Interventions aimed at preventing and reducing overweight/obesity among children and adolescents: a meta-synthesis.

The prevalence of child and adolescent obesity has been a major worldwide problem for decades. To stop the number of youth with overweight/obesity from increasing, numerous interventions focusing on improving children's weight status have been implemented. The growing body of research on weight-related interventions for youth has been summarized by several meta-analyses aiming to provide an overview of the effectiveness of interventions. Yet, the number of meta-analyses is expanding so quickly and overall results differ, making a comprehensive synopsis of the literature difficult. To tackle this problem, a meta-synthesis was conducted to draw informed conclusions about the state of the effectiveness of interventions targeting child and adolescent overweight. The results of the quantitative synthesis of 26 meta-analyses resulted in a standardized mean difference (SMD) of -0.12 (95%CI: -0.16, -0.08). Several moderator analyses showed that participant and intervention characteristics had little impact on the overall effect size. However, a moderator analysis distinguishing between obesity treatment and obesity prevention studies showed that obesity treatment interventions (SMD: -0.048, 95%CI: -0.60, -0.36) were significantly more effective in reducing body mass index than obesity prevention interventions (SMD: -0.08, 95%CI: -0.11, -0.06). Overall, the results of this meta-synthesis suggest that interventions result in statistically significant effects albeit of relatively little clinical relevance.

The Autism Birth Cohort: a paradigm for gene-environment-timing research.

The reported prevalence of autism spectrum disorders (ASDs) has increased by 5- to 10-fold over the past 20 years. Whether ASDs are truly more frequent is controversial; nonetheless, the burden is profound in human and economic terms. Although autism is among the most heritable of mental disorders, its pathogenesis remains obscure. Environmental factors are proposed; however, none is implicated. Furthermore, there are no biomarkers to screen for ASD or risk of ASD. The Autism Birth Cohort (ABC) was initiated to analyze gene x environment x timing interactions and enable early diagnosis. It uses a large, unselected birth cohort in which cases are prospectively ascertained through population screening. Samples collected serially through pregnancy and childhood include parental blood, maternal urine, cord blood, milk teeth and rectal swabs. More than 107,000 children are continuously screened through questionnaires, referral, and a national registry. Cases are compared with a control group from the same cohort in a 'nested case-control' design. Early screening and diagnostic assessments and re-assessments are designed to provide a rich view of longitudinal trajectory. Genetic, proteomic, immunologic, metagenomic and microbiological tools will be used to exploit unique biological samples. The ABC is a paradigm for analyzing the role of genetic and environmental factors in complex disorders.

Hansen's disease in a general hospital: uncommon presentations and delay in diagnosis.

BACKGROUND: The question was raised as to why 'obvious' signs of leprosy, Hansen's disease (HD), are often missed by medical doctors working in a HD endemic area. METHODS: This study describes a small sample of patients who were diagnosed with HD during their hospital admission and not before. The discussion is whether the typical early signs and symptoms of HD are just not recognized, or whether unusual presentations confuse the attending physician. RESULTS: A total of 23 HD patients were hospitalized during the study period, of which 6 (26%) were only diagnosed with HD during their admission. All were classified as lepromatous leprosy (LL) with a history of signs and symptoms of HD. In nearly all patients, a suspicion of HD might have been raised earlier if a careful history and dermato-neurological examination had been done. CONCLUSIONS: Multibacillary (MB) HD, especially close to the lepromatous end of the spectrum, may mimic other diseases, and the patient can not be diagnosed without a biopsy or a slit skin smear examination. Clinicians working in a HD endemic area (Rio de Janeiro) do not always include HD in their differential diagnosis, especially when the clinical presentation is unusual. HD should be considered in all patients with skin lesions not responding to treatment, especially when they have neurological deficits, and live or have lived in an HD endemic area. Due to the increase in global travel and immigration, doctors in low endemic areas need to consider HD as a possible diagnosis.

Sudden unexplained infant death in 20 regions in Europe: case control study.

BACKGROUND: After striking changes in rates of sudden unexplained infant death (SIDS) around 1990, four large case-control studies were set up to re-examine the epidemiology of this syndrome. The European Concerted Action on SIDS (ECAS) investigation was planned to bring together data from these and new studies to give an overview of risk factors for the syndrome in Europe. METHODS: We undertook case-control studies in 20 regions. Data for more than 60 variables were extracted from anonymised records of 745 SIDS cases and 2411 live controls. Logistic regression was used to calculate odds ratios (ORs) for every factor in isolation, and to construct multivariate models. FINDINGS: Principal risk factors were largely independent. Multivariately significant ORs showed little evidence of intercentre heterogeneity apart from four outliers, which were eliminated. Highly significant risks were associated with prone sleeping (OR 13.1 [95% CI 8.51-20.2]) and with turning from the side to the prone position (45.4 [23.4-87.9]). About 48% of cases were attributable to sleeping in the side or prone position. If the mother smoked, significant risks were associated with bed-sharing, especially during the first weeks of life (at 2 weeks 27.0 [13.3-54.9]). This OR was partly attributable to mother's consumption of alcohol. Mother's alcohol consumption was significant only when baby bed-shared all night (OR increased by 1.66 [1.16-2.38] per drink). For mothers who did not smoke during pregnancy, OR for bed-sharing was very small (at 2 weeks 2.4 [1.2-4.6]) and only significant during the first 8 weeks of life. About 16% of cases were attributable to bed-sharing and roughly 36% to the baby sleeping in a separate room. INTERPRETATION: Avoidable risk factors such as those associated with inappropriate infants' sleeping position, type of bedding used, and sleeping arrangements strongly suggest a basis for further substantial reductions in SIDS incidence rates.

Isolation of remnant particles by immunoseparation: a new approach for investigation of postprandial lipoprotein metabolism in normolipidemic subjects.

Abnormal postprandial lipoproteins are associated with an increased risk for cardiovascular disease. Postprandial remnant lipoproteins were usually analyzed indirectly using retinyl esters (RE) as a chylomicron core label during an oral fat loading test. Apo B-100 containing VLDL remnants in addition to apo B-48 containing chylomicron remnants can also be directly quantified using the RLP-Cholesterol Immunoseparation Assay. This recently available method uses monoclonal antibodies to apo A-I and apo B-100 to remove non-remnant lipoproteins and quantifies cholesterol in the remaining apo E-rich remnant fraction. In the present study we compared the analysis of retinyl ester with the immuno-based RLP-Cholesterol (RLP-C) analysis in measuring postprandial remnant lipoproteins in healthy normolipidemic subjects. Sixteen healthy normolipidemic subjects were selected for this study. Postprandial plasma retinyl esters peaked at 5.0+/-1.2 h, whereas plasma RLP-C showed a peak significantly earlier (P<0.001) at 3.5+/-0.6 h. In comparison, postprandial plasma TG and FFA peaked at 3.3+/-1.1 h (P<0.005 compared to retinyl esters). In conclusion, levels of RLP-C changed, during the postprandial phase, in parallel with plasma TG and FFA concentrations and peaked significantly earlier than retinyl esters. Postprandial measurements of RLP-C can be considered as a fast alternative method for the more laborious retinyl-ester analysis in clinical studies.

High dose of simvastatin normalizes postprandial remnant-like particle response in patients with heterozygous familial hypercholesterolemia.

Familial hypercholesterolemia (FH) and disturbances in postprandial lipoprotein metabolism are both associated with premature atherosclerosis. The effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors on plasma cholesterol levels in patients with FH is well established; however, it is not known whether postprandial lipoproteins are also influenced. In this case-controlled intervention study, we investigated the effects of high-dose simvastatin on postprandial lipoproteins. We used a new method to analyze remnant lipoproteins based on the immunoseparation principle (remnant-like particle cholesterol [RLP-C] assay) and the well-established measurement of retinyl ester (RE) analysis in plasma and in the Svedberg flotation unit (Sf)<1000 fraction. Seven heterozygous FH patients and 7 control subjects matched for sex, age, body mass index, triglycerides, and apolipoprotein E genotype were enrolled in the study. An oral vitamin A (RE) fat-loading test was performed at baseline in both groups and after 3 months of high-dose simvastatin (80 mg/d) treatment in the FH patients. Before treatment, FH patients had significantly higher fasting and postprandial concentrations of lipoprotein remnants (plasma RLP-C 42+/-19 mg/dL and area under the RLP-C curve 415+/-82 mg. L(-1). h(-1), respectively) than did control subjects (7+/-3 mg/dL and 101+/-35 mg. L( -1). h(-1), respectively; P<0.05), suggesting a delayed clearance of chylomicron remnant particles in the FH patients. Treatment with simvastatin significantly reduced fasting and postprandial remnant lipoprotein cholesterol concentrations (13+/-3 mg/dL and 136+/-53 mg. L(-1). h(-1), respectively; P<0.05 for both). Postprandial RE in the Sf<1000 fraction, not total RE in plasma, was also significantly higher in FH patients than in control subjects (24+/-10 versus 6.3+/-5.9 mg. L( -1). h(-1), P<0.05), but treatment with simvastatin did not result in improvement of the postprandial RE response, either in the Sf<1000 fraction or in plasma. It is concluded that heterozygous FH patients have increased fasting and postprandial remnant lipoprotein concentrations. Treatment with simvastatin significantly reduced the fasting and postprandial RLP-C concentrations but did not result in improved postprandial RE response.

Maternal smoking and birthweight: effect modification of period, maternal age and paternal smoking.

OBJECTIVE: To study the effect on birthweight of maternal smoking, and its modification by study period, maternal age and paternal smoking. DESIGN: A retrospective questionnaire based national survey comprising a random sample (n=34,799) of all mothers giving birth in Norway 1970-91. Variables studied were parental smoking during pregnancy, birthweight, maternal age and infant's year of birth. RESULTS: The overall difference in mean birthweight between non-smoking and smoking mothers was 197 g. The difference in birthweight between non-smoking and smoking mothers increased with maternal age from 182 g (<20 years of age) to 232 g (35+ years of age). There was no significant effect of paternal smoking on birthweight when the mother was a non-smoker. When the mother was a smoker and the father was a non-smoker, the birthweight, adjusted for maternal age, was reduced by 153 g (p<0.005). However, when both parents smoked, the birthweight, adjusted for maternal age, was reduced by 201 g (p<0.0005). Even though the prevalence of paternal smoking decreased by 38% during the study period, there was no significant increase in overall mean birthweight. IMPLICATION AND RELEVANCE OF RESULTS: The negative effect of maternal smoking on birthweight appears to increase with maternal age. For a non-smoking pregnant woman to live with a smoking partner has little, if any, effect on birthweight. The negative effect of paternal smoking was only observed when the mother was smoking and might reflect two possible mechanisms: (1) that a smoking mother has a greater cigarette consumption when the partner also smokes, and (2) that a smoking mother is less concerned about passive smoking than a non-smoking mother.

Growth hormone (GH) treatment decreases postprandial remnant-like particle cholesterol concentration and improves endothelial function in adult-onset GH deficiency.

Premature atherosclerosis is a clinical feature in adult-onset GH deficiency. Evidence is accumulating that disturbances in triglyceride metabolism, reflected by abnormalities in circulating remnant lipoproteins, are associated with increased atherogenic potential. In a case-controlled intervention study, we investigated postprandial lipoprotein metabolism using a new remnant lipoprotein method based on immunoseparation principle [RLP-cholesterol (RLP-C)]. In addition, we analyzed retinyl ester (RE) analysis in plasma and in Sf < 1000 fraction. Endothelial function was assessed as flow-mediated dilatation (FMD). Eight patients diagnosed with acquired adult-onset GH deficiency and eight controls matched for gender, age, body mass index, and apolipoprotein (apo) E genotype were enrolled in the study. Oral vitamin A fat loading tests were performed at baseline in both groups and after 6 months of treatment with recombinant human GH (rh-GH) in the adult-onset GH-deficient patients. Adult-onset GH-deficient patients had significantly higher fasting RLP-C, postprandial RLP-C concentrations (plasma RLP-C, 0.29 +/- 0.14 mmol/L; and incremental area under the curve-RLP-C, 2.13 +/- 1.60 mmol*h/L, respectively) than controls (0.19 +/- 0.06 mmol/L and 1.05 +/- 0.72 mmol*h/L (P: < 0.05), respectively). They also had significantly higher postprandial RE in plasma and Sf < 1000 fraction. Treatment with rh-GH significantly reduced postprandial RLP-C concentrations (incremental area under the curve-RPL-C 0.73 +/- 0.34 mmol*h/L; P: < 0.05) but had no effects on the fasting RLP-C concentrations (0.317 +/- 0.09 mmol/L, P: < 0.05), or on the postprandial RE in plasma and in Sf < 1000 fraction. Endothelial function measured as FMD was improved from 5.9 +/- 3.3% to 10.2 +/- 4.0% (P: < 0.05) in patients treated with rh-GH. It is concluded that patients with adult-onset GH deficiency have increased levels of fasting and postprandial RLP-C and an impaired endothelial function as measured as FMD. Treatment with rh-GH resulted in a decrease of postprandial RLP-C concentration, thereby improving the postprandial atherogenic lipoprotein profile and improvement of endothelial function, however, the clearance of large chylomicron particles as reflected by RE remained disturbed.

Secular trends in breastfeeding and parental smoking.

To explore the association between smoking and breastfeeding, we obtained data from a retrospective questionnaire-based national survey comprising a random sample (n = 34799) of all mothers giving birth in Norway 1970-91. Variables studied were postpartum smoking habits for both parents, duration of breastfeeding, infant's year of birth and parental age. The response rate was 70% (n = 24438). During the study period, the maternal postpartum smoking prevalence decreased from 38% to 26%. The proportion breastfeeding at 6 months increased from 15% to 44% among smokers, and from 30% to 72% among non-smokers. In spite of a considerable increase in breastfeeding both among smokers and non-smokers, the proportion of breastfeeding, non-smoking women at 6 months was twice that of smoking women during the whole period. Furthermore, the duration of breastfeeding was shorter among young mothers and when the fathers were smoking. There was epidemiological evidence that the effect on breastfeeding of smoking might represent both biological and social mechanisms.

The occurrence of reactions and impairments in leprosy: experience in the leprosy control program of three provinces in northeastern Thailand, 1987-1995 [correction of 1978-1995]. I. Overview of the study.

AIM: This paper is the first in a series of three reports on the occurrence of reactions and impairments in leprosy in Thailand. This first paper gives a general overview about the methodology of the study, some epidemiological observations, delay in detection, multidrug therapy (MDT) completion rates and relapses. The other two papers report on: II. Reactions and III. Neural and Other Impairments. This study was carried out from 1987 until 1995 in three neighboring provinces in northeastern Thailand. STUDY DESIGN: A population-based, prospective cohort study. STUDY POPULATION: All 640 newly diagnosed leprosy patients in the three provinces, registered between October 1987 and September 1990, were included [420 paucibacillary (PB) and 220 multibacillary (MB)]. This group was followed up (actively and passively) until the end of 1995. METHODS: Patients were found by active and passive case finding. All new, untreated leprosy patients from the area were enrolled and started on the World Health Organization (WHO) MDT (WHO/MDT) regimen. A vertical control service was run by specialized leprosy workers. During treatment the patients received their monthly doses at home. During surveillance the patients were followed up once a year by a special team. Patients were questioned about delay in detection. Treatment completion rates were calculated. The occurrence of reactions and neural and other impairments at the beginning of, during and after treatment was ascertained. After treatment, the occurrence of late reactions and relapses was recorded. RESULTS: A higher frequency of leprosy was found among the male patients, especially in the MB group. However, in the PB group a higher female/male ratio was found in the age group 55 years and older. There was an increase in the detection rate from the youngest age group to the age group 55 years and older, which showed the highest detection rate. Treatment completion rates were high, 95% in both in the PB and MB treatment groups. About 50% of the new cases reported a delay between onset and registration of 1 year or more. By 1995, 93% of the original patient group was still available for follow up. By the end of 1995, 8 PB and 2 MB relapses were recorded.

The occurrence of reactions and impairments in leprosy: experience in the leprosy control program of three provinces in northeastern Thailand, 1987-1995 [correction of 1978-1995]. II. Reactions.

AIM: This is the second paper in a series of three papers on the occurrence of reactions and impairments in leprosy in Thailand, and focuses on the prevalence and incidence of reactions, including silent neuropathy. STUDY DESIGN: A population-based, prospective cohort study. STUDY POPULATION: All 640 newly diagnosed and registered leprosy patients in three neighboring provinces in northeastern Thailand registered between October 1987 and September 1990 were included [420 paucibacillary (PB) and 220 multibacillary (MB)]. This group was followed up (actively and passively) until the end of 1995. METHODS: Clinical data and data on the sensibility and motor function of the eyes, hands and feet were obtained when appropriate. The occurrence of reactions, including silent neuropathy, at the beginning of, during and after treatment was ascertained. During surveillance mild late reactions were also recorded. RESULTS: Severe reversal reactions (RR) at the start of and during treatment were seen in 2.6% [confidence interval (CI) 1.1-4.1] of the PB and 29% (CI 23-35) of the MB patients. In the PB group the majority (82%) of severe RR were found at the start of treatment. In the MB group 35% of the severe RR were found at the start of treatment and another 59% during the first year of treatment. It is shown that there is a statistically highly significant increasing proportion of patients with severe RR starting from tuberculoid and going toward borderline lepromatous. The incidence rate of severe RR during treatment was 1.4 (CI 0.46-4.5) per 100 person-years at risk (PYAR) for PB patients and 12 (CI 9.0-16) per 100 PYAR for MB patients. Late (mild and severe) RR were seen in 2.7% of the PB and 9% of the MB patients (35% of these reactions being considered severe). Late reactions were mainly seen in borderline tuberculoid (PB group) and in borderline lepromatous patients. Recent silent neuropathies were seen at first examination and during treatment in 1.4% of the pB and 4.1% of the MB patients. During surveillance only a few silent neuropathies were seen. If all severe RR, severe erythema nodosum leprosum and silent neuropathies at the start of, during and after treatment were added together, then 53% of the borderline lepromatous and 42% of the lepromatous patients had or developed one or another serious complication in need of steroid treatment.

The occurrence of reactions and impairments in leprosy: experience in the leprosy control program of three provinces in northeastern Thailand, 1987-1995 [correction of 1978-1995]. III. Neural and other impairments.

AIM: This the third paper in a series of three papers on the occurrence of reactions and impairments in leprosy in Thailand, and focuses on the prevalence and incidence of neural and other impairments in leprosy. STUDY DESIGN: A population-based, prospective cohort study. STUDY SUBJECT: All 640 newly diagnosed and registered leprosy patients in three provinces of northeastern Thailand between October 1987 and September 1990 were included [420 paucibacillary (PB) and 220 multibacillary (MB)]. This group of patients was followed up until the end of 1995. METHODS: Clinical data; data on the sensibility and motor function of eyes, hands and feet, and data on wounds and bone loss were obtained where appropriate. The occurrence of neural and other impairments at first examination, during treatment and during surveillance was ascertained. RESULTS: The relationship between impairment prevalence (grade 2 of the combined PB and MB groups and grades 1 and 2 together of the combined PB and MB groups) and duration of disease (before diagnosis) was found to be statistically significant. Increased delay in detection led to increased problems of impairments. Too many patients still develop new/additional impairments while on treatment and thereafter. The incidence of nerve function impairment (NFI) among patients without impairments at first examination while on treatment was 1.7 [ 95% confidence interval (CI) 0.45-4.4] per 100 person-years at risk (PYAR) for the PB group and 12 (CI 8.4-17) per 100 PYAR for the MB group. Additionally, 2% of the PB and 11% of the MB patients who already had impairments at first examination developed new NFI while on treatment. The outcome, comparing the first examination with the last examination during/after surveillance [changes in the voluntary muscle test (VMT), the sensory test (ST), wound count and bone loss], indicated that of the PB patients 3.7% improved, 3.7% got worse and 3.9% kept the same impairment; of the MB patients 19% improved, 18% got worse and 2.9% kept the same impairment. During treatment most of the new/additional impairments were due to new/increase in NFI; during surveillance slightly more than 50% were due to new/increase in NFI. Eighty-three percent of the MB patients without impairments at first examination who developed NFI during treatment improved (completely or partially) after receiving prednisolone. Only 62% of the MB patients with a grade 1 impairment at first examination and who developed a severe reaction or recent silent neuropathy improved after receiving prednisolone. There is a need for an indicator to measure new/additional impairments while on treatment and thereafter. It is proposed to measure changes in impairment by measuring changes in VMT, ST, wound count and bone loss.

A study on the effectiveness and safety of the WHO/MDT regimen in the northeast of Thailand; a prospective study, 1984-1996.

The aim of this prospective study was to determine the effectiveness and safety of the multidrug therapy as recommended by the World Health Organization (WHO/MDT) in 1982. One-hundred-eighty-eight newly diagnosed leprosy patients [130 paucibacillary (PB) and 58 multibacillary (MB) patients] from three provinces in northeastern Thailand were recruited into a study from April 1984 to March 1985. The study lasted until May 1996. The results showed that 182 patients finished their course of WHO/MDT, representing a treatment completion rate of 95%; 167 (122 PB and 45 MB) were released from surveillance (RFS); 82 PB patients were still available for follow up by the end of 1994 and 31 MB patients by May 1996. Two PB patients were diagnosed with a relapse, showing a relapse rate of 0.2 per 100 person-years at risk. After an average of 8 years of follow up, no MB relapses have been diagnosed. The proportion of patients with a WHO grade 2 disability among PB and MB patients increased from 4% and 8% at the start of treatment to 7% and 13% at last examination, respectively. It is concluded that the fixed-duration, 6-month WHO/MDT regimen for PB leprosy and the 24-month regimen for MB leprosy are effective, acceptable and safe, and that clinical activity, histopathological activity and/or a positive skin smear at release from treatment (RFT) have no bearing on the efficacy of the WHO/MDT regimens. The relapse rates are low and in accordance with most published data available to date. The importance of skin-smear services for a reliable classification (WHO PB/MB classification for control programs) is stressed.

Rapid village survey to determine the size of the leprosy problem in Khon Kaen Province, Thailand.

The rapid village survey (RVS) method has been developed as a simpler, less-expensive alternative to random sample surveys for determining the prevalence of leprosy and was compared with a total population survey (TVS). In the RVS, the cluster population receives clear information about the disease, and those with symptoms are invited to be examined by the survey team. A list of household contacts and suspects was made and those on the list were actively traced. The registered population was 20,815; 10 new patients were found among the 2034 people self-reporting in the RVS, 0 among the household contacts and suspects, and an additional 2 new patients in the TVS. There were 12 registered patients among the sample population. The prevalence rate found by the RVS was 1.06 per 1000(95% CI = 0.49-1.63) and in the TVS 1.16 per 1000 (95% CI = 0.5-1.77). The man-days and costs of an RVS are considerably less than those for a TVS. It was concluded that the RVS is a valid replacement for the TVS as conducted in Khon Kaen Province, Thailand. The RVS can be applied under low-endemic conditions and could be carried out by the general health staff.

Sleeping position and sudden infant death syndrome in Norway 1967-91.

OBJECTIVE: To investigate, in a population based national study, the association between sleeping position of infants and the occurrence of sudden infant death syndrome (SIDS). DESIGN: A retrospective survey and registry based ecological study. A questionnaire based surveillance of sleeping position was obtained in a random sample (n = 34,799) and surveillance of SIDS was based on all infants born in Norway 1967-91, surviving the perinatal period. Variables studied from the questionnaire were usual sleeping position (placed), breast feeding at 3 months, and maternal smoking in pregnancy, and from the Medical Birth Registry maternal age, birth order, and birth weight. RESULTS: Proportion of infants sleeping prone increased from 1970 (7.4%) to 1989 (49.1%) and dropped in 1990 (26.8%) and 1991 (28.3%). Occurrence of SIDS increased from 1970 (1.1/1000) to 1989 (2.0) before dropping in 1990 and 1991 (1.1). IMPLICATION AND RELEVANCE OF RESULTS: A cause effect relationship between prone sleeping and SIDS as suggested in previous studies is supported by the present; and so far only, national study of infants' sleeping position.