Longitudinal associations between asthma and general and abdominal weight status among Norwegian adolescents and young adults: the HUNT Study.

BACKGROUND: In adolescents the temporal directionality to the asthma and adiposity association remains unclear. Asthma may be a consequence of obesity; however, asthma may increase adiposity. OBJECTIVES: This study aimed to assess the associations between (i) baseline weight status and subsequent asthma and (ii) baseline asthma and subsequent weight status after 4 and 11 years of follow-up (N = 1543 and N = 1596, respectively) using data from three, sequentially enrolled population-based surveys of Norwegians aged 12-30 years from 1995 to 2008. METHODS: Weight status was defined as general (body mass index) or abdominal (waist circumference) underweight, normal weight, overweight or obesity. Self-report physician-diagnosed asthma defined asthma status. RESULTS: Over the longitudinal 11-year follow-up, baseline generally overweight or abdominally obese adolescents had increased risk of asthma. Likewise, baseline asthmatics had increased risk of general overweight or abdominal obesity. After sex stratification, these associations were stronger in males. Generally (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.32, 2.73) or abdominally (OR 1.66; 95% CI 1.13, 2.44) overweight males were at increased risk of asthma. Baseline asthmatic males were also at increased risk of general (OR 2.14; 95% CI 1.54, 2.98) and abdominal (OR 1.77; 95% CI 1.27, 2.47) overweight. CONCLUSIONS: Among Norwegian adolescents, a bidirectional association of asthma and adiposity was observed in males. Each baseline condition increased the risk of the other condition over time. No association was observed in females.

Continuous infusion versus intermittent bolus doses of indomethacin for patent ductus arteriosus closure in symptomatic preterm infants.

BACKGROUND: Indomethacin is a prostaglandin inhibitor used for the prevention and the treatment of patent ductus arteriosus (PDA). Although a 3-dose schedule has been commonly used, there is no consensus on optimal dosage and duration of indomethacin therapy for PDA closure. There are potential adverse effects of indomethacin use in premature infants such as a reduction in cerebral, mesenteric and renal blood flow and platelet dysfunction. Administering indomethacin continuously over 36-hours has been suggested as a safer and more effective option to prevent such adverse effects. OBJECTIVES: To compare the efficacy and safety of continuous infusion versus bolus administration of indomethacin in closing a symptomatic PDA in preterm infants. SEARCH STRATEGY: The standard search strategy of Cochrane Neonatal Review was used: MEDLINE and EMBASE (1966 - March 2007), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007), bibliographies of reviews and trials were examined for references to other trials, previous symposia proceedings published in Pediatric Research (Pediatric Academic Societies Annual Meeting Abstract Book, 1972 - 2006). No language restrictions were applied. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing continuous indomethacin infusion to bolus doses for closure of a symptomatic PDA in preterm infants with a symptomatic PDA diagnosed clinically and/or by echocardiography. DATA COLLECTION AND ANALYSIS: The methodological quality of each study was assessed. Authors were contacted regarding missing data as well as to inquire about the outcomes that were not reported. Meta-analysis was performed to calculate relative risk (RR), risk difference (RD) and 95% confidence intervals (CI). MAIN RESULTS: Only two small trials comparing continuous versus bolus indomethacin were eligible. Analysis of these studies showed that, although the primary outcome of PDA closure on days two and five slightly favored bolus administration, there was no statistical difference between the two groups. The estimates for PDA closure were RR 1.57 (95% CI 0.54, 4.60), RD 0.10 (95% CI -0.13, 0.33) for day 2 and RR 2.77 (95% CI 0.33, 23.14), RD 0.15 (95% CI -0.13, 0.42) for day five. There was no statistical difference between the bolus and continuous groups for the secondary outcomes of reopening of PDA, neonatal mortality, intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC). These analyses were based on a very small number of events reported by these trials. None of the trials reported on outcomes such as requirement for retreatment with indomethacin or surgical ligation, mortality, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), neurodevelopmental outcome and isolated intestinal perforation. The review demonstrated that there was a decrease in cerebral blood flow velocity after bolus injections and that the difference between the bolus and continuous infusion groups remained significant for 12 - 24 hour. In one study (Christmann 2002), the decrease in blood flow was maximum at 10 minutes [MD -46.40 (95% CI -75.41, -17.39)], while the other study (Hammerman 1995) reported a maximum drop at 30 minutes [MD -55.60 (95% CI -62.92, -48.28)]. Similar decrease in blood flow to the renal and mesenteric circulations following bolus administration was reported in one study (Christmann 2002). In both of these circulations, the decrease was maximum 30 minutes after the bolus injection [typical estimates for renal and mesenteric circulations, respectively: MD -42.00 (95% CI -76.59, -7.41) and MD -26.50 (95% CI -45.34, -7.66)] and lasted about two hours. None of the trials detected predefined levels of decreased urine output and increased levels of BUN and creatinine. AUTHORS' CONCLUSIONS: Due to a paucity of events and lack of precision, the available data was found to be insufficient to draw conclusions regarding the efficacy of continuous indomethacin infusion versus bolus injections for the treatment of PDA. Although continuous indomethacin seems to cause less alterations in cerebral, renal and mesenteric circulations, the clinical meaning of this effect is unclear. Definitive recommendations about the preferred method of indomethacin administration i.e. continuous versus bolus infusions for the treatment of PDA in premature infants cannot be made based on the current findings of this review.

A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder.

As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967-2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive disorder'. Search results and analysis were limited to double-blind, randomized control trials involving the adult population. The proportion of subjects designated as treatment responders was defined by a greater than 35% reduction in Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of augmentation therapy. Nine studies involving 278 participants were included in the analysis. The meta-analysis of these studies demonstrated a significant absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22 (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with comorbid tics have a particularly beneficial response to this intervention, ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients should be treated with at least 3 months of maximal-tolerated therapy of an SRI before initiating antipsychotic augmentation owing to the high rate of treatment response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI-refractory OCD is indicated in patients who have been treated for at least 3 months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. There is sufficient evidence in the published literature, demonstrating the efficacy of haloperidol and risperidone, and evidence regarding the efficacy of quetiapine and olanzapine is inconclusive. Patients with comorbid tics are likely to have a differential benefit to antipsychotic augmentation.

The influence of air conditioning, humidity, temperature and other household characteristics on mite allergen concentrations in the northeastern United States.

BACKGROUND: Information about the influence of housing and occupant characteristics on mite allergen concentrations is crucial to determine which methods could be used to decrease exposure of susceptible subjects. OBJECTIVES: To identify housing and occupant characteristics that are associated with mite allergen concentrations in house dust collected from living rooms and mattresses. METHODS: We collected dust samples from 750 homes in the northeastern US. The influence of various characteristics on concentrations of mite allergens (Der p 1 and Der f 1) was studied using multiple linear regression analysis. RESULTS: Some characteristics, like absence of air conditioners, the presence of mold or mildew, and a lower temperature were consistently associated with higher concentrations of both mite allergens in dust from all sampling locations. However, none of these factors changed Der p 1 or Der f 1 concentrations by more than a factor of 2. People of white ethnic background had roughly two times higher mite allergen concentrations, while family income, family size, and education level only marginally influenced mite allergen concentrations. CONCLUSIONS: Various housing characteristics have some influence on mite allergen concentrations, and could possibly be used to decrease exposure of susceptible subjects. However, only a limited percentage of the variation in mite allergen concentrations was explained by these characteristics.

Steroids for acute spinal cord injury.

BACKGROUND: Acute spinal cord injury is a devastating condition typically affecting young people with a preponderance being male. Steroid treatment in the early hours of the injury is aimed at reducing the extent of permanent paralysis during the rest of the patient's life. OBJECTIVES: To review randomized trials of steroids for acute spinal cord injury. SEARCH STRATEGY: The review draws on the search strategy developed by the Cochrane Injuries Group. In addition, files of the National Acute Spinal Cord Injury Study have been reviewed and a Medline search conducted. SELECTION CRITERIA: All published or unpublished randomized controlled trials of steroid treatment for acute spinal cord injury in any language. DATA COLLECTION AND ANALYSIS: Data have been abstracted from original trial reports. For the NASCIS, Japanese and French trials, additional data (e.g. SDs) have been obtained from the original authors. MAIN RESULTS: There are few trials in this area of medical care. Only one steroid has been extensively studied, methylprednisolone sodium succinate, which has been shown to improve neurologic outcome up to one year post injury if administered within eight hours of injury and in a dose regimen of: bolus 30mg/kg administered over 15 minutes with a maintenance infusion of 5.4 mg/kg per hour infused for 23 hours. The initial North American trial was replicated in a Japanese trial but not in the one from France. Data has been obtained from the latter studies to permit appropriate meta-analysis of all three trials. This analysis indicates significant recovery in motor function after methylprednisolone therapy when administration commences within eight hours of injury. A more recent trial indicates that if methylprednisolone therapy is given for an additional 24 hours (for a total of 48 hours), additional improvement in motor neurologic function and functional status is observed. This is particularly observed if treatment cannot be started until between three to eight hours after injury. The same methylprednisolone therapy has been found effective in whiplash injuries and a modified regimen found to improve recovery after surgery for lumbar disc disease. REVIEWER'S CONCLUSIONS: High dose methylprednisolone steroid therapy is the only pharmacological therapy shown to have efficacy in a Phase Three randomized trial when it can be administered within eight hours of injury. A recent trial indicates additional benefit by extending the maintenance dose from 24 to 48 hours if start of treatment must be delayed to between three and eight hours after injury. There is an urgent need for more randomized trials of pharmacological therapy for acute spinal cord injury.

Use of health services by insurance status among children with asthma.

OBJECTIVES: It is well known that asthmatic children receiving Medicaid use the emergency department (ED) more frequently than otherwise-insured asthmatic children. However, the extent to which this difference is attributable to provider characteristics, medication use, access to primary care, and symptomatology is poorly understood. These factors were explored as independent predictors of health care utilization. METHODS: Baseline data from a prospective cohort study of childhood asthma severity were used. Subjects were recruited from seven New England hospitals. Home interviews collected data on monthly symptoms, health care visits, insurance status, as well as sociodemographics and asthma-related risk factors (n = 804). Characteristics of providers' practices, board certifications, and asthma specialty were obtained from Folio's Medical Dictionaries for Connecticut and Massachusetts. RESULTS: After adjusting for frequency of asthma-related primary care visits, primary provider practice type, use of asthma specialist, age, gender, medication use, and symptomatology, Medicaid children still used the ED more frequently for asthma services than privately insured children (RR, 1.7; 95% CI, 1.1, 2.5). In general, race/ethnicity did not modify the relationship between insurance status and health care use, except that black children receiving Medicaid were 90% (95% CI, 0.0, 0.7) less likely to have had > or = 3 routine primary care visits for asthma in the previous year than black privately insured children. White children receiving Medicaid were 2.5 (95% CI, 1.0, 6.9) times more likely to use the ED for asthma than privately insured white children. CONCLUSIONS: The results suggest that enabling, structural, and need factors do not necessarily explain observed differences in pediatric asthma health care use by insurance status. Future investigation must explore other explanatory factors such as maternal attitudes and beliefs and patient-provider communication.

Maternal caffeine intake and intrauterine growth retardation.

This study estimates the effect of maternal caffeine consumption throughout pregnancy on fetal growth. We studied 2,714 women who delivered a liveborn infant between 1988 and 1991. Detailed information regarding coffee, tea, and soda drinking during the first and third trimesters of pregnancy was obtained. Average caffeine intake during month 1 of pregnancy was higher than for month 7 (72.4 vs 54.0 mg per day). Consumption of >300 mg caffeine per day during month 1 (adjusted odds ratio = 0.91; 95% confidence interval = 0.44--1.90) and during month 7 (adjusted odds ratio = 1.00; 95% confidence interval = 0.37--2.70) was not associated with intrauterine growth retardation. There was little evidence for any effect modification due to cigarette smoking on the caffeine associations. This study provides evidence that antenatal caffeine consumption has no adverse effect on fetal growth.

A childhood asthma severity scale: symptoms, medications, and health care visits.

BACKGROUND: Although there are current measures to evaluate childhood asthma severity for clinical diagnosis and treatment, there is no standard valid measure to evaluate childhood asthma severity for large-scale epidemiologic studies. OBJECTIVES: To develop and test a childhood asthma severity scale (CHAS) for clinimetric validity and to determine differences in symptoms, medication use, and health care visits by participant characteristics. METHODS: Eight hundred ninety-seven actively asthmatic children under the age of 12 years were selected from a general population of children. Children were selected from a screening questionnaire administered at six Connecticut hospitals that serve large minority populations in Bridgeport, New Haven, Hartford, and Danbury and one hospital serving south central Massachusetts. Twelve-month baseline data for a prospective cohort study of childhood asthma severity were collected on a monthly basis through home interviews. Home interviews addressed questions on daily symptoms, medication use, and health care visits. A severity scale was constructed using three dimensions: symptoms, medication use, and health care visits. RESULTS: CHAS has sufficient preliminary content, construct, and predictive validity. Despite similarities in symptoms, there were health care utilization and medication differentials according to race and ethnicity, insurance status, family income, and maternal education. CONCLUSIONS: CHAS is a potentially useful measure of asthma severity for large-scale epidemiologic studies. It seems that CHAS has sufficient clinimetric properties.

The relation between fungal propagules in indoor air and home characteristics.

BACKGROUND: Questionnaires are commonly used in epidemiologic studies to obtain information about house characteristics in order to predict the household aeroallergen exposure levels. However, the reliability of the predictions made with the questionnaires has not been evaluated. To address this issue, we compared objectively measured fungal propagules including the most frequently isolated mold genera (i.e., Alternaria, Aspergillus, Cladosporium, Penicillium, etc.) in a large sample of homes and compared these measured values to the questionnaire-determined household characteristics. METHODS: As part of a prospective cohort study on the relation between residential allergen exposure and development of asthma in neonates, fungal air samples were collected from infant bedrooms and main living areas in 1000 homes in the Northeast USA, from December 1996 to January 1999. A Burkard portable air sampler was used in combination with DG-18 and MEA agars. A questionnaire was used to obtain information on host and house characteristics that may have an impact on the presence of fungal propagules in the air. This included information on observation of moisture problems (e.g., water leakage or damage, and mold or mildew growth), ventilation and heating facilities, building age and type, number of occupants, annual household income, presence of pets and pests, cleaning regimens, etc. RESULTS: The number of CFU/m3 air collected on MEA was significantly higher than on DG-18 (means, respectively, 1033.5 and 846.0 CFU/m3) (P < 0.0005). However, there was no significant difference between the numbers of CFU/m3 air collected from the main living area and from the infant bedroom. There was only a very weak relationship between the house characteristics, as described by questionnaire, and the presence of fungal propagules in indoor air. Only the temperature, relative humidity, season, and cats inside homes had a statistically significant impact on the presence of fungal propagules in indoor air. CONCLUSION: The presence of fungal propagules in indoor air cannot be reliably predicted by home characteristics. Actual measurements are required for fungal exposure assessment, and the use of only one medium to collect samples in one location in a home might be adequate to represent residential levels of fungi in indoor air.

Methylprednisolone and acute spinal cord injury: an update of the randomized evidence.

OBJECTIVES: Randomized trials are widely recognized as providing the most reliable evidence for assessing efficacy and safety of therapeutic interventions. This evidence base is used to evaluate the current status of methylprednisolone (MPSS) in the early treatment of acute spinal cord injury. METHODS: Medline, CINAHL, and other specified databases were searched for MeSH headings "methylprednisolone and acute spinal cord injury." The Cochrane Library and an existing systematic review on the topic were also searched. RESULTS: Five randomized controlled trials were identified that evaluated high-dose MPSS for acute spinal cord injury. Three trials by the NASCIS group were of high methodologic quality, and a Japanese and French trial of moderate to low, methodologic quality. Meta-analysis of the final result of three trials comparing 24-hour high-dose MPSS with placebo or no therapy indicates an average unilateral 4.1 motor function score improvement (95% confidence interval 0.6-7.6, P = 0.02) in patients treated with MPSS. This neurologic recovery is likely to be correlated with improved functional recovery in some patients. The safety of this regimen of MPSS is evident from the spinal cord injury trials and a systematic review of 51 surgical trials of high-dose MPSS. CONCLUSION: High-dose MPSS given within 8 hours of acute spinal cord injury is a safe and modestly effective therapy that may result in important clinical recovery for some patients. Further trials are needed to identify superior pharmacologic therapies and to test drugs that may sequentially influence the postinjury cascade.

Intergenerational effects of high socioeconomic status on low birthweight and preterm birth in African Americans.

As socioeconomic status (SES) increases, the incidence of low birthweight and preterm birth decreases irrespective of social class. However, low birthweight remains twice as high for African-American women as for white women even when SES is controlled. This study examines to what extent second generation high SES African-American women experience improvement in birthweight and gestational age. One hundred eighty-nine former Meharry students were surveyed. Identified were 934 births that are the children and grandchildren of these students who matriculated at Meharry. These infants are compared with a cohort of white mothers from a study in the School of Public Health at Yale University. Low birthweight was reduced in the third generation high SES African-American children (6.9%) from the second generation (11.4%) but remained higher than white children (3.3%). Results showed that African-American third generation children remained at higher risk for low birthweight than were white children (relative risk [RR], 1.78; 95% confidence interval [CI], 1.03, 3.09). Similar results were observed for preterm delivery where the increased risk to third generation African-American children was 3.16 (1.89, 5.27). Persistent strong ethnic differences in birthweight in this high SES cohort (OR = 3.16, 95% CI, 1.89-5.27) support a conclusion that African-American women have birthweight distributions that are somewhat lighter than white women. This may explain a portion of current ethnic differences in birthweight. It is also possible that persistent psychosocial and behavioral factors continue to negatively influence birthweight, even in second generation high SES African-American mothers. This explanation will require identification of powerful risk factors, which are largely unrelated to those presently under investigation.

Pharmacological interventions for acute spinal cord injury.

BACKGROUND: Acute spinal cord injury is a devastating condition typically affecting young people with a preponderance of males. Pharmacological treatment in the early hours of the injury is aimed at reducing the extent of permanent paralysis during the rest of the patient's life. OBJECTIVES: To review randomized trials of pharmacological therapies for acute spinal cord injury. SEARCH STRATEGY: The review draws on the search strategy developed by the Cochrane Injuries Group. In addition, files of the National Acute Spinal Cord Injury Study have been reviewed. SELECTION CRITERIA: All published or unpublished randomized controlled trials of pharmacological treatment for acute spinal cord injury in any language. DATA COLLECTION AND ANALYSIS: Data have been abstracted from original trial reports. For the NASCIS, Japanese and French trials, additional data (e.g. SDs) have been obtained from the original authors. MAIN RESULTS: There are few trials in this area of medical care. Only one therapy has been extensively studied, methylprednisolone sodium succinate, which has been shown to improve neurologic outcome up to one year post injury if administered within 8 hours of injury and in a dose regimen of: bolus 30mg/kg administered over 15 minutes with a maintenance infusion of 5.4 mg/kg per hour infused for 23 hours. The initial North American trial was replicated in a Japanese trial but not in the one from France. Data has been obtained from the latter study to permit appropriate meta-analysis of all three trials. This analysis indicates significant recovery in motor function after methylprednisolone therapy. A more recent trial indicates that if methylprednisolone therapy is given for an additional 24 hours (for a total of 48 hours), additional improvement in motor neurologic function and functional status is observed. This is particularly observed if treatment cannot be started until between 3 to 8 hours after injury. The same methylprednisolone therapy has been found effective in whiplash injuries and a modified regimen found to improve recovery after surgery for lumbar disc disease. REVIEWER'S CONCLUSIONS: High dose methylprednisolone steroid therapy is the only pharmacological therapy shown to have efficacy in a Phase Three randomized trial when it can be administered within 8 hours of injury. High dose methylprednisolone has been accepted as standard therapy in many countries. A recent trial indicates additional benefit by extending the maintenance dose from 24 to 48 hours if start of treatment must be delayed to between 3 and 8 hours after injury. There is an urgent need for more randomized trials of pharmacological therapy for acute spinal cord injury.