bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic use in ambulatory care in Europe (ESAC data 1997–2002): trends, regional differences and seasonal fluctuations
Authors: Elseviers Monique M. , Ferech Matus , Vander Stichele Robert H. , Goossens Herman ,   the ESAC project group
Published: May 2006

Purpose

The ESAC project (European Study on Antibiotic Consumption) aims to collect antibiotic‐use data through a European network of national surveillance systems. This paper reports on the retrospective data collection in ambulatory care for the period 1997–2002.

Methods

Valid data of antibiotic consumption of 24 European countries for 2002 and of 18 countries for the entire 6‐year period was classified according to the Anatomical Therapeutic Chemical Classification (ATC) and expressed in defined daily dose (DDD) per 1000 inhabitants per day (DID). Overall and subgroup comparison of antibiotic consumption over time as well as between geographical clusters was performed.

Results

Total use of antibiotics in Europe remained at a median level of 20 DID in the period 1997–2002 with a wide variation between countries ranging from 9.8 DID in The Netherlands to 32.2 DID in France. A substantial increase in subclass consumption of co‐amoxiclav and fluoroquinolones was noted while the use of narrow‐spectrum penicillins, erythromycin, quinolones and sulfonamides decreased. Total consumption as well as seasonal fluctuations showed remarkable geographical clustering with low consumption and low variation between summer and winter in the North, high consumption patterns in the South and a mixed model in the East.

Conclusions

Within the ESAC project, valid time series of antibiotic‐use data are publicly available now, enabling to improve the study of determinants of use, the evaluation of governmental antibiotic consumption policies and the investigation of the associated emergence of antibiotic resistance. Copyright © 2006 John Wiley & Sons, Ltd.
Developments of the incidence of osteoporosis in The Netherlands: a PHARMO study
Authors: Goettsch Wim G. , de Jong Romy B. , Kramarz Piotr , Herings Ron M.C.
Published: May 2006

Purpose

To assess recent and to predict future time trends in the incidence of osteoporosis using routine databases in The Netherlands in the period 1993–2015 and to compare estimations based on hip fractures versus a proxy based on pharmacy and hospitalisation data.

Methods

The incidence of hip fractures was estimated over the period 1986–2002 using information from the Dutch Medical Registry, covering more than 99% of all Dutch hospitalisations. Additionally, a proxy (hospitalisation for osteoporosis or osteoporotic fractures, treatment with glucocorticosteroids or treatment with anti‐osteoporosis drugs) was constructed in order to identify osteoporotic patients in the PHARMO database. Age and gender specific incidences of hip fractures and osteoporosis were calculated and extrapolated to The Netherlands. Results of both studies were extrapolated till 2015 using a power function.

Results

The incidence of hip fractures decreased slightly (270 per 100 000 in 1993, 260 per 100 000 in 2002). The incidence of osteoporosis using the constructed proxy decreased from 870 per 100 000 in 1993 to 700 per 100 000 in 2002.

The incidence of hip fractures and osteoporosis remained fairly constant when modelled till 2015. Both studies showed the same time trends.

Conclusion

Both the estimations based on the hospitalisations for hip fracture and on our proxy for osteoporosis showed that the increase in the incidence of osteoporosis as observed in the 1990s is levelling off. Due to ageing of the population the absolute number of hip fractures will however increase. Our definition of osteoporosis resulted in a higher estimation of the incidence of osteoporosis and may be used in future studies to follow developments in osteoporosis prevalence and incidence. Copyright © 2006 John Wiley & Sons, Ltd.
Co‐dispensing of contraindicated medications in patients using cisapride in Italy
Authors: Staniscia Tommaso , Romano Ferdinando , Festi Davide , Bilker Warren B. , Macones George A. , Strom Brian L.
Published: May 2006

Purpose

To investigate the co‐dispensing of contraindicated medications in patients using cisapride in an Italian population.

Methods

The study included patients who had at least one cisapride prescription dispensed between 1 April 1997 and 30 September 2000. The proportion of cisapride users with concomitant medications, the proportion of prescriptions of cisapride with an overlapping dispensing of a contraindicated medication and the proportion of person‐days of cisapride use concomitant with contraindicated medications, were calculated.

Results

In the 4‐year study period, 249 740 total cisapride prescriptions, which corresponded to 382 835 packages, were dispensed to 91 204 users (52 442 female, 57.5%). Concomitant use of contraindicated drugs was identified in 4403 cisapride users (4.83%). Throughout the study period, there was an increase in the proportion of cisapride users with contraindicated co‐prescriptions: 4.29% in 1997, 4.99% in 1998, 5.15% in 1999, but a decline to 3.34% in 2000. In each year, this figure was higher in males, with the highest proportion reported in 1999 (5.50%). A total of 7215 cisapride prescriptions (2.85%) were concomitant with contraindicated drugs, ranging from 2.27% in September 1998 to 3.55% in January 1999. Cisapride prescriptions were most frequently associated with macrolide antibiotics (1.14%) and class III antiarrhythmics (1.03%).

Conclusions

In the period 1997–2000, a substantial proportion of cisapride prescriptions were concomitant with contraindicated medications. In Italy in 1998, the National Health Authority issued a bulletin warning about the risk of serious arrhythmias after concomitant use of contraindicated drugs. Despite this warning, there was no reduction in contraindicated drug uses. Copyright © 2006 John Wiley & Sons, Ltd.
Measuring change in prescription drug utilization in Australia
Authors: Mandryk John A. , Mackson Judith M. , Horn Fiona E. , Wutzke Sonia E. , Badcock Caro‐Anne , Hyndman Rob J. , Weekes Lynn M.
Published: May 2006

Purpose

The National Prescribing Service Ltd (NPS) aims to improve prescribing and use of medicines consistent with evidence‐based best practice. This report compares two statistical methods used to determine whether multiple educational interventions influenced antibiotic prescription in Australia.

Methods

Monthly data (July 1996 to June 2003) were obtained from a national claims database. The outcome measures were the median number of antibiotic prescriptions per 1000 consultations for each general practitioner (GP) each month, and the mean proportion (across GPs) of each subgroup of antibiotics (e.g. roxithromycin) out of nine antibiotics having primary use for upper respiratory tract infection. Two approaches were used to investigate shifts in prescribing: augmented regression, which included seasonality, autocorrelation and one intervention; and seasonally adjusted piecewise linear dynamic regression, which removed seasonality prior to modelling, included several interventions, GP participation and autocorrelated errors. Both methods are variations of piecewise linear regression modelling.

Results

Both approaches described a similar decrease in rates, with a non‐significant change after the first intervention. The inclusion of more interventions and GP participation made no difference. Using roxithromycin as an example of the analyses of proportions, both approaches implied that after the first intervention the proportion decreased significantly. The statistical significance of this intervention disappears when other interventions are included.

Conclusions

The two analyses provide results which agree regarding the possible impact of the NPS interventions, but raise questions about what is the best way to model drug utilization, particularly regarding whether to include all intervention terms when they belong to an extended roll‐out of related interventions. Copyright © 2006 John Wiley & Sons, Ltd.
The nature of the scientific evidence leading to drug withdrawals for pharmacovigilance reasons in France
Authors: Olivier Pascale , Montastruc Jean‐Louis
Published: May 2006

Introduction

Because of design, objectives and number of included subjects, clinical studies are insufficient to assess the safety of new drugs. Sometimes, serious adverse drug reactions (ADRs) led to withdrawal of the drug from the market after their approval. The objective of our study was to determine the scientific evidences leading to drug withdrawal for pharmacovigilance reasons in France.

Methods

Data coming from French Health Products Safety Agency, literature and Toulouse Pharmacovigilance Center allowed to identify all drugs withdrawn from the French market for pharmacovigilance reasons from 1998 to 2004. We classified data according to their study design (Randomized Clinical Trial [RCT], case serie or case report, case‐control study, cohort study, observational study, animal study), the organ/system affected and the type of ADR.

Results

A total of 21 drugs were withdrawn for safety reasons between 1998 and 2004 in France. The most frequent ADRs were hepatic (n = 7), cardiovascular (n = 4) or neurological (n = 3) ones. Eleven withdrawals were due to type‐B (‘unexpected’) reactions (52%). For 19 out of 21 drugs, scientific evidence leading to drug withdrawal came from spontaneous case reports (or case series). Among these, case reports were the sole evidence in 12 cases. Withdrawals were based on evidence from case reports in combination with case‐control or cohort study in four cases, in combination with observational study in two cases or in combination with animal study in two other cases. In only one case, a RCT supported the decision.

Conclusions

This study underlines the importance of spontaneous case reports in detecting signals and supporting withdrawal of drug for pharmacovigilance reasons in France. Health authorities suffer from lack of comparative data resource. In this perspective, a pharmaco‐epidemiological population‐based database could represent a helpful tool to both generate and test safety hypotheses. Copyright © 2006 John Wiley & Sons, Ltd.
Quality of manufacturer provided information on safety and efficacy claims for dietary supplements for colonic health
Authors: Hass David J. , Lewis James D.
Published: May 2006

Purpose

Food and Drug Administration (FDA) approval of dietary supplements is not required. However, manufacturers must ensure that data exist to support safety and efficacy claims of their product. This study was designed to evaluate accessibility and quality of such data from manufacturers of dietary supplements for ‘colonic health.’

Methods

Supplements promoting ‘colonic health’ were identified at area stores. A physician contacted the manufacturers by mail and telephone requesting data to substantiate claims of efficacy and safety. MEDLINE was searched to identify reports of adverse events or medication interactions.

Results

Twelve manufacturers of 23 products were surveyed. Eight manufacturers responded, of whom four provided no clinical data to substantiate claims of efficacy or safety. No manufacturer provided data that directly evaluated their product. Our literature review identified a wide range of potential adverse events and drug‐supplement interactions, albeit mostly as case reports, animal studies, or in vitro experiments.

Conclusions

There is a need to increase availability of supplement safety data to physicians and the general public. Consideration should be given to various responses, including legislative actions that address this issue. Copyright © 2006 John Wiley & Sons, Ltd.
How is leflunomide prescribed and used in Australia? Analysis of prescribing and adverse effect reporting
Authors: Chan Vivien , Tett Susan E.
Published: May 2006

Purpose

To evaluate the use of leflunomide in the Australian community since introduction in 2000. Trends in adverse drug reaction (ADR) reporting were also studied.

Methods

Annual Australian prescription and dispensing statistics were analysed. Drug utilisation was estimated as defined daily doses (DDD)/1000 inhabitants/day. ADR data from the Therapeutic Goods Administration's Adverse Drug Reactions Advisory Committee (ADRAC) national monitoring system were compared with the World Health Organisation (WHO) Vigibase records.

Results

Leflunomide use in Australia (dispensing data) increased from 0.2 in 2000 to 0.4 DDD/1000 inhabitants/day in 2002. The same overall pattern was observed in the ‘authority to prescribe’ data. From 2000–2002, prescribing of the starter pack (3 × 100 mg loading dose plus 30 × 20 mg tablets) declined (down 74%); likewise for the 20 mg (30 tablets) pack. Gradual increases were noted for the 10 mg (30 tablets) pack (up 40%). Approximately 135 reports, detailing about 370 individual ADR, were generated annually. Gastro‐intestinal disorders predominated, accounting for 24% of reactions reported to ADRAC. Skin and appendages disorders constituted 14% of reported reactions. Deaths in leflunomide users were attributed to a combination of haematological and gastro‐intestinal complications, but it was not possible to ascertain other medication usage or contributing factors. Trends observed with the ADRAC reports were consistent with the WHO database.

Conclusions

Leflunomide was the first registered DMARD in Australia in over a decade and its use has increased within the community. The ADR reports might have contributed to Australian rheumatologists gradually abandoning loading patients with high doses of leflunomide in favour of starting therapy at lower doses. Copyright © 2006 John Wiley & Sons, Ltd.
Systemic lupus erythematosus prevalence in the U.K.: methodological issues when using the General Practice Research Database to estimate frequency of chronic relapsing‐remitting disease
Authors: Nightingale A. L. , Farmer R. D. T. , de Vries C. S.
Published: May 2006

Purpose

The purpose of this study was to calculate the prevalence of systemic lupus erythematosus (SLE) between 1992 and 1998 using the General Practice Research Database (GPRD)

Methods

We identified all individuals who had contributed at least 3 years of data to the GPRD and who had a diagnosis of SLE with supporting evidence of their diagnosis. We calculated the annual age‐ and sex‐specific prevalence of SLE. Additionally, we stratified the prevalence by years of data contributed to the GRPD.

Results

In males the point estimate of the prevalence of SLE increased from 7.5/100 000 (CI95 6.3, 8.8) to 10.1/100 000 (CI95 7.8, 12.2) but this rise was not statistically significant. However, prevalence appeared to increase significantly amongst females from 42.6/100 000 (CI95 39.6, 45.6) in 1992 to 70.8/100 000 (CI95 65.1, 76.6) in 1998. This increase was mainly amongst women aged 50–79 and in those contributing more than 5 years of data and could not be explained by increasing incidence of SLE or decreasing mortality during the study period.

Conclusions

We found an increasing prevalence of SLE that could not be explained by increasing incidence or decreasing mortality. This is almost certainly an artefact caused by the increased likelihood of detecting or confirming cases of chronic relapsing‐remitting diseases with increasing time contributed to the GPRD. Copyright © 2006 John Wiley & Sons, Ltd.
Changes in use of disease‐modifying anti‐rheumatic drugs in Australia over the period 1992–2004
Authors: Chan Vivien , Tett Susan E.
Published: May 2006

Purpose

Evidence is growing that early use of disease‐modifying anti‐rheumatic drugs (DMARDs) and combinations of these drugs provide optimal care for people with rheumatoid arthirits. The aim of this study was to describe objectively the pattern of consumption of DMARDs in the Australian community (community‐based prescribing, specialist and general practitioner) 1992–2004, and to compare this with prescribing patterns reported in other countries.

Method

Dispensing statistics from the Pharmaceutical Benefit Scheme (PBS—Australia's universal prescription subsidy scheme) were analysed and temporal trends evaluated. Drug consumption was calculated as the number of dispensed defined daily doses (DDD)/1000 inhabitants/day (WHO ATC/DDD classification 2005).

Results

The consumption of DMARDs in the Australian community increased steadily from 2.6 DDD/1000 inhabitants/day in 1992 to 5.5 DDD/1000 inhabitants/day. Over the period 1992–2004, methotrexate (MTX) was the most commonly used DMARD (from 0.6 to 3.0 DDD/1000 inhabitants/day). Consumption of gold (parenteral and oral) and penicillamine declined during this time. The inclusion of leflunomide on the PBS in 2000 contributed to the increase in DMARD usage.

Conclusion

Use of DMARDs within the Australian community has increased in recent years, coinciding with the change in guidelines for therapy for rheumatoid arthritis (RA) to earlier use of DMARDs and the more common use of combinations. This study used DDD methodology to quantify trends for DMARD consumption and these trends are broadly consistent with international prescribing patterns assessed using different methodologies. Copyright © 2006 John Wiley & Sons, Ltd.
Anxiolytics, hypnotics, and antidepressants dispensed to adolescents in a French region in 2002
Authors: Mancini Julien , Thirion Xavier , Masut Alain , Saillard Carine , Pradel Vincent , Romain Fanny , Pastor Marie‐Joseph Jean , Coudert Christine , Micallef Joëlle
Published: May 2006

Purpose

This study proposes to complete declarative studies by describing the prescriptions of anxiolytics, hypnotics, and antidepressants dispensed to adolescents in a French region in 2002.

Methods

This cross‐sectional study analyzes all the hypnotic, anxiolytic, and antidepressant prescriptions (ATC codes beginning with N05B, N05C, and N06A, respectively) sent by adolescents (aged 13–17 years) to the French Health Insurance system of the study region for reimbursement during one year (2002). It was performed in a southern France area with 120 908 adolescents covered by this insurance scheme. Adverse drug reactions (ADRs) recorded in the Pharmacovigilance database were also studied.

Results

Three thousand two hundred and eighty‐six adolescents (2.7% of adolescent population) had at least one prescription of the studied drugs. This prevalence increased with age and female sex, leading to a maximum of 6.3% for the 17‐year‐old girls. Two thousand four hundred and thirty‐one of adolescents were dispensed anxiolytics, 935 antidepressants, and 548 hypnotics. The most dispensed drugs were zolpidem, zopiclone, and niaprazine for hypnotics; hydroxyzine, etifoxine, and bromazepam for anxiolytics; and paroxetine, sertraline, and fluoxetine for antidepressants. Zolpidem, hydroxyzine, and paroxetine accounted, respectively, for 82.9%, 57.1%, and 59.8% of the prescriptions. 75.5% of hypnotics users had only one prescription, 77.4% for anxiolytics, and 57.4% for antidepressants. Three ADRs were reported.

Conclusions

This study confirms the large use of psychotropics in French adolescents and the influence of age and sex. Also, the results underline treatment for most adolescents is short, which may be beneficial for hypnotics and anxiolytics but not for antidepressants. Copyright © 2006 John Wiley & Sons, Ltd.
Six‐minute walk test in children and adolescents with cystic fibrosis
Authors: Cunha Maristela Trevisan , Rozov Tatiana , de Oliveira Rosangela Caitano , Jardim José R.
Published: May 2006

The 6‐min walk test is a simple, rapid, and low‐cost method that determines tolerance to exercise. We examined the reproducibility of the 6‐min walk test in 16 children with cystic fibrosis (11 female, 5 male; age range, 11.0 ± 1.9 years). We related the distance walked and the work performed (distance walked × body weight) with nutritional (body mass index and respiratory muscle strength) and clinical (degree of bronchial obstruction and Shwachman score) status. Patients were asked to walk as far as possible upon verbal command on two occasions. There was no statistical difference between distances walked (582.3 ± 60 and 598.2 ± 56.8 m, P = 0.31), heart rate, respiratory rate, pulse oxygen saturation, arterial blood pressure, dyspnea, and percentage of maximal heart rate for age in the two tests. Distance walked correlated (Pearson) with maximal expiratory pressure (98.6 ± 28.1 cmH2O, r = 0.60, P < 0.01), maximal heart rate (157.9 ± 10.1 bpm, r = 0.59, P < 0.02), Borg dyspnea scale (1.7 ± 2.4, r = 0.55, P < 0.03), and double product (blood pressure × heart rate; r = 0.59, P < 0.02). The product of distance walked and body weight (work) correlated (Pearson) with height (r = 0.83, P = 0.000), maximal expiratory pressure (r = 0.64, P < 0.01), systolic blood pressure (r = 0.56, P < 0.02), and diastolic blood pressure (r = 0.55, P < 0.03). We conclude that the 6‐min walk test is reproducible and easy to perform in children and adolescents with cystic fibrosis. The distance walked was related to the clinical variables studied. Work in the 6‐min walk test may be an additional parameter in the determination of physical capacity. Pediatr Pulmonol. 2006; 41: 618–622. © 2006 Wiley‐Liss, Inc.
Clinical scoring systems in cystic fibrosis
Authors: Hafen Gaudenz M. , Ranganathan Sarath C. , Robertson Colin F. , Robinson Philip J.
Published: May 2006

The first cystic fibrosis (CF) scoring system was published in 1958. Since then, many other scoring systems were developed. Clinical parameters, details about statistical evaluations, and recent strategic uses of scores were identified. Several similar scores aiming to assess chronic illness severity (Shwachman‐Kulczycki score and a modification, Cooperman, Berneze‐score and the NIH score) have not been evaluated and are out of date, given the changing natural history of CF. Of the current scoring systems, the modified Shwachman score by Doershuk is perhaps most reliable for describing follow‐up studies. Scores designed for acute changes and short‐term evaluation were also developed. The modified Huang score may be useful in the prognostic evaluation of patients with end‐stage disease. It could also be used for discrimination of adult patients with differing disease severity and for longitudinal evaluation. Scores assessing pulmonary exacerbations could help provide consensus among clinicians regarding the need for intervention. Most of these scores require further evaluation. Although scores could provide an objective measure of disease severity, progression, need for and response to interventions, including value in selecting patients for lung transplantation and as an outcome measure for research studdies, no scoring system can fulfill all these objectives. Nevertheless, there is a need for the development of a modern day longitudinal score that is sensitive, valid and reproducible, to reflect the milder disease status of patients. Pediatr Pulmonol. 2006; 41: 602–617. © 2006 Wiley‐Liss, Inc.
Superior vena cava syndrome related to indwelling intravenous catheters in patients with cystic fibrosis
Authors: Garwood Susan , Flume Patrick A. , Ravenel James
Published: May 2006

Patients with cystic fibrosis (CF) often need long‐term implanted vascular‐access devices for intravenous antibiotics for chronic lower respiratory tract infections. These devices are not without complications, including infection, occlusion, and vascular thrombosis. Such thrombosis can result in superior vena cava (SVC) syndrome due to the position of the catheter proximal to the right atrium. SVC syndrome in CF patients, however, is rarely reported in the literature, suggesting that its incidence is uncommon. We describe three patients with SVC syndrome as a consequence of implanted vascular‐access devices. Pediatr Pulmonol. 2006; 41: 683–687. © 2006 Wiley‐Liss, Inc.
Complication of mediastinal mass: Acquired tracheoesophageal fistula associated with T‐cell lymphoblastic lymphoma
Authors: Moree John S. , Bhakta Manoo G. , Ledbetter Joel
Published: May 2006

The occurrence of a tracheoesophageal fistula (TEF) in the setting of lymphoma has only rarely been reported in the world literature. Most cases reported were associated with radiation therapy vs. chemotherapy alone. This report presents one case illustrating the difficulty encountered managing a TEF that developed while undergoing chemotherapy for T‐cell lymphoblastic lymphoma. Pediatr Pulmonol. 2006; 41: 688–689. © 2006 Wiley‐Liss, Inc.
Necrotizing pneumococcal pneumonia in children: The role of pulmonary gangrene
Authors: Hsieh Yu‐Chia , Hsiao Cheng‐Hsiang , Tsao Po‐Nien , Wang Jann‐Yuan , Hsueh Po‐Ren , Chiang Bor‐Luen , Lee Wen‐Sen , Huang Li‐Min
Published: May 2006

Little is known about the mechanism of necrotizing pneumonia caused by Streptococcus pneumoniae in children. Pulmonary gangrene secondary to vascular thrombosis was reported in adults with necrotizing pneumococcal pneumonia. We conducted a retrospective study of 15 children with a diagnosis of necrotizing pneumococcal pneumonia at National Taiwan University Hospital to explore its association with pulmonary gangrene, based on evidence from chest computed tomography, serial chest radiographic patterns, and pathologic results. S. pneumoniae serotype 14 was the prevalent pneumococcal serotype. Overall, 63.6% of isolates were not susceptible to penicillin. One child with pneumonia caused by S. pneumoniae serotype 3 complicated by hemolytic uremic syndrome had a rapidly fatal course. An autopsy in this patient documented lung necrosis and pulmonary gangrene. Radiographic follow‐up was performed during the clinical course in 9 patients, and showed no evidence of pulmonary gangrene. Four children had no radiographic follow‐up. The relationship between pulmonary gangrene and necrotizing pneumonia was unclear in the remaining one. In conclusion, necrotizing pneumococcal pneumonia may be infrequently associated with pulmonary gangrene in children. Pediatr Pulmonol. 2006; 41: 623–629. © 2006 Wiley‐Liss, Inc.
Zinc status in infantile wheezing
Authors: Tahan Fulya , Karakukcu Cigdem
Published: May 2006

The increase in prevalence of asthma is strongly dependent on environmental factors, including diet. Significant decreases in the intake of dietary zinc may be an important contributing factor to the increasing incidence of wheezing and asthma, but there have been no studies evaluating zinc levels in wheezy infants. Our objective was to investigate the zinc status of wheezy infants. Wheezy infants (n = 34) and healthy children (n = 14) were included in the study. Total IgE and eosinophil counts were obtained, and skin testing was done with a battery of 25 antigens with appropriate positive and negative controls. Levels of zinc were determined in hair, using a Polarized Zeeman Atomic Absorption Spectrophotometer (Hitachi Z‐800). No significant difference was observed in peripheral blood eosinophil counts and total IgE levels among groups (P > 0.05). Hair zinc levels were significantly lower in wheezy infants (P < 0.001). In conclusion, hair zinc levels were lower in wheezy infants than in healthy controls, suggesting that zinc deficiency may influence the risk of wheezing in early childhood. Pediatr Pulmonol. 2006; 41: 630–634. © 2006 Wiley‐Liss, Inc.
Conservative treatment of spontaneous tracheal rupture
Authors: Akyol Ahmet , Çay Ali , İmamoglu Mustafa , Ulusoy Hülya , Özen İbrahim
Published: May 2006

Spontaneous tracheobronchial ruptures are uncommon injuries, especially in the pediatric age group. Tracheal injuries, independent of their origin, may be life‐threatening. Here we present the first report of a 14‐year‐old boy who presented with subcutaneous emphysema, pneumomediastinum, and pneumothorax on day 3, due to spontaneous posterior tracheal‐wall rupture following paroxysmal productive coughing. The diagnosis was established using a computed tomography scan of the chest, and tracheobronchoscopy and esophagoscopy under general anesthesia. He was endotracheally intubated and ventilated in the intensive care unit. Such tracheal defects, bridgeable by an endotracheal tube, may permit conservative treatment. The patient was discharged on day 10, and follow‐up revealed no late complications. Pediatr Pulmonol. 2006; 41: 690–693. © 2006 Wiley‐Liss, Inc.
Exhaled nitric oxide in healthy nonatopic school‐age children: Determinants and height‐adjusted reference values
Authors: Malmberg L.P. , Petäys T. , Haahtela T. , Laatikainen T. , Jousilahti P. , Vartiainen E. , Mäkelä M.J.
Published: May 2006

Exhaled nitric oxide (FENO) was proposed as a marker of airway inflammation, but data about FENO in healthy children measured with standardized methods are so far limited. In order to assess the determinants of FENO in healthy children, we investigated a population‐based sample of school‐age children (n = 276) with a questionnaire, skin‐prick tests, spirometry, and the measurement of FENO. The FENO of 114 nonatopic and nonsmoking children considered healthy were analyzed with stepwise multiple regression analysis, which showed significant associations with age, standing height, weight, and body surface area, but not with gender. Height was found to be the best independent variable for the regression equation for FENO, which on average showed an increase in the height range of 120–180 cm from 7 to 14 ppb. In the random sample of children, increased FENO was associated with atopy (odds ratio, 9.0; 95% confidence interval, 3.9–21.1; P < 0.0001), and significantly with allergic rhinitis and atopic dermatitis, but not with asthma. Respiratory symptom‐free children with skin‐prick test positivity had significantly higher FENO than healthy nonatopic subjects. We conclude that height is the best determinant of FENO in healthy children. Due to the strong effect of atopy, FENO data should not be interpreted without knowing the atopic status of the child. The present reference values of FENO may serve in clinical assessments for measuring airway inflammation in children. Pediatr Pulmonol. 2006; 41: 635–642. © 2006 Wiley‐Liss, Inc.
Primary pulmonary Hodgkin's disease and tuberculosis in an 11‐year‐old boy: Case report and review of the literature
Authors: Codrich Daniela , Monai Margherita , Pelizzo Gloria , Bussani Rossana , Rabusin Marco , Guastalla Pierpaolo , Barbi Egidio , Schleef Jürgen
Published: May 2006

Tuberculosis (TB) has been described in association with different malignancies including Hodgkin's disease. However, the association with primary pulmonary Hodgkin's disease (PPHD) is hardly reported in literature and in teenage is quite exceptional. We report a case of an 11 years old boy in whom the diagnosis of tuberculosis preceded and delayed the diagnosis of PPHL. Pediatr Pulmonol. 2006; 41: 694–698. © 2006 Wiley‐Liss, Inc.
Association of birth weight with asthma‐related outcomes at age 2 years
Authors: Taveras Elsie M. , Camargo Carlos A. , Rifas‐Shiman Sheryl L. , Oken Emily , Gold Diane R. , Weiss Scott T. , Gillman Matthew W.
Published: May 2006

Background

Although lower birth weight associated with prematurity raises the risk of asthma in childhood, few prospective studies have examined higher birth weight, and few have separated the two components of birth weight, fetal growth and length of gestation.

Objective

To examine the associations of fetal growth and length of gestation with asthma‐related outcomes by age 2 years.

Methods

We studied 1,372 infants and toddlers born after 34 weeks' gestation in Project Viva, a prospective cohort study of pregnant mothers and their children. The main outcome measures were parent report of (1) any wheezing (or whistling in the chest) from birth to age 2 years, (2) recurrent wheezing during the first 2 years of life, and (3) doctor's diagnosis of asthma, wheeze or reactive airway disease (“asthma”) by age 2. We calculated gestational age from the last menstrual period or ultrasound examination, and determined birth weight for gestational age z‐value (“fetal growth”) using US national reference data.

Results

Infants' mean birth weight was 3,527 (SD, 517; range, 1,559–5,528) grams. By age 2 years, 34% of children had any wheezing, 14% had recurrent wheezing, and 16% had doctor‐diagnosed asthma. After adjusting for several parent, child, and household characteristics in logistic regression models, we found that infants with birth weight ≥4,000 g were not more likely to have any wheezing (odds ratio (OR), 0.91; 95% confidence interval (CI): 0.62, 1.34) or doctor‐diagnosed asthma (OR, 0.80; 95% CI: 0.49, 1.31) than infants with birth weight 3,500–3,999 g. In models examining length of gestation and fetal growth separately, neither the highest nor the lowest groups of either predictor were associated with the three outcomes. Boys had a higher incidence of asthma‐related outcomes than girls, and exposure to passive smoking, parental history of asthma, and exposure to older siblings were all associated with greater risk of recurrent wheeze or asthma‐related outcomes at age 2 years.

Conclusion

Although male sex, exposure to smoking, parental history of asthma, and exposure to older siblings were associated with increased risk of wheezing and asthma‐related outcomes in this prospective study of children born after 34 weeks gestation, fetal growth and length of gestation were not. Pediatr Pulmonol. 2006; 41: 643–648. © 2006 Wiley‐Liss, Inc.
Lack of association between NOS2 pentanucleotide repeat polymorphism and asthma phenotypes or exhaled nitric oxide concentration
Authors: Leung Ting F. , Liu Eric K.H. , Li Chung Y. , Chan Iris H.S. , Yung Edmund , Lam Christopher W.K. , Wong Gary W.K.
Published: May 2006

Nitric oxide (NO) plays an immunoregulatory role in balancing cellular immunity. The expression of inducible nitric oxide synthase gene (NOS2) is upregulated upon exposure to proinflammatory cytokines and microbial exposure. The (CCTTT)n polymorphism in NOS2 promoter confers protection against infections and immunological disorders including atopy. We investigated the association between (CCTTT)n and asthma traits in Chinese children. Asthmatic children between 5 and 18 years of age and non‐allergic controls were recruited. Plasma total and specific IgEs were measured by immunoassays, and exhaled NO concentration was quantified online by chemiluminescence. NOS2 (CCTTT)n was genotyped by GeneScan analysis. The mean (SD) age of 291 asthmatics and 172 controls were 11.1 (3.8) years and 11.6 (4.0) years, respectively (P = 0.259). NOS2 (CCTTT)n followed Hardy–Weinberg equilibrium in both groups, and its uni‐modal allele distribution peaks at 12‐repeat. Significant interethnic differences in (CCTTT)n alleles were observed, with our Chinese having less 13‐repeat (Pc = 0.022) but more 17‐repeat (Pc = 0.033) than Caucasians. The frequency of 14‐repeat allele was similar in our Chinese as compared to Japanese (Pc = 0.32). Multivariate regression analyses failed to detect any association between this polymorphic marker and asthma diagnosis (P = 0.949), atopy (P = 0.305), IgE sensitization to aeroallergens (P > 0.2 for all), or FeNO (P = 0.847). These findings do not support NOS2 to be a major candidate gene for asthma or IgE‐mediated allergic diseases in Chinese children. Pediatr Pulmonol. 2006; 41: 649–655. © 2006 Wiley‐Liss, Inc.
Microbiology, safety, and pharmacokinetics of aztreonam lysinate for inhalation in patients with cystic fibrosis
Authors: Gibson Ronald L. , Retsch‐Bogart George Z. , Oermann Christopher , Milla Carlos , Pilewski Joseph , Daines Cori , Ahrens Richard , Leon Kevin , Cohen Morty , McNamara Sharon , Callahan Tracy L. , Markus Richard , Burns Jane L.
Published: May 2006

Background

Aztreonam lysinate for inhalation (AI) is a novel monobactam formulation being investigated for pulmonary Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF).

Methods

Pre‐clinical studies investigated the pre‐ and post‐nebulization activity of AI and its activity in the presence of CF sputum. A double‐blind, placebo‐controlled, dose‐escalation trial determined pharmacokinetics and tolerability of AI in subjects with CF. Single daily escalating doses of AI 75, 150, or 225 mg, or placebo were self‐administered using an eFlow® Electronic Nebulizer. Sputum samples were collected up to 4 hr and blood samples up to 8 hr post‐dose.

Results

AI activity against multiple CF isolates was retained after nebulization via eFlow, and activity was not inhibited by CF sputum. All 12 adult subjects and 11/12 adolescents tolerated all AI doses. One patient had an asymptomatic FEV1 decrease >20% with the 150 mg dose. Median aztreonam sputum concentrations in adults 10 min after AI 75, 150, and 225 mg were 383, 879, and 985 µg/g, respectively. Median sputum concentrations in adolescents 10 min after AI 75, 150, and 225 mg were 324, 387, and 260 µg/g, respectively. Systemic exposure to AI was low. Plasma pharmacokinetics in adults receiving AI 75 mg were Cmax = 419 ng/g, Tmax = 0.99 hr, t1/2 = 2.1 hr. Aztreonam concentrations in sputum were at or above the MIC50 for at least 4 hr post‐dose.

Conclusion

These data support the continued development of AI for treatment of pulmonary infections in patients with CF. Pediatr Pulmonol. 2006; 41: 656–665. © 2006 Wiley‐Liss, Inc.
Nebulized therapies for childhood pulmonary hypertension: An in vitro model
Authors: Katz Sherri L. , Adatia Ian , Louca Emily , Leung Kitty , Humpl T. , Reyes Janette T. , Coates Allan L.
Published: May 2006

Objectives

Sildenafil, tezosentan, and prostacyclin reduce pulmonary vascular pressures in pulmonary hypertension, but have potential to vasodilate the systemic circulation. Nebulized vasodilators allow targeted drug delivery, high local drug concentrations, less systemic hypotension, and better matching of the lung's ventilation and perfusion. We aimed to estimate pulmonary deposition of these drugs from commonly employed nebulizers using in vitro techniques and to create a mathematical model to predict inspired mass of aerosol.

Design

Lung deposition was estimated by characterization of drug output and particle size distribution (PSD) of nebulizers using helium‐neon laser diffraction techniques. A mathematical model for each device was created to estimate pulmonary deposition using patients' breathing patterns and was verified with a mechanical‐breathing model.

Results

Total output and PSD were similar for the Hudson Updraft II and Whisperjet nebulizers, consisting of half the nebulizer's charge, with ¼ of particles ≤5 µm, in the respirable fraction (RF). Drug output increased with inspiratory flow for the Pari LC Star. Differences were noted in device performance, depending on the drug tested. Estimated pulmonary deposition (mean, 95% CI) was 8.1 (7.2, 9.0)% of the initial drug charge for the Hudson Updraft II, 6.4 (5.8, 7.0)% for the Whisperjet, and 33.0 (28.3, 37.9)% for the Pari LC Star. A mechanical model was consistent with our mathematical model.

Conclusions

All drugs could be nebulized, but expected pulmonary deposition varied depending on the nebulizer and drug. Pediatr Pulmonol. 2006; 41: 666–673. © 2006 Wiley‐Liss, Inc.
Plasma concentrations of soluble CTLA‐4, CD28, CD80 and CD86 costimulatory molecules reflect disease severity of acute asthma in children
Authors: Ip W.K. , Wong C.K. , Leung T.F. , Lam C.W.K.
Published: May 2006

Recent studies have demonstrated an elevation of plasma soluble costimulatory molecules B7.1 (CD80) and B7.2 (CD86), and their T lymphocyte counter receptors cytotoxic T lymphocyte associated antigen‐4 (CTLA‐4) and CD28 in asthmatic patients. We hypothesized that these costimulatory molecules may reflect the severity of asthma and investigated the longitudinal changes of these soluble costimulatory molecules, and their clinical significance in children with an asthmatic exacerbation. Sixteen children hospitalized for asthmatic exacerbation were recruited and treated with systemic corticosteroid (CS) for 5 days. Plasma total Immunoglobulin E (IgE) and eosinophil cationic protein (ECP) concentrations were measured by microparticle immunoassay and fluorescence enzyme immunoassay, respectively. Soluble CTLA‐4 (sCTLA‐4), sCD28, sCD80, and sCD86 concentrations in plasma were measured by enzyme‐linked immunosorbent assay, and their relationships with asthma severity, total IgE, ECP concentrations, and blood eosinophil count were analyzed. Plasma sCTLA‐4, sCD28, sCD80, and sCD86 concentrations in patients were highest during the acute attack. They decreased significantly with a parallel increase of peak expiratory flow rate (PEFR) after CS treatment (all P < 0.05). Plasma sCTLA‐4, sCD28, and sCD86 concentrations of patients at recruitment were inversely correlated with PEFR, whereas plasma sCD28 and sCD86 concentrations correlated positively with eosinophil count and plasma ECP concentration (all P < 0.05). Although there was no such correlation with IgE concentration, sCD28 was correlated very significantly with eosinophil count (r = 0.83, P < 0.0001). In conclusion, plasma sCTLA‐4, sCD28, sCD86, and sCD80 concentrations may reflect the severity of acute asthma and more studies on larger cohorts are needed to assess whether these markers are useful for assessing asthmatic exacerbation in children. Pediatr Pulmonol. 2006; 41: 674–682. © 2006 Wiley‐Liss, Inc.
HighfTandfmaxAlGaN/GaN HFETs achieved by using thin and high‐Al‐composition AlGaN barrier layers and Cat‐CVD SiN passivation
Authors: Higashiwaki M. , Onojima N. , Matsui T. , Mimura T.
Published: May 2006

We fabricated sub‐0.1 μm‐gate Al0.4Ga0.6N/GaN heterostructure field‐effect transistors (HFETs) with AlGaN barrier thicknesses of 4–10 nm. The devices were passivated with 2 nm‐thick SiN layers formed by catalytic chemical vapor deposition (Cat‐CVD). The Cat‐CVD SiN passivation greatly increased electron density, and the effect became more significant with decreasing AlGaN barrier thickness. The HFETs had maximum drain current densities of 1.1–1.5 A/mm and peak extrinsic transconductances of 305–438 mS/mm. Peak current‐gain cutoff frequency of 163 GHz and maximum oscillation frequency of 192 GHz were obtained for the devices with 8 nm‐thick AlGaN barriers. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Conduction and valence band edge properties of hexagonal InN characterized by optical measurements
Authors: Ishitani Y. , Terashima W. , Che S. B. , Yoshikawa A.
Published: May 2006

The optical properties of hexagonal InN crystal are investigated by reflectance, absorption and photoluminescence method. With use of the theoretical formula of these spectra, both of conduction and valence band properties are analysed. As a result, the average effective electron and hole mass values at the band edge are found to be about 0.046(±0.01)m 0 and 0.2(±0.05)m 0, respectively. The photoluminescence emitted from the cleaved edge was strongly polarized. The agreement of the peak energies of π and σ polarized light means that A, B, and C band edges are closely located in energy space. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Influence of gas composition on the synthesis of gallium nitride powders by two‐stage chemical vapor method
Authors: Hara K. , Yonemura A. , Uchida T.
Published: May 2006

The systematic characterization of undoped GaN powders was carried out focusing on the composition of gases at the second stage of particle growth in the two‐stage chemical vapor synthesis. The particle growth proceeded on the surface of GaN seed particles transported from the first stage with sources of GaCl and NH3 at 1000 °C. The GaN particles grew very fast at the second stage, and their size increased monotonically with increasing partial pressure of GaCl (P (GaCl)). The photoluminescence (PL) property and the crystallinity tended to decrease with P (GaCl), whereas they were improved for higher partial pressures of NH3. Based on these results, we have shown that both of high‐rate growth and excellent PL property of GaN particles can be achieved by the two‐stage chemical vapor synthesis. Addition of H2 to the ambient gas caused degradation of the luminescence property and the crystalline quality as well as decrease in the particle size. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fabrication of GaN‐based striped structures along the <11$ \bar 2 $0> direction by the combination of RIE dry‐etching and KOH wet‐etching techniques to recover dry‐etching damage
Authors: Itoh Morimichi , Kinoshita Toru , Kawasaki Koji , Takeuchi Misaichi , Koike Choshiro , Aoyagi Yoshinobu
Published: May 2006

GaN‐based striped structures were fabricated using Al0.2Ga0.8N/GaN single heterostructure by combination of dry/wet etching with taking into account GaN crystal structure. After following wet‐etching, the sidewalls of striped structures along the <11$ \bar 2 $0> direction became very smooth and straight compared with that of as dry‐etched. We estimated mobility of electron in field effect transistors (FETs) consists striped structures along the <11$ \bar 2 $0> direction from I‐V characteristics. The mobility of the as dry‐etched striped structures was drastically reduced from the not‐patterned Al0.2Ga0.8N/GaN single heterostructure. In contrast, the mobility of the smooth striped structure FETs were effectively recovered to that of the not‐patterned one. These results suggest that following KOH wet‐etching can remove the damaged/rough layer indued by the RIE dry‐etching. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Analysis of the local structure of AlN:Mn using X‐ray absorption fine structure measurements
Authors: Miyajima Takao , Kudo Yoshihiro , Uruga Tomoya , Hara Kazuhiko
Published: May 2006

The local structure around the Mn atoms in MOCVD‐grown AlN:Mn films which show Mn‐related red‐orange photoluminescence with a 600nm‐peak at room temperature was investigated using the X‐ray absorption fine structure (XAFS) measurements. We found that Mn atoms occupy Al lattice sites in the AlN film and that the Mn ions have a charge between +2 and +3. From these results, we think that the red‐orange luminescence is caused by the transition of d‐electrons in the Mn ions. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Direct correlation between nonradiative recombination centers and threading dislocations in InGaN quantum wells by near‐field photoluminescence spectroscopy
Authors: Kaneta Akio , Funato Mitsuru , Narukawa Yukio , Mukai Takashi , Kawakami Yoichi
Published: May 2006

We performed near‐field photoluminescence (PL) mapping and atomic force microscopy at the same scanning area to clarify relationship between luminescence dynamics and threading dislocations in violet and blue light emitting InGaN single‐quantum‐well structures on epitaxially laterally overgrown GaN templates at room temperature. Clear correlation has been found between the distribution of dark area in PL mapping data and threading dislocations with screw and mixed types in the violet sample. On the other hand, such correlation has not been found in the blue sample. These results indicated that the carriers/excitons are captured easily in nonradiative recombination centers (NRCs) originating from the threading dislocations in the violet sample, because the lateral diffusion length of carriers/excitons is large due to a small potential fluctuation induced by compositional fluctuation of In comparing to those in the blue sample. However, the capture to such NRCs is hindered effectively in the blue one because of the localization to potential minima. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Bending in HVPE GaN free‐standing films: effects of laser lift‐off, polishing and high‐pressure annealing
Authors: Paskova T. , Darakchieva V. , Paskov P. P. , Monemar B. , Bukowski M. , Suski T. , Ashkenov N. , Schubert M. , Hommel D.
Published: May 2006

We have studied the effects of laser lift‐off and polishing processes on the bending of free‐standing HVPE grown GaN thick films. Their structural characteristics were accessed by reciprocal space mapping and lattice parameters measurements as well as by Raman scattering and photoluminescence. The in‐plane strain difference between the two faces was found to have determining effect on the bending of the free‐standing films. Removing the high‐defect‐density near‐interface region either by melting caused by laser lift‐off, or by polishing, or by point defects dissociation caused by high‐pressure annealing was found to lead to flattening of the strain distribution along the film thickness and a significant reduction of the bending of the free‐standing films. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)