone use, seizures treated with anticonvulsive therapy, and prolonged fever. When 10 was taken as a cut-off point for the risk score computed using this rule, 76% of the children with limitations could be identified, while 38% of the children in the cohort were selected as at risk for these limitations. CONCLUSION: With a prediction rule based on nine risk factors, postmeningitic children at high risk of developing academic and/or behavioural limitations could be identified. Additional research is required to further validate this prediction rule. In the future, a careful follow-up of high risk children may enhance early detection and treatment of these limitations.     

Nerve conduction in children suffering Insulin Dependent Diabetes Mellitus

Objective: To determine the incidence of peripheral neuropathy in children suffering Insulin Dependent Diabetes Mellitus (IDDM) as well as to determine the relationship between other criteria of the disease and neuropathy.Methods : 40 children (17 males, mean age 11.9 years) suffering IDDM and receiving insulin therapy involving two injections a day and 30 healthy children (17 males, mean age 11.7 years) were included in the study. They were inquired about their demographical characteristics as well as the presence of neurological symptoms. Their detailed neurological examinations were conducted. Their glycemic control values (Hb A¹C) were recorded, and their nerve conduction studies were performed from right upper and lower extremities.Results : All nerve conduction values of children with IDDM were found to be significantly lower (p <0.0001) as compared to the control group. 60% of diabetic children (n=24) were found to suffer peripheral neuropathy. Statistically significant relationships were found between the glycemic control values and the peroneal, sural, tibial, ulnar and median nerve conduction velocities, and also between the duration of disease and the peroneal, sural, tibial and median nerve conduction velocities.Conclusion : The peripheral neuropathy is rather a frequently observed complication in diabetic children. The duration of disease and impaired glycemic control play an important role in the development of neuropathy. The introduction of new methods designed to ensure better glycemic control will reduce the incidence of the complication.     

Historical control data on reproductive abilities and incidences of spontaneous fetal malformations in Wistar Hannover GALAS rats

ABSTRACT  Wistar Hannover rats, which have recently been introduced into Japan, are expected to be used in reproductive and developmental toxicity studies, yet the accumulation of background data is insufficient. This paper describes our historical data on the reproductive ability of this strain of rat Three lots of sexually matured females (40 each) were received from CLEA JAPAN, Inc. with males of the same strain (30 or 36 each) and mated. A total of 47 dams were killed on gestation day 20 to examine their fetuses. The remaining 71 pregnant females were allowed to deliver spontaneously and observed for common reproductive parameters. The mating and fertility indices of females were both 99.2%. Overall mean numbers of implants and live fetuses at cesarean sectioning were 12.5 and 11.5, respectively. Fetal resorptions and deaths occurred at an incidence of 8.6%. Morphological examinations of fetuses revealed low incidences of spontaneous malformations (each one case of double aortic arch and absent cervical vertebral arch) and a variety of common variations. The followings are overall means of major reproductive parameters obtained from females with live birth: no. of implants, 12.5; no. of pups delivered, 11.8; viability index of pups at birth, 99.8%; and days of age at sexual maturation (vaginal opening and preputial separation), 30.3 and 42.8, respectively. Our present observations confirmed a minimal deviation among 3 lots of animals in terms of reproductive abilities. These results suggest that this strain of rat can be used in reproductive and developmental toxicity studies, although the sensitivity to toxicants remains to be elucidated.     

An anthropometric study of body size in Down syndrome

Thirty anthropometric measurements were recorded in 59 cases of Down syndrome. The most affected segments of the body were length and circumference of the head. The head form in Down syndrome varied from brachycephaly to hyperbrachycephaly, and a flat occiput. Down syndrome cases were notably shorter in stature, however, trunk height was only slightly reduced. Legs were more severely affected. Shortness of stature was due to failure of the legs to grow in normal fashion. Dimensions of face lagged in both height and width. The Down syndrome cases retained their round facies. Ears were small in size. This represents persistence of infantile body proportions. Weight was only slightly reduced.     

胆道闭锁多中心综合诊断治疗方案研究

目的 探讨胆道闭锁综合诊疗方案应用的有效性和安全性.方法 根据具有地域代表性的四家儿童医院专家确定的胆道闭锁诊疗方案,2007年1月开始对胆道闭锁进行诊断及治疗.收集2004年1月至2006年12月四家医院经确诊为胆道闭锁并进行根治手术的病例作为对照组2007年1月至2009年12月病例作为观察组.使用标准化量表统计首次就诊年龄、手术年龄、术前及术后3个月,6个月和1年黄疸清除率,术后胆管炎发生率,2年自体肝生存率.结果 符合诊断标准498例,实施Kasai术456例,其中对照组184例,手术168例;观察组314例,手术288例.二组首次就诊年龄无明显差异[(33±27)d比(34±26)d,P＞0.05],使用标准化诊断方案后平均手术年龄由(64±24)d下降为(74±31)d,P＜0.05;观察组术后3个月、6个月及1年退黄率(53.9%、56.9%、58.0%)较对照组(38.9%、39.9%、43.4%)明显提高(P＜0.05);其术后胆管炎发生率亦显著降低(31.8%比47.8%,P＜0.05);对照组2年自体肝生存率39.3%,观察组56.1%(P＜0.05).结论 标准化胆道闭锁综合诊断治疗方案可降低手术年龄、提高术后黄疸清除率、减少术后反流性胆管炎,显著提高术后2年自体肝生存率.

Abstract：

Objective To evaluate the efficacy and safety of a standardized protocol for the diagnosis and treatment of biliary atresia (BA) in children.Methods This study enrolled 498 patients from 4 hospitals diagnosed with BA from January 2004 to December 2009.The BA patients of the standardized protocol group,who enrolled in this study after January 2007,were diagnosed and treated using the standardized protocol.The rest of the patients were taken as controls.The patients were followed up for 2 years.The age of the first diagnosis,the age at operation,jaundice clearance,the occurrence of cholangitis and two year survival rates with native liver were retrospectively reviewed and compared between the 2 groups.Results Among the 498 patients,456 patients underwent Kasai procedure.Age of the first diagnosis between the two groups showed no difference (33 ± 27 vs 34 ± 26 days,P＞0.05),but the patients of the standardized protocol group received surgeries at earlier ages (64 ± 24 vs 74 ± 31 days,P＜0.05).The jaundice clearance rates of 3,6 and 12 months after operation in the patients of the standardize protocol group were higher than those of controls (53.9%,56.9%,58.0% vs 38.9%,39.9%,43.4%,P＜0.05).Patients of the standard protocol group had lower occurrence of cholangitis (31.8% vs 47.8%,P＜0.05),and better two years survival rate (56.1% vs 39.3%,P＜0.05).Conclusions The standardized protocol for the diagnoses and treatment of BA improves the clinical outcomes of the children with BA.     

CONGENITAL DEFECTS IN A COHORT FOLLOWED FOR SEVEN YEARS

ABSTRACT. A geographically limited cohort of Finnish children was followed from birth for seven years, and all congenital abnormalities were recorded and classified and special attention was given to the cumulative detection rate, and the time of detection of various defects. Of 3674 pregnancies 135 babies with or without defects were stillborn or died during the neonatal period. The remaining 3539 were followed up to seven years, when the percentage follow-up was 81.7%. Detailed information on 76 malformed livebirths registered in the neonatal period was available in 63 cases (82.9%). The diagnosis was found to be incorrect in 6 cases and additional defects were registered in 7 of these children. Additional congenital abnormalities detected in the follow-up study were divided into three groups: all congenital disorders or abnormalities with prenatal etiology (248 children), all congenital defects (111 of these 248) and structural malformations (31 of these 111). The cumulative detection rates in these groups increased with time and at the end of the study when the children were aged seven were 9.4%, 5.6% and 2.6%, respectively.     

Intracluster correlation coefficient in multicenter childhood trauma studies.

OBJECTIVE: To calculate the intracluster correlation coefficient (ICC) for emergency department (ED) shock rate, early trauma death (ie, death during the first 24 h after arrival at hospital), and in-hospital trauma death rate for multicenter childhood injuries. METHODS: The National Trauma Data Bank (5th revision), the largest multicenter trauma registry in the US, was used. Data from 80 trauma centers were used to calculate the ICC for in-hospital trauma death rate. Thirty three states provided data for calculation of the ICC for ED shock and early trauma death rate. RESULTS: From 2000 to 2004, 13% of the 952 242 patients in the National Trauma Data Bank were <15 years old. Approximately 17 000 of these children had injuries with an injury severity score >15, of whom 84% (14 095 subjects) were hospitalized at 80 level I or II trauma centers in 33 states. The ICCs for ED shock rate, early trauma death rate, and in-hospital death rate were 0.005 (95% CI 0.000 to 0.010), 0.014 (95% CI 0.004 to 0.024), and 0.023 (95% CI 0.013 to 0.033), respectively. These ICCs were calculated for boys and girls and also for blunt and penetrating injuries. CONCLUSION: Clustered childhood trauma studies that aim to compare different aspects of pre-hospital and hospital trauma care should incorporate these ICCs for sample calculation. When cluster randomized clinical trials are mounted, if sample sizes are calculated without adjustment for ICC, then the planned trial is likely to be seriously underpowered.     

Home visiting the newborn baby as a basis for developmental surveillance at child welfare centres

Home visiting is a part of the Swedish child health surveillance programme. In the present study, part of a longitudinal prospective project, the predictive power of observations at home visits to 338 newborn babies was evaluated. The regular home visit was made by the nurse at the Child Welfare Centre also using a check-list developed for this project. Her check-list assessments seemed valid in identifying families with stressful psychosocial conditions. When the general home situation was judged as "poor" or "dubious", the boys showed signs of a delayed mental development at 4-5 years of age. Assessments of "feeding problems" among boys were associated with behavioural problems at 4-5 years of age. The results underline the importance of an early home visit as a base for the developmental surveillance at Child Welfare Centres. However, the results of the home visit observations were not followed by any extra interventions at CWC. It seems the nurse should feel confident in her check-list judgement and initiate interventions where appropriate.     

人类白细胞抗原对肾病综合征临床过程的预测价值

为了解人类白细胞抗原（ＨＬＡ）是否对原发性肾病综合征（简称肾病）的临床过程有预测价值，对ＨＬＡ分型为ＤＲ７、ＤＲ９及ＤＲ４的三组肾病患儿共３８例进行了前瞻性研究。ＨＬＡ分型用标准的微量淋巴细胞毒试验方法；对３８例患儿随访１．５～２年。结果表明，ＨＬＡ－ＤＲ４组镜下血尿例数比例较另二组显著增高，应用激素后ＨＬＡ－ＤＲ７组患儿９２．９％在４周内起效，ＨＬＡ－ＤＲ４组７５．０％耐药。ＨＬＡ－ＤＲ９组患儿８８．３％为频复发，该组患儿感染情况与另外二组无显著性差异，未发现激素起效时间与复发次数有关。ＤＲ４组患儿病理变化较严重，缓解率低。提示ＨＬＡ在预测肾病临床过程、帮助判断本病亚型方面有应用价值。     

小儿重症肌无力1381例临床综合分析

目的分析我国小儿重症肌无力(MG)的临床特点.方法回顾性分析1956～1999年诊治的1381例小儿MG病例资料,并与同时期诊治的1069例成人期MG进行对比.结果同期小儿MG的患病人数较成人多,性别差异较小,发病年龄以1～5岁为主,因各类药物、感染及外伤而诱发或加重者较多,以眼肌症状首发者多见,改良Osserman分型以Ⅰ型为主,危象发生率及病死率低,合并胸腺瘤者少见.结论本文小儿MG的临床特点不同于成人期及国外报道,充分认识此特点将有利于指导临床的诊断和治疗.     

Current status of treatment for pediatric rhabdomyosarcoma in the USA and Japan

This article reviews the current status of treatment for children with rhabdomyosarcoma, according to the four risk groups. Low‐risk subgroup A: the Children's Oncology Group in the USA recently performed a clinical trial consisting of a chemotherapy regimen with a shortened treatment period and a reduced drug dosage. Patients in this group received only four cycles of vincristine and actinomycin D (VA) after four cycles of vincristine, actinomycin D, and cyclophosphamide (VAC) with cyclophosphamide (CPM) 1.2 g/m² and their outcome was no worse than that obtained with previous regimens. Low‐risk subgroup B: although marked improvement in survival was seen with an intensive VAC regimen with CPM 2.2 g/m²/cycle (Intergroup Rhabdomyosarcoma Study [IRS]‐V, 1997–2004), the total dose of CPM in this regimen caused serious and fatal hepatic veno‐occlusive disease during treatment and probably cannot avoid infertility or possible secondary cancer as a late effect. Thereafter, a reduced‐dose regimen consisting of four cycles of VAC with CPM 1.2 g/m² followed by 12 cycles of VA was investigated in the next study, but the outcome appeared to be worse than in IRS‐V. Intermediate‐risk group: no significant difference was found between VAC/vincristine, topotecan and cyclophispahamide (VTC) and intensive VAC in IRS‐V. The results of a subsequent regimen of VAC with CPM 1.2 g/m² alternating with vincristine and irinotecan are awaited. High‐risk group: overall survival is approximately 30% and has not improved over the last 25 years. Although 18 month failure‐free survival (FFS) was improved with an intensive combination therapy regimen, 36 month FFS dropped to 32% and thus better novel approaches or additive treatments are needed.     

Prevalence of appendectomy in Japanese families

We investigated the prevalence of appendectomy in Japan to determine the tendency of familial aggregation on appendicitis using a large scale study. A total of 517 Japanese women (aged 20 to 45 years) served as the subjects and were questioned regarding their family history of appendectomy due to appendicitis. We compared the prevalence of appendectomy in children (subjects + their siblings) of three groups of families: (i) both parents affected; (ii) one parent affected; (iii) no parents affected. The differences between groups were statistically significant using contingency table and Chi-squared test. Our results suggest that about 40% of children with both parents affected, and about 20% of children with one parent affected may develop the disorder during childhood. This study may provide useful information in the nature of the development of appendicitis.     

Beta-haemolytic non-group A streptococci and pharyngitis: A case-control study

A case-control study was conducted to examine the association of beta-haemolytic non-group A streptococci and pharyngitis in a paediatric population (n=502). No association could be found between disease and traditional Lancefield groups B, C, F, or G. When the analysis included the clustering of genetically related subgroups from different Lancefield groups, an association was evident for moderate and heavy quantitations of beta-haemolytic large colony group C and G streptococci (Streptococcus equisimilis and human biotypes of large colony group G streptococci) (p=0.021). This study further defines a subset of the beta-haemolytic non-group A streptococci that merit recognition by both the laboratory and physician.     

RESULTS OF TREATMENT IN MYELOMENINGOCELE

Abstract. A follow-up study was made in 48 surviving children with myelomeningocele, the material being derived from a time when all infants were operated upon in the newborn period without primary selection. The follow-up revealed several children with severe physical handicap, whereas relatively few were both physically and intellectually handicapped. The results were compared with two earlier published studies of which one from Sheffield comprised cases where selection had not been applied and the other from Edinburgh in which certain criteria had been set up as contra-indications to early closure of the lesion. The effect of a hypothetical selection applied to the Swedish material is discussed. It is recommended that a uniform system of assessment in grading of handicap is applied to facilitate a comparison between different follow-up investigations.     

NOCTURNAL ENURESIS IN A LONGITUDINAL PERSPECTIVE

ABSTRACT. Klackenberg, G. (Clinic for the Study of Development and Health in Children, Department of Paediatrics, Karolinska Hospital, Stockholm, Sweden). Nocturnal enuresis in a longitudinal perspective. A primary problem of maturity and/or a secondary environmental reaction? Acta Paediatr Scand, 70:453,.–The study is part of a prospective longitudinal investigation, involving annual somatic, psychological and social check-ups in a random sample of 212 children. Data are presented on the gradual achievement of bladder control, with relapses into wetting. Information is provided on relationships with training, with behavioural variables, with emotional maturity (Rorschach) and with sleep. It seems probable that primary enuresis usually ceases by the age of 8 at the latest and that enuresis in older children is a secondary emotional disorder which may, however, have started at an earlier age. The 6-year-old enuretic shows signs of delayed emotional maturity. The relation with somnambulism is ambiguous. Enuresis is not significantly related to training. None of the data obtained in this study conflict with the theory that primary enuresis is chiefly a maturity problem, the nature of which can be emotional. The neurophysiological aspect has not been investigated.